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Deleting the receptor, not the protein ghrelin itself, turns up the body’s fat-burning thermostat, giving aging mice an exothermic boost toward a svelte physique, researchers reported at the American Society of Cell Biology’s 50th Annual Meeting in Philadelphia.

The protein’s receptor, growth hormone secretagogue receptor (GHS-R), might make a better target than ghrelin for treating obesity, according to Yuxiang Sun, M.D., Ph.D., of the Baylor College of Medicine in Houston, TX.

Sun said that experimentally deleting the receptor from the body cells of laboratory mice prevented obesity by diminishing white adipose tissues and activating brown adipose tissue, thereby increasing heat production.

The new finding that ghrelin may not be as critical to energy expenditure as its receptor, GHS-R, came from research on body temperature regulation at Baylor, Sun explained. GHS-R acts as the “lock” for the “key-like” ligand ghrelin to dock; GHS-R subsequently activates down-stream metabolic signal pathways.

With colleagues from Baylor and other institutions, Sun created two sets of genetically modified mice: one was null for ghrelin, while the other group was null for GHS-R. When challenged by cold and fasting, only the mice without GHS-R maintained a normal body temperature.

Intrigued by this finding, the researchers generated two additional cohorts of these knockout mice — a young group 3 to 4 months old and an older group 10 to 12 months old – to determine whether obesity and physical activity levels were influenced by age.

The scientists compiled a complete energy metabolic profile for each mouse, charting the animal’s food intake against energy output. The energy profiles revealed that neither food intake nor activity levels differed in the gene-deleted mice compared to normal mice, regardless of age. But the GHS-R null mice were thinner because they were more exothermic.

Like aging humans, aging mice gain weight by accumulating fat. In contrast, the older GHS-R null mice maintained a lean physiological profile with lower circulating lipids and exhibited the high-energy expenditure levels that characterized the young mice.

These older GHS-R null mice weren’t more active. However, without extra effort, they burned as heat more calories and fat. Meanwhile the older ghrelin-deleted mice followed the pattern of obesity in normal again mice: growing older and fatter.

In the ghrelin-deleted and the GHS-R deleted mice, the researchers then compared levels of UCP1, an “uncoupling protein” known as a hallmark regulator of thermogenic functioning in brown fat.

Consistently UCP1 was significantly higher in the brown fat of GHS-R deleted mice than in the ghrelin-deleted mice. The brown fat of the older GHS-R deleted mice included a higher proportion of smaller fat droplets, an indication of enhanced heat production, said Sun.

The 1999 discovery of ghrelin’s role in appetite and energy balance ignited hopes that it was the body’s long-sought hunger thermostat. Ghrelin remains the only circulating peptide known to stimulate appetite and promote obesity in both humans and rodents, but it also plays other roles in regulating growth and metabolism.

“All this shows the complexity of ghrelin and its signaling pathway, and suggests the existence of additional unidentified regulators mediating the effect of ghrelin and/or GHS-R,” said Sun.

Source:
Cathy Yarbrough

John Fleischman
American Society for Cell Biology Continue reading →

Enigma Diagnostics, the decentralised and point-of-care molecular
diagnostics Company, announces that it has been awarded a grant of GBP1.8M
from the UK Government’s Technology Strategy Board under the “Technologies
for Health” programme.

The objective of the programme is to develop a “gold-standard”
portable, rapid, automated DNA analysis (PRADA) molecular test system for the
diagnosis of infectious diseases in decentralised and point-of-care settings
such as GP surgeries. The focus of the programme will be on sexually
transmitted diseases including Chlamydia and healthcare associated infections
including MRSA.

The PRADA system development will be led by Enigma Diagnostics
and based upon its proprietary technology. Researchers at the Centre for
Healthcare Associated Infections at Nottingham University and Nottingham
Trent University, will develop and validate real-time molecular assays for
the platform.

Point-of-care molecular tests for critical infectious diseases
are a significant unmet clinical need. Chlamydia is the most common sexually
transmitted infection in the developed world. Most people with Chlamydia have
no symptoms and many are unaware that they have the infection. If left
untreated, Chlamydia can lead to long term health problems, such as
infertility and pelvic inflammatory disease. Rapid systems for point-of-care
testing will enable healthcare professionals to accurately diagnose Chlamydia
and treat it immediately, removing the need to track down patients days or
weeks later.

