The Natural Orifice Surgery Consortium for Assessment and Research™ (NOSCAR™), a joint effort of the American Society for Gastrointestinal Endoscopy (ASGE) and the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES), announce the 2008 NOSCAR™ Research Award winners. The funds, granted through Olympus Medical Systems' Olympus Research Fund and by KARL STORZ Endoscopy-America, Inc., will be distributed among 14 grant recipients supporting 16 research projects in the emerging transdisciplinary therapy known as Natural Orifice Translumenal Endoscopic Surgery™ (NOTES™), an approach that could ultimately represent a major paradigm shift in minimally invasive therapy and patient care. NOSCAR™ received 32 grant applications for the $750,000 in research funds.
"We received an outstanding response for research funding reflecting the momentum this revolutionary technique has created," said Michael L. Kochman, MD, FASGE, NOSCAR™ Research Subcommittee co-chair. "These grant recipients are conducting research that is pointing us to the next phase in the evolution of the NOTES™ procedure, which is multicenter human studies."
The first NOSCAR™ Research Awards were announced in 2006. Since that time, 56 grants have been awarded. Recipients of the 2008 awards are conducting research in both animal models and humans. Past NOSCAR™ Research Award winners recently presented data from their projects at the 3rd International Conference on NOTES™ held in San Francisco, Calif., July 10-12, 2008. Presentations included research on improving patient safety and multidisciplinary team efficiency, the physiologic and immunologic impact of NOTES™, drainage of abdominal abscess, and gastric leak testing, among others.
"NOSCAR™ is grateful to Olympus Medical Systems and KARL STORZ Endoscopy-America for supporting NOTES™ research and helping to advance this minimally invasive technique," said Steven Schwaitzberg, MD, NOSCAR™ Research Subcommittee co-chair.
Awards Supported by Olympus Medical Systems
Juliane Bingener-Casey, MD, Mayo Clinic, Rochester, MN
Randomized Double-Blinded Trial Comparing Laparoscopy and Natural Orifice Translumenal Endoscopic Surgery Procedures in a Porcine Model
B. Joseph Elmunzer, MD, University of Michigan, Ann Arbor, MI
Endoscopic Full Thickness Resection of Gastric Lesions Using a Novel Grasp-and-Snare Technique: Evaluation in a Porcine Survival Model
Jeffrey Hazey, MD, Ohio State University Hospital, Columbus, OH
Feasibility of Diagnostic Translumenal Endoscopic Peritoneoscopy for Abdominal Insufflation, Adhesiolysis and Trocar Placement in Patients Who Require Laparoscopic Access
Michael Marohn, DO, Johns Hopkins University School of Medicine, Baltimore, MD
Immune & Baseline Alterations on the Physiologic Response to Natural Orifice Translumenal Endoscopic Surgery (NOTES™): A Comparison Between Human Transvaginal and Laparoscopic Cholecystectomy
Erica Moran, MD, Mayo Clinic, Rochester, MN пїЅпїЅ" 2 Awards
1) Randomized Controlled Trial Evaluating NOTES™ Repair of Hollow Viscus Perforation
2) Assessment of Methodology and Extended Outcome of Submucosal Endoscopy with Mucosal Flap (SEMF) Myotomy for Treatment of Achalasia
Kiyokazu Nakajima, MD, PhD, Osaka University School of Medicine, Osaka, Japan
Comprehension of Current Limitations in Endoscopic Automatic CO2 Insufflation: Towards Pure NOTES™
Brant K. Oelschlager, MD, University of Washington, Seattle, WA
Assessment of a Simple, Novel Endoluminal Method for Gastrotomy Closure in NOTES™
Adrian Park, MD, University of Maryland Medical Center, Baltimore, MD
Quantitative Ergonomic Assessment of NOTES™ Techniques: A Study of Physical and Mental Workload, Body Movement and Posture
Richard Rothstein, MD, Dartmouth-Hitchcock Medical Center, Lebanon, NH
Patient Quality of Life and Utility for Natural Orifice Translumenal Endoscopic Surgery
Awards Supported by KARL STORZ Endoscopy-America
Erica Moran, MD, Mayo Clinic, Rochester, MN
NOTES™ Retroperitoneal Access Using Prone Positioning in Humans
Mark Sawyer, MD, Case University Hospitals of Cleveland, Cleveland, OH
Transgastric Extravesical Partial Cystectomy: Acute and Chronic Porcine Study with Histopathologic Evaluation of Cystotomy Healing
Georg O. Spaun, MD, Legacy Health System, Clackamas, OR
The Role of Flexible Endoscopy in Mediastinal Dissection for Esophageal Surgery
Thadeus Trus, MD, University of Rochester, Rochester, NY
The NOSCAR™ Delphi Project: Towards a Research Agenda in Natural Orifice Translumenal Endoscopic Surgery
Mark Whiteford, MD, Legacy Health System, Portland, OR
An Incisionless Approach for Radical Sigmoid Resection and Primary Anastomosis
Oliver J. Wagner, MD, University Hospital Geneva, Geneva, Switzerland
NOTES™ Roux-en-Y Gastric Bypass: An Experimental Surgical Study in Pigs
NOTES™ Course Information
ASGE Masters Series Course
Insight into NOTES™: A Hands-on Course for Human Applications
November 7-8, 2008
Phoenix, AZ
Course Directors:
Brian J. Dunkin, MD, FACS, The Methodist Hospital, Houston, TX
Anthony N. Kalloo, MD, FASGE, Johns Hopkins Hospital, Baltimore, MD
For more information on this course, visit asge/.
About NOSCAR
Natural Orifice Translumenal Endoscopic Surgery™ (NOTES™) might represent the next major advancement in minimally invasive therapy. To address this emerging technology, a working group consisting of expert laparoscopic surgeons from SAGES and a group of expert interventional endoscopists representing ASGE have joined together as the Natural Orifice Surgery Consortium for Assessment and Research™ (NOSCAR™) Working Group on NOTES™. The growing capabilities of therapeutic flexible endoscopy have ushered in a new era in treatment of gastrointestinal conditions. Refinements in laparoscopic surgery have progressed to the point that complex surgical procedures, such as gastric bypass, can now be performed in a minimally invasive fashion. These trends have set the stage for the development of even less invasive methods to treat conditions in both the gut lumen and in the peritoneal cavity. It seems feasible that major intraperitoneal surgery may one day be performed without skin incisions. The natural orifices may provide the entry point for surgical interventions in the peritoneal cavity thereby avoiding abdominal wall incisions. For more information, visit wnoscar/.
About the Society of American Gastrointestinal and Endoscopic Surgeons
The Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) was founded in 1981 to foster, promote, support and encourage academic, clinical and research achievement in gastrointestinal endoscopic surgery. Our members are general and colorectal surgeons who perform endoscopy and laparoscopy as part of their practice as well as surgical residents, fellows, and other allied health personnel. The Society has grown from fewer than 50 original members to more than 5,500 from every state and over 80 countries. Visit sages/ for more information.
About the American Society for Gastrointestinal Endoscopy
Founded in 1941, the mission of the American Society for Gastrointestinal Endoscopy is to be the leader in advancing patient care and digestive health by promoting excellence in gastrointestinal endoscopy. ASGE, with 10,000 physician members worldwide, promotes the highest standards for endoscopic training and practice, fosters endoscopic research, recognizes distinguished contributions to endoscopy, and is the foremost resource for endoscopic education. Visit asge/ and screen4coloncancer/ for more information.
About Olympus Medical Systems Corporation
Olympus developed the first gastrocamera in 1950, and has since developed a wide range of fiberscopes and videoscopes for direct internal observation of the human body. Today, we are expanding our minimally invasive treatment business to offer a wide range of instruments and peripheral devices for medical treatment and clinical diagnoses, including endoscopic surgery. We are improving medical and healthcare services by developing "more patient-friendly medical care" technology for early detection and treatment of diseases, even "greater reliability" in our unsurpassed devices and "high efficiency" in our products and services to better serve our customers' needs. More information on the company can be found at olympus.co.jp/en/.
About KARL STORZ
Karl Storz Endoscopy-America, Inc. is an affiliate of Karl Storz GmbH & Co. KG, an international leader for over 60 years in reusable endoscope technology, encompassing all endoscopic specialties. Based in Tuttlingen, Germany, Karl Storz GmbH & Co. KG is a family-owned company that designs, engineers, manufactures and markets all its products with an emphasis on visionary design, precision craftsmanship and clinical effectiveness. For more information visit the company's Web site at karlstorz/.
Source: Anne Brownsey
American Society for Gastrointestinal Endoscopy
понедельник, 6 июня 2011 г.
'Ballooning' Spiders Grounded By Infection
Money spiders infected with Rickettsia bacteria are less likely to 'balloon' - that is, to use their silk as sails to catch gusts of wind and travel long distances. Researchers writing in the open access journal BMC Biology suggest that it may be in the bacteria's interests to ground the spiders and that this reduction in dispersal could reduce gene flow and impact on reproductive isolation within the meta-population.
While working at the University of East Anglia, Sara Goodacre led an international team of researchers who investigated the microbes' effect on the spiders' ballooning behavior. She said, "Because we found no reduction in fitness associated with Rickettsia infection, the reduced long-distance dispersal seems unlikely to be simply due to decreased body condition caused by illness. Rather, we believe that reducing long-distance dispersal could be an evolved adaptive modification by bacterial infections to promote their own transmission".
The researchers treated the spiders with antibiotics to reduce the bacterial infection and showed that this increased their ballooning frequency. They also observed that Rickettsia-infected spiders reared in the laboratory had reduced long-distance (but not short-distance) dispersal. This parasite-induced change in a non-reproductive trait has never been shown before and, according to Goodacre, "Clearly shows that the dynamics of ecosystem services such as a spider's pest-controlling function may be altered as a consequence of bacterial infection".
Notes:
Microbial modification of host long-distance dispersal capacity
Sara L Goodacre, Oliver Y Martin, Dries Bonte, Linda Hutchings, Chris Woolley, Kamal Ibrahim, C.F. George Thomas and Godfrey M Hewitt
BMC Biology (in press)
Article
All articles are available free of charge, according to BioMed Central's open access policy.
Source:
Graeme Baldwin
BioMed Central
While working at the University of East Anglia, Sara Goodacre led an international team of researchers who investigated the microbes' effect on the spiders' ballooning behavior. She said, "Because we found no reduction in fitness associated with Rickettsia infection, the reduced long-distance dispersal seems unlikely to be simply due to decreased body condition caused by illness. Rather, we believe that reducing long-distance dispersal could be an evolved adaptive modification by bacterial infections to promote their own transmission".
The researchers treated the spiders with antibiotics to reduce the bacterial infection and showed that this increased their ballooning frequency. They also observed that Rickettsia-infected spiders reared in the laboratory had reduced long-distance (but not short-distance) dispersal. This parasite-induced change in a non-reproductive trait has never been shown before and, according to Goodacre, "Clearly shows that the dynamics of ecosystem services such as a spider's pest-controlling function may be altered as a consequence of bacterial infection".
Notes:
Microbial modification of host long-distance dispersal capacity
Sara L Goodacre, Oliver Y Martin, Dries Bonte, Linda Hutchings, Chris Woolley, Kamal Ibrahim, C.F. George Thomas and Godfrey M Hewitt
BMC Biology (in press)
Article
All articles are available free of charge, according to BioMed Central's open access policy.
Source:
Graeme Baldwin
BioMed Central
Discovering What Lies Beneath Unlearned Behavioral Response
Try this at home: If fruit flies are buzzing around your kitchen, switch on your hairdryer and aim it at the flies. A gentle stream of air will stop them in their tracks, putting them in prime position for swatting.
The reaction of fruit flies to wind was something that had intrigued biologist David J. Anderson for some time. When the flies sensed the wind, they went into a defensive, hunkering-down position until the feel of the wind ceased, then resumed flying around.
With an interest in animals' defensive behavior and its evolutionary ties to emotion, Anderson became interested in the neural connections underlying the flies' response to wind. In a study described in the March 12 issue of the journal Nature, Anderson and his team zeroed in on how the flies process the feel of the wind and respond by freezing in place. They found that that the flies' wind-sensitive neurons exist in the same sensory organ in the flies' antennae as the neurons that process the sound of the song of a potential mate.
The next challenge was determining how the same organ processed two distinct stimuli, leading to two distinct behavioral responses. Anderson and his team, including graduate student Suzuko Yorozu, were able to dissect the neural circuits that underlie this defensive behavior and see a different set of neurons "light up" in response to wind versus the sound of courtship song.
The team mounted a fly upside down under a very powerful two-photon microscope. Cutting a hole in the cuticle--the shell that covers the fly's brain--the team had a detailed view into the fly's brain. Having used sophisticated techniques to selectively visualize the activity of particular genes in the fly, the researchers could see when any neurons in the fly's brain were activated by a particular stimulus.
"So we positioned a loudspeaker in front of the fly, and we delivered courtship sound recordings and wind, and as we did that we could watch in real time the neurons that were lighting up in the brain," said Anderson. "And it was absolutely obvious that neurons in different regions of the brain were being activated by the sound or activated by the wind, and these regions were different, even if we applied the two stimuli simultaneously."
This kind of detailed understanding of the neurons involved in defensive behavior has potential application to treatment of mental illnesses in humans, though Anderson admits this is a long way off. But knowing more about neural circuits could provide the means to target medications to precisely where they are needed, as opposed to treating the brain globally and prompting many unpleasant side-effects.
"To be able to pinpoint the parts of the brain that process behavior responses, including emotional responses would be very useful," said Anderson. "So that someday we'll be able to hone in in a more laser-like manner and be able to have drugs that are targeted to specific circuits in the brain."
Source:
Maria C. Zacharias
National Science Foundation
The reaction of fruit flies to wind was something that had intrigued biologist David J. Anderson for some time. When the flies sensed the wind, they went into a defensive, hunkering-down position until the feel of the wind ceased, then resumed flying around.
With an interest in animals' defensive behavior and its evolutionary ties to emotion, Anderson became interested in the neural connections underlying the flies' response to wind. In a study described in the March 12 issue of the journal Nature, Anderson and his team zeroed in on how the flies process the feel of the wind and respond by freezing in place. They found that that the flies' wind-sensitive neurons exist in the same sensory organ in the flies' antennae as the neurons that process the sound of the song of a potential mate.
The next challenge was determining how the same organ processed two distinct stimuli, leading to two distinct behavioral responses. Anderson and his team, including graduate student Suzuko Yorozu, were able to dissect the neural circuits that underlie this defensive behavior and see a different set of neurons "light up" in response to wind versus the sound of courtship song.
The team mounted a fly upside down under a very powerful two-photon microscope. Cutting a hole in the cuticle--the shell that covers the fly's brain--the team had a detailed view into the fly's brain. Having used sophisticated techniques to selectively visualize the activity of particular genes in the fly, the researchers could see when any neurons in the fly's brain were activated by a particular stimulus.
"So we positioned a loudspeaker in front of the fly, and we delivered courtship sound recordings and wind, and as we did that we could watch in real time the neurons that were lighting up in the brain," said Anderson. "And it was absolutely obvious that neurons in different regions of the brain were being activated by the sound or activated by the wind, and these regions were different, even if we applied the two stimuli simultaneously."
This kind of detailed understanding of the neurons involved in defensive behavior has potential application to treatment of mental illnesses in humans, though Anderson admits this is a long way off. But knowing more about neural circuits could provide the means to target medications to precisely where they are needed, as opposed to treating the brain globally and prompting many unpleasant side-effects.
"To be able to pinpoint the parts of the brain that process behavior responses, including emotional responses would be very useful," said Anderson. "So that someday we'll be able to hone in in a more laser-like manner and be able to have drugs that are targeted to specific circuits in the brain."
Source:
Maria C. Zacharias
National Science Foundation
How running made us human
Endurance running let us evolve to look the way we do -
Humans evolved from ape-like ancestors because they needed to run long distances - perhaps to hunt animals or scavenge carcasses on Africa's vast savannah - and the ability to run shaped our anatomy, making us look like we do today.
That is the conclusion of a study published in the Nov. 18 issue of the journal Nature by University of Utah biologist Dennis Bramble and Harvard University anthropologist Daniel Lieberman. The study is featured on Nature's cover.
Bramble and Lieberman argue that our genus, Homo, evolved from more ape-like human ancestors, Australopithecus, 2 million or more years ago because natural selection favored the survival of australopithecines that could run and, over time, favored the perpetuation of human anatomical features that made long-distance running possible.
"We are very confident that strong selection for running - which came at the expense of the historical ability to live in trees - was instrumental in the origin of the modern human body form," says Bramble, a professor of biology. "Running has substantially shaped human evolution. Running made us human - at least in an anatomical sense. We think running is one of the most transforming events in human history. We are arguing the emergence of humans is tied to the evolution of running."
That conclusion is contrary to the conventional theory that running simply was a byproduct of the human ability to walk. Bipedalism - the ability to walk upright on two legs - evolved in the ape-like Australopithecus at least 4.5 million years ago while they also retained the ability to travel through the trees. Yet Homo with its "radically transformed body" did not evolve for another 3 million or more years - Homo habilis, Homo erectus and, finally, our species, Homo sapiens - so the ability to walk cannot explain anatomy of the modern human body, Bramble says.
"There were 2.5 million to 3 million years of bipedal walking [by australopithecines] without ever looking like a human, so is walking going to be what suddenly transforms the hominid body?" he asks. "We're saying, no, walking won't do that, but running will."
Walking cannot explain most of the changes in body form that distinguish Homo from Australopithecus, which - when compared with Homo - had short legs, long forearms, high permanently "shrugged" shoulders, ankles that were not visibly apparent and more muscles connecting the shoulders to the head and neck, Bramble says. If natural selection had not favored running, "we would still look a lot like apes," he adds.
