Lack Of Fragile X And Related Gene Fractures Sleep

Lack of both the fragile X syndrome gene and one that is related could account for sleep problems associated with the disorder, which is the common cause of inherited mental impairment, said a consortium of researchers led by scientists at Baylor College of Medicine in Houston. Their findings appear in a report in the current issue of the American Journal of Human Genetics.



Mice deficient in the fragile X mental retardation 1 gene (FMR1) and a similar gene called fragile X-related gene 2 (FXR2) have no rhythm to their wake and sleep pattern, said Dr. David Nelson, professor of molecular and human genetics at BCM and co-director of the Interdepartmental Program in Cell and Molecular Biology.



Normal mice have a sleep-wake cycle of just under 12 hours awake and 12 hours asleep. Exposed to light and dark, they are awake in the dark and asleep during the light because they are nocturnal animals. If they are kept in the dark, their cycle reduces by about 10 minutes per sleep-wake period but remains fairly normal. When mice do not have either FMR1 or FXR2, they have a slightly shorter cycle but the difference is not dramatic.



"However, the double-mutants (those without both genes) have no rhythm at all," said Nelson. "This has never been seen in a mouse before." The animals, usually kept in a cage with a wheel on which they run when awake, sleep a little, run a little, sleep a little - but there is no rhythm to it.



The finding is important because parents whose children have autism or fragile X report problems getting their children to go to sleep and stay asleep. Fragile X is the most common known cause of autism. While there are few studies on the topic, said Nelson, "the impression I have is that many fragile X patients have a period of time that's like an extended infancy when they don't settle into a typical sleep-wake period."



Understanding how the gene associated with fragile X affect the circadian clock or the sleep-wake cycle could help explain some of the symptoms experienced by patients, he said.



After ruling out the possibility that the animals without the two genes could not perceive light, Nelson collaborated with a group in The Netherlands to test whether the cell's "central clock" called the suprachiasmatic nucleus in the animals was normal. They concluded that the clock was normal but that somehow the expression of genes that govern it is altered in these mice.



"These genes (FMR1 and FXR2) are new players in the control of circadian (daily) rhythms," said Nelson. Currently, the genes are thought to have a role in translating RNAs (ribonucleic acids) - particularly at the receiving side of the connections between neurons called dendrites. Dendrites are characterized by the fine branches that reach out into tissue. Scientists theorize that FMR1 and FXR2 may be involved in transporting the RNAs to the areas of those branches where the synapse is present.







Others who took part in this work include Jing Zhang and Zhe Fang of BCM, Corinne Jud and Urs Albrecht of the University of Fribourg in Switzerland, Mariska J. Van Steensel and Johanna H. Meijer of Leiden University Medical Center in The Netherlands, Krista Kaasik and Cheng Chi Lee of The University of Texas Health Science Center at Houston and Ben A. Oostra of Erasmus University Medical Center in Rotterdam, The Netherlands.



Funding for this work came from the U.S. National Institute of Child Health and Human Development, the BCM Mental Retardation and Developmental Disability Research Center, the Fragile X Research (FRAXA) Foundation, the Swiss National Science Foundation and EUCLOCK, a project on the circadian clock sponsored by the European Commission.



The article is available at ajhg/



For more information on basic science at Baylor College of Medicine, go to bcm/fromthelab.



Source: Glenna Picton


Baylor College of Medicine

New Tumor Suppressor For Lung Cancer Identified By Cell Biologists

Cancer and cell biology experts at the University of Cincinnati (UC) have identified a new tumor suppressor that may help scientists develop more targeted drug therapies to combat lung cancer.



The study, led by Jorge Moscat, PhD, appears in the January 2009 issue of Molecular and Cellular Biology.




Proto-oncogenes are genes that play a role in normal cell growth (turnover of cells and tissue) but, when genetically modified, can cause the out-of-control cell division that leads to cancer. Previous research had established that Ras, a proto-oncogene, is abnormally expressed in up to 25 percent of human lung cancers; however, researchers did not understand the specific cellular events by which abnormal Ras expression leads to transformation.




UC researchers sought to define the interim steps that occur in Ras-induced tumor development to better understand the underlying biological mechanisms leading to cancer.



"These interim steps are critical because they help us determine how best to intervene and stop cancer growth along the way," explains Moscat, corresponding author of the study and chair of UC's cancer and cell biology department. "Right now, cancer therapy is delivered with a sledgehammer and it needs to be more like a scalpel so we avoid unnecessary harm to the body."



Using a genetically modified mouse model, the UC team found that animals who didn't express a certain gene (protein kinase C (PKC)-zeta) developed more Ras-induced lung cancer, suggesting a new role for the gene as a tumor suppressor.



"PKC-zeta would normally slow down Ras transformation and put the brakes on tumor development, but when PKC-zeta is missing or inactive as a result of genetic alterations, tumor growth actually accelerates," explains Moscat. "Until now, we did not know the specific chain of events that led to Ras-induced lung cancer. Our study fills in important missing information that will enhance our overall understanding of how lung cancer tumors grow and spread."



UC's Anita Galvez, PhD, Angeles Duran, PhD, Juan Linares, PhD, Peterson Pathrose, Elias Castilla, Shadi Abu-Baker, PhD, Michael Leitges and Maria Diaz-Meco, PhD, also participated in this National Institutes of Health-funded study.



UC's cancer and cell biology department is part of the Cincinnati Cancer Consortium (formerly Joint Cancer Program), a collaborative initiative involving the UC College of Medicine, Cincinnati Children's Hospital Medical Center and University Hospital. It brings together interdisciplinary research teams of caring scientists and health professionals to research and develop new cures, while providing a continuum of care for children, adults and families with cancer.



Source: Amanda Harper


University of Cincinnati

The Discovery Of A New Signaling Pathway May Provide A Target For Structure-Based Drug Design

Over the past decade various pieces of the puzzle of how signal transmission controls immunity have been coming together. Now, in Cell an international team reports a paradigm shift in the regulation of immune response. Their results show that interaction with a linear ubiquitin chain is crucial for nuclear factor kappa B activation. Their findings may also contribute towards structure-based drug design to target the defective NF-ОєB pathway in diseases such as cancer, inflammation and immunodeficiency.



The body's first line of defence against bacteria and viruses is the innate immune system where phagocytes identify the foreign organism and initiate an alarm reaction, often accompanied by inflammation. As a consequence, molecular cues are produced in the blood, such as Tumor Receptor Factors (TNF) or interleukin-1, and these stimulate further reactions in the immune system. But what exactly happens after the molecular cues have docked onto the cell receptors that specialize in immune response? What is the basis of signal transmission from the cellular receptors into the cellular interior? Over the past decade, the overall picture of this large puzzle has been gradually pieced together to show that modifications in the cell protein - including the addition of phosphate groups (phosphorylation) or the conjugation of small modifier ubiquitin (ubiquitination) - play a central role in controlling the immune system.



Scientists at Frankfurt's Goethe University led by Prof. Ivan Dikic have established an international collaboration to investigate the role of ubiquitin modification in these pathways. The international team includes the laboratories of Soichi Wakatsuki (Photon factory, Tsukuba, Japan), Fumiyo Ikeda (MedILS, Split, Croatia), Felix Randow (LMB, Cambridge, UK) and David Komander (LMB, Cambridge, UK). They have been investigating how a transcription factor known as the nuclear factor kappa-B (NF-ОєB) coordinates the gene expression necessary for the cell's immune response. NF-ОєB is activated by an enzyme (IkappaB-Kinase, IKK) with a regulatory subunit that brings to mind the mysterious captain in Jules Verne's science fiction novels: NEMO.



The question that had to be answered was how does NEMO activate NF-ОєB? This is where the work of the Frankfurt biochemists came in. They identified a subdomain of NEMO, called UBAN that binds selectively to a specific type of ubiquitin. This protein is ubiquitous in the cell and has various functions, acting as a multifaceted molecular signal. It can function as a single molecule (monoubiquitin) or in the form of chains (polyubiquitin).



In the scientific journal Cell, Ivan Dikic and his colleagues report that NEMO specifically binds to linear ubiquitin chains and that this is an essential step for NF-ОєB activation. This came as a big surprise to the team, since it was previously thought that other types of ubiquitin signals were critical for NEMO-dependent NF-ОєB activation. "This results in a paradigm change", says Ivan Dikic, "it means, that current knowledge on NF-ОєB activation and the role of linear ubiquitin chains needs to be updated".
















In cooperation with the group of Soichi Wakatsuki, NEMO's structure could be solved. The work demonstrates that the UBAN domain binds to a linear ubiquitin chain according to the key-and-lock-principle. "These new findings not only explain the atomic details of ubiquitin chain selectivity, but can also provide useful insights into developing therapy for targeting the NF-ОєB pathway", reports Soichi Wakatsuki. Increased activation of the NF-ОєB pathway is known to be linked to development of different diseases such as cancer and inflammation.



The discovery also has direct medical relevance. "We are happy that this basic scientific discovery may explain the detrimental effect of NEMO mutations in patients suffering from X-linked ectodermal dysplasia and immunodeficiency", Ivan Dikic points out. Ectodermal dysplasia is a hereditary disease, which affects 1 to 5 children in 10,000 newborn. It causes the skin to be very thin and the perspiratory glands to malfunction. In some cases it is combined with immune deficiency. The molecular defect is a mutation in the NEMO gene, which blocks the activation of the NF-ОєB pathway in epidermal and immune cells.



Notes:


This work will be published in the March 20, 2009 issue of the scientific journal Cell published by Cell Press, USA.



The Goethe University, with its strong research focus, is based in Frankfurt, Europe's financial metropolis. It was founded 1914 by Frankfurt citizens and is now one of Germany's ten largest universities. On January 1, 2008 it returned to its historical roots as a university financed by foundations, guaranteeing it an exceptional degree of autonomy. The historical ensemble of buildings designed by Hans Poelzig back in the 1920s in Frankfurt's Westend is now the hub of what, when complete, will be Germany's most beautiful campus - the construction work will cost a total of about EUR 600 million. Since 2000, over 50 new foundation-financed professorships and visiting professorships have been established, meaning the Goethe University is again a trailblazer in Germany, and has been well up with leaders for three consecutive issues of the CHE's three research ranking table and the German Academic Excellence Initiative.