MRSA is a significant public health problem and rapid point-of-care
testing is essential for effective patient management. The NHS
is introducing MRSA screening for patients admitted to hospitals in order to
help reduce severe infections. The new PRADA system will allow rapid testing
for emergency and out of hour’s admissions, allowing doctors to make quick
decisions about how their patients are managed while effectively reducing
healthcare costs.

John McKinley, Chairman of Enigma Diagnostics, said: “We are delighted
to have received such substantial funding to support this project
and to be working with two leading UK clinical partners. We are committed to
delivering rapid, cost effective diagnostic systems that will substantially
improve patient care and help eliminate the spread of infectious diseases.”

About Enigma Diagnostics

Enigma Diagnostics Limited is a private UK based company specialising in
developing the next generation of rapid molecular diagnostic instrument
platforms for decentralised and point-of-care settings.

Enigma’s innovative and proprietary technology combines the
speed and sensitivity of real-time PCR (polymerase chain reaction) with the
simplicity needed for field-based, decentralised and point-of-care tests
providing results from a raw sample in less than 45 minutes.

The Company is targeting a number of multi-billion pound
markets, core among which are the Clinical and high value Applied Markets.
Enigma’s commercialisation strategy is to maximise revenues from a continuous
flow of market leading rapid diagnostic point-of-care and in-field instrument
and assay platforms, derived from its broad Intellectual Property portfolio
of issued and filed patents. Enigma will partner with market leaders where
global penetration of markets is required and where appropriate will build an
in-house sales and marketing capability to direct distribution of its
products.

Enigma has an exclusive licence from the Defence Science
Technology Laboratory to a portfolio of patents which represent over 15 years
of UK Ministry of Defence funded research and has licences from Applied
Biosystems and Celera Licences for the commercialisation of real-time PCR
instruments. Enigma’s R&D activities have generated a portfolio of over 50
plus worldwide patent families dedicated to real-time PCR and wider molecular
technologies. Many of these patents are granted across a range of core
commercial territories including US, EU and Japan with more extensive filing
and grants across a number of other key territories.

Enigma Diagnostics Continue reading →

Gene therapy holds promise in the treatment of a myriad of diseases, including cancer, heart disease and diabetes, among many others. However, developing a scalable system for delivering genes to cells both efficiently and safely has been challenging.

Now a team of Northwestern University researchers has introduced the power of nanodiamonds as a novel gene delivery technology that combines key properties in one approach: enhanced delivery efficiency along with outstanding biocompatibility.

“Finding a more efficient and biocompatible method for gene delivery than is currently available is a major challenge in medicine,” said Dean Ho, who led the research. “By harnessing the innate advantages of nanodiamonds we now have demonstrated their promise for gene therapy.”

Ho is an assistant professor of biomedical engineering and mechanical engineering in the McCormick School of Engineering and Applied Science and a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University.

Ho and his research team engineered surface-modified nanodiamond particles that successfully and efficiently delivered DNA into mammalian cells. The delivery efficiency was 70 times greater than that of a conventional standard for gene delivery. The new hybrid material could impact many facets of nanomedicine.

The results are published online by the journal ACS Nano.

“A low molecular weight polymer called polyethyleneimine-800 (PEI800) currently is a commercial approach for DNA delivery,” said Xue-Qing Zhang, a postdoctoral researcher in Ho’s group and the paper’s first author. “It has good biocompatibility but unfortunately is not very efficient at delivery. Forms of high molecular weight PEI have desirable high DNA delivery efficiencies, but they are very toxic to cells.”

Multiple barriers confront conventional approaches, making it difficult to integrate both high-efficiency delivery and biocompatibility into one gene delivery system. But the Northwestern researchers were able to do just that by functionalizing the nanodiamond surface with PEI800.

The combination of PEI800 and nanodiamonds produced a 70 times enhancement in delivery efficiency over PEI800 alone, and the biocompatibility of PEI800 was preserved. The process is highly scalable, which holds promise for translational capability.