I Run, Therefore I Am
Bramble and Lieberman examined 26 traits of the human body - many also seen in fossils of Homo erectus and some in Homo habilis - that enhanced the ability to run. Only some of them were needed for walking. Traits that aided running include leg and foot tendons and ligaments that act like springs, foot and toe structure that allows efficient use of the feet to push off, shoulders that rotate independently of the head and neck to allow better balance, and skeletal and muscle features that make the human body stronger, more stable and able to run more efficiently without overheating.
"We explain the simultaneous emergence of a whole bunch of anatomical features, literally from head to toe," Bramble says. "We have a hypothesis that gives a functional explanation for how these features are linked to the unique mechanical demands of running, how they work together and why they emerged at the same time."
Humans are poor sprinters compared with other running animals, which is partly why many scientists have dismissed running as a factor in human evolution. Human endurance running ability has been inadequately appreciated because of a failure to recognize that "high speed is not always important," Bramble says. "What is important is combining reasonable speed with exceptional endurance."
Another reason is that "scientists are in developed societies that are highly dependent on technology and artificial means of transport," he adds. "But if those scientists had been embedded in a hunter-gatherer society, they'd have a different view of human locomotor abilities, including running."
Why Did Humans Start Running?
The researchers do not know why natural selection favored human ancestors who could run long distances. For one possibility, they cite previous research by University of Utah biologist David Carrier, who hypothesized that endurance running evolved in human ancestors so they could pursue predators long before the development of bows, arrows, nets and spear-throwers reduced the need to run long distances.
Another possibility is that early humans and their immediate ancestors ran to scavenge carcasses of dead animals - maybe so they could beat hyenas or other scavengers to dinner, or maybe to "get to the leftovers soon enough," Bramble says.
Scavenging "is a more reliable source of food" than hunting, he adds. "If you are out in the African savannah and see a column of vultures on the horizon, the chance of there being a fresh carcass underneath the vultures is about 100 percent. If you are going to hunt down something in the heat, that's a lot more work and the payoffs are less reliable" because the animal you are hunting often is "faster than you are."
Anatomical Features that Help Humans Run
Here are anatomical characteristics that are unique to humans and that play a role in helping people run, according to the study:
• Skull features that help prevent overheating during running. As sweat evaporates from the scalp, forehead and face, the evaporation cools blood draining from the head. Veins carrying that cooled blood pass near the carotid arteries, thus helping cool blood flowing through the carotids to the brain.
• A more balanced head with a flatter face, smaller teeth and short snout, compared with australopithecines. That "shifts the center of mass back so it's easier to balance your head when you are bobbing up and down running," Bramble says.
• A ligament that runs from the back of the skull and neck down to the thoracic vertebrae, and acts as a shock absorber and helps the arms and shoulders counterbalance the head during running.
• Unlike apes and australopithecines, the shoulders in early humans were "decoupled" from the head and neck, allowing the body to rotate while the head aims forward during running.
• The tall human body - with a narrow trunk, waist and pelvis - creates more skin surface for our size, permitting greater cooling during running. It also lets the upper and lower body move independently, "which allows you to use your upper body to counteract the twisting forces from your swinging legs," Bramble says.
• Shorter forearms in humans make it easier for the upper body to counterbalance the lower body during running. They also reduce the amount of muscle power needed to keep the arms flexed when running.
• Human vertebrae and disks are larger in diameter relative to body mass than are those in apes or australopithecines. "This is related to shock absorption," says Bramble. "It allows the back to take bigger loads when human runners hit the ground."
• The connection between the pelvis and spine is stronger and larger relative to body size in humans than in their ancestors, providing more stability and shock absorption during running.
• Human buttocks "are huge," says Bramble. "Have you ever looked at an ape? They have no buns." He says human buttocks "are muscles critical for stabilization in running" because they connect the femur - the large bone in each upper leg - to the trunk. Because people lean forward at the hip during running, the buttocks "keep you from pitching over on your nose each time a foot hits the ground."
• Long legs, which chimps and australopithecines lack, let humans to take huge strides when running, Bramble says. So do ligaments and tendons - including the long Achilles tendon - which act like springs that store and release mechanical energy during running. The tendons and ligaments also mean human lower legs that are less muscular and lighter, requiring less energy to move them during running.
• Larger surface areas in the hip, knee and ankle joints, for improved shock absorption during running by spreading out the forces.
• The arrangement of bones in the human foot creates a stable or stiff arch that makes the whole foot more rigid, so the human runner can push off the ground more efficiently and utilize ligaments on the bottom of the feet as springs.
• Humans also evolved with an enlarged heel bone for better shock absorption, as well as shorter toes and a big toe that is fully drawn in toward the other toes for better pushing off during running.
The study by Bramble and Lieberman concludes: "Today, endurance running is primarily a form of exercise and recreation, but its roots may be as ancient as the origin of the human genus, and its demands a major contributing factor to the human body form."
University of Utah Public Relations
201 S Presidents Circle, Room 308
Salt Lake City, Utah 84112-9017
(801) 581-6773 fax: 585-3350
Contact: Dennis Bramble, professor of biology
bramblebioscience.utah
801-581-3549 (office)
University of Utah
Lee Siegel, science news specialist
leesiegelucomm.utah
801-581-8993 (office) / 801-244-5399 (cellular)
University of Utah Public Relations
To contact Dan Lieberman, call Steve Bradt
steve_bradtharvard
617-496-8070
Harvard University Communications
University of Utah
Humans evolved from ape-like ancestors because they needed to run long distances - perhaps to hunt animals or scavenge carcasses on Africa's vast savannah - and the ability to run shaped our anatomy, making us look like we do today.
That is the conclusion of a study published in the Nov. 18 issue of the journal Nature by University of Utah biologist Dennis Bramble and Harvard University anthropologist Daniel Lieberman. The study is featured on Nature's cover.
Bramble and Lieberman argue that our genus, Homo, evolved from more ape-like human ancestors, Australopithecus, 2 million or more years ago because natural selection favored the survival of australopithecines that could run and, over time, favored the perpetuation of human anatomical features that made long-distance running possible.
"We are very confident that strong selection for running - which came at the expense of the historical ability to live in trees - was instrumental in the origin of the modern human body form," says Bramble, a professor of biology. "Running has substantially shaped human evolution. Running made us human - at least in an anatomical sense. We think running is one of the most transforming events in human history. We are arguing the emergence of humans is tied to the evolution of running."
That conclusion is contrary to the conventional theory that running simply was a byproduct of the human ability to walk. Bipedalism - the ability to walk upright on two legs - evolved in the ape-like Australopithecus at least 4.5 million years ago while they also retained the ability to travel through the trees. Yet Homo with its "radically transformed body" did not evolve for another 3 million or more years - Homo habilis, Homo erectus and, finally, our species, Homo sapiens - so the ability to walk cannot explain anatomy of the modern human body, Bramble says.
"There were 2.5 million to 3 million years of bipedal walking [by australopithecines] without ever looking like a human, so is walking going to be what suddenly transforms the hominid body?" he asks. "We're saying, no, walking won't do that, but running will."
Walking cannot explain most of the changes in body form that distinguish Homo from Australopithecus, which - when compared with Homo - had short legs, long forearms, high permanently "shrugged" shoulders, ankles that were not visibly apparent and more muscles connecting the shoulders to the head and neck, Bramble says. If natural selection had not favored running, "we would still look a lot like apes," he adds.
I Run, Therefore I Am
Bramble and Lieberman examined 26 traits of the human body - many also seen in fossils of Homo erectus and some in Homo habilis - that enhanced the ability to run. Only some of them were needed for walking. Traits that aided running include leg and foot tendons and ligaments that act like springs, foot and toe structure that allows efficient use of the feet to push off, shoulders that rotate independently of the head and neck to allow better balance, and skeletal and muscle features that make the human body stronger, more stable and able to run more efficiently without overheating.
"We explain the simultaneous emergence of a whole bunch of anatomical features, literally from head to toe," Bramble says. "We have a hypothesis that gives a functional explanation for how these features are linked to the unique mechanical demands of running, how they work together and why they emerged at the same time."
Humans are poor sprinters compared with other running animals, which is partly why many scientists have dismissed running as a factor in human evolution. Human endurance running ability has been inadequately appreciated because of a failure to recognize that "high speed is not always important," Bramble says. "What is important is combining reasonable speed with exceptional endurance."
Another reason is that "scientists are in developed societies that are highly dependent on technology and artificial means of transport," he adds. "But if those scientists had been embedded in a hunter-gatherer society, they'd have a different view of human locomotor abilities, including running."
Why Did Humans Start Running?
The researchers do not know why natural selection favored human ancestors who could run long distances. For one possibility, they cite previous research by University of Utah biologist David Carrier, who hypothesized that endurance running evolved in human ancestors so they could pursue predators long before the development of bows, arrows, nets and spear-throwers reduced the need to run long distances.
Another possibility is that early humans and their immediate ancestors ran to scavenge carcasses of dead animals - maybe so they could beat hyenas or other scavengers to dinner, or maybe to "get to the leftovers soon enough," Bramble says.
Scavenging "is a more reliable source of food" than hunting, he adds. "If you are out in the African savannah and see a column of vultures on the horizon, the chance of there being a fresh carcass underneath the vultures is about 100 percent. If you are going to hunt down something in the heat, that's a lot more work and the payoffs are less reliable" because the animal you are hunting often is "faster than you are."
Anatomical Features that Help Humans Run
Here are anatomical characteristics that are unique to humans and that play a role in helping people run, according to the study:
• Skull features that help prevent overheating during running. As sweat evaporates from the scalp, forehead and face, the evaporation cools blood draining from the head. Veins carrying that cooled blood pass near the carotid arteries, thus helping cool blood flowing through the carotids to the brain.
• A more balanced head with a flatter face, smaller teeth and short snout, compared with australopithecines. That "shifts the center of mass back so it's easier to balance your head when you are bobbing up and down running," Bramble says.
• A ligament that runs from the back of the skull and neck down to the thoracic vertebrae, and acts as a shock absorber and helps the arms and shoulders counterbalance the head during running.
• Unlike apes and australopithecines, the shoulders in early humans were "decoupled" from the head and neck, allowing the body to rotate while the head aims forward during running.
• The tall human body - with a narrow trunk, waist and pelvis - creates more skin surface for our size, permitting greater cooling during running. It also lets the upper and lower body move independently, "which allows you to use your upper body to counteract the twisting forces from your swinging legs," Bramble says.
• Shorter forearms in humans make it easier for the upper body to counterbalance the lower body during running. They also reduce the amount of muscle power needed to keep the arms flexed when running.
• Human vertebrae and disks are larger in diameter relative to body mass than are those in apes or australopithecines. "This is related to shock absorption," says Bramble. "It allows the back to take bigger loads when human runners hit the ground."
• The connection between the pelvis and spine is stronger and larger relative to body size in humans than in their ancestors, providing more stability and shock absorption during running.
• Human buttocks "are huge," says Bramble. "Have you ever looked at an ape? They have no buns." He says human buttocks "are muscles critical for stabilization in running" because they connect the femur - the large bone in each upper leg - to the trunk. Because people lean forward at the hip during running, the buttocks "keep you from pitching over on your nose each time a foot hits the ground."
• Long legs, which chimps and australopithecines lack, let humans to take huge strides when running, Bramble says. So do ligaments and tendons - including the long Achilles tendon - which act like springs that store and release mechanical energy during running. The tendons and ligaments also mean human lower legs that are less muscular and lighter, requiring less energy to move them during running.
• Larger surface areas in the hip, knee and ankle joints, for improved shock absorption during running by spreading out the forces.
• The arrangement of bones in the human foot creates a stable or stiff arch that makes the whole foot more rigid, so the human runner can push off the ground more efficiently and utilize ligaments on the bottom of the feet as springs.
• Humans also evolved with an enlarged heel bone for better shock absorption, as well as shorter toes and a big toe that is fully drawn in toward the other toes for better pushing off during running.
The study by Bramble and Lieberman concludes: "Today, endurance running is primarily a form of exercise and recreation, but its roots may be as ancient as the origin of the human genus, and its demands a major contributing factor to the human body form."
University of Utah Public Relations
201 S Presidents Circle, Room 308
Salt Lake City, Utah 84112-9017
(801) 581-6773 fax: 585-3350
Contact: Dennis Bramble, professor of biology
bramblebioscience.utah
801-581-3549 (office)
University of Utah
Lee Siegel, science news specialist
leesiegelucomm.utah
801-581-8993 (office) / 801-244-5399 (cellular)
University of Utah Public Relations
To contact Dan Lieberman, call Steve Bradt
steve_bradtharvard
617-496-8070
Harvard University Communications
University of Utah
Study Of Tumor Growth And Tissue Disruption Identifies Key Components In The Immune Response To Cancers
Knee scrapes and tumor growth might have more in common than you think.
The idea that tumor growth triggers the same immune response as a cut or wound was once a highly controversial notion. However, increasing evidence supports the idea that the same cellular mechanisms which heal a skinned knee might also have a role in preventing the growth of tumors. A report published in Disease Models & Mechanisms (DMM), dmm.biologists/, now reveals more details about the common links between tumor growth and tissue damage in flies.
Tian Xu and colleagues at the Yale University School of Medicine examined the activity of hemocytes, a type of immune cell, in response to genetically-induced tumor growth in the fruit fly Drosophila. They found that tumors caused circulating hemocytes to replicate and adhere to the tumor surface, thereby limiting tumor growth. They compared this hemocyte response to cell activity in normal flies which were wounded and had tissue damage. Hemocyte profileration in these flies occurred just as in the tumor-producing fly. Furthermore, by examining the molecular signals triggered in the immune response, Xu's team discovered that the tumor's physical disruption and damage of nearby tissues at least in part triggered the hemocyte response.
This study not only supports previously reported links between immune responses and cancer, but also identifies key pathways in the fly's immune response to tumor growth and tissue disruption. These pathways are likewise shared in humans, demonstrating that the fly can be used to study potential drug targets which could enhance the body's natural immune response against cancer.
Commentary on this work by researcher Tian Xu will be featured in the DMM Podcast for issue 2/3 of DMM. Podcasts are available via the DMM website at: dmm.biologists/.
The report was written by JosГ© Carlos Pastor-Pareja, Ming Wu, and Tian Xu of the Yale University School of Medicine, New Haven, CT. The report was published in the September/October issue of a new research journal, Disease Models & Mechanisms (DMM), published by The Company of Biologists, a non-profit based in Cambridge, UK.
About Disease Models & Mechanisms:
Disease Models & Mechanisms (DMM) is a new research journal publishing both primary scientific research, as well as review articles, editorials, and research highlights. The journal's mission is to provide a forum for clinicians and scientists to discuss basic science and clinical research related to human disease, disease detection and novel therapies. DMM is published by the Company of Biologists, a non-profit organization based in Cambridge, UK.
The Company also publishes the international biology research journals Development, Journal of Cell Science, and The Journal of Experimental Biology. In addition to financing these journals, the Company provides grants to scientific societies and supports other activities including travelling fellowships for junior scientists, workshops and conferences. The world's poorest nations receive free and unrestricted access to the Company's journals.
Source: Nick Birch
The Company of Biologists
The idea that tumor growth triggers the same immune response as a cut or wound was once a highly controversial notion. However, increasing evidence supports the idea that the same cellular mechanisms which heal a skinned knee might also have a role in preventing the growth of tumors. A report published in Disease Models & Mechanisms (DMM), dmm.biologists/, now reveals more details about the common links between tumor growth and tissue damage in flies.
Tian Xu and colleagues at the Yale University School of Medicine examined the activity of hemocytes, a type of immune cell, in response to genetically-induced tumor growth in the fruit fly Drosophila. They found that tumors caused circulating hemocytes to replicate and adhere to the tumor surface, thereby limiting tumor growth. They compared this hemocyte response to cell activity in normal flies which were wounded and had tissue damage. Hemocyte profileration in these flies occurred just as in the tumor-producing fly. Furthermore, by examining the molecular signals triggered in the immune response, Xu's team discovered that the tumor's physical disruption and damage of nearby tissues at least in part triggered the hemocyte response.
This study not only supports previously reported links between immune responses and cancer, but also identifies key pathways in the fly's immune response to tumor growth and tissue disruption. These pathways are likewise shared in humans, demonstrating that the fly can be used to study potential drug targets which could enhance the body's natural immune response against cancer.
Commentary on this work by researcher Tian Xu will be featured in the DMM Podcast for issue 2/3 of DMM. Podcasts are available via the DMM website at: dmm.biologists/.
The report was written by JosГ© Carlos Pastor-Pareja, Ming Wu, and Tian Xu of the Yale University School of Medicine, New Haven, CT. The report was published in the September/October issue of a new research journal, Disease Models & Mechanisms (DMM), published by The Company of Biologists, a non-profit based in Cambridge, UK.
About Disease Models & Mechanisms:
Disease Models & Mechanisms (DMM) is a new research journal publishing both primary scientific research, as well as review articles, editorials, and research highlights. The journal's mission is to provide a forum for clinicians and scientists to discuss basic science and clinical research related to human disease, disease detection and novel therapies. DMM is published by the Company of Biologists, a non-profit organization based in Cambridge, UK.
The Company also publishes the international biology research journals Development, Journal of Cell Science, and The Journal of Experimental Biology. In addition to financing these journals, the Company provides grants to scientific societies and supports other activities including travelling fellowships for junior scientists, workshops and conferences. The world's poorest nations receive free and unrestricted access to the Company's journals.