Source: Dr. Ivan Dikic


Goethe University Frankfurt

In Sleep Deprivation Astrocytes Regulate Sleep Pressure And Memory Deficits

Scientists have discovered an unexpected brain mechanism that modulates the regulation of sleep and the consequences of sleep deprivation. The research, published by Cell Press in the January 29th issue of the journal Neuron, opens new avenues for development of treatments for disorders and cognitive deficits associated with sleep loss.



Glial cells are brain cells that do not transmit nerve impulses the way that neurons do. Astrocytes are a type of glial cell that play multiple supportive roles and modulate signaling around neurons. Astrocytes can release chemical transmitters that influence synaptic activity through a process called gliotransmission. Senior study author Dr. Philip G. Haydon from Tufts University School of Medicine and his colleagues had previously shown that astrocytes release ATP and regulate extracellular adenosine that acts on synaptic A1 receptors.



Although it has been established that adenosine is a transmitter involved in the drive for sleep following prolonged wakefulness, the cellular source and mechanisms of action of adenosine in the process of sleep are not well understood. Dr. Haydon and colleagues used astrocyte-specific transgenic mice to explore the role of astrocytes and adenosine in the regulation of sleep. Using their transgenic model, they could selectively and reversibly interfere with gliotransmission.



The researchers found that genetic inhibition of neurotransmitter release from astrocytes reversibly decreased the accumulation of sleep pressure after sleep deprivation and prevented cognitive deficits associated with sleep loss. Further, the A1 antagonist CPT failed to suppress sleep following inhibition of gliotransmission, and administration of CPT in control animals was protective against the memory-degrading effects of sleep deprivation.



" Taken together these studies provide the first demonstration that a nonneuronal cell type in the brain, the astrocyte, modulates behavior and provides strong evidence of the important role of A1 receptors in the regulation of sleep and the cognitive decline associated with sleep loss," explains Dr. Haydon. "Given that astrocytes express novel receptors; these glial cells may offer a distinct target for the development of therapeutics for sleep and cognitive disorders."







The researchers include Michael M. Halassa, University of Pennsylvania School of Medicine, Philadelphia, PA, Tufts University Schools of Medicine, Boston, MA; Cedrick Florian, University of Pennsylvania School of Medicine, Philadelphia, PA Tommaso Fellin, University of Pennsylvania School of Medicine, Philadelphia, PA; James R. Munoz, University of Pennsylvania School of Medicine, Philadelphia, PA; So-Young Lee, University of Pennsylvania School of Medicine, Philadelphia, PA, Tufts University Schools of Medicine, Boston, MA; Ted Abel, University of Pennsylvania School of Medicine, Philadelphia, PA , Philip G. Haydon, University of Pennsylvania School of Medicine, Philadelphia, PA, Tufts University Schools of Medicine, Boston, MA; and Marcos G. Frank, University of Pennsylvania School of Medicine, Philadelphia, PA.



Source: Cathleen Genova


Cell Press

Ovarian Cancer Clues From Flaxseed-Fed Chickens

In the race to find answers about ovarian cancer, researchers now have something to cluck about. For five years, University of Illinois researchers have been using the chicken as a model to study this deadly disease and have recently discovered that a diet enriched with flaxseed decreases severity of ovarian cancer and increases survival in hens.



Flaxseed is the richest plant source of alpha-linolenic acid, one type of omega-3 fatty acid. Several studies have already shown that flaxseed inhibits the formation of colon, breast, skin and lung tumors.



For these reasons, it was logical to study how omega-3 fatty acids affect ovarian cancer as there continues to be no effective treatment at this time, said Janice Bahr, a professor emerita in the U of I Department of Animal Sciences and one of the nation's leading poultry researchers.



According to Bahr, 25,000 women are diagnosed with ovarian cancer each year and 15,000 die. The incidences of death in other cancers have dropped recently, but ovarian cancer death rates have remained the same.



"The chicken is the only animal that spontaneously develops ovarian cancer on the surface of the ovaries like humans," Bahr said. "In this study, we evaluated how a flaxseed-enriched diet affected 2-year-old laying hens (hens that have ovulated as many times as a woman entering menopause)."



The results showed that hens fed a flaxseed-enriched diet for one year experienced a significant reduction in late-stage ovarian tumors.



"Most women diagnosed with ovarian cancer have a very poor prognosis because they are not diagnosed until stage 3 or 4 when the cancer has metastasized and spread to other parts of the body," Bahr said.



Hens fed the control diet had significantly more late-stage tumors that presented with fluid and metastases as compared to the hens fed a flaxseed diet. Though hens fed the flaxseed diet did not have a decreased incidence of ovarian cancer, they did experience fewer late-stage tumors and higher survival rates.



"In hens fed flaxseed, we found that more tumors were confined to the ovary and they had less metastatic spread," she said. "This is an important finding as the metastases that accompany late-stage ovarian cancer are the main cause of death from this disease. If the cancer is found at an early stage, when the tumor is still confined to the ovary, women have a much better prognosis and more treatment options."



In addition, researchers found that hens fed the flaxseed diet had better weight control which is important because obesity increases cancer risk. Both diets had equal caloric content, however the flaxseed-fed hens weighed less at six months than the control-fed hens. But at 12 months, the flaxseed-fed hens were the same weight and the control-fed hens had loss significant weight, which was indicative of their failing health. Ultimately, the flaxseed-enriched diet helped the birds maintain a healthy weight and resulted in less sickness and death.



"Through this research, we have proven that flaxseed supplementation for one year is able to reduce the severity of ovarian cancer in hens," she said. "These findings may provide the basis for a clinical trial that evaluates the efficacy of flaxseed as a chemosuppressant of ovarian cancer in women."



The cause of ovarian cancer remains unknown, but one of the most prevalent theories is the "incessant ovulation hypothesis," proposed by MF Fathalla in 1971. He suggests that inflammation associated with continuous ovulation leaves ovarian surface epithelial cells susceptible to malignant transformation. The observation that egg-laying domestic hens frequently develop ovarian cancer supports this hypothesis.



Bahr believes this hypothesis is valid and is currently in the middle of a four-year study to determine if long-term dietary intervention with flaxseed will reduce the incidence of ovarian cancer development. The hens started the flaxseed-supplemented diet at 22 weeks of age, as soon as they commenced egg laying and before damage from ovulation had accumulated.



This research was published in Gynecologic Oncology and funded by a National Institutes of Health (NIH) National Center for Complementary and Alternative Medicine Grant, an American Institute for Cancer Research Grant, and an NIH Training Grant.



Researchers included principal investigator Dale Buchanan Hales of Southern Illinois University. Co-principal investigators include Janice Bahr of the University of Illinois at Urbana-Champaign; Kristine Ansenberger and Cassandra Richards of the University of Illinois at Chicago; and Yan Zhuge, Judith Luborsky and Animesh Barua of Rush University Medical Center.



Source:

Jennifer Shike

University of Illinois College of Agricultural, Consumer and Environmental Sciences

New Book On Signal Transduction

In biology, 'signal transduction' refers to any process by which a cell converts one kind of signal or stimulus into another. Most processes of signal transduction involve ordered sequences of biochemical reactions inside the cell, which are carried out by enzymes and activated by second messengers, resulting in a signal transduction pathway. Such processes are usually rapid, lasting on the order of milliseconds in the case of ion flux, or minutes for the activation of protein- and lipid-mediated kinase cascades, but some can take hours, and even days to complete.



Elsevier, the world-leading publisher of scientific, technical and medical information products and services, announces the publication of the new second edition of Signal Transduction edited by Bastien D. Gomperts, Ijsbrand M. Kramer and Peter E.R. Tatham.



This book is a thorough, well-illustrated study in cellular signaling processes. Beginning with the basics, this book shows how cells respond to external cues, hormones, growth factors, cytokines, cell surfaces, etc., and further instructs how these inputs are integrated. Instruction continues with up-to-date, inclusive coverage of intracellular calcium, nuclear receptors, tyrosine protein kinases and adaptive immunity, and targeting transduction pathways for research and medical intervention. Signal Transduction serves as an invaluable resource for advanced undergraduates, graduate researchers, and established scientists working in cell biology, pharmacology, immunology, and related fields.



Signal Transduction, 2e

Edited by: Bastien D. Gomperts, Ijsbrand M. Kramer and Peter E.R. Tatham

ISBN: 9780123694416

PAGES: 576

PUB DATE: August 2009



Source:
Leah Ackerson


Elsevier

A Novel Approach To Cancer Therapy

Cancer sometimes involves processes that should only occur in the embryo being mistakenly reactivated in adult cells. Researchers at the Postgraduate Medical School at the University of Surrey have exploited this to develop a novel therapeutic strategy. This has led to the development of a new drug, HXR9 that blocks the activity of a group of genes known as the HOX family.


The project leader, Dr Richard Morgan, explains 'HOX genes are important in determining the identity of cells and tissues in the early embryo, but they are also expressed by cancer cells. HXR9 blocks HOX activity thereby killing cancer cells in a highly specific manner'. HXR9 shows particular promise in treating malignant melanoma together with lung, prostate and kidney cancer. The results appear this week in the prestigious 'Cancer Research' Journal. Work on HXR9 was started by Dr Morgan whilst he was a senior lecturer at St. George's, University of London, and the University of Surrey has recently agreed a licensing deal to allow Dr Morgan to continue with the work at the PGMS.


Further work by the PGMS group has shown that embryonic genes expressed in cancer cells could also be important diagnostic markers. A number of embryonic proteins are secreted by prostate tumours and can be detected in blood serum, thereby providing a potential method for detecting prostate cancer and ultimately even assessing the extent of the disease without an invasive procedure. These findings have now been patented by the University of Surrey. Dr Morgan and his colleagues would like to acknowledge the support of both the University and the Prostate Project charity.