The researchers used a human cervical cancer cell line called HeLa to test the efficiency of gene delivery using the functionalized nanodiamonds. Glowing green cells confirmed the delivery and insertion into the cells of a “Green Fluorecent Protein (GFP)”-encoding DNA sequence. This served as a demonstrative model of how specific disease-fighting DNA strands could be delivered to cells. As a platform, the nanodiamond system can carry a broad array of DNA strands.

Regarding toxicity measurements, cellular viability assays showed that low doses of the toxic high-molecular PEI resulted in significant cell death, while doses of nanodiamond-PEI800 that were three times higher than that of the high-molecular weight PEI revealed a highly biocompatible complex.

Ho and his research team originally demonstrated the application of nanodiamonds for chemotherapeutic delivery and subsequently discovered that the nanodiamonds also are extremely effective at delivering therapeutic proteins. Their work further has shown that nanodiamonds can sustain delivery while enhancing their specificity as well.

Having demonstrated the safety of nanodiamonds and their applicability toward a variety of biological uses, Ho’s team is pursuing aggressively the steps necessary to push them towards clinical relevance. Current studies are boosting the targeting capabilities of the nanodiamonds while also evaluating their pre-clinical efficiency.

“There’s a long road ahead before the technology is ready for clinical use,” Ho said, “but we are very pleased with the exciting properties and potential of the nanodiamond platform.”

The title of the ACS Nano paper is “Polymer-Functionalized Nanodiamond Platforms as Vehicles for Gene Delivery.” In addition to Ho (senior author) and Zhang, other authors of the paper are Mark Chen, Robert Lam and Xiaoyang Xu, all from Northwestern, and Eiji Osawa, from the NanoCarbon Research Institute at Shinshu University, Nagano, Japan.

Source:
Megan Fellman

Northwestern University Continue reading →

A biological pathway that transforms normal cells into aggressive tumors has been discovered by researchers at Cleveland Clinic’s Lerner Research Institute.

This research, led by Philip Howe, Ph.D., of the Cancer Biology Department of the Lerner Research Institute of Cleveland Clinic, was recently published in Molecular Cell.

This research helps define the cellular events that lead to metastasis. While the study used breast cells, the pathway offers characteristics that are applicable to cancers in general. It is hoped that this improved understanding of cancer development will lead to better diagnostic, preventative, and therapeutic procedures for the disease.

These studies build on those published by the same group last year in Nature Cell Biology, which identified the components of a molecular complex that prevents the processing of genetic material necessary for tumor development – and a protein that reverses this to permit tumor-forming ability.

The current publication further defines this mechanism by showing evidence in a mouse model that tumor progression hinges on the role of a specific molecular factor called “hnRNP E1.” Mice lacking hnRNP E1 developed metastatic tumors when challenged with normal, non-invasive breast cells: mice with hnRNP E1 did not.

The genetic material whose expression is regulated by this mechanism is necessary for what is known as the epithelial-mesenchymal transition (EMT). EMT describes how cells that are normally stationary become mobile. This process is essential for embryonic development. Once development is complete, the process is silenced – except when a tumor forms. That is when the “safety” (i.e. hnRNP E1) is removed from the EMT-blocking complex, and the ensuing cell mobility promotes tumor progression.

Since EMT is not necessary in the normal adult, identifying the status of hnRNP E1 may be useful as a diagnostic approach for cancer. Furthermore, a strategy that prevents removing it from the complex may make it possible to specifically target cancerous versus normal tissue.

Source:
Dan Doron
Lerner Research Institute Continue reading →

Dr. Judith A. Potashkin, Ph.D. and her colleagues at Rosalind Franklin University of Medicine and Science recently completed a study investigating one of the changes in gene expression that occurs when individuals take addictive drugs. The findings of this study will be published in the September 5 issue of the online, open-access journal PLoS ONE.

Dr. Potashkin, Associate Professor and Vice Chair of the Department of Cellular and Molecular Pharmacology, is an expert in gene expression. She commented, “Addiction is a brain disorder that manifests itself by repetitive behaviors despite negative consequences. Currently, there is an abundance of information known about the cellular and behavioral changes that occur during addiction, but little is understood concerning the changes that occur at the molecular level with regards to gene expression. Understanding the changes that occur between transcription and protein synthesis is key to revealing the mechanism that leads to addiction.”