Source: Nick Birch
The Company of Biologists
What's 'Up' With A Class Of Retinal Cells In Mice?
Harvard University researchers have discovered a new type of retinal cell that plays an exclusive and unusual role in mice: detecting upward motion. The cells reflect their function in the physical arrangement of their dendrites, branch-like structures on neuronal cells that form a communicative network with other dendrites and neurons in the brain.
The work, led by neuroscientists Joshua R. Sanes and Markus Meister, is described this week in the journal Nature.
"The structure of these cells resembles the photos you see in the aftermath of a hurricane, where all the trees have fallen down in the same direction," says Meister, the Jeff C. Tarr Professor of Molecular and Cellular Biology in Harvard's Faculty of Arts and Sciences. "When you look at these neurons in the microscope, they all point the same way. There's no other cell type in the retina that has that degree of directionality."
The cells, like other retinal neurons, are composed of a round cell body surrounded by a tangle of dendrites. Most retinal neurons distribute their dendrites evenly around the cell body, but the upward motion-detecting cells arrange almost 90 percent of their dendrite tangle exclusively on one side of the cell body.
"This lopsided arrangement literally directs the cell's function, orienting the dendrites downward like roots of great trees," says Sanes, professor of molecular and cellular biology and Paul J. Finnegan Family Director of Harvard's Center for Brain Science. "Because the eye's lens acts as a camera, reversing incoming light rays as they strike the retinal tissue, an object moving up will result in a downward-moving image at the back of the eye -- the exact orientation of the cells' dendrites."
The research builds on efforts by Meister to understand neural processing in the retina, as well as work in Sanes's laboratory to identify and mark neurons in the retina using molecular tags. Recently, they tracked down a family of molecules expressed exclusively by small subsets of retinal cells in mice. One in particular, called JAM-B, was present in cells that had a peculiar distribution and orientation.
According to Sanes, developmental neurologists have long tried to identify different types of neural cells based on their function and anatomy -- how they appeared on the outside.
"But it's a huge limitation because it's essentially a qualitative assessment," he says. "We really need some way to reliably identify and track these cells if we ever hope to study their development. So the emergence of cell-specific molecular markers is a very big deal, because it will do just that. Already we've seen that it helps us identify new kinds of cells we didn't know existed before. Once we have a promising molecule, we can track down the cells that it corresponds to."
"The other important result," continues Sanes, "is that we're actually mimicking how the brain itself identifies its cells. The brain has to be able to reliably recognize and tell apart different kinds of cells, and that's going to happen on a molecular basis. In fact, it's possible that some of the molecules we've identified are, in fact, the same molecules the brain uses to distinguish cell types."
By identifying molecules that are solely expressed by specific types of neurons, scientists hope to gain insights into how nerve cells form synapses, or connections, with other nerve cells -- in short, how the brain controls its development on a molecular basis.
For the moment, however, researchers are busy puzzling over the results of the JAM-B mouse retinal cells.
"Why in the world would mice need to develop cells to detect upward motion?" Sanes wonders. "It's a great mystery."
Sanes and Meister's co-authors on the Nature paper are In-Jung Kim, Yifeng Zhang, and Masahito Yamagata, all of Harvard's Department of Molecular and Cellular Biology. In a separate Nature paper published earlier this year, Yamagata and Sanes demonstrated a type of target recognition not previously shown anywhere in the brain: They identified four recognition molecules, each of which marks and specifies a circuit in the retina, and showed the role of each for specific connectivity in that circuit.
The current research was funded by the National Institutes of Health.
Source: Steve Bradt
Harvard University
The work, led by neuroscientists Joshua R. Sanes and Markus Meister, is described this week in the journal Nature.
"The structure of these cells resembles the photos you see in the aftermath of a hurricane, where all the trees have fallen down in the same direction," says Meister, the Jeff C. Tarr Professor of Molecular and Cellular Biology in Harvard's Faculty of Arts and Sciences. "When you look at these neurons in the microscope, they all point the same way. There's no other cell type in the retina that has that degree of directionality."
The cells, like other retinal neurons, are composed of a round cell body surrounded by a tangle of dendrites. Most retinal neurons distribute their dendrites evenly around the cell body, but the upward motion-detecting cells arrange almost 90 percent of their dendrite tangle exclusively on one side of the cell body.
"This lopsided arrangement literally directs the cell's function, orienting the dendrites downward like roots of great trees," says Sanes, professor of molecular and cellular biology and Paul J. Finnegan Family Director of Harvard's Center for Brain Science. "Because the eye's lens acts as a camera, reversing incoming light rays as they strike the retinal tissue, an object moving up will result in a downward-moving image at the back of the eye -- the exact orientation of the cells' dendrites."
The research builds on efforts by Meister to understand neural processing in the retina, as well as work in Sanes's laboratory to identify and mark neurons in the retina using molecular tags. Recently, they tracked down a family of molecules expressed exclusively by small subsets of retinal cells in mice. One in particular, called JAM-B, was present in cells that had a peculiar distribution and orientation.
According to Sanes, developmental neurologists have long tried to identify different types of neural cells based on their function and anatomy -- how they appeared on the outside.
"But it's a huge limitation because it's essentially a qualitative assessment," he says. "We really need some way to reliably identify and track these cells if we ever hope to study their development. So the emergence of cell-specific molecular markers is a very big deal, because it will do just that. Already we've seen that it helps us identify new kinds of cells we didn't know existed before. Once we have a promising molecule, we can track down the cells that it corresponds to."
"The other important result," continues Sanes, "is that we're actually mimicking how the brain itself identifies its cells. The brain has to be able to reliably recognize and tell apart different kinds of cells, and that's going to happen on a molecular basis. In fact, it's possible that some of the molecules we've identified are, in fact, the same molecules the brain uses to distinguish cell types."
By identifying molecules that are solely expressed by specific types of neurons, scientists hope to gain insights into how nerve cells form synapses, or connections, with other nerve cells -- in short, how the brain controls its development on a molecular basis.
For the moment, however, researchers are busy puzzling over the results of the JAM-B mouse retinal cells.
"Why in the world would mice need to develop cells to detect upward motion?" Sanes wonders. "It's a great mystery."
Sanes and Meister's co-authors on the Nature paper are In-Jung Kim, Yifeng Zhang, and Masahito Yamagata, all of Harvard's Department of Molecular and Cellular Biology. In a separate Nature paper published earlier this year, Yamagata and Sanes demonstrated a type of target recognition not previously shown anywhere in the brain: They identified four recognition molecules, each of which marks and specifies a circuit in the retina, and showed the role of each for specific connectivity in that circuit.
The current research was funded by the National Institutes of Health.
Source: Steve Bradt
Harvard University
Glenn Foundation For Medical Research Commits $5 Million To Study Aging
The Glenn Foundation for Medical Research, founded by philanthropist Paul F. Glenn, has announced a $5 million commitment to the American Federation for Aging Research (AFAR) to provide grants to scientists studying the biology of aging and age-related diseases. This grant provides timely support as current cutbacks in federal funding jeopardize the careers of hundreds of promising investigators who are working to understand how aging influences disease.
The Glenn Foundation funds will go toward the AFAR Research Grant Program and the Glenn/AFAR Breakthroughs in Gerontology (BIG) Awards. AFAR Research Grants provide start-up funding to scientists in the early phases of their careers, enabling them to study the basic mechanisms of aging, age-related diseases and processes underlying common geriatric functional disorders. The Glenn/AFAR Breakthroughs in Gerontology Awards support innovative higher-risk research that may offer significant promise of yielding transforming discoveries in the fundamental biology of aging that could lead to major new insights into the factors that regulate aging.
"As the number of older adults in the United States continues to grow, there is a greater need not only to provide high-quality medical care but also to develop new scientific knowledge about aging processes and age-related diseases and disorders that will allow more people to live healthier longer, free of disability. Aging research is about studying the young, before the body breaks down. Scientists search for clues about why we develop diseases later in life," said Stephanie Lederman, executive director, AFAR. "The forward-thinking vision of Paul Glenn and the Glenn Foundation will allow greater distribution of resources to novel research that will benefit all of us as we age," she added.
"We are proud to support the work of AFAR," said Mark R. Collins, president of the Glenn Foundation for Medical Research. "Longer life brings with it vulnerability to diseases such as Alzheimer's, Parkinson's, osteoporosis, diabetes and others. Funding of aging research is an important path to the alleviation of suffering and reduced healthcare costs. This research forms the backbone of scientific advances in our understanding of aging. AFAR is a key organization in assuring that the best research remains supported."
Nearly 2,500 researchers have been recipients of AFAR-supported grant awards, many of whom have gone on to distinguish themselves as leaders in the field of aging research, chairing departments and running laboratories at major academic institutions. Many of the nation's leaders in biogerontology have been beneficiaries of AFAR grant programs.
The Glenn Foundation for Medical Research was founded in 1965 to extend the healthy productive years of life through research on the mechanisms of biological aging. For more information, visit glennfoundation/.
The American Federation for Aging Research is a nonprofit organization whose mission is to support biomedical research on aging. It is devoted to creating the knowledge that all of us need to live healthy, productive, and independent lives. Since 1981, AFAR has awarded more than $100 million to nearly 2,500 talented scientists as part of its broad-based series of grant programs. Its work has led to significant advances in our understanding of the aging process, age-related diseases, and healthy aging practices. AFAR communicates news of these innovations through its organizational web site afar/ and educational web sites Infoaging (infoaging) and Health Compass (healthcompass/).
Source: Stacey Harris
American Federation for Aging Research
The Glenn Foundation funds will go toward the AFAR Research Grant Program and the Glenn/AFAR Breakthroughs in Gerontology (BIG) Awards. AFAR Research Grants provide start-up funding to scientists in the early phases of their careers, enabling them to study the basic mechanisms of aging, age-related diseases and processes underlying common geriatric functional disorders. The Glenn/AFAR Breakthroughs in Gerontology Awards support innovative higher-risk research that may offer significant promise of yielding transforming discoveries in the fundamental biology of aging that could lead to major new insights into the factors that regulate aging.
"As the number of older adults in the United States continues to grow, there is a greater need not only to provide high-quality medical care but also to develop new scientific knowledge about aging processes and age-related diseases and disorders that will allow more people to live healthier longer, free of disability. Aging research is about studying the young, before the body breaks down. Scientists search for clues about why we develop diseases later in life," said Stephanie Lederman, executive director, AFAR. "The forward-thinking vision of Paul Glenn and the Glenn Foundation will allow greater distribution of resources to novel research that will benefit all of us as we age," she added.
"We are proud to support the work of AFAR," said Mark R. Collins, president of the Glenn Foundation for Medical Research. "Longer life brings with it vulnerability to diseases such as Alzheimer's, Parkinson's, osteoporosis, diabetes and others. Funding of aging research is an important path to the alleviation of suffering and reduced healthcare costs. This research forms the backbone of scientific advances in our understanding of aging. AFAR is a key organization in assuring that the best research remains supported."
Nearly 2,500 researchers have been recipients of AFAR-supported grant awards, many of whom have gone on to distinguish themselves as leaders in the field of aging research, chairing departments and running laboratories at major academic institutions. Many of the nation's leaders in biogerontology have been beneficiaries of AFAR grant programs.
The Glenn Foundation for Medical Research was founded in 1965 to extend the healthy productive years of life through research on the mechanisms of biological aging. For more information, visit glennfoundation/.
The American Federation for Aging Research is a nonprofit organization whose mission is to support biomedical research on aging. It is devoted to creating the knowledge that all of us need to live healthy, productive, and independent lives. Since 1981, AFAR has awarded more than $100 million to nearly 2,500 talented scientists as part of its broad-based series of grant programs. Its work has led to significant advances in our understanding of the aging process, age-related diseases, and healthy aging practices. AFAR communicates news of these innovations through its organizational web site afar/ and educational web sites Infoaging (infoaging) and Health Compass (healthcompass/).
Source: Stacey Harris
American Federation for Aging Research
Studying The Effect Of An Anti-Inflammatory COX-2 Inhibitor On The Development Of Pancreatic Cancer
Nimesulide, a cyclooxygenase-2 (COX-2) inhibitor, delays the progression of precancerous pancreatic lesions in mice, according to researchers at David Geffen School of Medicine at UCLA. While inflammation has been shown to be a factor in many forms of cancer, the researchers say this is the first study to demonstrate the effect of an anti-inflammatory COX-2 inhibitor on the development of pancreatic cancer.
The study, published in the August 1 issue of Cancer Research, a journal of the American Association for Cancer Research, suggests a potential role for COX-2 inhibitors in pancreatic cancer prevention among high-risk patients. Pancreatic cancer is one of the leading causes of cancer death in America -- over 33,000 Americans will likely die from the disease in 2007, according to projections from the American Cancer Society.
"By inhibiting COX-2 in human patients, we may have an option to delay the progression of lesions," said lead author Guido Eibl, M.D., scientific director of the Hirshberg Laboratory of Pancreatic Cancer Research and adjunct assistant professor at UCLA .
Researchers believe pancreatic cancer arises from abnormal tissues, or lesions in the pancreas, known as pancreatic intraepithelial neoplasias (PanINs). By stalling the growth of PanINs, researchers hope to slow the development of or prevent pancreatic cancer.
COX-2, an enzyme which causes inflammation, is no stranger to cancer researchers. Studies of breast, colon, and pancreatic cancers have led researchers to believe COX-2 plays a key role in the development and growth of tumors.
To study the effects of COX-2 on PanIN progression, Dr. Eibl and colleagues focused on the KrasG12D mouse, an animal model that mimics the early stages of pancreatic cancer. In the KrasG12D mouse, low-grade PanINs (stage I or II) begin to appear in the pancreas of mice at one month. Starting at six months, high-grade PanINs (stage III) can be found in the mouse pancreas. According to Dr. Eibl, most researchers agree that stage III PanINs are a direct precursor to pancreatic cancer in humans as well as mice. Between 12 and 15 months, Dr. Eibl says the majority of KrasG12D mice will develop pancreatic tumors.
The UCLA researchers divided the mice into two groups -- one set received a nimesulide-enriched diet for 10 months; the other was offered only regular mouse chow. Their analyses revealed that the nimesulide diet greatly reduced the number of late-stage PanINs in KrasG12D (10 percent of pancreatic ducts had PanIN-2 or -3 in KrasG12D mice on nimesulide diet versus 40 percent of pancreatic ducts had PanIN-2 or -3 in KrasG12D mice on normal diet).
Because the pancreases of mice were analyzed at 10 months, before the typical appearance of pancreatic tumors, additional studies will be needed for researchers to conclude whether or not nimesulide can delay the onset of or prevent pancreatic cancer.
"With these results, I certainly wouldn't say everyone should be taking COX-2 inhibitors to protect against cancer," said Eibl. "However, with additional studies, we may find COX-2 inhibitors could help prevent pancreatic cancer in high risk populations."
"Pancreatic cancer is so deadly because it often goes undetected until it's too late," said Dr. Eibl. "If a patient is at a high-risk for developing pancreatic cancer, a COX-2 inhibitor may offer some protection."
In the future, Dr. Eibl and others plan to study the long-term effects of nimesulide and additional COX-2 inhibitors on the onset and progression of pancreatic cancer.
This study was funded by the National Institutes of Health, the Jonsson Cancer Center Foundation at UCLA, and the Hirshberg Foundation for Pancreatic Cancer Research.
The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes nearly 26,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries.
AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care.
AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.
Source: Greg Lester
American Association for Cancer Research
The study, published in the August 1 issue of Cancer Research, a journal of the American Association for Cancer Research, suggests a potential role for COX-2 inhibitors in pancreatic cancer prevention among high-risk patients. Pancreatic cancer is one of the leading causes of cancer death in America -- over 33,000 Americans will likely die from the disease in 2007, according to projections from the American Cancer Society.
"By inhibiting COX-2 in human patients, we may have an option to delay the progression of lesions," said lead author Guido Eibl, M.D., scientific director of the Hirshberg Laboratory of Pancreatic Cancer Research and adjunct assistant professor at UCLA .
Researchers believe pancreatic cancer arises from abnormal tissues, or lesions in the pancreas, known as pancreatic intraepithelial neoplasias (PanINs). By stalling the growth of PanINs, researchers hope to slow the development of or prevent pancreatic cancer.
COX-2, an enzyme which causes inflammation, is no stranger to cancer researchers. Studies of breast, colon, and pancreatic cancers have led researchers to believe COX-2 plays a key role in the development and growth of tumors.
To study the effects of COX-2 on PanIN progression, Dr. Eibl and colleagues focused on the KrasG12D mouse, an animal model that mimics the early stages of pancreatic cancer. In the KrasG12D mouse, low-grade PanINs (stage I or II) begin to appear in the pancreas of mice at one month. Starting at six months, high-grade PanINs (stage III) can be found in the mouse pancreas. According to Dr. Eibl, most researchers agree that stage III PanINs are a direct precursor to pancreatic cancer in humans as well as mice. Between 12 and 15 months, Dr. Eibl says the majority of KrasG12D mice will develop pancreatic tumors.
The UCLA researchers divided the mice into two groups -- one set received a nimesulide-enriched diet for 10 months; the other was offered only regular mouse chow. Their analyses revealed that the nimesulide diet greatly reduced the number of late-stage PanINs in KrasG12D (10 percent of pancreatic ducts had PanIN-2 or -3 in KrasG12D mice on nimesulide diet versus 40 percent of pancreatic ducts had PanIN-2 or -3 in KrasG12D mice on normal diet).
Because the pancreases of mice were analyzed at 10 months, before the typical appearance of pancreatic tumors, additional studies will be needed for researchers to conclude whether or not nimesulide can delay the onset of or prevent pancreatic cancer.