SURREY UNIVERSITY

Guildford

Surrey

GU2 7XH

surrey.ac.uk

Researchers Discover Enzyme That Makes Us Genetically Unique

Have you ever wondered why you inherited your mother's smile but not your father's height? Researchers at the Universities of Leeds and Dundee are one step closer to unravelling how nature combines both maternal and paternal DNA to create genetically unique offspring.



In a world first, Leeds researchers Professor Simon Phillips, Dr Stephen Carr and Dr Jonathan Hadden, together with Professor David Lilley at Dundee, have mapped the 3 dimensional structure of an enzyme responsible for splitting DNA strands -- a process at the heart of human individuality.



The discovery of the T7 endonuclease 1 enzyme's structure was made by using x-ray crystallography techniques. The enzyme is derived from a bacteriophage -- a naturally occurring virus-like agent that attacks bacteria -- but the molecular processes are expected to be similar in other organisms, including humans.



"Whilst the enzyme was known to play a central role, its physical structure, which is crucial to understanding the splitting process, has never been seen before. We've now got a 3D picture of it at work, and seen it at the point at which it is about to cut through the DNA strands. This is a major breakthrough in investigating the fundamental mechanisms at work behind the formation of a person's DNA and how viruses replicate their DNA in the body," says Professor Phillips.



In humans, this process starts at conception when maternal and paternal DNA strands join together at random points in their sequence(1). Enzymes such as T7 endonuclease 1 are then responsible for severing the strands at this junction, thus creating a third, unique DNA sequence for the offspring.



However, Professor Phillips says it will be some time before this process can be observed in humans. "It's too important a discovery to rush. Our next step is to examine the process in a more complex system than bacteriophage, such as yeast," he says.







The work is the result of a long collaboration between the research groups at Leeds and Dundee and has been funded by the Wellcome Trust and the Biotechnology and Biological Sciences Research Council (BBSRC) and Cancer Research UK.



Source: Clare Elsley


University of Leeds

Two Hutchinson Center Researchers Named HHMI Early Career Scientists

The Howard Hughes Medical Research Institute has announced that two researchers at Fred Hutchinson Cancer Research Center are among 50 scientists nationwide to be appointed HHMI Early Career Scientists.



Harmit Singh Malik, Ph.D., an associate member of the Center's Basic Sciences Division, and Toshiyasu Taniguchi, M.D., Ph.D., an assistant member in the Center's Human Biology and Public Health Sciences divisions, each will receive a six-year appointment to the HHMI and, along with it, the freedom to explore his or her best ideas without worrying about where to find the money to fund the work. Each will receive $1.5 million over the six-year appointment. The Institute will also cover other expenses, including research space and the purchase of critical equipment.



"These scientists are at the early stage of their careers, when they are full of energy and not afraid to try something new," said Jack Dixon, HHMI vice president and chief scientific officer. "They have already demonstrated that they are not apt to play it safe - and we hope they will continue to do something really original."



Malik, an evolutionary biologist, sees conflicts raging within a cell's nucleus as genes jockey for evolutionary dominance. These clashes can have a long-term impact on organisms, as they sometimes alter the function of essential genes. Malik uses biochemistry and genomics to study the causes and consequences of these genetic conflicts in yeast, fruit flies and other model organisms. His work has offered novel explanations for host-pathogen interactions and for the evolution of structural DNA elements (centromeres) that are critical for proper cell division. For example, to explore why humans are susceptible to HIV, Malik and his colleagues resurrected an extinct retrovirus that infected chimps and gorillas, but not humans, 4 million years ago. Malik's research suggests that we may be vulnerable to HIV infection because our defenses evolved to fight off other viruses instead. Recently, Malik and colleagues have shown that host proteins can evolve to defeat "viral mimicry," providing yet another nuance to a never-ending "arms race" between hosts and viruses.



Taniguchi, as a physician in Tokyo, treated many lymphoma patients with DNA-damaging chemotherapy, only to watch the drugs lose their power as the tumors developed resistance. He then became a researcher in cancer genetics to find ways to save more patients. At the Hutchinson Center, Taniguchi studies the role of DNA repair in promoting drug resistance in cancer cells. He identified a repair pathway that is often inactivated in patients with breast and ovarian cancers, as well as the childhood predisposition to cancer known as Fanconi anemia. Reactivation of the pathway, he discovered, can help tumors become resistant to chemotherapy drugs. Taniguchi intends to dig deeper into this mechanism of drug resistance and use the information he uncovers to develop drugs that will re-sensitize tumors to cancer therapies.



Malik and Taniguchi will begin their six-year, nonrenewable HHMI appointments in September 2009. The Institute anticipates another Early Career Scientist competition in 2012.


Notes:


In addition to Malik and Taniguchi, the Hutchinson Center is home to four current HHMI investigators.



At Fred Hutchinson Cancer Research Center, our interdisciplinary teams of world-renowned scientists and humanitarians work together to prevent, diagnose and treat cancer, HIV/AIDS and other diseases. Our researchers, including three Nobel laureates, bring a relentless pursuit and passion for health, knowledge and hope to their work and to the world.



Source:
Kristen Woodward


Fred Hutchinson Cancer Research Center

An AIDS Related Virus Reveals More Ways To Cause Cancer

Researchers at the University of Pennsylvania School of Medicine have shed new light on how Kaposi's Sarcoma-associated Herpes Virus (KSHV) subverts normal cell machinery to cause cancer. A KSHV protein called latency-associated nuclear antigen, LANA for short, helps the virus hide out from the immune system in infected cells. When LANA takes the place of other proteins that control cell growth, it can cause uncontrolled cell replication.


The findings appear in a recent issue of the Proceedings of the National Academy of Sciences (USA).


"This is the first report of LANA interfering with the crucial cellular protein called intracellular Notch," says lead author Erle Robertson, PhD, Professor of Microbiology and the Program Leader of Tumor Virology at Penn's Abramson Cancer Center. Notch is a signaling molecule that triggers cell development and maintains the stability of cells in many organs, such as the brain, heart, blood, and muscle.


"Intracellular notch, or ICN, promotes cell growth and proliferation, therefore it must be regulated so that these processes do not lead to cancer," says Robertson. "We found that regulation of ICN through binding to another protein called Sel10, a cell-cycle regulatory protein, is derailed. The large complex of ICN, Sel10, and other factors is marked for degradation by a process called ubiquitination," says Robertson. In normal uninfected cells, the level of ICN, and thus cell growth and proliferation, is fine-tuned by regulating ICN degradation.


LANA interferes with the degradation of ICN because it competes with ICN for the same binding site on Sel10. If LANA sits on Sel10, ICN cannot be degraded and cell growth and proliferation are no longer controlled. Kaposi's sarcoma and primary effusion lymphoma are two of the viral-associated cancers that are common in immune-compromised patients.


This is the second mechanism discovered by Robertson and his associates by which KSHV subverts control of normal cell growth. Robertson's group previously found that LANA marks tumor suppressors, such as p53 and VHL, for degradation.


Other herpes viruses, such as the one that causes cold sores and Epstein-Barr virus, which causes mononucleosis, are able to hide out in cells as well. "Whether these latent herpes viruses use some of the same strategies that we have found for LANA in KSHV has not been determined," says Robertson.


This new role for LANA was discovered using specific human cell lines. The next step is to test whether LANA works the same way in animals infected with KSHV. "We have completed some studies in mice that indicate that LANA can contribute to tumor development in an animal in ways similar to what we have observed in cell culture," says Robertson. The animal models will be useful for testing new drug therapies that may inhibit the activity of LANA and eventually prevent the growth of viral-associated cancers.















This work was funded by the National Institutes of Health and the Leukemia and Lymphoma Society of America. Co-authors are Ke Lan of Penn and the Chinese Academy of Science, and S.C. Verma, M. Marakami, B. Bajaj and R. Kaul, all from Penn.


The Abramson Cancer Center (ACC) of the University of Pennsylvania is a national leader in cancer research, patient care, and education. The pre-eminent position of the Cancer Center is reflected in its continuous designation as a Comprehensive Cancer Center by the National Cancer Institute for 30 years, one of 39 such Centers in the United States. The ACC is dedicated to innovative and compassionate cancer care. The clinical program, comprised of a dedicated staff of physicians, nurse practitioners, nurses, social workers, physical therapists, nutritionists and patient support specialists, currently sees over 50,000 outpatient visits, 3400 inpatient admissions, and provides over 25,000 chemotherapy treatments, and more than 65,000 radiation treatments annually. Not only is the ACC dedicated to providing state-of-the-art cancer care, the latest forms of cancer prevention, diagnosis, and treatment are available to our patients through clinical themes that developed in the relentless pursuit to eliminate the pain and suffering from cancer. In addition, the ACC is home to the 300 research scientists who work relentlessly to determine the pathogenesis of cancer. Together, the faculty is committed to improving the prevention, diagnosis and treatment of cancer.


PENN Medicine is a $3.5 billion enterprise dedicated to the related missions of medical education, biomedical research, and excellence in patient care. PENN Medicine consists of the University of Pennsylvania School of Medicine (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System.


Penn's School of Medicine is currently ranked #3 in the nation in U.S.News & World Report's survey of top research-oriented medical schools; and, according to most recent data from the National Institutes of Health, received over $379 million in NIH research funds in the 2006 fiscal year. Supporting 1,400 fulltime faculty and 700 students, the School of Medicine is recognized worldwide for its superior education and training of the next generation of physician-scientists and leaders of academic medicine.


The University of Pennsylvania Health System includes three hospitals its flagship hospital, the Hospital of the University of Pennsylvania, rated one of the nation's "Honor Roll" hospitals by U.S.News & World Report; Pennsylvania Hospital, the nation's first hospital; and Penn Presbyterian Medical Center a faculty practice plan; a primary-care provider network; two multispecialty satellite facilities; and home care and hospice.