Dr. Potashkin’s studies focus on how the primary RNA transcript is processed by splicing to produce a mature transcript. The fidelity of splicing must be maintained since errors may lead to the development of disease. One immediate and prominent alteration that occurs with administration of amphetamine or cocaine is the accumulation in one region of the brain of very stable truncated isoform of the transcription factor FosB termed DFosB that is produced by alternative splicing of the transcript. DFosB mediates some of the neural and behavioral modifications that occur with drug addiction. The results from the study identified a splicing factor, polypyrimidine tract binding protein, as a key factor in regulating the switch in splicing that result in the truncated form of FosB being produc ed instead of the less stable full-length protein. The study also provided clues about the signaling pathway that is activated that leads to splicing regulation. This information provides several potential therapeutic targets for drug addiction.

Dr. Potashkin has been studying gene expression for the past 22 years. This research was funded by the National Institute of Drug Addiction, a division of the National Institutes of Health. Dr. Potashkin is also funded by the Department of Defense.

Rosalind Franklin University of Medicine and Science educates medical doctors, health professionals and biomedical scientists in a personalized atmosphere. The University is located at 3333 Green Bay Road, North Chicago, IL 60064, and encompasses Chicago Medical School, College of Health Professions, Dr. William M. Scholl College of Podiatric Medicine, and School of Graduate and Postdoctoral Studies. Visit at rosalindfranklin.edu and lifeindiscovery

Contact:

Priscilla Khoury, MS, FAHP
Vice President for Institutional Advancement
rosalindfranklin.edu

Citation: Marinescu V, Loomis PA, Ehmann S, Beales M, Potashkin JA (2007) Regulation of Retention of FosB Intron 4 by PTB. PLoS ONE 2(9): e828.doi:10.1371/journal.pone.0000828

LINK TO THE PUBLISHED ARTICLE: plosone/doi/pone.0000828

Disclaimer

This press release refers to an upcoming article in PLoS ONE. The release has been provided by the article authors and/or their institutions. Any opinions expressed in this are the personal views of the contributors, and do not necessarily represent the views or policies of PLoS. PLoS expressly disclaims any and all warranties and liability in connection with the information found in the release and article and your use of such information.

Contact: Priscilla Khoury
Public Library of Science Continue reading →

Researchers from Boston University School of Medicine (BUSM) have discovered a new gene therapy that may prevent the progression of emphysema. The study, which appears on-line in the Journal of Clinical Investigation, describes a method to express therapeutic genes in lung tissue for a lifetime after only a single treatment.

Alpha-1 Anti-trypsin Deficiency is the most common inherited form of emphysema seen in young people due to a mutation in the Alpha-1 Anti-trypsin gene. This genetic disease predisposes affected individuals to early emphysema and cirrhosis of the liver.

According to the researchers, gene transfer into specific cell lineages in vivo remains an attractive yet elusive approach for correcting inherited mutations. Although a variety of techniques have been developed to deliver DNA molecules to cells in vitro, in vivo gene transfer has been limited in many cell types by inefficient gene delivery as well as the limited life-span of differentiated cell types

Using mice, the BUSM researchers discovered a system to deliver genes selectively to as many as 70 percent of a mouse lung’s alveolar macrophages (AM), a key cell type contributing to emphysema.

“We applied this novel approach to achieve sustained in vivo expression of normal human alpha-1 antitrypsin (hAAT) protein at levels able to ameliorate emphysema in mice,” said senior author Darrell Kotton, MD, an associate professor of medicine and pathology and co-director, Center for Regenerative Medicine at BUSM. “The lung macrophages carrying the therapeutic gene survived in the lungs air sacks for the two-year lifetime of the treated mice following a single intra-tracheal injection of the lentiviral vector we had engineered,” he added.

Kotton and his colleagues utilized this method of gene transfer to achieve localized secretion of therapeutic levels of human alpha-1 antitrypsin (hAAT) protein in lung epithelial lining fluid. “The progression of emphysema in mice exposed to elastase was significantly improved by the gene therapy as evidenced by improvements in lung compliance and alveolar size,” said Andrew Wilson, MD, lead author of the study and an assistant professor of medicine at BUSM.