"With these results, I certainly wouldn't say everyone should be taking COX-2 inhibitors to protect against cancer," said Eibl. "However, with additional studies, we may find COX-2 inhibitors could help prevent pancreatic cancer in high risk populations."
"Pancreatic cancer is so deadly because it often goes undetected until it's too late," said Dr. Eibl. "If a patient is at a high-risk for developing pancreatic cancer, a COX-2 inhibitor may offer some protection."
In the future, Dr. Eibl and others plan to study the long-term effects of nimesulide and additional COX-2 inhibitors on the onset and progression of pancreatic cancer.
This study was funded by the National Institutes of Health, the Jonsson Cancer Center Foundation at UCLA, and the Hirshberg Foundation for Pancreatic Cancer Research.
The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes nearly 26,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries.
AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care.
AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.
Source: Greg Lester
American Association for Cancer Research
Two Views Of Medical Science - Observational Research Versus Randomized Trials
"Two views about medical science seem to have split ever more apart over the past decades," says Jan Vandenbroucke (Royal Netherlands Academy of
Arts and Sciences and Leiden University Medical Centre, The Netherlands) in an essay in this week's PLoS Medicine.
One view, says the author, is that of medical researchers who rejoice in discoveries and explanations of causes of disease. "Discoveries happen when
things are suddenly seen in another light: the odd course of a disease in a patient, the strange results of a lab experiment, a peculiar subgroup in
the analysis of data, or some juxtaposition of papers in the literature."
The other view is that of medical researchers "whose aim is to set up studies to evaluate whether the patient's lot is really improved by the new
therapies or diagnostics that looked so wonderful initially." The most developed branch of evaluation research is the randomized trial of a drug
therapy.
Professor Vandenbrouke analyses in what respects these two views differ, and how they lead to opposite research hierarchies (with randomization on top
for evaluation and at bottom for discovery and explanation), and explores the reasons why we need both views.
"We need both hierarchies," says the author, "the hierarchy of discovery and explanation as well as that of evaluation. Without new discoveries
leading to potentially better diagnosis, prevention, or therapy, what would we do randomized trials on? Conversely, how could we know that a discovery
is useful, if not rigidly evaluated?"
Professor Vandenbrouke's essay is based upon the prestigious Austin Bradford Hill Memorial Lecture given at the London School of Hygiene and
Tropical Medicine on April 24, 2007.
On the 11th March, responses from John Ioannidis and Philippe Autier will also appear alongside the essay. You will be able to view them online
here.
Observational research, randomised trials, and two views of medical science
Vandenbroucke JP (2008)
PLoS Med 5(3): e67
Please click here to view article online
About PLoS Medicine
PLoS Medicine is an open access, freely available international medical journal. It publishes original research that enhances our understanding of
human health and disease, together with commentary and analysis of important global health issues.
plosmedicine
About the Public Library of Science
The Public Library of Science (PLoS) is a non-profit organization of scientists and physicians committed to making the world's scientific and medical
literature a freely available public resource.
Public Library of Science
185 Berry Street, Suite 3100
San Francisco, CA 94107
USA
Arts and Sciences and Leiden University Medical Centre, The Netherlands) in an essay in this week's PLoS Medicine.
One view, says the author, is that of medical researchers who rejoice in discoveries and explanations of causes of disease. "Discoveries happen when
things are suddenly seen in another light: the odd course of a disease in a patient, the strange results of a lab experiment, a peculiar subgroup in
the analysis of data, or some juxtaposition of papers in the literature."
The other view is that of medical researchers "whose aim is to set up studies to evaluate whether the patient's lot is really improved by the new
therapies or diagnostics that looked so wonderful initially." The most developed branch of evaluation research is the randomized trial of a drug
therapy.
Professor Vandenbrouke analyses in what respects these two views differ, and how they lead to opposite research hierarchies (with randomization on top
for evaluation and at bottom for discovery and explanation), and explores the reasons why we need both views.
"We need both hierarchies," says the author, "the hierarchy of discovery and explanation as well as that of evaluation. Without new discoveries
leading to potentially better diagnosis, prevention, or therapy, what would we do randomized trials on? Conversely, how could we know that a discovery
is useful, if not rigidly evaluated?"
Professor Vandenbrouke's essay is based upon the prestigious Austin Bradford Hill Memorial Lecture given at the London School of Hygiene and
Tropical Medicine on April 24, 2007.
On the 11th March, responses from John Ioannidis and Philippe Autier will also appear alongside the essay. You will be able to view them online
here.
Observational research, randomised trials, and two views of medical science
Vandenbroucke JP (2008)
PLoS Med 5(3): e67
Please click here to view article online
About PLoS Medicine
PLoS Medicine is an open access, freely available international medical journal. It publishes original research that enhances our understanding of
human health and disease, together with commentary and analysis of important global health issues.
plosmedicine
About the Public Library of Science
The Public Library of Science (PLoS) is a non-profit organization of scientists and physicians committed to making the world's scientific and medical
literature a freely available public resource.
Public Library of Science
185 Berry Street, Suite 3100
San Francisco, CA 94107
USA
Anti-Inflammation Molecule Helps Fight MS-Like Disease
An immune system messenger molecule that normally helps quiet inflammation could be an effective tool against multiple sclerosis (MS). Neurology researchers led by Abdolmohamad Rostami, M.D., Ph.D., professor and chair of the Department of Neurology at Jefferson Medical College of Thomas Jefferson University and the Jefferson Hospital for Neuroscience in Philadelphia, have found that the protein interkeukin-27 (IL-27) helped block the onset or reverse symptoms in animals with an MS-like disease.
The results suggest that IL-27 may someday be part of a therapy to temper over-active immune responses, which are thought to be at the heart of MS, an autoimmune disease (in which the body attacks its own tissue) affecting the central nervous system. The Jefferson neuroscientists report their findings November 11, 2007 in the journal Nature Immunology. The paper first appears in an advance online publication.
In MS, one of the most common neurological diseases affecting young adults, the myelin coating of nerve fibers becomes inflamed and scarred. As a result, "messages" cannot be sent through the nervous system. Dr. Rostami's team was trying to understand the mechanisms of how immune responses damage the myelin sheath and axons in the brain.
They had previously observed that IL-27, a signaling molecule called a cytokine, could suppress IL-17, another cytokine, and inflammation. They also knew that in other MS models, mice that lacked receptors for IL-27 developed excessive inflammation.
Dr. Rostami, who is also director of the Neuroimmunology Laboratory in the Department of Neurology at Jefferson Medical College, Denise Fitzgerald, Ph.D., a postdoctoral research fellow in Dr. Rostami's laboratory, and their colleagues used an animal model of MS called experimental autoimmune encephalomyelitis (EAE) for the investigation.
When the scientists gave IL-27 to the experimental mice, it significantly suppressed active disease. They saw similar effects from IL-27 in cultured cells that were transferred into "naГЇve" animals, which then produced significantly milder disease. At the same time, they also showed that IL-27 enhanced the production of IL-10, a crucial anti-inflammatory cytokine.
"We previously showed that IL-27 could suppress IL-17," he notes. "Here we also show that IL-27 can enhance the production of IL-10. These may both be different and complementary mechanisms by which IL-27 can suppress EAE."
The findings suggest that increasing IL-27 concentrations might raise IL-10 levels, and help quell an over-active immune response. "This is the first time that we have direct evidence that by actively giving IL-27 like a drug, we can suppress EAE in mice."
Dr. Rostami explains that after an MS flare-up, patients recover from the disease, though the reasons are poorly understood. "We think that one of the ways that recovery from a disease flare-up occurs is that part of the immune system is shut off, suppressing the immune response in the brain. IL-27 appears to be crucial in this process," he says.
The team would like to study MS patients' blood samples to see if similar processes are at work, Dr. Rostami notes. "If we get similar findings in human disease, then perhaps IL-27 could be used therapeutically as a compound to suppress inflammation in the brains of MS patients."
Source: Steve Benowitz
Thomas Jefferson University
The results suggest that IL-27 may someday be part of a therapy to temper over-active immune responses, which are thought to be at the heart of MS, an autoimmune disease (in which the body attacks its own tissue) affecting the central nervous system. The Jefferson neuroscientists report their findings November 11, 2007 in the journal Nature Immunology. The paper first appears in an advance online publication.
In MS, one of the most common neurological diseases affecting young adults, the myelin coating of nerve fibers becomes inflamed and scarred. As a result, "messages" cannot be sent through the nervous system. Dr. Rostami's team was trying to understand the mechanisms of how immune responses damage the myelin sheath and axons in the brain.
They had previously observed that IL-27, a signaling molecule called a cytokine, could suppress IL-17, another cytokine, and inflammation. They also knew that in other MS models, mice that lacked receptors for IL-27 developed excessive inflammation.
Dr. Rostami, who is also director of the Neuroimmunology Laboratory in the Department of Neurology at Jefferson Medical College, Denise Fitzgerald, Ph.D., a postdoctoral research fellow in Dr. Rostami's laboratory, and their colleagues used an animal model of MS called experimental autoimmune encephalomyelitis (EAE) for the investigation.
When the scientists gave IL-27 to the experimental mice, it significantly suppressed active disease. They saw similar effects from IL-27 in cultured cells that were transferred into "naГЇve" animals, which then produced significantly milder disease. At the same time, they also showed that IL-27 enhanced the production of IL-10, a crucial anti-inflammatory cytokine.
"We previously showed that IL-27 could suppress IL-17," he notes. "Here we also show that IL-27 can enhance the production of IL-10. These may both be different and complementary mechanisms by which IL-27 can suppress EAE."
The findings suggest that increasing IL-27 concentrations might raise IL-10 levels, and help quell an over-active immune response. "This is the first time that we have direct evidence that by actively giving IL-27 like a drug, we can suppress EAE in mice."
Dr. Rostami explains that after an MS flare-up, patients recover from the disease, though the reasons are poorly understood. "We think that one of the ways that recovery from a disease flare-up occurs is that part of the immune system is shut off, suppressing the immune response in the brain. IL-27 appears to be crucial in this process," he says.
The team would like to study MS patients' blood samples to see if similar processes are at work, Dr. Rostami notes. "If we get similar findings in human disease, then perhaps IL-27 could be used therapeutically as a compound to suppress inflammation in the brains of MS patients."
Source: Steve Benowitz
Thomas Jefferson University
Fifty One Genes Predict Breast Cancer Survival
It may be possible in the future to use a specimen from the tumour to determine which patients with breast cancer have a good chance of overcoming the disease, and which patients should be given more intensive treatments. Fifty-one genes may together provide information about the prognosis for an individual patient. These are the conclusions of a thesis presented at the Sahlgrenska Academy, University of Gothenburg, Sweden.
The research group has analysed specimens from a number of breast tumours, both from patients that died from the disease and from patients surviving at least 10 years from diagnosis. The levels of expression of 51 genes differed between the two groups. It should be possible to use the differences in order to classify the patients into one of two groups: a favourable prognosis group and a poor prognosis group.
"Many breast cancer patients are currently overtreated, while some are undertreated. If it was possible to identify patients with poor prognosis, it would be possible to use greater treatment resources on these patients. At the same time, patients with a favourable prognosis could avoid unnecessary treatment", says Elin Karlsson who successfully defended her thesis on June 5.
Comparing the amounts of the gene products of these 51 genes with data from a previous study has allowed the research team to show that the genes have the ability to predict survival also for the new material.
The research group has also studied the protein BTG2, and shown that it is involved at several levels in the tumours that were examined. The protein was present more often in specimens from patients who had survived at least 5 years after diagnosis than in patients who had died within 5 years from diagnosis. It has been previously determined that this protein is a tumour suppressor, but the study at the Sahlgrenska Academy is the first to indicate it as a prognostic marker.
"We consider it to be a promising marker: it will maybe be possible to use it to determine which patients with breast cancer require particularly close surveillance. More research, however, will be required in order to confirm our results before analysis of the protein can be used in the clinic", says Elin Karlsson.
Source: University of Gothenburg
The research group has analysed specimens from a number of breast tumours, both from patients that died from the disease and from patients surviving at least 10 years from diagnosis. The levels of expression of 51 genes differed between the two groups. It should be possible to use the differences in order to classify the patients into one of two groups: a favourable prognosis group and a poor prognosis group.
"Many breast cancer patients are currently overtreated, while some are undertreated. If it was possible to identify patients with poor prognosis, it would be possible to use greater treatment resources on these patients. At the same time, patients with a favourable prognosis could avoid unnecessary treatment", says Elin Karlsson who successfully defended her thesis on June 5.
Comparing the amounts of the gene products of these 51 genes with data from a previous study has allowed the research team to show that the genes have the ability to predict survival also for the new material.
The research group has also studied the protein BTG2, and shown that it is involved at several levels in the tumours that were examined. The protein was present more often in specimens from patients who had survived at least 5 years after diagnosis than in patients who had died within 5 years from diagnosis. It has been previously determined that this protein is a tumour suppressor, but the study at the Sahlgrenska Academy is the first to indicate it as a prognostic marker.
"We consider it to be a promising marker: it will maybe be possible to use it to determine which patients with breast cancer require particularly close surveillance. More research, however, will be required in order to confirm our results before analysis of the protein can be used in the clinic", says Elin Karlsson.
Source: University of Gothenburg
Human Embryonic Stem Cell Research Could Be Advanced By New Culture Dish
A new synthetic Petri dish coating could overcome a major challenge to the advancement of human embryonic stem cell research, say University of Michigan researchers.
Under today's regulations, current stem cell lines have limitations in yielding human therapies because the cells have been grown on animal-based substances that don't behave in predictable ways.
"These nondefined, animal-based components create issues with the FDA (the U.S. Food and Drug Administration) and hinder clinical applications," said Joerg Lahann, associate professor of chemical engineering.
Lahann and Gary Smith, an associate professor in obstetrics and gynecology in the U-M Health System, and their co-workers built a new stem cell growth matrix that is completely synthetic and doesn't contaminate the stem cells with foreign substances that could interfere with their normal function.
A paper on the research was published online this week in Nature Biotechnology.
Today's most commonly used matrices are mouse embryonic fibroblast cells and Matrigel, which is made from mouse tumors.
"The problem is that the mouse-derived cells have batch-to-batch variability, and they secrete factors that nobody really understands. Stem cells are very sensitive to their environment," Lahann said.
The unknown factors hamper researchers' attempts to pinpoint how and under what conditions stem cells differentiate---questions paramount to the development of future stem cell therapies.
The team tested six different polymer coatings and found that a water-soluble gel with the acronym PMEDSAH performed well when attached to the Petri dish even after 25 rounds of harvesting stem cells to grow new colonies.
"We have designed a fully synthetic, fully chemically defined hydrogel that has long-term stability and no batch-to-batch variability," Smith said. "Moreover, we have established that it can be used for long-term growth of human embryonic stem cells while maintaining all of their known normal functions.
"These include normal genetic makeup, lack of spontaneous differentiation and maintenance of pluripotency, which means they can still become any cell type of the human body. This is a perfect example of an interdisciplinary collaboration leading to information gained and future discovery of cures and improvements of human health."
Smith is also an associate professor in the departments of Molecular and Integrative Physiology and Urology, as well as director of the Reproductive Sciences Program. Lahann is also an associate professor in the departments of Materials Science and Engineering and Biomedical Engineering.
The paper is called "Synthetic Polymer Coatings for Long-term Growth of Human Embryonic Stem Cells."
This research is funded by the National Science Foundation and the National Institutes of Health. The university is pursuing patent protection for the intellectual property and is seeking commercialization partners to help bring the technology to market.
Source:
Nicole Casal Moore
University of Michigan
Under today's regulations, current stem cell lines have limitations in yielding human therapies because the cells have been grown on animal-based substances that don't behave in predictable ways.
"These nondefined, animal-based components create issues with the FDA (the U.S. Food and Drug Administration) and hinder clinical applications," said Joerg Lahann, associate professor of chemical engineering.
Lahann and Gary Smith, an associate professor in obstetrics and gynecology in the U-M Health System, and their co-workers built a new stem cell growth matrix that is completely synthetic and doesn't contaminate the stem cells with foreign substances that could interfere with their normal function.
A paper on the research was published online this week in Nature Biotechnology.
Today's most commonly used matrices are mouse embryonic fibroblast cells and Matrigel, which is made from mouse tumors.
"The problem is that the mouse-derived cells have batch-to-batch variability, and they secrete factors that nobody really understands. Stem cells are very sensitive to their environment," Lahann said.
The unknown factors hamper researchers' attempts to pinpoint how and under what conditions stem cells differentiate---questions paramount to the development of future stem cell therapies.
The team tested six different polymer coatings and found that a water-soluble gel with the acronym PMEDSAH performed well when attached to the Petri dish even after 25 rounds of harvesting stem cells to grow new colonies.
"We have designed a fully synthetic, fully chemically defined hydrogel that has long-term stability and no batch-to-batch variability," Smith said. "Moreover, we have established that it can be used for long-term growth of human embryonic stem cells while maintaining all of their known normal functions.
"These include normal genetic makeup, lack of spontaneous differentiation and maintenance of pluripotency, which means they can still become any cell type of the human body. This is a perfect example of an interdisciplinary collaboration leading to information gained and future discovery of cures and improvements of human health."
Smith is also an associate professor in the departments of Molecular and Integrative Physiology and Urology, as well as director of the Reproductive Sciences Program. Lahann is also an associate professor in the departments of Materials Science and Engineering and Biomedical Engineering.
The paper is called "Synthetic Polymer Coatings for Long-term Growth of Human Embryonic Stem Cells."
This research is funded by the National Science Foundation and the National Institutes of Health. The university is pursuing patent protection for the intellectual property and is seeking commercialization partners to help bring the technology to market.