University of Pennsylvania School of Medicine

3600 Market St., Ste 240

Philadelphia, PA 19104

United States

med.upenn

Possible Safer Target For Anti Clotting Drugs Found

Researchers at the University of Illinois at Chicago College of Medicine have identified a new molecular target in blood clot formation, which seems to reduce clotting without excessive bleeding, the common side effect of anti clotting agents.


The findings are reported in the September issue of Molecular and Cellular Biology.


"It was very surprising to find an enzyme whose inhibition lessened platelet aggregation without abnormal bleeding, and we immediately realized that it could have very important implications for the treatment of cardiovascular disease," said Shafi Kuchay, a graduate student in pharmacology and first author of the paper.


When clots form, small blood cells called platelets begin to clump together. Aspirin and other anti clotting agents reduce the risk of heart attack and stroke by blocking the biochemical pathway that causes platelets to become sticky. But all these drugs put patients at risk of excessive bleeding.


The UIC researchers made a mouse model that lacked a gene for a protease enzyme most commonly found in blood cells called calpain 1, in order to determine its function. They found that mice lacking calpain 1 had reduced platelet aggregation but did not have any abnormal bleeding.


The mice lacking calpain-1 (called "knockout" mice) had increased levels of another enzyme, known as protein tyrosine phosphatase-1B. When the mice were given a PTP1B inhibitor, the reduced platelet aggregation was restored. When calpain-1 knockout mice and mice lacking PTP1B were crossed to create double knockout mice, platelet aggregation was restored in the offspring that lacked the genes for both enzymes. The researchers were thus able to establish that PTP1B turns off the signal for platelet aggregation and that calpain-1 regulated the amount and activity of this "off switch."


"Because of the danger of excessive bleeding, people taking anti-clotting medications are monitored carefully and warned not to exceed their recommended doses," said Dr. Athar Chishti of the UIC Cancer Center, and senior author of the study. "Our research unveils a new molecular target for anti-platelet drugs, which may avoid the dangerous side-effects of the current drugs."


In a secondary, serendipitous finding, the fact that the calpain-1 knockout mice have elevated PTP1B levels may prove important to research into diabetes and obesity.


"Mice that lack the gene for PTP1B have been known for some time to display increased insulin sensitivity and resistance to diet-induced obesity," said Chishti, who is professor of pharmacology. He noted that PTP1B inhibition has already been identified as a therapeutic goal by many researchers in diabetes and obesity.


"Our calpain-1 knockout mice with their elevated PTP1B levels offer a good model system for testing the potency of novel PTP1B inhibitors," he said.


The study was supported by a grant from the National Institutes of Health. Nayoung Kim of Tufts St. Elizabeth's Medical Center in Boston and Elizabeth Grunz and William Fay of the University of Missouri-Columbia also contributed to this study.


For more information about UIC, visit uic.


University of Illinois at Chicago

601 S. Morgan St. MC 288

Chicago, IL 60607-7113

United States

uic/index.html

Database Provides A Key To Unlock The Causes Of Illnesses

Five years after the inception of the DECIPHER database - researchers have published a report that reveals the developing role of the database in revolutionising both clinical practice and genetic research.



The report explores the growing benefits of DECIPHER for researchers, clinicians and patients - highlighting how the data, provided by around 100 centres and shared openly worldwide, can benefit all three groups.



DECIPHER - the Database of Chromosomal Imbalance and Phenotype in Humans using Ensembl Resources - is hosted at the Wellcome Trust Sanger Institute. It was established in 2004 to catalogue submicroscopic structural duplications, deletions and rearrangements in the genome - called copy number variants (CNVs) - and to uncover their possible role in disease.



"The first comprehensive map of human copy number variation was produced just three years ago, changing our understanding of human genetics" explains Nigel Carter, a lead member of the DECIPHER team from the Wellcome Trust Sanger Institute. "Since then, over 10,000 CNVs have been found, covering about 5 per cent of the human genome. This rate of advance has been remarkable: using new technologies, we are able to uncover the smaller, elusive variants at a 50 fold-higher resolution. But the pivotal role that DECIPHER plays is in looking at how these variants affect human health."



The problem researchers face is that while many CNVs initially appear to have no visible effect on individual health, others appear to have minor effects, and some are harmful. What DECIPHER helps clinicians to do is to evaluate CNVs and determine whether or not they are linked to the patient's problems. In some cases, the findings are novel or have been observed only a handful of times before. With consent from the patient, data can be shared worldwide and clusters of people with overlapping genetic rearrangements can be identified.



By looking at genetic information first in an unbiased and less subjective manner, recurrent genetic changes can be found, researchers can then seek matching symptoms. This reverses the traditional practice of identification where researchers would move from individuals with shared symptoms back to a chromosomal cause and is particularly helpful for conditions such as learning disability and congenital disorders which have a large number of different genetic causes.



"We need new ways to uncover those rearrangements that cause human disease. But we must also be wary of dismissing CNVs if they appear to have no physical effect," says Charles Lee, an Associate Professor at Harvard Medical School and a Clinical Cytogeneticist at Brigham and Women's Hospital in Boston, USA. "For example, there may be variants that only affect people with a specific genetic makeup; or sometimes specific combinations of variants may result in pathology."



The report provides case studies in which DECIPHER played a pivotal role. In one example a four-year-old girl with symptoms of developmental delay and poor eye contact had a novel genetic finding and remained without a clear diagnosis. However, two new cases with similar structural variants were submitted to the database one year later, to provide the elusive diagnosis. The case studies exemplify increasing value of the database as clinicians add case information.
















"DECIPHER is particularly useful when we look at patients with developmental delay, learning disability, dysmorphic features or congenital abnormalities, where, using genomic array technology, we can assign a diagnosis in 15 per cent of previously undiagnosed cases," explains Helen Firth, Consultant Clinical Geneticist at Addenbrookes Hospital and lead author on the study. "This improvement is dependent on a fantastic level of collaboration. More than 2000 patient cases have been contributed to the DECIPHER database since its inception: its diagnostic power strengthens as new cases are added"



DECIPHER is built upon the Ensembl genome browser. It is the only open-access, web-based interactive database of its type, although data from other databases are available. The report's authors suggest that while combination of all data in one resource would be ideal, providing access to the data in one genome browser is a realistic and practical method of harnessing the combined power of the datasets.



Sharing data between researchers is increasingly important. As the role of CNVs in human disease is better understood, so resources such as DECIPHER will gain momentum that will drive significant health benefits and improvements to genetic counselling.


Notes:


Publication Details

Firth H et al. (2009) DECIPHER: Database of Chromosomal Imbalance and Phenotype in Humans Using Ensembl Resources.

American Journal of Human Genetics.

Published online before print as doi: 10.1016/j.ajhg.2009.03.010



Funding



This work was supported by the Wellcome Trust



Collaborating Institutions
Cambridge University Department of Medical Genetics, Addenbrookes Hospital, Cambridge, UK.


The Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, UK.


K. U. Leuven, ESAT/SCD, Kasteelpark Arenberg, Leuven-Heverlee, Belgium.

The Wellcome Trust Sanger Institute, which receives the majority of its funding from the Wellcome Trust, was founded in 1992. The Institute is responsible for the completion of the sequence of approximately one-third of the human genome as well as genomes of model organisms and more than 90 pathogen genomes. In October 2006, new funding was awarded by the Wellcome Trust to exploit the wealth of genome data now available to answer important questions about health and disease.



As the University of Cambridge celebrates its eight-hundredth anniversary in 2009, it is looking to the future. Its mission is to contribute to society through the pursuit of education, learning and research at the highest international levels of excellence. It admits the very best and brightest students, regardless of background, and offers one of the UK's most generous bursary schemes.



The University of Cambridge's reputation for excellence is known internationally and reflects the scholastic achievements of its academics and students, as well as the world-class original research carried out by its staff. Some of the most significant scientific breakthroughs occurred at the University, including the splitting of the atom, invention of the jet engine and the discoveries of stem cells, plate tectonics, pulsars and the structure of DNA. From Isaac Newton to Stephen Hawking, the University has nurtured some of history's greatest minds and has produced more Nobel Prize winners than any other UK institution with over 80 laureates.



The Wellcome Trust is the largest charity in the UK. It funds innovative biomedical research, in the UK and internationally, spending around ВЈ650 million each year to support the brightest scientists with the best ideas. The Wellcome Trust supports public debate about biomedical research and its impact on health and wellbeing.



Source:
Don Powell


Wellcome Trust Sanger Institute

Cleaning Up Uranium-Polluted Soils With Fungi

Fungi may have an important role to play in the fate of potentially dangerous depleted uranium left in the environment after recent war campaigns, according to a new report in the May 6th issue of Current Biology, a publication of Cell Press.



The researchers found evidence that fungi can "lock" depleted uranium into a mineral form that may be less likely to find its way into plants, animals, or the water supply.



"This work provides yet another example of the incredible properties of microorganisms in effecting transformations of metals and minerals in the natural environment," said Geoffrey Gadd of the University of Dundee in Scotland. "Because fungi are perfectly suited as biogeochemical agents, often dominate the biota in polluted soils, and play a major role in the establishment and survival of plants through their association with roots, fungal-based approaches should not be neglected in remediation attempts for metal-polluted soils."



The testing of depleted-uranium ammunition and its recent use in Iraq and the Balkans has led to contamination of the environment with the unstable metal, Gadd explained. Depleted uranium differs from natural uranium in the balance of isotopes it contains. It is the byproduct of uranium enrichment for use in nuclear reactors or nuclear weapons and is valued for its very high density. Although less radioactive than natural uranium, depleted uranium is just as toxic and poses a threat to people.



In the new study, the researchers found that free-living and plant symbiotic (mycorrhizal) fungi can colonize depleted-uranium surfaces and transform the metal into uranyl phosphate minerals.



While they probably still pose some threat, he said, "The fungal-produced minerals are capable of long-term uranium retention, so this may help prevent uptake of uranium by plants, animals, and microbes. It might also prevent the spent uranium from leaching out from the soil."