According to the researchers after 24 weeks of sustained gene expression, no humoral or cellular immune responses to the human hAAT protein were detected. “Our results challenge the dogma that lung macrophages are short-lived and suggest these differentiated cells as a target cell that may be considered for in vivo gene therapy applications including the sustained correction of hAAT deficiency,” added Wilson.

Source: Gina M. DiGravio

Boston University Medical Center Continue reading →

If you have had a hard day at work, you may change your eating habits, perhaps favoring comfort food, but you don’t suddenly develop the ability to
eat the plate and cutlery. A new paper, published in this week’s issue of PLoS Biology, describes an evolutionary mechanism in yeast that allows
cells to respond to environmental stress in novel ways, including digesting materials that they were previously unable to use – though admittedly,
they aren’t eating crockery just yet! The work shows that a protein-misfolding mechanism that can reveal hidden genetic variation is far more likely
to be triggered when yeast is under environmental stress, and is therefore an evolutionary strategy to trigger rapid evolution.

All animal cells contain DNA that is never used, which includes old copies of genes that have become defunct during the evolutionary process, and even
parasitic bits of DNA introduced by viruses that now lie dormant. It has been suggested by evolutionary theorists that difficult environmental
conditions would favour organisms that have increased ‘evolvability’ – i.e. those that are capable of adapting rapidly to the environment. One
way of having increased ‘evolvability’ is to utilize some of the variation encoded in this unused DNA. A new paper, by Dr. Susan Lindquist and
colleagues at the Whitehead Institute for Biomedical Research and Howard Hughes Medical Institute, suggests that such a mechanism exists in yeast, a
mechanism based on the presence of a prion called [PSI+].

Best known as the infectious agents in mad cow disease, prions also can play positive roles in biology, the scientists emphasize. “A prion is not
necessarily detrimental; in yeast it can be a different way for a cell to code information,” says Jens Tyedmers a lead author. In yeast, the [PSI+]
prion is a mis-folded version of a protein that plays a key role in making other proteins. Earlier studies showed that the presence of [PSI+] in a
yeast cell changes protein production such that hidden genetic variations are included in the proteins that a cell produces. Most of the resulting
phenotypes (variants of the organism) have no effect on cell survival, or make things worse. “But about a quarter of the time, the phenotypes are
good,” says Lindquist. “Sometimes the yeast can grow on energy sources it couldn’t grow on before, or withstand antibiotics it couldn’t
withstand.”

This heightened ability to adapt to changing environments may be maintained in yeast as a way to accelerate evolutionary changes. Under stress, yeast
cells can unleash a remarkable mechanism based on these misfolded proteins that give them new characteristics without a prior genetic mutation. This
mechanism is triggered much more often as the cells undergo stress, suggesting that it is tailored to play exactly this role in evolution.

To test their hypothesis, the scientists first examined what genes might help to induce the prion state, plowing through the entire genome of
Saccharomyces cerevisiae, the common baker’s yeast that biologists have studied intensively for many years. Tyedmers tested 4700 yeast strains that
each lacked one of the genes in the yeast genome, and then tested each strain’s ability to create the prion. Among the strains most successful at
generating prions, many had changes in regulating the response of a cell to stress.

With that encouragement, Maria Lucia Madariaga, another lead author on the paper, went on to do stress tests on the yeast. Madariaga notes,”We
wanted to use some conditions you would find in nature. Yeast hanging out in a vineyard are subject to heat, salt and other stresses.”

They found that the more stress experienced by the organism, the more likely it is to flip into a prion state. Otherwise, “when things are
hunky-dory, only one in a million yeast cells flips into the prion state,” observes Lindquist.

That finding helps to make the case that this mechanism aids in accelerating evolution. “It’s always difficult to prove any argument about how a
mechanism evolved, but this does offer a coherent logical story,” she says.

Citation:
“Prion switching in response to environmental stress.”br>Tyedmers J, Madariaga ML, Lindquist S (2008)
PLoS Biol 6(11): e294. doi:10.1371/journal.pbio.0060294
Click here to view article online.

PLoS Biology

PLoS Biology (eISSN-1545-7885; ISSN-1544-9173) is an open-access, peer-reviewed general biology journal published by the Public Library of Science (PLoS) , a nonprofit organization of scientists and physicians committed to making the world’s scientific and medical literature a public resource. New articles are published online weekly; issues are published monthly.