Source:
Nicole Casal Moore
University of Michigan
Bodily Breakdown Explained: How Cell Differentiation Patterns Suppress Somatic Evolution
Natural selection can occur at the cellular level, where it is detrimental
to health. Fortunately it is normally controlled by a well-known pattern
of
ongoing cell differentiation in the mature tissues of animals, according
to a new study published December 14 in PLoS Computational Biology.
The failure of normal cell differentiation patterns may explain cancer and
senescent decline with aging, say researchers at the University of
Arizona,
the Santa Fe Institute, the University of Pennsylvania, and the Wistar
Institute.
Darwinian natural selection and evolution is usually studied in
populations of organisms, but it also applies to cellular populations;
this is called
"somatic" evolution. Such somatic evolution tends to reduce cooperation
among cells, thus threatening the integrity of the organism.
In this study the authors proposed that a well-known pattern of ongoing
cell differentiation in the mature tissues of animals functions to
suppress
somatic evolution, which is essential to the origin and sustainability of
multicellular organisms.
The team, lead by Dr. John Pepper, tested this hypothesis using a computer
simulation of cell population dynamics and evolution. The results were
consistent with the hypothesis, suggesting that familiar patterns of
ongoing cell differentiation were crucial to the evolution of
multicellular
animals, and remain crucial as a bodily defense against cancer.
Citation: Pepper JW, Sprouffske K, Maley CC (2007) Animal cell
differentiation patterns suppress somatic evolution. PLoS Comput Biol
3(12): e250.
doi:10.1371/journal.pcbi.0030250
Please click here
Disclaimer
This press release refers to an upcoming article in PLoS Computational
Biology. The release is provided by journal staff. Any opinions expressed
in
this release or article are the personal views of the journal staff and/or
article contributors, and do not necessarily represent the views or
policies of PLoS. PLoS expressly disclaims any and all warranties and
liability in connection with the information found in the releases and
articles
and your use of such information.
About PLoS Computational Biology
PLoS Computational Biology features works of
exceptional significance that further our understanding of living systems
at all
scales through the application of computational methods. All works
published in PLoS Computational Biology are open access. Everything is
immediately
available subject only to the condition that the original authorship and
source are properly attributed. Copyright is retained by the authors. The
Public Library of Science uses the Creative Commons Attribution License.
ploscompbiol
About the Public Library of Science
The Public Library of Science (PLoS) is a non-profit organization of
scientists and physicians committed to making the world's scientific and
medical
literature a freely available public resource.
Public Library of Science
185 Berry Street, Suite 3100
San Francisco, CA 94107
USA
to health. Fortunately it is normally controlled by a well-known pattern
of
ongoing cell differentiation in the mature tissues of animals, according
to a new study published December 14 in PLoS Computational Biology.
The failure of normal cell differentiation patterns may explain cancer and
senescent decline with aging, say researchers at the University of
Arizona,
the Santa Fe Institute, the University of Pennsylvania, and the Wistar
Institute.
Darwinian natural selection and evolution is usually studied in
populations of organisms, but it also applies to cellular populations;
this is called
"somatic" evolution. Such somatic evolution tends to reduce cooperation
among cells, thus threatening the integrity of the organism.
In this study the authors proposed that a well-known pattern of ongoing
cell differentiation in the mature tissues of animals functions to
suppress
somatic evolution, which is essential to the origin and sustainability of
multicellular organisms.
The team, lead by Dr. John Pepper, tested this hypothesis using a computer
simulation of cell population dynamics and evolution. The results were
consistent with the hypothesis, suggesting that familiar patterns of
ongoing cell differentiation were crucial to the evolution of
multicellular
animals, and remain crucial as a bodily defense against cancer.
Citation: Pepper JW, Sprouffske K, Maley CC (2007) Animal cell
differentiation patterns suppress somatic evolution. PLoS Comput Biol
3(12): e250.
doi:10.1371/journal.pcbi.0030250
Please click here
Disclaimer
This press release refers to an upcoming article in PLoS Computational
Biology. The release is provided by journal staff. Any opinions expressed
in
this release or article are the personal views of the journal staff and/or
article contributors, and do not necessarily represent the views or
policies of PLoS. PLoS expressly disclaims any and all warranties and
liability in connection with the information found in the releases and
articles
and your use of such information.
About PLoS Computational Biology
PLoS Computational Biology features works of
exceptional significance that further our understanding of living systems
at all
scales through the application of computational methods. All works
published in PLoS Computational Biology are open access. Everything is
immediately
available subject only to the condition that the original authorship and
source are properly attributed. Copyright is retained by the authors. The
Public Library of Science uses the Creative Commons Attribution License.
ploscompbiol
About the Public Library of Science
The Public Library of Science (PLoS) is a non-profit organization of
scientists and physicians committed to making the world's scientific and
medical
literature a freely available public resource.
Public Library of Science
185 Berry Street, Suite 3100
San Francisco, CA 94107
USA
Innovative Approach To Biomimetic Nanofiber Bone Regeneration Funded By NSF
Every year nearly 6.2 million bone fractures occur in the United States as a result of trauma and disease. Current standards for bone repair can lead to rapid bone fusion but with limited mechanical strength often due to the lack of cortical bone tissue which is difficult to harvest without pain and severe morbidity. Funded by the National Science Foundation, Dr. Hongjun Wang, a professor in the Department of Chemistry, Chemical Biology and Biomedical Engineering at Stevens Institute of Technology and his collaborators have developed a revolutionary "bottom-up" approach for reconstructing intricate bone tissue with the potential to form hierarchical cortical bone.
Dr. Wang's research project, "Biomimetic Creation of Cortical-like Bone with Hierarchical Structure," will develop robust, controllable and effective platforms for the creation of tissues with complex and hierarchical structure for potential applications in reconstructive and transplant surgery.
Biomimetics is the study and development of synthetic systems that mimic the formation, function, or structure of biologically produced substances, materials, mechanisms and processes. Wang's research team is part of a thriving tissue engineering industry that uses a combination of cells, engineering and materials methods, and suitable biochemical and physio-chemical factors to repair or replace portions of damaged tissues.
In contrast to current state-of-the-art research that focuses on creating highly porous cancellous bone, Dr. Wang focuses on engineering cortical bone, the major load bearing component. He takes a modular approach to generating dense cortical bone by synthesizing osteon-like repeating units and fusing these units together to form large, compacted cortical-like bone tissue. This "bottom-up" methodology uses nanotechnology to enable the development of scaffolds that focus on the smallest level possible and build upward. Incorporating nanofibers into bone tissue engineering to form the small cortical bone repeating units, these biomimetic scaffolds offer large surface areas and well-interconnected pores for nutrient transport and cell penetration, and more importantly, provide a biomimetic cell-friendly microenvironment to facilitate the bone tissue formation, needed for successful repair of large bone defects.
"The results of Dr. Wang's research will have a far-reaching impact on tissue engineering," says Dr. Michael Bruno, Dean of the Schaefer School of Engineering and Science. "The wealth of basic and applied knowledge learned at Stevens will lay the foundation for our long-term research efforts and the development of real-world applications."
Over the next-three years, Dr. Wang's research team plans to make substantial strides in synergistically integrating nanobiomaterials with bone tissue engineering for the creation of cortical bone with hierarchical structure and functional complexity.
"We hope to establish a family of biomimetic nanofibers containing collagen and calcium phosphate to support the phenotype of bone-forming cells; new practical approaches to creating osteon-like units using biomimetic nanofibers and osteoblasts; formulation of calcium phosphate containing collagen gel for bone tissue formation; and most importantly, an innovative approach to generating cortical-like bone by assembling osteon-like structures into one fused construct," explains Dr. Wang.
"The intellectually rich environment established by Dr. Wang and his team is inspiring to our graduate and undergraduate students who are participating in the transformative benefits of cutting-edge research and its profound application," says Dr. Philip Leopold, Director of the Department of Chemistry, Chemical Biology and Biomedical Engineering.
Source:
Dr. Hongjun Wang
Stevens Institute of Technology
Dr. Wang's research project, "Biomimetic Creation of Cortical-like Bone with Hierarchical Structure," will develop robust, controllable and effective platforms for the creation of tissues with complex and hierarchical structure for potential applications in reconstructive and transplant surgery.
Biomimetics is the study and development of synthetic systems that mimic the formation, function, or structure of biologically produced substances, materials, mechanisms and processes. Wang's research team is part of a thriving tissue engineering industry that uses a combination of cells, engineering and materials methods, and suitable biochemical and physio-chemical factors to repair or replace portions of damaged tissues.
In contrast to current state-of-the-art research that focuses on creating highly porous cancellous bone, Dr. Wang focuses on engineering cortical bone, the major load bearing component. He takes a modular approach to generating dense cortical bone by synthesizing osteon-like repeating units and fusing these units together to form large, compacted cortical-like bone tissue. This "bottom-up" methodology uses nanotechnology to enable the development of scaffolds that focus on the smallest level possible and build upward. Incorporating nanofibers into bone tissue engineering to form the small cortical bone repeating units, these biomimetic scaffolds offer large surface areas and well-interconnected pores for nutrient transport and cell penetration, and more importantly, provide a biomimetic cell-friendly microenvironment to facilitate the bone tissue formation, needed for successful repair of large bone defects.
"The results of Dr. Wang's research will have a far-reaching impact on tissue engineering," says Dr. Michael Bruno, Dean of the Schaefer School of Engineering and Science. "The wealth of basic and applied knowledge learned at Stevens will lay the foundation for our long-term research efforts and the development of real-world applications."
Over the next-three years, Dr. Wang's research team plans to make substantial strides in synergistically integrating nanobiomaterials with bone tissue engineering for the creation of cortical bone with hierarchical structure and functional complexity.
"We hope to establish a family of biomimetic nanofibers containing collagen and calcium phosphate to support the phenotype of bone-forming cells; new practical approaches to creating osteon-like units using biomimetic nanofibers and osteoblasts; formulation of calcium phosphate containing collagen gel for bone tissue formation; and most importantly, an innovative approach to generating cortical-like bone by assembling osteon-like structures into one fused construct," explains Dr. Wang.
"The intellectually rich environment established by Dr. Wang and his team is inspiring to our graduate and undergraduate students who are participating in the transformative benefits of cutting-edge research and its profound application," says Dr. Philip Leopold, Director of the Department of Chemistry, Chemical Biology and Biomedical Engineering.
Source:
Dr. Hongjun Wang
Stevens Institute of Technology
Plant-Cell-Produced Technologies - Cutting Edge Approach To Bringing Highly Novel And Differentiated Solutions To The Market
Science Conference: Innovations in Bioscience for Animal and Human Health
Four months after the world's first vaccine made in plant cells has received regulatory approval in the US, Dow AgroSciences is organising a Science Conference in Brussels on 7 June 2006 in order to share this knowledge with European researchers, scientists, decision-makers and industry representatives.
The pioneering vaccine developed by Dow AgroSciences works against the Newcastle disease virus (NDV) in poultry. The latest technology could be applied quite quickly to other diseases - with avian flu a prime target. This approval represents an innovative milestone for the company and the industry.
The Dow AgroSciences Concert Plant-Cell-Produced System represents a new category of plant-made vaccines. This leading edge technology utilises plant cells instead of whole plants in a secure, bio-contained environment to produce vaccines. Because of this bio-contained production system, concerns and challenges associated with making vaccines in whole plants or food crops are eliminated. The Concert Plant-Cell-Produced System uses only the necessary parts of the disease causing agent to stimulate immunity in a manufacturing process that is totally free of animal components:
"Being the first company to ever register a plant-made vaccine is another example of Dow AgroSciences' cutting edge approach to bringing highly novel and differentiated solutions to the market," said Jerome Peribere, Dow AgroSciences' president and CEO.
The conference on 7 June, entitled "Innovations in Biosciences for Animal and Human Health" will highlight major bioscience developments and scientific solutions that could prevent diseases and reduce animal and human health risks in Europe. Dow AgroSciences President and Chief Executive Officer Mr. Jerome A. Peribere will deliver a welcome address. Dow AgroSciences's R&D capability will be presented by Mr. Antonio Galindez, (Dow AgroSciences VicePresicent, Europe, Latin America, Pacific) and Dr. Dan Kittle (Dow AgroSciences VicePresicent, Research and Development). Dr. Maurice Lex (European Commission, DG Research) will open discussion on Science Policy and R&D collaboration under the Seventh Framework Programme (FP7) in the area of biosciences for animal and human health.
Two parallel seminars will examine innovative plant-cell technologies and will present the benefit of healthy oils for consumers, agriculture and the food industry. The conference will also explore R&D collaboration under the EU's Seventh Framework Programme (FP7) in the area of biosciences for animal and human health.
Science Conference "Innovations in Bioscience for Animal and Human Health"
Date: 7 June 2006
Time: 08:30-16:00
Location: Renaissance Hotel, Rue du Parnasse 19, 1050 Brussels, Belgium
Admission Free
Online registration and the detailed programme is available at:
isc-europe/dasconference/registration.php
isc-europe/dasconference/index.php
Dow AgroSciences LLC, based in Indianapolis, Indiana, USA, is a top tier agricultural company providing innovative crop protection, seeds, and biotechnology solutions to serve the world's growing population. A wholly owned subsidiary of The Dow Chemical Company, global sales for Dow AgroSciences are $3.4 billion. For further information on Dow AgroSciences, please visit:
dowagro/homepage/index.htm
ISC
Park Leopold
Rue Wiertz, 50/28
B-1050 Brussels
Belgium
isc-europe
Four months after the world's first vaccine made in plant cells has received regulatory approval in the US, Dow AgroSciences is organising a Science Conference in Brussels on 7 June 2006 in order to share this knowledge with European researchers, scientists, decision-makers and industry representatives.
The pioneering vaccine developed by Dow AgroSciences works against the Newcastle disease virus (NDV) in poultry. The latest technology could be applied quite quickly to other diseases - with avian flu a prime target. This approval represents an innovative milestone for the company and the industry.
The Dow AgroSciences Concert Plant-Cell-Produced System represents a new category of plant-made vaccines. This leading edge technology utilises plant cells instead of whole plants in a secure, bio-contained environment to produce vaccines. Because of this bio-contained production system, concerns and challenges associated with making vaccines in whole plants or food crops are eliminated. The Concert Plant-Cell-Produced System uses only the necessary parts of the disease causing agent to stimulate immunity in a manufacturing process that is totally free of animal components:
"Being the first company to ever register a plant-made vaccine is another example of Dow AgroSciences' cutting edge approach to bringing highly novel and differentiated solutions to the market," said Jerome Peribere, Dow AgroSciences' president and CEO.
The conference on 7 June, entitled "Innovations in Biosciences for Animal and Human Health" will highlight major bioscience developments and scientific solutions that could prevent diseases and reduce animal and human health risks in Europe. Dow AgroSciences President and Chief Executive Officer Mr. Jerome A. Peribere will deliver a welcome address. Dow AgroSciences's R&D capability will be presented by Mr. Antonio Galindez, (Dow AgroSciences VicePresicent, Europe, Latin America, Pacific) and Dr. Dan Kittle (Dow AgroSciences VicePresicent, Research and Development). Dr. Maurice Lex (European Commission, DG Research) will open discussion on Science Policy and R&D collaboration under the Seventh Framework Programme (FP7) in the area of biosciences for animal and human health.
Two parallel seminars will examine innovative plant-cell technologies and will present the benefit of healthy oils for consumers, agriculture and the food industry. The conference will also explore R&D collaboration under the EU's Seventh Framework Programme (FP7) in the area of biosciences for animal and human health.
Science Conference "Innovations in Bioscience for Animal and Human Health"
Date: 7 June 2006
Time: 08:30-16:00
Location: Renaissance Hotel, Rue du Parnasse 19, 1050 Brussels, Belgium
Admission Free
Online registration and the detailed programme is available at:
isc-europe/dasconference/registration.php
isc-europe/dasconference/index.php
Dow AgroSciences LLC, based in Indianapolis, Indiana, USA, is a top tier agricultural company providing innovative crop protection, seeds, and biotechnology solutions to serve the world's growing population. A wholly owned subsidiary of The Dow Chemical Company, global sales for Dow AgroSciences are $3.4 billion. For further information on Dow AgroSciences, please visit:
dowagro/homepage/index.htm
ISC
Park Leopold
Rue Wiertz, 50/28
B-1050 Brussels
Belgium
isc-europe
Neurons For Numerosity: Parietal Neurons "Sum Up" Individual Items In A Group
As any child knows, to answer the question "how many," one must start by adding up individual objects in a group. This cognitive ability is shared
by animals as diverse as humans and birds. Surprisingly, the exact brain mechanisms responsible for this process remained unknown until now. This week
in the online open-access journal PLoS Biology, Jamie Roitman, Elizabeth Brannon, and Michael Platt from the University of Illinois at Chicago report
novel evidence for the existence of "accumulator neurons," which respond to increasing numbers of items in a display with progressively increasing
activity, in the parietal cortex of monkeys.
The authors focused on the parietal cortex based on evidence that damage to this brain region disrupts basic mathematical skills, and is activated
during functional imaging studies when people perform basic computations. To understand how parietal cortex contributes to numerical behavior, the
authors studied the activity of neurons in the lateral intraparietal area in monkeys while they looked at arrays of dots on a computer screen.
Parietal neurons responded with progressively increasing activity as the total number of elements in the display was varied across a wide range of
values (2-32). These neurons resemble "accumulator neurons" that have been suggested to serve the first stage in counting. This information could
be used by other neurons that respond best for a particular cardinal number, such as "4," as have been reported in prior studies. These findings
support computer models that separate the processes of summing and numerical identification, and may also explain the fact that parietal cortex damage
causes both numerical and spatial confusion.