Gadd said that a combination of environmental and biological factors is involved in the process. First, the unstable uranium metal gets coated with a layer of oxides. Moisture in the environment also "corrodes" the depleted uranium, encouraging fungal colonization and growth. While the fungi grow, they produce acidic substances, which corrode the depleted uranium even further. Some of the substances produced include organic acids that convert the uranium into a form that the fungi can take up or that can interact with other compounds. Ultimately, he said, the interaction of soluble forms of uranium with phosphate leads to the formation of the new uranium minerals that get deposited around the fungal biomass.



"We have shown for the first time that fungi can transform metallic uranium into minerals, which are capable of long-term uranium retention," the researchers concluded. "This phenomenon could be relevant to the future development of various remediation and revegetation techniques for uranium-polluted soils."







The researchers include Marina Fomina of University of Dundee in Dundee, Scotland; John M. Charnock of Synchrotron Radiation Source (SRS) Daresbury Laboratory in Daresbury, Warrington, Cheshire; Stephen Hillier of Macaulay Institute in Craigiebuckler, Aberdeen, Scotland; Rebeca Alvarez and Francis Livens of University of Manchester in Manchester, UK; and Geoffrey M. Gadd of University of Dundee in Dundee, Scotland.



This work was financially supported by the MOD/NERC DU Programme (Grant NE/C506799/1), CCLRC Daresbury SRS (SRS beamtime allocation 45100), and the Scottish Executive Environmental and Rural Affairs Department (SEERAD).



Fomina et al.: "Role of fungi in the biogeochemical fate of depleted uranium." Publishing in Current Biology 18, R375 - R377, May 6, 2008. current-biology/



Source: Cathleen Genova


Cell Press

Two-Armed Nanorobotic Device To Maneuver World's Tiniest Particles

Chemists at New York University and China's Nanjing University have developed a two-armed nanorobotic device that can manipulate molecules within a device built from DNA. The device is described in the latest issue of the journal Nature Nanotechnology.



"The aim of nanotechnology is to put specific atomic and molecular species where we want them and when we want them there," said NYU Chemistry Professor Nadrian Seeman, one of the co-authors. "This is a programmable unit that allows researchers to capture and maneuver patterns on a scale that is unprecedented."



The device is approximately 150 x 50 x 8 nanometers. A nanometer is one billionth of a meter. Put another way, if a nanometer were the size of a normal apple, measuring approximately 10 centimeters in diameter, a normal apple, enlarged proportionally, would be roughly the size of the earth.



The creation enhances Seeman's earlier work - a single nanorobotic arm, completed in 2006, marking the first time scientists had been able to employ a functional nanotechnology device within a DNA array.



The new, two-armed device employs DNA origami, a method unveiled in 2006 that uses a few hundred short DNA strands to direct a very long DNA strand to form structures that adopt any desired shape. These shapes, approximately 100 nanometers in diameter, are eight times larger and three times more complex than what could be created within a simple crystalline DNA array.



As with Seeman's previous creation, the two-armed nanorobotic device enables the creation of new DNA structures, thereby potentially serving as a factory for assembling the building blocks of new materials. With this capability, it has the potential to develop new synthetic fibers, advance the encryption of information, and improve DNA-scaffolded computer assembly.



In the two-armed nanorobotic device, the arms face each other, ready to capture molecules that make up a DNA sequence. Using set strands that bind to its molecules, the arms are then able to change the structure of the device. This changes the sticky ends available to capture a new pattern component.



The researchers note that the device performs with 100 percent accuracy. Earlier trials revealed that it captured targeted molecules only 60 to 80 percent of the time. But by heating the device in the presence of the correct species, they found that the arms captured the targeted molecules 100 percent of the time.



They confirmed their results by atomic force microscopy (AFM), which permits features that are a few billionths of a meter to be visualized.







The study's other co-authors were Hongzhou Gu, a graduate student in NYU's Department of Chemistry, and Jie Chao, who had been a visiting graduate student at NYU, and Professor Shou-Jun Xiao, both based at China's Nanjing University.



Source: James Devitt


New York University

Small Molecules Give EMBL Scientists Bigger Picture Of Animal Evolution

The last ancestor we shared with worms, which roamed the seas around 600 million years ago, may already have had a sophisticated brain that released hormones into the blood and was connected to various sensory organs. The evidence comes not from a newly found fossil but from the study of microRNAs - small RNA molecules that regulate gene expression - in animals alive today. Scientists at the European Molecular Biology Laboratory (EMBL) in Heidelberg, Germany, have discovered that these molecules are found in the exact same tissues in animals as diverse as sea anemones, worms, and humans, hinting at an early origin of these tissues in animal evolution. Their findings, published in Nature, also open new avenues for studying the current functions of specific microRNAs.



Animals from different branches of the evolutionary tree - different lineages - possess specific microRNAs that evolved only in their lineage. But they also have microRNAs in common: ones which they inherited from their last common ancestor, and which have been conserved throughout animal evolution.



The EMBL scientists looked at the marine annelid Platynereis dumerilii, which is thought to have changed little over the past 600 million years. They visualised where these conserved microRNAs are expressed, and compared Platynereis with other animals. They found that in Platynereis these microRNAs are highly specific for certain tissues and cell types and, what is more, discovered that tissue specificity was conserved over hundreds of millions of years of evolutionary time.



The scientists reasoned that if an ancient microRNA is found in a specific part of the brain in one species and in a very similar location in another species, then this brain part probably already existed in the last common ancestor of those species. Thus, they were able to glean a glimpse of the past, an idea of some of the traits of the last common ancestor of worms and humans.



"By looking at where in the body different microRNAs evolved, we can build a picture of ancestors for which we have no fossils, and uncover traits that fossils simply cannot show us," says Detlev Arendt, who headed the study: "But uncovering where these ancient microRNAs are expressed in animals from different branches of the evolutionary tree has so far been very challenging."



"We found that annelids such as Platynereis and vertebrates such as ourselves share some microRNAs that are specific to the parts of the central nervous system that secrete hormones into the blood, and others that are restricted to other parts of the central or peripheral nervous systems, or to gut or musculature", explains Foteini Christodoulou, who carried out most of the experimental work. "This means that our last common ancestor already had all these structures."



Knowing where microRNAs were expressed in our ancestors could also help scientists understand the role of specific microRNA molecules today, as it gives them a clue of where to look.



"If a certain microRNA is known to have evolved in the gut, for instance, it is likely to still carry out a function there", explains EMBL scientist Peer Bork, who also contributed to the study. Next, Arendt and colleagues would like to investigate the exact function of each of these conserved microRNAs - what genes they regulated, and what processes those genes were involved in - in an attempt to determine what their role might have been in the ancient past.



Reference:
Christodoulou, F., Raible, F., Tomer, R., Simakov, O., Trachana, K., Klaus, S., Snyman, H., Hannon, G.J., Bork, P. & Arendt, D. Ancient animal microRNAs and the evolution of tissue identity. Nature, Advance Online Publication 31st January 2010.



Source:

Sonia Furtado

European Molecular Biology Laboratory

Pain Response To Heat Reduced By Comfort Food

People often eat food to feel better, but researchers have found that eating chocolate or drinking water can blunt pain, reducing a rat's response to a hot stimulus. This natural form of pain relief may help animals in the wild avoid distraction while eating scarce food, but in modern humans with readily available food, the effect may contribute to overeating and obesity.



The study, published Wednesday in the Journal of Neuroscience by authors Peggy Mason, PhD, professor of neurobiology, and Hayley Foo, PhD, research associate professor of neurobiology at the University of Chicago, is the first to demonstrate that this powerful painkilling effect occurs while the animals are ingesting food or liquid even in the absence of appetite.



"It's a strong, strong effect, but it's not about hunger or appetite," Mason said. "If you have all this food in front of you that's easily available to reach out and get, you're not going to stop eating, for basically almost any reason."



In the experiments, rats were given either a chocolate chip to eat or had sugar water or regular water infused directly into their mouth. As the rat swallowed the chocolate or fluid, a light-bulb beneath the cage was switched on, providing a heat stimulus that normally caused the animal to lift its paw off the floor. Mason and Foo found that rats were much slower to raise their paw while eating or drinking, compared to tests conducted while they were awake, but not eating.



Surprisingly, the researchers found no difference in the delayed paw-lift response between when the rat was eating chocolate and when it was drinking water, despite previous research indicating that only sugary substances were protective against pain.



"This really shows it has nothing to do with calories," Mason said. "Water has no calories, saccharine has no sugar, but both have the same effect as a chocolate chip. It's really shocking."



Mason and Foo then repeated the heat test as the rats were given quinine, a bitter drink that causes rats to make an expression called a gape that's akin to a child's expression of "yuck." During quinine administration, the rats reacted to heat as quickly as when not eating, suggesting that a non-pleasurable food or drink fails to trigger pain relief.



The context of ingesting was also important to whether eating or drinking blunted pain, the researchers found. When rats were made ill by a drug treatment, eating chocolate no longer delayed their response. However, drinking water still caused a reduced pain response, indicating that drinking water was considered a positive experience while ill.



By selectively inactivating a region in the brainstem called the raphe mangus - an area previously shown to blunt pain during sleep and urination - Mason and Foo were able to remove the effect of drinking water on the rat's pain response. The brainstem controls subconscious responses such as breathing and perspiration during exercise.
















"You're essentially at the mercy of your brainstem, and the raphe magnus is part of that," Mason said. "It tells you, 'you're going to finish eating this, whether you like it or not,' just like you sweat while running whether you like it or not."



In the wild, Mason said, rats and other animals would not want to be distracted during the rare but important times that they were able to eat or drink. Therefore, the activation of the raphe magnus during eating or drinking would allow the rat to filter out distractions until their meal was completed. For obvious reasons, this natural pain relief would be activated when an animal is eating or drinking something pleasurable, but not when it tastes something that could be toxic or harmful.



Don Katz, an associate professor of psychology and neuroscience at Brandeis University who studies taste, said that Mason and Foo's paper brings together two systems - taste and pain - that are usually studied separately.



"They're saying the purpose of the taste system is to give the animal a cue that helps it decide what stimulus they should or shouldn't pay attention to," Katz said. "This shows there is a whole region there to enable the animal to keep eating."