Public Library of Science Continue reading →

The major challenge for public health in the era of genomics is to generate the base of evidence necessary to demonstrate when use of genomic information in public health can improve health outcomes in a safe, effective and cost-effective manner, participants at an international meeting have concluded.

In their report, “Public health in an era of genomic and personalized medicine,” experts in medicine, law, bioethics, public health, and genetics have identified key issues for the future of global public health in light of rapid developments in genomic medicine and associated technologies.

“This report reflects some very innovative thinking about the way genomics will inform and influence public health research and practice, so we’re hoping that the public health community will implement our recommendations,” said Eric M. Meslin, Ph.D., director of the Indiana University Center for Bioethics and a member of the steering committee for the international meeting, held in May 2010 at Ickworth House in Suffolk, England.

The experts concluded that genomic medicine was very much an international issue, recommending that appropriate genetic health services and research should be fostered in low and middle-income countries. They also called for increased global collaboration and ongoing efforts to integrate genomics into public health research and practice, including creation of a research infrastructure for generating an evidence base for genomic medicine.

“Genomics is relevant and important to all countries and populations,” said Tikki Pang, Ph.D., director of research policy & cooperation for the World Health Organization. “This report will help clinicians, public health practitioners and relevant decision-makers frame and focus their strategies and approaches.”

The group included representation from many countries including Argentina, Australia, Canada, France, Italy, the Netherlands, Nigeria, the United Kingdom and the US, and was co-organized by four partners: the PHG Foundation, Cambridge, UK; the IU Center for Bioethics through a grant from the Richard M. Fairbanks Foundation; the McGill University Centre of Genomics and Policy in Montreal, Canada, and the University of Western Australia Telethon Institute for Child Health Research.

The full report, “Public health in an era of genomic and personalized medicine,” including recommendations, is available from the PHG Foundation website.

Source:
Eric Schoch
Indiana University School of Medicine Continue reading →

Bionovo, Inc. (Nasdaq: BNVI) announced that a study of the gene regulation in multiple cell lines by several of their estrogen receptor beta (ERb) candidates will be published in Public Library of Science One.

“In this study we show that plant-derived ERb compounds are as selective as synthetic compounds, but regulate different genes. Specifically, we have discovered that these compounds do not promote breast or endometrial cancer in animal models, unlike many estrogen therapies. This suggests that these plant-derived ERb-selective compounds could lead to safer, more attractive alternative therapies for menopausal symptoms,” said Dr. Dale Leitman, the Principal Investigator of the study.

The publication describes the analyses of three distinct classes of ERb selective drugs. The study determines the relative ER selectivity and pattern of gene expression of the three classes of ERb selective compounds compared to the natural hormone estradiol, which non-selectively regulates both ERa and ERb . The most significant finding in the study was that the ERb-selective compounds regulate a number of genes differently than estradiol, a hormone therapy commonly used to treat women’s health issues. This discovery indicates that ERb agonists might be safer than current estrogens used in hormone therapy. The study also demonstrates the cell type selectivity of Menerba (MF101) and Liquiritigenin, two of Bionovo’s ERb selective drugs, in different cell types. These compelling findings will serve as a strong impetus for Bionovo, Inc. to continue investigating the unique abilities of their drugs to safely and effectively treat menopausal symptoms.

“It is essential that new drug candidates demonstrate drug selectivity and tissue specificity in order to minimize adverse effects, particularly when the drug is being developed for the treatment of common, recurring symptoms associated with menopause, such as hot flashes. This is particularly important when developing drugs that mediate their effects through estrogen receptors, which are responsible for many functions in the body and are present in a range of different tissues. Bionovo stands alone in its dedication to identifying novel pathways in estrogen receptor signaling as drug targets for the treatment of women’s conditions,” said Isaac Cohen, Chairman and CEO of Bionovo, Inc. “We have been endeavoring to develop more selective drugs in women’s health, and Dr. Leitman’s study highlights the solid scientific underpinnings of our ER beta selective drugs and underlines the deep biological understanding we have of the mechanisms through which they work.”

Bionovo, Inc.