Roitman JD, Brannon EM, Platt ML (2007)
Monotonic coding of numerosity in macaque lateral intraparietal area.
PLoS Biol. 5(8): e208. doi:10.1371/journal.pbio. 0050208.
Please click here.
About the Public Library of Science
The Public Library of Science (PLoS) is a non-profit organization of scientists and physicians committed to making the world's scientific and medical
literature a freely available public resource.
Public Library of Science
185 Berry Street, Suite 3100
San Francisco, CA 94107
USA
by animals as diverse as humans and birds. Surprisingly, the exact brain mechanisms responsible for this process remained unknown until now. This week
in the online open-access journal PLoS Biology, Jamie Roitman, Elizabeth Brannon, and Michael Platt from the University of Illinois at Chicago report
novel evidence for the existence of "accumulator neurons," which respond to increasing numbers of items in a display with progressively increasing
activity, in the parietal cortex of monkeys.
The authors focused on the parietal cortex based on evidence that damage to this brain region disrupts basic mathematical skills, and is activated
during functional imaging studies when people perform basic computations. To understand how parietal cortex contributes to numerical behavior, the
authors studied the activity of neurons in the lateral intraparietal area in monkeys while they looked at arrays of dots on a computer screen.
Parietal neurons responded with progressively increasing activity as the total number of elements in the display was varied across a wide range of
values (2-32). These neurons resemble "accumulator neurons" that have been suggested to serve the first stage in counting. This information could
be used by other neurons that respond best for a particular cardinal number, such as "4," as have been reported in prior studies. These findings
support computer models that separate the processes of summing and numerical identification, and may also explain the fact that parietal cortex damage
causes both numerical and spatial confusion.
Roitman JD, Brannon EM, Platt ML (2007)
Monotonic coding of numerosity in macaque lateral intraparietal area.
PLoS Biol. 5(8): e208. doi:10.1371/journal.pbio. 0050208.
Please click here.
About the Public Library of Science
The Public Library of Science (PLoS) is a non-profit organization of scientists and physicians committed to making the world's scientific and medical
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A Tiny Protein Plays A Big Role In DNA Repair
Two of DNA's worst enemies, ultraviolet light and chemical carcinogens, can wreak havoc on the molecule by mutating individual nucleotides or changing its physical structure. In most cases, genomic integrity is restored by specialized suites of proteins dedicated to repairing specific types of injuries. One mending mechanism, called nucleotide excision repair (NER), recruits and coordinates the services of roughly 25 proteins to recognize and remove structure-impairing lesions, including those induced by ultraviolet light. At the center of this effort is the ten-subunit transcription/repair factor IIH (TFIIH) complex. As its name suggests, in addition to its role in DNA repair, TFIIH also regulates transcription.
In a new study published in this month's PLoS Biology, Giuseppina Giglia-Mari, Jan Hoeijmakers, Catherine Miquel, Wim Vermeulen, and colleagues present their study investigating the contribution of trichothiodystrophy group A (TTDA) in DNA repair and transcription. TTDA is one of three TFIIH genes--XPB, XPD, and TTDA-- that have been implicated in the photosensitive form of a rare inherited premature aging syndrome called trichothiodystrophy (TTD), which is characterized by brittle hair and nails, scaly skin, and neurological degeneration.
To study the role of the TTDA subunit in the TFIIH complex's functions, the researchers tagged TTDA and the XPD subunit with green fluorescent protein (GFP) to monitor and compare their movement and behavior using high-resolution confocal microscopy. Both TTDA-GFP and XPD-GFP could stably incorporate into TFIIH and function in DNA repair; TTDA-GFP and XPD-GFP were observed in the cytoplasm and nucleus, in contrast to the XPB subunit, which is known to localize only in the nucleus. To determine if TTDA and XPD assemble with TFIIH in the cytoplasm, the researchers used a customized version of a motility-monitoring technique called fluorescence recovery after photobleaching (FRAP). They observed that TTDA dynamically associates with TFIIH, and that TTDA becomes stably incorporated only while the complex is engaged in NER (not while it is engaged in transcription).
Giglia-Mari et al. propose that once TTDA nestles into place after the core TFIIH complex attaches to a lesion, it triggers a conformational change that recruits the other subunits required for repair. TTDA may also help TFIIH fold properly, preventing it from being degraded and allowing it to accumulate to the levels necessary for NER function. These observations may explain why people who can't produce TTDA experience such debilitating symptoms.
Citation: Giglia-Mari G, Miquel C, Theil AF, Mari PO, Hoogstraten D, et al. (2006) Dynamic interaction of TTDA with TFIIH is stabilized by nucleotide excision repair in living cells. PLoS Biol 4(6): e156.
CONTACT:
Wim Vermeulen
Erasmus Medical Center
Dr Molenwaterplein
Rotterdam, Netherlands 3000 DR
PLEASE MENTION THE OPEN-ACCESS JOURNAL PLoS BIOLOGY (plosbiology/) AS THE SOURCE FOR THESE ARTICLES AND PROVIDE A LINK TO THE FREELY-AVAILABLE TEXT. THANK YOU.
All works published in PLoS Biology are open access. Everything is immediately available--to read, download, redistribute, include in databases, and otherwise use--without cost to anyone, anywhere, subject only to the condition that the original authorship and source are properly attributed. Copyright is retained by the authors. The Public Library of Science uses the Creative Commons Attribution License.
Contact: Paul Ocampo
Public Library of Science
In a new study published in this month's PLoS Biology, Giuseppina Giglia-Mari, Jan Hoeijmakers, Catherine Miquel, Wim Vermeulen, and colleagues present their study investigating the contribution of trichothiodystrophy group A (TTDA) in DNA repair and transcription. TTDA is one of three TFIIH genes--XPB, XPD, and TTDA-- that have been implicated in the photosensitive form of a rare inherited premature aging syndrome called trichothiodystrophy (TTD), which is characterized by brittle hair and nails, scaly skin, and neurological degeneration.
To study the role of the TTDA subunit in the TFIIH complex's functions, the researchers tagged TTDA and the XPD subunit with green fluorescent protein (GFP) to monitor and compare their movement and behavior using high-resolution confocal microscopy. Both TTDA-GFP and XPD-GFP could stably incorporate into TFIIH and function in DNA repair; TTDA-GFP and XPD-GFP were observed in the cytoplasm and nucleus, in contrast to the XPB subunit, which is known to localize only in the nucleus. To determine if TTDA and XPD assemble with TFIIH in the cytoplasm, the researchers used a customized version of a motility-monitoring technique called fluorescence recovery after photobleaching (FRAP). They observed that TTDA dynamically associates with TFIIH, and that TTDA becomes stably incorporated only while the complex is engaged in NER (not while it is engaged in transcription).
Giglia-Mari et al. propose that once TTDA nestles into place after the core TFIIH complex attaches to a lesion, it triggers a conformational change that recruits the other subunits required for repair. TTDA may also help TFIIH fold properly, preventing it from being degraded and allowing it to accumulate to the levels necessary for NER function. These observations may explain why people who can't produce TTDA experience such debilitating symptoms.
Citation: Giglia-Mari G, Miquel C, Theil AF, Mari PO, Hoogstraten D, et al. (2006) Dynamic interaction of TTDA with TFIIH is stabilized by nucleotide excision repair in living cells. PLoS Biol 4(6): e156.
CONTACT:
Wim Vermeulen
Erasmus Medical Center
Dr Molenwaterplein
Rotterdam, Netherlands 3000 DR
PLEASE MENTION THE OPEN-ACCESS JOURNAL PLoS BIOLOGY (plosbiology/) AS THE SOURCE FOR THESE ARTICLES AND PROVIDE A LINK TO THE FREELY-AVAILABLE TEXT. THANK YOU.
All works published in PLoS Biology are open access. Everything is immediately available--to read, download, redistribute, include in databases, and otherwise use--without cost to anyone, anywhere, subject only to the condition that the original authorship and source are properly attributed. Copyright is retained by the authors. The Public Library of Science uses the Creative Commons Attribution License.
Contact: Paul Ocampo
Public Library of Science
ScienceDirect To Host French-Language Journals From Elsevier Masson
Elsevier, a leading publisher of scientific, technical and medical (STM) information, has announced that 45 French-language medical journals from Elsevier Masson will be available on ScienceDirect beginning January 3, 2008.
The titles, including Feuillets de Radiologie, Journal de Chirurgie and La Press MГ©dicale, represent a wide range of high-quality journals and complement the 27 Г‰ditions Scientifique et MГ©dicales Elsevier (ESME) titles already hosted on the platform. The importance of this content addition is two-fold: it is a response to growing customer demand in French-speaking territories for French-language content, and it furthers Elsevier's local-language publishing program, which is making a wealth of important content accessible globally.
"We are always striving to respond positively to customer requests and deliver the content that will help them in their research," said Jay Katzen, Managing Director, Academic & Government Products. "The addition of this world-class local-language content meets both of these objectives and ensures that ScienceDirect continues to remain a comprehensive and complete platform."
The 45 titles that will be added date from the early 19th and 20th centuries and have strong ties with some of the most revered French Societies including the French Society of Rheumatology, the French Society of Anaesthesiology and the French Society of Pediatrics. The variety of specialist coverage is notable, with journal subjects ranging from anaesthesiology to pharmacology.
All of the journals to be added consist of high-quality articles, reviews and case reports. In addition, a number of the journals include some abstracts and articles in English. Subscribers will benefit from the current (2008) articles as well as four years in backfiles.
The Elsevier Masson collection on ScienceDirect will evolve with new titles added each year through new launches and acquisitions. For more information on ScienceDirect and for a complete list of titles that will be added, please visit info.sciencedirect/.
About ScienceDirect
Over a quarter of the world's full text scientific, technical and medical (STM) articles - managed by renowned editors, written by respected authors and read by researchers from around the globe - are available in one place: ScienceDirect (sciencedirect).
Elsevier's extensive and unique full-text collection covers authoritative titles from the core scientific literature including high impact factor titles such as THE LANCET, Cell and Tetrahedron. Over eight million articles are available online, including Articles in Press which offer rapid access to recently accepted manuscripts. The critical mass of information available on ScienceDirect is unsurpassed. Coverage includes over 2,000 journals published by Elsevier and dynamic linking to journals from approximately 2,000 STM publishers through CrossRef. An expanding program of online major reference works, handbooks, book series and eBooks in all fields of science seamlessly interlinks with primary research referenced in journal articles.
About Elsevier
Elsevier is a world-leading publisher of scientific, technical and medical information products and services. Working in partnership with the global science and health communities, Elsevier's 7,000 employees in over 70 offices worldwide publish more than 2,000 journals and 1,900 new books per year, in addition to offering a suite of innovative electronic products, such as ScienceDirect (sciencedirect/), MD Consult (mdconsult/), Scopus (info.scopus/), bibliographic databases, and online reference works.
Elsevier (elsevier/) is a global business headquartered in Amsterdam, The Netherlands and has offices worldwide. Elsevier is part of Reed Elsevier Group plc (reedelsevier/), a world-leading publisher and information provider. Operating in the science and medical, legal, education and business-to-business sectors, Reed Elsevier provides high-quality and flexible information solutions to users, with increasing emphasis on the Internet as a means of delivery. Reed Elsevier's ticker symbols are REN (Euronext Amsterdam), REL (London Stock Exchange), RUK and ENL (New York Stock Exchange).
Source: Lauren Hillman
elsevier/
Elsevier
The titles, including Feuillets de Radiologie, Journal de Chirurgie and La Press MГ©dicale, represent a wide range of high-quality journals and complement the 27 Г‰ditions Scientifique et MГ©dicales Elsevier (ESME) titles already hosted on the platform. The importance of this content addition is two-fold: it is a response to growing customer demand in French-speaking territories for French-language content, and it furthers Elsevier's local-language publishing program, which is making a wealth of important content accessible globally.
"We are always striving to respond positively to customer requests and deliver the content that will help them in their research," said Jay Katzen, Managing Director, Academic & Government Products. "The addition of this world-class local-language content meets both of these objectives and ensures that ScienceDirect continues to remain a comprehensive and complete platform."
The 45 titles that will be added date from the early 19th and 20th centuries and have strong ties with some of the most revered French Societies including the French Society of Rheumatology, the French Society of Anaesthesiology and the French Society of Pediatrics. The variety of specialist coverage is notable, with journal subjects ranging from anaesthesiology to pharmacology.
All of the journals to be added consist of high-quality articles, reviews and case reports. In addition, a number of the journals include some abstracts and articles in English. Subscribers will benefit from the current (2008) articles as well as four years in backfiles.
The Elsevier Masson collection on ScienceDirect will evolve with new titles added each year through new launches and acquisitions. For more information on ScienceDirect and for a complete list of titles that will be added, please visit info.sciencedirect/.
About ScienceDirect
Over a quarter of the world's full text scientific, technical and medical (STM) articles - managed by renowned editors, written by respected authors and read by researchers from around the globe - are available in one place: ScienceDirect (sciencedirect).
Elsevier's extensive and unique full-text collection covers authoritative titles from the core scientific literature including high impact factor titles such as THE LANCET, Cell and Tetrahedron. Over eight million articles are available online, including Articles in Press which offer rapid access to recently accepted manuscripts. The critical mass of information available on ScienceDirect is unsurpassed. Coverage includes over 2,000 journals published by Elsevier and dynamic linking to journals from approximately 2,000 STM publishers through CrossRef. An expanding program of online major reference works, handbooks, book series and eBooks in all fields of science seamlessly interlinks with primary research referenced in journal articles.
About Elsevier
Elsevier is a world-leading publisher of scientific, technical and medical information products and services. Working in partnership with the global science and health communities, Elsevier's 7,000 employees in over 70 offices worldwide publish more than 2,000 journals and 1,900 new books per year, in addition to offering a suite of innovative electronic products, such as ScienceDirect (sciencedirect/), MD Consult (mdconsult/), Scopus (info.scopus/), bibliographic databases, and online reference works.
Elsevier (elsevier/) is a global business headquartered in Amsterdam, The Netherlands and has offices worldwide. Elsevier is part of Reed Elsevier Group plc (reedelsevier/), a world-leading publisher and information provider. Operating in the science and medical, legal, education and business-to-business sectors, Reed Elsevier provides high-quality and flexible information solutions to users, with increasing emphasis on the Internet as a means of delivery. Reed Elsevier's ticker symbols are REN (Euronext Amsterdam), REL (London Stock Exchange), RUK and ENL (New York Stock Exchange).
Source: Lauren Hillman
elsevier/
Elsevier
Rice Responsible For Asians' Alcohol Flush Reaction
The mutation responsible for the alcohol flush reaction, an unpleasant response to alcohol that is relatively common in people of Asian descent, may have occurred following the domestication of rice. Researchers writing in the open access journal BMC Evolutionary Biology traced the history of the version of the gene responsible, finding that the ADH1B 47His allele appeared around the same time that rice was first cultivated in southern China.
Bing Su, from the Chinese Academy of Sciences, China, worked with a team of researchers to study 38 populations (2,275 individuals) including Han Chinese, Tibetan and other ethnic populations across China. He said, "Our molecular dating suggests that the emergence of the ADH1B 47His allele occurred about 10,000-7,000 years ago. The geographic distribution of the allele in East Asia is also consistent with the unearthed culture relic sites of rice domestication in China, suggesting that distribution of the alcohol flush mutation can be explained by the origin and expansion of the Neolithic rice culture. This is one of the few cases reported demonstrating the genetic adaptation of human populations to the dramatic changes in agriculture and diet during Neolithic times".
Rice was fermented to gain the benefits of ethanol's combined analgesic, disinfectant and profound mind-altering effects. In addition, fermentation can help to preserve and enhance the nutritional value of food and drink. Su and his colleagues believe that the flushing response may be an adaptation to counter the negative effects of alcohol consumption. They write, "Individuals carrying ADH1B 47His have a lower risk for alcoholism, as the unpleasant reaction they experience can influence drinking behavior and so protect them from overconsumption. The allele can also protect their organs from the damage caused by alcohol consumption".
Source: BioMed Central Limited
Bing Su, from the Chinese Academy of Sciences, China, worked with a team of researchers to study 38 populations (2,275 individuals) including Han Chinese, Tibetan and other ethnic populations across China. He said, "Our molecular dating suggests that the emergence of the ADH1B 47His allele occurred about 10,000-7,000 years ago. The geographic distribution of the allele in East Asia is also consistent with the unearthed culture relic sites of rice domestication in China, suggesting that distribution of the alcohol flush mutation can be explained by the origin and expansion of the Neolithic rice culture. This is one of the few cases reported demonstrating the genetic adaptation of human populations to the dramatic changes in agriculture and diet during Neolithic times".
Rice was fermented to gain the benefits of ethanol's combined analgesic, disinfectant and profound mind-altering effects. In addition, fermentation can help to preserve and enhance the nutritional value of food and drink. Su and his colleagues believe that the flushing response may be an adaptation to counter the negative effects of alcohol consumption. They write, "Individuals carrying ADH1B 47His have a lower risk for alcoholism, as the unpleasant reaction they experience can influence drinking behavior and so protect them from overconsumption. The allele can also protect their organs from the damage caused by alcohol consumption".
Source: BioMed Central Limited
Molecular Defect Involved In Hearing Loss Discovered By Scripps Research Scientists
Scientists from The Scripps Research Institute have elucidated the action of a protein, harmonin, which is involved in the mechanics of hearing. This finding sheds new light on the workings of mechanotransduction, the process by which cells convert mechanical stimuli into electrical activity. Defects in mechanotransduction genes can cause devastating diseases, such as Usher's syndrome, which is characterized by deafness, gradual vision loss, and kidney disease, which can lead to kidney failure.