Mason believes that this effect is also present in humans (studies by other labs have observed similar pain reduction in infants receiving sugar water during a booster shot), but that it has detrimental effects in modern society given our ready access to large quantities of pleasurable and fattening foods. Opening up a bag of chips could activate the brainstem such that you don't stop eating until the bag is empty, even while realizing that such behavior is bad for you.



"We've gotten a lot more overweight in last 100 to 150 years," Mason said. "We're not more hungry; the fact of the matter is that we eat more because food is readily available and we are biologically destined to eat what's readily available."



But the painkilling effect can be turned to our advantage, Mason said, perhaps as a replacement for the practice of using candy to calm children - or even adults - in the doctor's office.



"Ingestion is a painkiller but we don't need the sugar," Mason said. "So replace the doctor's lollipop with a drink of water."



The research was funded by a grant from the National Institute on Drug Abuse and the Women's Council of the Brain Research Foundation. The paper, "Analgesia accompanying food consumption requires ingestion of hedonic foods," appears in the October 14th issue of the Journal of Neuroscience.



Source:
Rob Mitchum


University of Chicago Medical Center

The Climate's Influence On Human Evolution -- March 31 Public Event

Examining how a new research program may shed light on how climate over millions of years influenced human evolution is the subject of a public event that will discuss the findings and recommendations of the National Research Council report Understanding Climate's Influence on Human Evolution. Several members of the committee that wrote the report will present research initiatives that could be carried out in the next 10 to 20 years and answer audience questions.



Climate and fossil records suggest that some events in human evolution -- such as the evolution of new species or movements out of Africa -- coincided with substantial changes in African and Eurasian climate. This raises the intriguing possibility that environmental factors affected or controlled our species' evolution. By altering the landscape, past changes in climate may have exerted pressures that led to innovation and genetic selection in humans. However, because the human fossil record and our understanding of past climate conditions are limited, the details of how climates influenced human evolution remain unclear.



DETAILS: Free and open to the public, the event will begin at 1 p.m. on Wednesday, March 31, in the Baird Auditorium of the Smithsonian National Museum of Natural History, 10th Street and Constitution Avenue, N.W.



Click here for additional information.



Source:

Jennifer Walsh


National Academy of Sciences

Longevity Study In Flies Reveals That Just 14 Brain Cells Guard The Secret

Two years ago, Brown University researchers discovered something startling: Decrease the activity of the cancer-suppressing protein p53 and you can make fruit flies live significantly longer.



Now the same team reports an intriguing follow-up finding. The p53 protein, they found, may work its lifespan-extending magic in only 14 insulin-producing cells in the fly brain.



"It's quite surprising," said Johannes Bauer, a postdoctoral research fellow at Brown. "In the fruit fly brain, there are tens of thousands of cells. But we found that it takes a reduction of p53 activity in only 14 of those brain cells to extend lifespan. It was like finding a needle in the haystack -- a very small needle at that."



Bauer is the lead author of the research report, published in the Proceedings of the National Academy of Sciences. Brown biology professor Stephen Helfand, senior scientist on the project, will discuss the findings in his keynote address at the Gordon Research Conferences on the Biology of Aging, to be held Sept. 23-28, 2007, in Les Diablerets, Switzerland.



P53 is sometimes called "guardian of the genome" for defending cells against DNA damage. Not enough of the protein can cause cancer; too much, however, can shorten lifespan. But in 2005, Helfand and his lab showed that a targeted decrease of p53 in fruit flies -- a decrease specifically in their brain cells -- allowed flies to live healthy lives that were as much as 58 percent longer.



But how, exactly, does p53 do its work in the brain" To find out, Bauer spent a year conducting painstaking experiments. He'd take a batch of young flies, each genetically altered to reduce p53 activity in a small portion of their nervous systems, and watch the flies age. Time and again, the flies lived for about two months -- the average lifespan for these insects.



But when Bauer manipulated a cluster of 14 insulin-producing cells in their brains, the flies lived about 15 to 20 percent longer. Bauer ran the experiment again and again -- and got the same result.



Bauer and Helfand then wanted to know if this was caloric restriction at work. Studies have shown that low-calorie diets can significantly increase the lifespan of flies, worms, mice and rats. The phenomenon is of intense interest to researchers who study aging. They want to know if caloric restriction works in people and if drugs could be made to mimic its effects.



So researchers restricted the diets of the flies and ran the same experiments. The calorie-restricted flies didn't live any longer when p53 was reduced in the insulin-producing cells. This evidence supports the notion that p53 reduction is one of the direct effects of caloric restriction.



Even more intriguing, Helfand said, is the fact that the 14 insulin-producing cells that seem to be critical for lifespan extension are the equivalent of beta cells in the human pancreas. Beta cells make and release insulin, the hormone that controls the level of glucose in the blood. The research team found that when p53 activity drops, so does insulin-responsive activity in the fat body, the major metabolic organ in the fruit fly.



"Our findings suggest that lifespan regulation is linked to metabolic regulation," said Helfand, a professor in Brown's Department of Molecular Biology, Cell Biology and Biochemistry. "The findings also suggest a tight connection between aging and diabetes. And we may have a new laboratory model for studying diabetes and other metabolic diseases."







The rest of the team included senior research assistants Suzanne Hosier and Chengyi Chang and undergraduate students Siti Nur Sarah Morris, Sandra Andersen, and Joshua Waitzman.



The National Institute on Aging, the Donaghue Foundation, the Ellison Medical Foundation and the American Federation for Aging Research supported the research.



Source: Wendy Lawton


Brown University

News From The Journal Of Neuroscience

1. Optical Stimulation of Olfactory Cilia


Hiroko Takeuchi and Takashi Kurahashi



A novel technique for studying sensory transduction in olfactory sensory cilia is described this week by Takeuchi and Kurahashi. The binding of odorant molecules to olfactory receptors leads to activation of adenylyl cyclase and increased cAMP concentration in the cilium. cAMP, in turn, activates calcium channels, which, together with calcium-dependent chloride channels, depolarizes the cell. To study these transduction mechanisms more closely, Takeuchi and Kurahashi used laser-scanning confocal microscopy to locally release caged cyclic nucleotides (in 1 Ојm spots) in the cytoplasm of dissociated olfactory cells, while simultaneously obtaining whole-cell electrical recordings. Although these studies did not discriminate between the contribution of calcium and chloride channels, they did reveal that the transduction channels are distributed throughout cilia, with a higher channel density proximally. In addition, responses to stimuli at different points along a cilium summed linearly. And different cilia on the same cell responded similarly to the same stimulus.



2. Regulation of Opsin Expression in Cones


Hong Liu, Paige Etter, Susan Hayes, Iwan Jones, Branden Nelson, Byron Hartman, Douglas Forrest, and Thomas A. Reh



The transcription factor NeuroD1 is known to play a role in photoreceptor development, but its precise role in genesis, specification, and/or maintenance is not clear. Liu et al. now report that NeuroD1 helps to specify medium-wavelength M-opsin cone photoreceptors by activating the thyroid hormone receptor TRОІ2 via an intron control region. Like TRОІ2 knock-outs, NeuroD1-/- knock-out mice had as many cones as wild type, but all the cones expressed short-wavelength S-opsin, and none expressed M-opsin. TRОІ2 expression was reduced 10-fold in NeuroD1-/- mice but was restored by transfecting the mutant retinas with NeuroD1. Furthermore, mutation of a sequence in the intron control region prevented induction of TRОІ2 by NeuroD1. Both the roles of NeuroD1 and the regulation of opsin expression are more complicated than described here, however. NeuroD1 by itself cannot induce TRОІ2 (and thus M-opsin) expression, and photoreceptor degeneration occurs in NeuroD1, but not TRОІ2 knock-outs.



3. Somatosensory Processing of Orientation Information


Sliman J. Bensmaia, Peter V. Denchev, J. Frank Dammann, James C. Craig, and Steven S. Hsiao



The neural processing that allows us to feel the orientation of a bar resembles that involved in seeing the orientation, according to experiments on somatosensory processing reported by Bensmaia et al. in this issue. Many neurons recorded in macaque somatosensory cortex (areas 3b and 1) fired preferentially when bars were presented in a particular orientation, regardless of stimulus amplitude (how hard the stimulus was pressed) or motion (whether or how fast the bar was scanned along the finger). The firing pattern of these neurons suggested that they receive input primarily from slow-adapting type 1 mechanosensory afferents (which do not themselves show orientation selectivity). Based on their firing patterns, orientation-selective neurons could discriminate between angles that differed by >15°- a slightly smaller difference than humans perceived in psychophysical studies. Modeling the receptive fields of orientation-sensitive neurons suggested that they, like visual receptive fields, have an excitatory center and inhibitory surround.
















4. Tau Aggregation Forms Persistent Neurofibrillary Tangles


Maria-Magdalena Mocanu, Astrid Nissen, Katrin Eckermann, Inna Khlistunova, Jacek Biernat, Dagmar Drexler, Olga Petrova, Kai Schönig, Hermann Bujard, Eckhard Mandelkow, Lepu Zhou, Gabriele Rune, and Eva-Maria Mandelkow



Tauopathies are neurodegenerative diseases that involve dysfunction of the microtubule-associated protein Tau. For example, hyperphosphorylated Tau forms the paired helical filaments (PHFs) found in Alzheimer's disease. Tauopathies could potentially result from disruption of axonal transport or from abnormal expression, phosphorylation, and/or aggregation of Tau. Support for the last possibility is presented by Mocanu et al. They isolated the effects of aggregation by creating transgenic mice that expressed proaggregation or antiaggregation forms of the Tau repeat domain, which is involved in PHF formation but lacks most of the phosphorylation sites involved in tauopathy and does not bind well to microtubules. Neurofibrillary tangles (NFTs), neurodegeneration, and synapse loss were all observed in the proaggregation, but not the antiaggregation, mouse lines. Endogenous Tau colocalized with mutant Tau in NFTs and became hyperphosphorylated in proaggregation lines. Surprisingly, NFTs containing endogenous Tau persisted even after mutant Tau expression was turned off and disappeared from NFTs.