The research, led by Scripps Research Professor Ulrich Mueller, was published in the May 14, 2009 issue of the journal Neuron.
"We're constantly confronted with mechanical signals of many different kinds and we have sensors all over our bodies that respond to those signals," Mueller says. "For example, mechanosensors in the muscles control posture, while those in skin allow us to feel touch. Though many of our other senses, such as taste and smell, are well understood, mechanosensory perception is a world about which we know next to nothing."
By gaining a better appreciation of the molecular mechanics of hearing, scientists can learn a great deal about the workings of similar types of body processes and the defects in these processes that can cause disease.
Hearing: An Exquisite Molecular Dance
Sound starts as waves of mechanical vibrations that travel through the air to the ear by compressing air molecules. The waves first hit the outer ear, then travel down the ear canal into the middle ear before striking the eardrum. The vibrating eardrum moves a set of delicate bones that communicate with a fluid-filled spiral structure in the inner ear, the cochlea. Inside the cochlea are specialized "hair cells" lined with symmetric arrays of stereocilia - mechanosensing organelles that respond to fluid motion or fluid pressure changes. The movement of the fluid inside the cochlea causes the stereocilia, in turn, to move.
When sterocilia are deflected, molecular complexes called "tip links," which connect the tips of stereocilia, transmit physical force to the gated ion channels that are attached to them. The opening of these ion channels, which are monitored by sensory neurons, communicate the electrical signals to neurons in the brain, enabling hearing. In Usher syndrome and some other sensory neuronal diseases that cause deafness, the symmetry of the stereocilia - and the process of mechanotransduction - is disrupted, resulting in deafness.
"It has been known for some time that defects in the hair cells make people deaf, but no one knew why - it was thought that perhaps synapses in the hair cells somehow degenerate or the cells don't develop normally," Mueller says. "The idea that the hair cells' basic function as mechanotransducers were impaired as a result of molecular defects has never been shown before."
Building on Earlier Research
In part because stereocilia are extremely small, scarce, and difficult to handle, the molecules that make up the tip link remained elusive until 2007, when Mueller and his colleagues identified cadherin 23 and protocadherin 15 as the two proteins responsible for opening the ion channels. They also showed that cadherin 23 formed a complex with another protein, myosin 1c, which helped close the channel.
"Cadherin 23 and protocadherin 15 were two of the first known components of any mechanotransduction machinery of sensory cells in vertebrates," Mueller says. "Having these two components, we then went looking for others and found harmonin, which localizes to the tip link where cadherin 23 is also localized, and which we now know is required for mechanotransduction."
Having identified harmonin as yet another molecule involved in mechanotransduction, scientists may be able to move a little closer to addressing a basic science puzzle: How do biological systems build gating systems that act as mechanical devices, almost like switches? Similar switches are present in almost every cell in the body and are the gatekeepers that let ions flow in and out of a cell. Any given cell might have hundreds or thousands of channels. The right stimulus can throw a channel open, allowing ions to pass through; the surge of ions across the cell membrane generates tiny electrical currents that enable a multitude of bodily functions.
"Many different diseases are related to mechanical phenomena," Mueller says. "Understanding the components of this machinery may help shed light on many of them, leading ultimately to new treatments."
The first authors of the paper, "Harmonin (protein) mutations cause mechanotransduction defects in cochlear hair cells," are Nicolas Grillet, Wei Xiong, and Anna Reynolds of Scripps Research. Additional authors include Takashi Sato and Bechar Kachar of the National Institute of Deafness and other Communication Disorders, National Institutes of Health (NIH); Conception Lillo and David Williams of the University of California, Los Angeles, School of Medicine; Rachel Dumont and Peter Gillespie of the Oregon Health & Science University; and Piotr Kazmierczak, Edith Hintermann, Anna Sczaniecka, and Martin Schwander of Scripps Research.
The work was funded by the NIH, the Skaggs Institute for Chemical Biology, a Jules and Doris Stein RPB professorship, a C.J. Martin fellowship NHMRC (Australia), and a fellowship from the Bruce Ford and Anne Smith Brady Foundation.
Source:
Mika Ono
Scripps Research Institute
The research, led by Scripps Research Professor Ulrich Mueller, was published in the May 14, 2009 issue of the journal Neuron.
"We're constantly confronted with mechanical signals of many different kinds and we have sensors all over our bodies that respond to those signals," Mueller says. "For example, mechanosensors in the muscles control posture, while those in skin allow us to feel touch. Though many of our other senses, such as taste and smell, are well understood, mechanosensory perception is a world about which we know next to nothing."
By gaining a better appreciation of the molecular mechanics of hearing, scientists can learn a great deal about the workings of similar types of body processes and the defects in these processes that can cause disease.
Hearing: An Exquisite Molecular Dance
Sound starts as waves of mechanical vibrations that travel through the air to the ear by compressing air molecules. The waves first hit the outer ear, then travel down the ear canal into the middle ear before striking the eardrum. The vibrating eardrum moves a set of delicate bones that communicate with a fluid-filled spiral structure in the inner ear, the cochlea. Inside the cochlea are specialized "hair cells" lined with symmetric arrays of stereocilia - mechanosensing organelles that respond to fluid motion or fluid pressure changes. The movement of the fluid inside the cochlea causes the stereocilia, in turn, to move.
When sterocilia are deflected, molecular complexes called "tip links," which connect the tips of stereocilia, transmit physical force to the gated ion channels that are attached to them. The opening of these ion channels, which are monitored by sensory neurons, communicate the electrical signals to neurons in the brain, enabling hearing. In Usher syndrome and some other sensory neuronal diseases that cause deafness, the symmetry of the stereocilia - and the process of mechanotransduction - is disrupted, resulting in deafness.
"It has been known for some time that defects in the hair cells make people deaf, but no one knew why - it was thought that perhaps synapses in the hair cells somehow degenerate or the cells don't develop normally," Mueller says. "The idea that the hair cells' basic function as mechanotransducers were impaired as a result of molecular defects has never been shown before."
Building on Earlier Research
In part because stereocilia are extremely small, scarce, and difficult to handle, the molecules that make up the tip link remained elusive until 2007, when Mueller and his colleagues identified cadherin 23 and protocadherin 15 as the two proteins responsible for opening the ion channels. They also showed that cadherin 23 formed a complex with another protein, myosin 1c, which helped close the channel.
"Cadherin 23 and protocadherin 15 were two of the first known components of any mechanotransduction machinery of sensory cells in vertebrates," Mueller says. "Having these two components, we then went looking for others and found harmonin, which localizes to the tip link where cadherin 23 is also localized, and which we now know is required for mechanotransduction."
Having identified harmonin as yet another molecule involved in mechanotransduction, scientists may be able to move a little closer to addressing a basic science puzzle: How do biological systems build gating systems that act as mechanical devices, almost like switches? Similar switches are present in almost every cell in the body and are the gatekeepers that let ions flow in and out of a cell. Any given cell might have hundreds or thousands of channels. The right stimulus can throw a channel open, allowing ions to pass through; the surge of ions across the cell membrane generates tiny electrical currents that enable a multitude of bodily functions.
"Many different diseases are related to mechanical phenomena," Mueller says. "Understanding the components of this machinery may help shed light on many of them, leading ultimately to new treatments."
The first authors of the paper, "Harmonin (protein) mutations cause mechanotransduction defects in cochlear hair cells," are Nicolas Grillet, Wei Xiong, and Anna Reynolds of Scripps Research. Additional authors include Takashi Sato and Bechar Kachar of the National Institute of Deafness and other Communication Disorders, National Institutes of Health (NIH); Conception Lillo and David Williams of the University of California, Los Angeles, School of Medicine; Rachel Dumont and Peter Gillespie of the Oregon Health & Science University; and Piotr Kazmierczak, Edith Hintermann, Anna Sczaniecka, and Martin Schwander of Scripps Research.
The work was funded by the NIH, the Skaggs Institute for Chemical Biology, a Jules and Doris Stein RPB professorship, a C.J. Martin fellowship NHMRC (Australia), and a fellowship from the Bruce Ford and Anne Smith Brady Foundation.
Source:
Mika Ono
Scripps Research Institute
Easing Concerns About The Toxicity Of Diamond Nanoparticles
New research has brightened the prospects for using nanodiamonds as drug carriers, implant coatings, nanorobots and other medical applications that take advantage of diamond nanoparticles' attractive properties. The research is scheduled for publication Dec. 28 in ACS' weekly The Journal of Physical Chemistry B.
Liming Dai (University of Dayton), Saber M. Hussain (Wright-Patterson Air Force Base) and colleagues, including PhD student Amanda Schrand, explain that advances in technology have made a new generation of nanodiamonds available. Although diamond in bulk form is inert and biocompatible, nano-materials often behave differently than their bulk counterparts. That led to concern that diamond nanoparticles might have toxic effects on cells.
"We have for the first time assessed the cytotoxicity of nanodiamonds ranging in size from 2 to 10 nm," the researchers state, adding that nanodiamonds were not toxic to a variety of different cell types. "These results suggest that nanodiamonds could be ideal for many biological applications in a diverse range of cell types," they add.
ARTICLE #4
"Are Diamond Nanoparticles Cytotoxic?"
CONTACT:
Liming Dai, Ph.D.
University of Dayton
Dayton, Ohio
ACS News Service Weekly PressPac -- Dec. 20, 2006
The American Chemical Society -- the world's largest scientific society -- is a nonprofit organization chartered by the U.S. Congress and a global leader in providing access to chemistry-related research through its multiple databases, peer-reviewed journals and scientific conferences. Its main offices are in Washington, D.C., and Columbus, Ohio.
Contact: Michael Woods
American Chemical Society
Liming Dai (University of Dayton), Saber M. Hussain (Wright-Patterson Air Force Base) and colleagues, including PhD student Amanda Schrand, explain that advances in technology have made a new generation of nanodiamonds available. Although diamond in bulk form is inert and biocompatible, nano-materials often behave differently than their bulk counterparts. That led to concern that diamond nanoparticles might have toxic effects on cells.
"We have for the first time assessed the cytotoxicity of nanodiamonds ranging in size from 2 to 10 nm," the researchers state, adding that nanodiamonds were not toxic to a variety of different cell types. "These results suggest that nanodiamonds could be ideal for many biological applications in a diverse range of cell types," they add.
ARTICLE #4
"Are Diamond Nanoparticles Cytotoxic?"
CONTACT:
Liming Dai, Ph.D.
University of Dayton
Dayton, Ohio
ACS News Service Weekly PressPac -- Dec. 20, 2006
The American Chemical Society -- the world's largest scientific society -- is a nonprofit organization chartered by the U.S. Congress and a global leader in providing access to chemistry-related research through its multiple databases, peer-reviewed journals and scientific conferences. Its main offices are in Washington, D.C., and Columbus, Ohio.
Contact: Michael Woods
American Chemical Society
Faster Post-Op' Healing With The Help Of Shellfish And Inkjet Printers
Using the natural glue that marine mussels use to stick to rocks, and a variation on the inkjet printer, a team of researchers led by North Carolina State University has devised a new way of making medical adhesives that could replace traditional sutures and result in less scarring, faster recovery times and increased precision for exacting operations such as eye surgery.
Traditionally, there have been two ways to join tissue together in the wake of a surgery: sutures and synthetic adhesives. Sutures work well, but require enormous skill and longer operating times. Additionally, the use of sutures is associated with a number of surgical complications, including discomfort, infection and inflammation. Synthetic adhesives are also widely used, but they are the source of increasing concerns over their toxicological and environmental effects. One such concern with some synthetic medical adhesives is that - because they are not biodegradable - they do not break down in the body and therefore may cause inflammation, tissue damage, or other problems.
But new research shows that adhesive proteins found in the "glue" produced by marine mussels may be used in place of the synthetic adhesives without these concerns, because they are non-toxic and biodegradable, according to study co-author Dr. Roger Narayan. In addition, the mussel proteins can be placed in solution and applied using inkjet technology to create customized medical adhesives, which may have a host of applications. For example, Narayan says this technique may "significantly improve wound repair in eye surgery, wound closure and fracture fixation." Narayan is an associate professor in the joint biomedical engineering department of NC State and the University of North Carolina at Chapel Hill.
"This is an improved way of joining tissues," Narayan says, "because the use of the inkjet technology gives you greater control over the placement of the adhesive. This helps ensure that the tissues are joined together in just the right spot, forming a better bond that leads to improved healing and less scarring." This increased control would be a boon for surgery that relies on extreme precision, such as eye repair, Narayan explains.
Notes:
The study was performed in collaboration with Professor Jon Wilker in the Department of Chemistry at Purdue University. The Journal of Biomedical Materials Research B will publish the study, "Inkjet printing of adhesives," in April. The National Science Foundation, the National Institutes of Health and the Office of Naval Research funded the research.
Source: Matt Shipman
North Carolina State University
Traditionally, there have been two ways to join tissue together in the wake of a surgery: sutures and synthetic adhesives. Sutures work well, but require enormous skill and longer operating times. Additionally, the use of sutures is associated with a number of surgical complications, including discomfort, infection and inflammation. Synthetic adhesives are also widely used, but they are the source of increasing concerns over their toxicological and environmental effects. One such concern with some synthetic medical adhesives is that - because they are not biodegradable - they do not break down in the body and therefore may cause inflammation, tissue damage, or other problems.
But new research shows that adhesive proteins found in the "glue" produced by marine mussels may be used in place of the synthetic adhesives without these concerns, because they are non-toxic and biodegradable, according to study co-author Dr. Roger Narayan. In addition, the mussel proteins can be placed in solution and applied using inkjet technology to create customized medical adhesives, which may have a host of applications. For example, Narayan says this technique may "significantly improve wound repair in eye surgery, wound closure and fracture fixation." Narayan is an associate professor in the joint biomedical engineering department of NC State and the University of North Carolina at Chapel Hill.
"This is an improved way of joining tissues," Narayan says, "because the use of the inkjet technology gives you greater control over the placement of the adhesive. This helps ensure that the tissues are joined together in just the right spot, forming a better bond that leads to improved healing and less scarring." This increased control would be a boon for surgery that relies on extreme precision, such as eye repair, Narayan explains.
Notes:
The study was performed in collaboration with Professor Jon Wilker in the Department of Chemistry at Purdue University. The Journal of Biomedical Materials Research B will publish the study, "Inkjet printing of adhesives," in April. The National Science Foundation, the National Institutes of Health and the Office of Naval Research funded the research.
Source: Matt Shipman
North Carolina State University
Researchers Create First Molecule Able To Block Key Component Of Cancer Genes' On-Off Switch
In the quest to arrest the growth and spread of tumors, there have been many attempts to get cancer genes to ignore their internal instruction manual. In a new study, a team led by Dana-Farber Cancer Institute scientists has created the first molecule able to prevent cancer genes from "hearing" those instructions, stifling the cancer process at its root.
The study, published online by the journal Nature, demonstrates that proteins issuing stop and start commands to a cancer gene known as epigenetic "reader" proteins can be targeted for future cancer therapies. The research is particularly relevant to a rare but devastating cancer of children and young adults known as NUT midline carcinoma (NMC) a disease so obstinate that no potential therapy for it has ever reached the stage of being tested in a clinical trial.
"In recent years, it has become clear that being able to control gene activity in cancer manipulating which genes are 'on' or 'off' can be a high-impact approach to the disease," says the study's senior author, James Bradner, MD, of Dana-Farber. "If you can switch off a cancer cell's growth genes, the cell will die. Alternatively, switching on a tissue gene can cause a cancer cell to become a more normal tissue cell."
In this study, Bradner's lab synthesized a molecule that has both effects: by blocking a specific abnormal protein in NUT midline carcinoma cells, it stops them from dividing so prolifically and makes them 'forget' they're cancer cells and start appearing more like normal cells.
The assembled molecule affects the cell's multi-layered apparatus for controlling gene activity, a set of structures collectively known as the epigenome. Vast portions of each gene play a regulatory role, dictating whether the gene is active, busily sending orders for new proteins, or inactive, and temporarily at rest. The gene's DNA is packaged in a substance called chromatin, which is the slate on which instructions to begin or cease activity are inscribed.
The instructions themselves take the form of "bookmarks," substances placed on the chromatin by so-called epigenetic "writer" proteins. Another group of epigenetic proteins, known as "erasers," are able to remove the bookmarks. Both types of proteins have successfully been disabled by scientists, using molecules made in the lab or taken from nature. Their success has sparked intense interest in the development of anti-cancer therapies that work by blocking such proteins.
A third variety of epigenetic proteins potentially the most appealing as therapeutic targets, because they switch genes on or off by "reading" the bookmarks has received scant scientific attention. Bradner and his colleagues turned to this little-explored corner of biology by focusing on NMC cells.
The disease is caused by a chromosomal "translocation," in which two genes from different chromosomes become connected and give rise to an abnormal, fused protein known as BRD4-NUT. A review of the scientific literature suggested that some members of the benzodiazepine family of drugs, which includes Valium, Xanax and Ativan, are active against "bromodomain" proteins such as BRD4. With that as a clue, Bradner and his Dana-Farber colleague Jun Qi, PhD, created an array of molecules to see if any inhibited a "reader" protein of the BRD4-NUT gene. One did, quite convincingly a hybrid molecule, which researchers named JQ1, for Qi.
The investigators worked with researchers in the U.S. and overseas to learn more about the properties of JQ1 and how it works in cells. Stefan Knapp, PhD, of Oxford University in England, provided crystal-clear images of the molecule bound to a protein; Olaf Wiest, PhD, of the University of Notre Dame, showed that the molecule is less flexible in the presence of a protein, explaining why it so effectively blocks the protein; and Andrew Kung, MD, PhD, of Dana-Farber, engineered animal models in which the molecule could be tested against NMC tumors.