Please click here for the current table of contents.



Source: Sara Harris


Society for Neuroscience

COX 2 Expression Is Marker For Cancer Development In Some Benign Breast Biopsies

It's a good news, bad news situation. Some women who have a breast biopsy are told that while they don't have cancer, they do have atypical hyperplasia -- cells that aren't quite normal and might become cancerous someday. This happens to one-fourth of women undergoing breast biopsies but no one knows which individuals are at risk.


In their quest to discover who is at risk, researchers at Mayo Clinic (mayoresearch.mayo/mayo/research/womens_cancer/breast_excellence.cfm) are building a biopsy profile to try to predict cancer outcome, and in the March 11 online edition of the Journal of the National Cancer Institute (jnci.oxfordjournals/rss/recent.xml), they report finding a new variable to add to this profile.


The research team discovered that women whose atypia tissue expressed COX 2 enzymes were more likely to develop breast cancer subsequently, and that the more the enzyme expressed, the higher the risk.


Specifically, 20 years after a biopsy in which atypia was found, 31 percent of women with high levels of COX-2 in their atypia sample had developed breast cancer, versus 14 percent of those with no COX-2 expression. For those with moderate levels of COX-2, 24 percent had developed breast cancer.


"Based on these findings, COX-2 expression in atypia may be a biomarker of risk of progression to breast cancer," says the study's senior investigator, Mayo Clinic oncologist Lynn Hartmann, M.D (mayoresearch.mayo/mayo/research/staff/hartmann_lc.cfm). "COX-2 is a relevant candidate because it drives a number of malignant features and has been shown to be important in breast cancer.


"Each year in the United States, about 1 million women have a benign breast biopsy; and some of them receive the worrisome news that they have atypical hyperplasia," Dr. Hartmann says. If other studies validate these findings, she notes that one strategy to help manage patients may be to use a COX-2 inhibiting agent, such as celecoxib or rofecoxib, to prevent breast cancer from developing. "This study raises the possibility of targeting COX-2 in selected women to reduce their risk of breast cancer," she says.


In the biopsy profile thus far, the Mayo risk model includes age, the number of regions of atypical cells in the biopsy, COX-2 expression and the status of the normal lobules in the breast.


"Our goal is to individualize risk for breast cancer so that we can provide effective care and risk reduction for each of our patients," says Dr. Hartmann.















Cyxlooxygenase (COX) enzymes produce prostaglandin compounds responsible for pain and inflammation, and nonsteroidal anti-inflammatory drugs (NSAIDs) are designed to reduce expression of COX enzymes, although some NSAID use has been associated with side effects (most notably possible kidney failure). COX-2 is a form of COX that is not usually found in normal tissues but which has been associated with several cancers, including ductal carcinoma in situ and invasive breast cancers.


In this study, researchers examined breast biopsy samples that contained atypia for COX-2 expression which has never been done before.


Investigators looked at 235 women who had a breast biopsy following a mammogram at Mayo Clinic from 1967 through 1991, and who were diagnosed with the atypical hyperplasia cell growth disorder.


During an average follow-up period of 15 years, 41 (17 percent) of the women developed breast cancer. The average time for that breast cancer to be diagnosed was 11.4 years.


The researchers examined the biopsies for the level of COX-2 expression and for other variables, such as the number of areas (or foci) within the biopsy that contained atypical growth. They found that moderate expression was identified in 71 (30 percent) of the samples and that 34 (14 percent) of the biopsies exhibited strong expression of the enzyme.


The researchers calculated that, among the women in the study group, the absolute risk of developing breast cancer 15 years after a diagnosis of atypical hyperplasia was 13 percent in biopsies with little or no COX-2 expression, 19 percent with moderate COX-2 expression, and 25 percent with strong COX-2 expression. In women who had been followed for 20 years or more, the association was more definitive: stratification of risk was 14 percent, 24 percent, and 31 percent, respectively. (Because the participants had atypical hyperplasia, they were all at increased baseline risk of developing breast cancer.)


The finding that risk of later breast cancer was associated with increasing levels of COX-2 expression was of borderline statistical significance (p=.07), likely due to the small sample size Dr. Hartmann says. "But higher expression levels were tightly linked to an increased number of abnormal foci in the biopsy, which we had earlier found to be a strong risk factor for breast cancer."


The researchers also assessed the relative risk of developing breast cancer, based on COX-2 expression in atypical hyperplasia, compared to a "control" population of unaffected women, and found that little COX-2 expression was associated with 2.6 times the risk, moderate COX-2 expression increased risk by 3.5 times, and a strong expression of COX-2 elevated risk by more than 5.6 times, compared to women in the general population.


"COX-2 appears to be a biomarker that further stratifies breast cancer risk among women with atypia and may be a relevant target for chemoprevention strategies," says Dr. Hartmann.


Other Mayo Clinic researchers included V. Shane Pankratz, Ph.D.; Marta Santisteban, M.D., Ph.D.; Carol Reynolds, M.D.; Robert Vierkant; Wilma Lingle, Ph.D.; and Marlene Frost, Ph.D. Additional contributors included Daniel Visscher, M.D., from the University of Michigan, Ann Arbor and Ari Ristimaki, M.D., from the University of Helsinki, Finland.


Funding for the study was provided by the U.S. Department of Defense, and grants from Martha and H. Bruce Atwater Jr. and the Regis Foundation for Breast Cancer Research.


Mayo Clinic

200 First St. SW

Rochester, MN 55902

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mayoclinic

Too Much Of A Good Thing: Extra Copies Of A Gene Carry Extra Risk

Is more of a good thing better? A gene known as LIS1 is crucial for ensuring the proper placement of neurons in the developing brain. When an LIS1 gene is missing, brains fail to develop the characteristic folds; babies with lissencephaly or 'smooth brain' are born severely mentally retarded. But new research by Prof. Orly Reiner of the Institute's Molecular Genetics Department, which recently appeared in Nature Genetics, shows that having extra LIS1 genes can cause problems as well.



Reiner was the first to discover LIS1's tie to lissencephaly, in 1993. Their latest study shows that it works by helping to determine polarity in the cell - how the various organelles are arranged inside the cell as well as where it connects to neighboring cells. Neurons alter their polarity several times during development, especially when they take on an elongated shape and migrate to new locations in the brain.



But what if, rather than too little, the body has too much LIS1? One of the surprises to come out of the recent spate of post-human-genome research is the number of genes that can be repeated or deleted in an individual's genome. Most extra copies of genes may be no more harmful than a computer backup disk, but scientists have been finding that some repeats can cause disease.



Research associate Dr. Tamar Sapir and lab technician Talia Levy, working in Reiner's lab, developed a mouse model in which additional LIS1 protein was produced in the brain. The scientists found that the brains of these mice were a bit smaller than average. On closer inspection, they discovered a range of subtle changes in cell polarity and movement: Nuclei within the proliferating zone tended to move faster, but with less control; rates of cell death were higher; and various factors in the cell became more disordered.



Reiner then asked whether their findings might apply to humans. Together with Jim Lupski and Drs. Weimin Bi and Oleg A. Shchelochkov of Baylor College of Medicine in Houston, Texas, they searched through blood samples using a technique that matches a patient's DNA with control DNA to identify additions or deletions in its sequence. They identified seven individuals with extra copies of either LIS1 or adjacent genes that are also involved in brain development. All suffered developmental abnormalities. Two of the patients - children with a second LIS1 gene - had previously been diagnosed with failure to thrive and delayed development, and were found to have small brain sizes. A third, who had three copies of the gene, was mentally retarded and suffered from bone deformation as well.



Reiner: 'Several brain diseases, including schizophrenia, epilepsy and autism, have been linked to faulty neuron migration, and recent research has hinted that some of these may involve variations in gene number. Our study is the first to demonstrate the effects of the duplication of a single gene in a mouse model and tie it to a new 'copy number variation' human disease.'






Prof. Orly Reiner's research is supported by the Nella and Leon Benoziyo Center for Neurological Diseases; the Kekst Family Center for Medical Genetics; the David and Fela Shapell Family Center for Genetic Disorders Research; the PW-Iris Foundation; and the PW- Jani.M Research Fund. Prof. Reiner is the incumbent of the Bernstein-Mason Chair of Neurochemistry.



For the scientific paper, please see: nature/ng/journal/v41/n2/pdf/ng.302.pdf



The Weizmann Institute of Science in Rehovot, Israel, is one of the world's top-ranking multidisciplinary research institutions. Noted for its wide-ranging exploration of the natural and exact sciences, the Institute is home to 2,600 scientists, students, technicians and supporting staff. Institute research efforts include the search for new ways of fighting disease and hunger, examining leading questions in mathematics and computer science, probing the physics of matter and the universe, creating novel materials and developing new strategies for protecting the environment.



Source: Yivsam Azgad


Weizmann Institute of Science

A New Theoretical Model Of Tumor Growth And Metastasis Based On Differences In Tissue Pressure

The HFSP Journal, the interdisciplinary journal for scientists conducting high quality, innovative research at the interface between biology and the physical sciences is pleased to announce that the latest article modelling of tumor growth and metastasis in now available online at hfspj.aip/.



The progression of cancer is a multi-step process. Over 80% of malignant tumors are carcinomas that originate in epithelial tissues from where they invade the connective tissue. At some point, subpopulations of cells may detach from the primary tumor and spread via the bloodstream and the lymphatic system. Some of them give rise to metastases in distant organs.



The metastatic cascade is a very inefficient process, as only one in about a thousand cells that leave the primary tumor goes on to form a macroscopic secondary tumor. The main contribution to metastatic inefficiency arises from the failure of cancerous cells to grow inside invaded organs. Metastatic tumors also show preferential growth in different organs. Hence, the efficiency of the metastatic process depends on specific interactions between the invading cancer cells and the local organ tissues.