The animal studies were especially encouraging. Investigators transplanted NMC cells from patients into laboratory mice, which were then given the JQ1 molecule.
"The activity of the molecule was remarkable," says Bradner, who is also an associate member of the Chemical Biology Program at the Broad Institute of Harvard and MIT. "All the mice that received JQ1 lived; all that did not, died."
For now, JQ1's main utility is as a probe for better understanding the biology underlying NUT midline carcinoma. Bradner, Qi and their colleagues are tweaking the molecule to maximize its effectiveness as a BRD4-NUT stopper. Eventually, it, or a similar molecule, could be the basis for the first effective therapy against NMC.
"The disease tends to arise in the chest, head, or neck, along the vertical centerline of the body, with aggressive tumor growth and metastasis," Bradner explains. "Patients may have a brief response to chemotherapy, but they eventually succumb to the spread of the disease."
Unlike most cancers, NMC's tissue of origin isn't known. It is a disease defined entirely by its genetic signature the presence of the translocated gene BRD4-NUT. Prior to its genetic identification by Christopher French, MD, of Brigham and Women's Hospital and a study co-author, NMC wasn't recognized as a distinct disease.
"This research further illustrates the promise of personalized medicine," Bradner remarks, "which is the ability to deliver selected molecules to cancer-causing proteins to stop the cancer process while producing a minimum of residual side effects. The development of JQ1 or similar molecule into a drug may produce the first therapy specifically designed for patients with NMC."
In addition to Qi, the study's other lead authors are Panagis Filippakopoulos and Sarah Picaud, of Oxford University, England. The paper's co-authors include William Smith, Elizabeth Morse, Michael McKeown, Yuchuan Wang, PhD, Amanda Christie, and Nathan West, of Dana-Farber; Oleg Fedorov, Tracey Keates, Ildiko Felletar, Martin Philpott, Shonagh Munro, Tom Heightman, and Nicholas La Thangue, of Oxford University; and Tyler Hickman, Michael Cameron, and Brian Schwartz, PhD, of Brigham and Women's Hospital.
The study was supported in part by the Chemistry Biochemistry Biology Interface Program at the University of Notre Dame, Dana-Farber/Harvard Cancer Center, the National Institute of General Medical Sciences, the National Institutes of Health, the Burroughs Welcome Fund, and the Leukemia & Lymphoma Society.
Source: Dana-Farber Cancer Institute
The study, published online by the journal Nature, demonstrates that proteins issuing stop and start commands to a cancer gene known as epigenetic "reader" proteins can be targeted for future cancer therapies. The research is particularly relevant to a rare but devastating cancer of children and young adults known as NUT midline carcinoma (NMC) a disease so obstinate that no potential therapy for it has ever reached the stage of being tested in a clinical trial.
"In recent years, it has become clear that being able to control gene activity in cancer manipulating which genes are 'on' or 'off' can be a high-impact approach to the disease," says the study's senior author, James Bradner, MD, of Dana-Farber. "If you can switch off a cancer cell's growth genes, the cell will die. Alternatively, switching on a tissue gene can cause a cancer cell to become a more normal tissue cell."
In this study, Bradner's lab synthesized a molecule that has both effects: by blocking a specific abnormal protein in NUT midline carcinoma cells, it stops them from dividing so prolifically and makes them 'forget' they're cancer cells and start appearing more like normal cells.
The assembled molecule affects the cell's multi-layered apparatus for controlling gene activity, a set of structures collectively known as the epigenome. Vast portions of each gene play a regulatory role, dictating whether the gene is active, busily sending orders for new proteins, or inactive, and temporarily at rest. The gene's DNA is packaged in a substance called chromatin, which is the slate on which instructions to begin or cease activity are inscribed.
The instructions themselves take the form of "bookmarks," substances placed on the chromatin by so-called epigenetic "writer" proteins. Another group of epigenetic proteins, known as "erasers," are able to remove the bookmarks. Both types of proteins have successfully been disabled by scientists, using molecules made in the lab or taken from nature. Their success has sparked intense interest in the development of anti-cancer therapies that work by blocking such proteins.
A third variety of epigenetic proteins potentially the most appealing as therapeutic targets, because they switch genes on or off by "reading" the bookmarks has received scant scientific attention. Bradner and his colleagues turned to this little-explored corner of biology by focusing on NMC cells.
The disease is caused by a chromosomal "translocation," in which two genes from different chromosomes become connected and give rise to an abnormal, fused protein known as BRD4-NUT. A review of the scientific literature suggested that some members of the benzodiazepine family of drugs, which includes Valium, Xanax and Ativan, are active against "bromodomain" proteins such as BRD4. With that as a clue, Bradner and his Dana-Farber colleague Jun Qi, PhD, created an array of molecules to see if any inhibited a "reader" protein of the BRD4-NUT gene. One did, quite convincingly a hybrid molecule, which researchers named JQ1, for Qi.
The investigators worked with researchers in the U.S. and overseas to learn more about the properties of JQ1 and how it works in cells. Stefan Knapp, PhD, of Oxford University in England, provided crystal-clear images of the molecule bound to a protein; Olaf Wiest, PhD, of the University of Notre Dame, showed that the molecule is less flexible in the presence of a protein, explaining why it so effectively blocks the protein; and Andrew Kung, MD, PhD, of Dana-Farber, engineered animal models in which the molecule could be tested against NMC tumors.
The animal studies were especially encouraging. Investigators transplanted NMC cells from patients into laboratory mice, which were then given the JQ1 molecule.
"The activity of the molecule was remarkable," says Bradner, who is also an associate member of the Chemical Biology Program at the Broad Institute of Harvard and MIT. "All the mice that received JQ1 lived; all that did not, died."
For now, JQ1's main utility is as a probe for better understanding the biology underlying NUT midline carcinoma. Bradner, Qi and their colleagues are tweaking the molecule to maximize its effectiveness as a BRD4-NUT stopper. Eventually, it, or a similar molecule, could be the basis for the first effective therapy against NMC.
"The disease tends to arise in the chest, head, or neck, along the vertical centerline of the body, with aggressive tumor growth and metastasis," Bradner explains. "Patients may have a brief response to chemotherapy, but they eventually succumb to the spread of the disease."
Unlike most cancers, NMC's tissue of origin isn't known. It is a disease defined entirely by its genetic signature the presence of the translocated gene BRD4-NUT. Prior to its genetic identification by Christopher French, MD, of Brigham and Women's Hospital and a study co-author, NMC wasn't recognized as a distinct disease.
"This research further illustrates the promise of personalized medicine," Bradner remarks, "which is the ability to deliver selected molecules to cancer-causing proteins to stop the cancer process while producing a minimum of residual side effects. The development of JQ1 or similar molecule into a drug may produce the first therapy specifically designed for patients with NMC."
In addition to Qi, the study's other lead authors are Panagis Filippakopoulos and Sarah Picaud, of Oxford University, England. The paper's co-authors include William Smith, Elizabeth Morse, Michael McKeown, Yuchuan Wang, PhD, Amanda Christie, and Nathan West, of Dana-Farber; Oleg Fedorov, Tracey Keates, Ildiko Felletar, Martin Philpott, Shonagh Munro, Tom Heightman, and Nicholas La Thangue, of Oxford University; and Tyler Hickman, Michael Cameron, and Brian Schwartz, PhD, of Brigham and Women's Hospital.
The study was supported in part by the Chemistry Biochemistry Biology Interface Program at the University of Notre Dame, Dana-Farber/Harvard Cancer Center, the National Institute of General Medical Sciences, the National Institutes of Health, the Burroughs Welcome Fund, and the Leukemia & Lymphoma Society.
Source: Dana-Farber Cancer Institute
A new species of amyloid peptide
Scientists have identified a new, longer species of amyloid в-peptide that has the potential to be a new target for the
treatment of Alzheimer's disease.
The research appears as the "Paper of the Week" in the December 3 issue of the Journal of Biological Chemistry, an American
Society for Biochemistry and Molecular Biology journal.
One of the characteristic features of Alzheimer's disease is the deposition of amyloid в-peptides in the brain. These amyloid
в-peptides are derived from a large amyloid precursor protein through a series of cleavage events. Under normal conditions,
cleavage first by б-secretase and then by г-secretase results in a soluble ectodomain, a short peptide called p3, and an
intracellular C-terminal domain, none of which are amyloidogenic. Alternatively, amyloid precursor protein can be processed
by the enzymes в-secretase and г-secretase to produce a soluble ectodomain along with the full-length amyloidogenic amyloid
в-peptide and the intracellular C-terminal domain.
Although amyloid precursor protein is found in many cells, its normal biological function is not well understood. "It has
been suggested that amyloid precursor protein may function as a receptor or growth factor precursor," notes Dr. Xuemin Xu of
The University of Tennessee. "Recent studies also suggest that the intracellular C-terminal domain of the amyloid precursor
protein may function as a transcription factor."
While the exact pathogenic role of amyloid в-peptide in Alzheimer's disease has not yet been definitely established,
accumulating evidence supports the hypothesis that amyloid в-peptide production and deposition in the brain could be a
causative event in Alzheimer's disease. Dr. Xu explains that the literature indicates amyloid в-peptide itself could be toxic
to synapses and the accumulation of amyloid в-peptide could initiate a series of events contributing to cell death, including
activation of cell death programs, oxidation of lipids and disruption of cell membranes, an inflammatory response, and
possibly neurofibrillary tangle formation, which is a close correlate of neuron loss. Therefore, the problem of production,
accumulation, and clearance of amyloid в-peptide in the brain emerges as one of the possible rational approaches for the
treatment of Alzheimer's disease.
Generally, amyloid в-peptides are around 39-43 amino acid long. Studies have shown that the longer amyloid в-peptides are
more amyloidogenic and more pathogenic than the shorter ones. Now, Dr. Xu and his colleagues have discovered a new species of
amyloid в-peptide that is 46 amino acids long, called Aв46. This Aв46 peptide is produced by г-secretase at a novel cleavage
site, the ж-site. This site also happens to be the site of a mutation found in early-onset familial Alzheimer's disease
called the APP717 or London mutation.
"Another well characterized Alzheimer's disease-linked amyloid precursor protein mutation, the Swedish mutation, also occurs
at a major cleavage site, the в-cleavage site at the N-terminus of amyloid в-peptide," adds Dr. Xu. "Studies have shown that
Swedish mutation at the в-cleavage site makes the amyloid precursor protein more susceptible to в-secretase activity. The
finding that ж-cleavage site is the APP717 mutation site suggests that the APP717 mutation may cause enhanced production of
the longer amyloid в-peptide, Aв42, by influencing the ж-cleavage. Therefore, this finding may open a new avenue for studying
the mechanism by which APP717 mutations cause enhanced production of the longer amyloid в-peptide."
Dr. Xu and his colleagues also discovered that г-secretase cleavage at the new ж-site is specifically inhibited by compounds
known as transition state analogs, but is less affected by compounds known as non-transition state inhibitors. Specifically,
some of these inhibitors, which were previously known to inhibit the formation of secreted amyloid в-peptides, were found to
cause an intracellular accumulation of an even longer amyloid в-peptide species, Aв46. "These novel findings provide
information important for the strategy of prevention and treatment of Alzheimer's disease, aimed at the design of г-secretase
inhibitors," concludes Dr. Xu. "Since amyloid в-peptide is produced by the sequential actions of в- and г-secretases,
inhibition of these secretases to reduce the production of amyloid в-peptide is believed to be one of the more promising
avenues of treatment of the disease. To date, more than one dozen г-secretase inhibitors have been developed or identified."
The Journal of Biological Chemistry's Papers of the Week is an online feature which highlights the top one percent of papers
received by the journal. Brief summaries of the papers and explanations of why they were selected for this honor can be
accessed directly from the home page of the Journal of Biological Chemistry online at jbc.
The American Society for Biochemistry and Molecular Biology (ASBMB) is a nonprofit scientific and educational organization
with over 11,000 members in the United States and internationally. Most members teach and conduct research at colleges and
universities. Others conduct research in various government laboratories, nonprofit research institutions, and industry.
Founded in 1906, the Society is based in Bethesda, Maryland, on the campus of the Federation of American Societies for
Experimental Biology. The Society's primary purpose is to advance the sciences of biochemistry and molecular biology through
its publications, the Journal of Biological Chemistry, The Journal of Lipid Research, Molecular and Cellular Proteomics, and
Biochemistry and Molecular Biology Education, and the holding of scientific meetings.
For more information about ASBMB, see the Society's website at asbmb.
Contact: Nicole Kresge
nkresgeasbmb
301-634-7415
American Society for Biochemistry and Molecular Biology
treatment of Alzheimer's disease.
The research appears as the "Paper of the Week" in the December 3 issue of the Journal of Biological Chemistry, an American
Society for Biochemistry and Molecular Biology journal.
One of the characteristic features of Alzheimer's disease is the deposition of amyloid в-peptides in the brain. These amyloid
в-peptides are derived from a large amyloid precursor protein through a series of cleavage events. Under normal conditions,
cleavage first by б-secretase and then by г-secretase results in a soluble ectodomain, a short peptide called p3, and an
intracellular C-terminal domain, none of which are amyloidogenic. Alternatively, amyloid precursor protein can be processed
by the enzymes в-secretase and г-secretase to produce a soluble ectodomain along with the full-length amyloidogenic amyloid
в-peptide and the intracellular C-terminal domain.
Although amyloid precursor protein is found in many cells, its normal biological function is not well understood. "It has
been suggested that amyloid precursor protein may function as a receptor or growth factor precursor," notes Dr. Xuemin Xu of
The University of Tennessee. "Recent studies also suggest that the intracellular C-terminal domain of the amyloid precursor
protein may function as a transcription factor."
While the exact pathogenic role of amyloid в-peptide in Alzheimer's disease has not yet been definitely established,
accumulating evidence supports the hypothesis that amyloid в-peptide production and deposition in the brain could be a
causative event in Alzheimer's disease. Dr. Xu explains that the literature indicates amyloid в-peptide itself could be toxic
to synapses and the accumulation of amyloid в-peptide could initiate a series of events contributing to cell death, including
activation of cell death programs, oxidation of lipids and disruption of cell membranes, an inflammatory response, and
possibly neurofibrillary tangle formation, which is a close correlate of neuron loss. Therefore, the problem of production,
accumulation, and clearance of amyloid в-peptide in the brain emerges as one of the possible rational approaches for the
treatment of Alzheimer's disease.
Generally, amyloid в-peptides are around 39-43 amino acid long. Studies have shown that the longer amyloid в-peptides are
more amyloidogenic and more pathogenic than the shorter ones. Now, Dr. Xu and his colleagues have discovered a new species of
amyloid в-peptide that is 46 amino acids long, called Aв46. This Aв46 peptide is produced by г-secretase at a novel cleavage
site, the ж-site. This site also happens to be the site of a mutation found in early-onset familial Alzheimer's disease
called the APP717 or London mutation.
"Another well characterized Alzheimer's disease-linked amyloid precursor protein mutation, the Swedish mutation, also occurs
at a major cleavage site, the в-cleavage site at the N-terminus of amyloid в-peptide," adds Dr. Xu. "Studies have shown that
Swedish mutation at the в-cleavage site makes the amyloid precursor protein more susceptible to в-secretase activity. The
finding that ж-cleavage site is the APP717 mutation site suggests that the APP717 mutation may cause enhanced production of
the longer amyloid в-peptide, Aв42, by influencing the ж-cleavage. Therefore, this finding may open a new avenue for studying
the mechanism by which APP717 mutations cause enhanced production of the longer amyloid в-peptide."
Dr. Xu and his colleagues also discovered that г-secretase cleavage at the new ж-site is specifically inhibited by compounds
known as transition state analogs, but is less affected by compounds known as non-transition state inhibitors. Specifically,
some of these inhibitors, which were previously known to inhibit the formation of secreted amyloid в-peptides, were found to
cause an intracellular accumulation of an even longer amyloid в-peptide species, Aв46. "These novel findings provide
information important for the strategy of prevention and treatment of Alzheimer's disease, aimed at the design of г-secretase
inhibitors," concludes Dr. Xu. "Since amyloid в-peptide is produced by the sequential actions of в- and г-secretases,
inhibition of these secretases to reduce the production of amyloid в-peptide is believed to be one of the more promising
avenues of treatment of the disease. To date, more than one dozen г-secretase inhibitors have been developed or identified."
The Journal of Biological Chemistry's Papers of the Week is an online feature which highlights the top one percent of papers
received by the journal. Brief summaries of the papers and explanations of why they were selected for this honor can be
accessed directly from the home page of the Journal of Biological Chemistry online at jbc.
The American Society for Biochemistry and Molecular Biology (ASBMB) is a nonprofit scientific and educational organization
with over 11,000 members in the United States and internationally. Most members teach and conduct research at colleges and
universities. Others conduct research in various government laboratories, nonprofit research institutions, and industry.
Founded in 1906, the Society is based in Bethesda, Maryland, on the campus of the Federation of American Societies for
Experimental Biology. The Society's primary purpose is to advance the sciences of biochemistry and molecular biology through
its publications, the Journal of Biological Chemistry, The Journal of Lipid Research, Molecular and Cellular Proteomics, and
Biochemistry and Molecular Biology Education, and the holding of scientific meetings.
For more information about ASBMB, see the Society's website at asbmb.
Contact: Nicole Kresge
nkresgeasbmb
301-634-7415
American Society for Biochemistry and Molecular Biology
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