In an Article published on The HFSP Journal website, Risler, Prost and Joanny from Institut Curie in Paris suggest that this is due to a difference of pressure between tumor cells and the host tissue. Combining the laws of mechanics and the biological state of homeostasis, the authors propose that every biological tissue regulates to a preferred pressure called homeostatic pressure, and that an increased homeostatic pressure is a generic trait of neoplastic tissues. This property can drive tumour growth at the expense of the host tissue. Metastases account for the majority of patients' deaths due to cancer, and thus understanding the metastatic process is of critical importance.



Notes:



Markus Basan, Thomas Risler, Jean-Francois Joanny, Xavier Sastre-Garau and Jacques Prost, Homeostatic competition drives tumor growth and metastasis nucleation, The HFSP Journal (2009), doi: 10.2976/1.3086732



About The HFSP Journal



The HFSP Journal is operated by HFSP Publishing, a not-for-profit publisher founded by the International Human Frontier Science Program Organization (HFSPO), which has been supporting innovative research at the frontiers of biology since its establishment in 1989. The Journal publishes primary research articles as well as commentaries and perspectives which provide an interdisciplinary context to the articles and encourage broader understanding and synthesis of the results. All members of the Editorial Board are actively involved in interdisciplinary research and are dedicated to a truly multidisciplinary review process which will insure that the very best research is published.



Source: Valerie Ferrier


HFSP Publishing

Biological Difference In Tumors Likely Cause Of Black Women's Increased Mortality For Breast Cancer, Study Finds

Black women are more likely than other women to develop tumors that do not respond to common hormone-based treatments, according to a study to be presented at an American Society of Clinical Oncology conference that begins on Friday, the AP/Los Angeles Times reports (Marchione, AP/Los Angeles Times, 9/5).

The study, led by M. Catherine Lee, a clinical lecturer at the University of Michigan Comprehensive Cancer Center's department of surgery, is the largest to indicate a biological factor as the cause of black women's increased mortality from the disease, according to the Newark Star-Ledger. Previous research has attributed fewer mammograms and less aggressive treatment to the racial disparity (Stewart, Newark Star-Ledger, 9/6). Black women are less likely than white women to develop breast cancer but are more likely to die from the disease.

For the study, Lee and colleagues analyzed data on more than 170,000 breast cancer diagnoses from 1998 that were included in the American College of Surgeons' National Cancer Data Base. Ten percent of the cases were among black women.

Researchers focused on 95,500 women whose cancers were invasive rather than confined to a milk duct. They found that roughly 39% of such tumors in black women were estrogen receptor-negative, or ER-negative, compared with 22% of tumors in white women. ER-negative tumors are resistant to common hormone-based therapies like tamoxifen and are more difficult to treat, according to the AP/Times (AP/Los Angeles Times, 9/5). The high prevalence of ER-negative tumors among black women was consistent regardless of the age or stage at which they were diagnosed, the study found (Newark Star-Ledger, 9/6).

The study also found that black women were diagnosed at an average age of 57, compared with 62 for white women. Black women's tumors also were more advanced than white women's, with 29% of black women having stage 1 tumors that had not yet spread, compared with 42% of white women.

Lee said, "Differences in tumor biology have a significant impact on survival," adding, "The fact that breast cancers in black women are more aggressive biologically suggests that we need to focus more of our research energy on developing better treatments targeting ER-negative tumors." She said the "findings also point to a need for improved cancer education and screening in black women, particularly those in younger age groups" (Fox, Reuters, 9/5).

Reprinted with kind permission from kaisernetwork. You can view the entire Kaiser Daily Health Policy Report, search the archives, or sign up for email delivery at kaisernetwork/dailyreports/healthpolicy. The Kaiser Daily Health Policy Report is published for kaisernetwork, a free service of The Henry J. Kaiser Family Foundation© 2005 Advisory Board Company and Kaiser Family Foundation. All rights reserved.

Physics, Palaeontology And Chemistry Collide Yielding Insight Into The Building Blocks Of Fossilized Soft Tissue

Published in the journal Royal Society Proceedings B: Biology, a brightly-coloured image shows the presence of amides - the organic compounds, or building blocks of life - in the ancient skin of a reptile, found in the 50 million year-old rocks of the Green River Formation in Utah, USA.



This image had never been seen by the human eye, until a team led by Dr Roy Wogelius and Dr Phil Manning used state-of-the-art infra-red technology at The University of Manchester to reveal and map the fossilized soft tissue of a beautifully-preserved reptile.



These infra-red maps are backed up by the first ever element-specific maps of organic material in fossil skin generated using X-rays at the Stanford synchrotron in the USA, also by the Manchester researchers.



Chemical details are clear enough that the scientists, from the School of Earth, Atmospheric and Environmental Sciences, are even able to propose how this exceptional preservation occurs.



When the original compounds in the skin begin to break down they can form chemical bonds with trace metals, and under exceptional conditions these trace metals act like a 'bridge' to minerals in the sediments. This protects the skin material from being washed away or decomposing further.



Geochemist Roy Wogelius: "The mapped distributions of organic compounds and trace metals in 50 million year old skin look so much like maps we've made of modern lizard skin as a check on our work, it is sometimes hard to tell which is the fossil and which is fresh."



"These new infra-red and X-ray methods reveal intricate chemical patterns that have been overlooked by traditional methods for decades."



The new images are compelling, and represent the next step in the academics' research programme to use modern analytical chemistry and 21st century techniques to understand how such remarkable preservation occurs, and ultimately to discover the chemistry of ancient life.



These new results imply that trace metal inventories and patterns in ancient reptile skin, even after fossilisation, can indeed be compared to modern reptiles.



The infra-red light causes vibrations in the fossilized skin, and a map of where these vibrations occur can be obtained from a fossil by using a trick: a tiny crystal (like an old phonograph record stylus) which moves from point-to-point in a programmable grid across the surface.



At each point where the tiny crystal touches the fossil, an infra-red beam that shines through the crystal reflects off of the crystal base, but a small amount of the beam probes beyond the interface- and if organic compounds are present, they absorb portions of the beam and change the reflected signal.



This allows the team to non-destructively map large fossils which do not themselves transmit or reflect the beam - a revolutionary process for paleontologists.



Nick Edwards, first author on the publication, said: "The ability to chemically analyse rare and precious fossils such as these without the need to remove material and destroy them is an important and long overdue addition to field of palaeontology.



"Hopefully this will provide future opportunities to unlock the information stored in other similarly preserved specimens."



Dr Manning said: "Here physics, palaeontology and chemistry have collided to yield incredible insight to the building blocks of fossilized soft tissue.



"The results of this study have wider implications, such as understanding what happens to buried wastes over long periods of time. The fossil record provides us with a long-running experiment, from which we can learn in order to help resolve current problems."



Source:

Daniel Cochlin


University of Manchester

Following Stroke, Mouse Brain Rewires Its Neural Circuits To Recuperate From Damaged Neural Function

Japanese research group led by Professor Junichi Nabekura in National Institute for Physiological Sciences, NIPS, Japan, found that, after cerebral stroke in one side of the mouse brain, another side of the brain rewires its neural circuits to recuperate from damaged neural function. The Japan Science and Technology Agency (JST) supported this study. They report their finding in Journal of Neuroscience, on August 12, 2009.



The research group investigated how neural circuits rearrange themselves after cerebral strokes by using two-photon laser microscopy in vivo. In a specific period after strokes in the right side of the moue brain, namely one to two weeks after strokes, the left side of the brain rearranged its neural circuits actively. After three to four weeks, the left side of the brain became to receive sensory information from the left leg that is usually received by the right side of the brain. In conclusion, the stroke in the right side of the brain activated the rearrangement of the neural circuits in the left side of the brain, and then these rearrangements helped to recuperate from stroke-induced damaged neural function.



"We found that the active rearrangement of the neural circuits in the opposite side of the brain happens only in the specific period after strokes. Our findings can be applied to rehabilitative programs for stroke survivors", said Professor Nabekura.



Source:
Junichi Nabekura


National Institute for Physiological Sciences

A New Code Of Conduct For Researchers

A new European Code of Conduct for Research Integrity will be presented by the European Science Foundation at the World Conference on Research Integrity. The code addresses good practice and bad conduct in science, offering a basis for trust and integrity across national borders.



This Europe-wide code offers a reference point for all researchers, complementing existing codes of ethics and complying with national and European legislative frameworks. It is not intended to replace existing national or academic guidelines, but represents agreement across 30 countries on a set of principles and priorities for self-regulation of the research community. It provides a possible model for a global code of conduct for all research.



"Science is an international enterprise with researchers continually working with colleagues in other countries. The scientists involved need to understand that they share a common set of standards. There can be no first-class research without integrity," said Marja Makarow, Chief Executive of the European Science Foundation. "Researchers build on each other's results so they must be honest with themselves, and with each other, and share the same standards of fairness, which makes the European Code of Conduct for Research Integrity a vital document."



The code describes the proper conduct and principled practice of systematic research in the natural and social sciences and the humanities. Research misconduct is quite rare, but just one extraordinary case can endanger the reputation of a university, a research community or even the reputation of science itself. One well-publicised allegation of research dishonesty or malpractice can call to question the efforts of thousands of scientists and decades of research effort. Europe has experienced several well publicised cases recently at, for example, the University of East Anglia in the UK, and at the Karolinska Institute in Sweden.



The term 'research misconduct' embraces many things, including insufficient care for the people, animals or objects that are the subject of or participants in research; breaches of confidentiality, violation of protocols, carelessness of the kind that leads to gross error and improprieties of publication involving conflict of interest or appropriation of ideas. Many of these unacceptable research practices are addressed in the European Code of Conduct for Research Integrity.



The code was developed from meetings and workshops involving the European Science Foundation (ESF) Member Organisations who are 79 national funding bodies, research-performing agencies, academies and learned societies from 30 countries. They worked with the All European Academies (ALLEA). The next steps in implementing the code will be discussed in the autumn by ESF Member Organisations.



The code is published in the report Fostering Research Integrity in Europe.



Source:

Chloe Kembery


European Science Foundation