Bionovo is a pharmaceutical company focused on the discovery and development of safe and effective treatments for women’s health and cancer, markets with significant unmet needs and billions in potential annual revenue. The company applies its expertise in the biology of menopause and cancer to design new drugs derived from botanical sources which have novel mechanisms of action. Based on the results of early and mid-stage clinical trials, Bionovo believes they have discovered new classes of drug candidates within their rich pipeline with the potential to be leaders in their markets. Bionovo is headquartered in Emeryville, California and is traded on the NASDAQ Capital Market under the symbol, “BNVI”.

Forward Looking Statements

This release contains certain forward-looking statements relating to the business of Bionovo, Inc. that can be identified by the use of forward-looking terminology such as “believes,” “expects,” or similar expressions. Such forward-looking statements involve known and unknown risks and uncertainties, including uncertainties relating to product development, efficacy and safety, regulatory actions or delays, the ability to obtain or maintain patent or other proprietary intellectual property protection, market acceptance, physician acceptance, third party reimbursement, future capital requirements, competition in general and other factors that may cause actual results to be materially different from those described herein as anticipated, believed, estimated or expected.

Source: Bionovo, Inc

View drug information on Estradiol Transdermal System. Continue reading →

Scientists at the Zucker Hillside Hospital campus of the Feinstein Institute for Medical Research have identified nine genetic markers that can increase a person’s risk for schizophrenia. In a study published this week in the Proceedings of the National Academy of Sciences, the research team uncovered original evidence that this disabling brain disease can be inherited in a recessive manner. A recessive trait is one that is inherited from both parents.

“If a person inherits identical copies of these markers from each parent, his or her risk for schizophrenia increases substantially,” said Todd Lencz, PhD, associate director of research at Zucker Hillside and the lead author of the study. “If these results are confirmed, they could open up new avenues for research in schizophrenia and severe mental illness,” said Anil Malhotra, MD, director of psychiatric research at Zucker Hillside and senior investigator of the study.

The scientists developed a complex mathematical approach called whole genome homozygosity association (WGHA) that provides a new way of analyzing genetic information. It enables scientists to simultaneously look at genetic information derived from the patient’s mother and father, and identify pieces of chromosomes that are identical. They tested genetic material from 178 patients and 144 controls.

It has been the prevailing view in psychiatric genetics that there are probably dozens, if not hundreds, of genetic variations that could lead to schizophrenia, but each gene has a small effect. It is the wrong mix of many genes, plus unknown environmental stressors, that trigger the onset of symptoms. One in every 100 people suffer from schizophrenia, a condition marked by episodes of hallucinations, delusions and disordered thinking.

The new findings suggest another scenario, at least for a subset of patients. Dr. Lencz and his colleagues identified nine regions along the chromosomes that might play a large role in triggering the disease when two identical variants are inherited. Four of these regions contain genes that have been previously associated with schizophrenia, providing validation for the technique. The remaining five regions provide an additional set of newly discovered genetic risk factors. Many genes located in these regions are involved with the structure and survival of neurons.

In genetic parlance, several of these markers demonstrated high penetrance, meaning that their effect on disease risk was large. In the study, 81 percent of the schizophrenia patients had at least one of these recessive markers, compared to only 45 percent of the normal control group. Nearly half of the patients had two or more compared to 11 percent of the controls. And while no one in the healthy group had identical chunks of chromosomes in four or more of these risk regions, subjects with more than three demonstrated a 24-fold increased risk of developing schizophrenia. “This type of analysis could greatly improve our ability to diagnose schizophrenia and clarify specific subtypes of patients,” Dr. Lencz said. “The critical next step is confirming these results in independent datasets.”

“What is most exciting is that the study implicates new genes in schizophrenia,” said David Goldman, MD, chief of laboratory of neurogenetics at the National Institute on Alcohol Abuse and Alcoholism. “Now, they have to trace down the genes that mediate this vulnerability.” Identifying these novel genes will eventually help improve understanding of the disease and lead to the development of more effective treatments, the scientists said.

The Feinstein scientists worked in collaboration with software developers from Golden Helix, Inc. in Bozeman, MT and researchers at Harvard Medical School to develop the statistical method. The WGHA technique can now be applied to any other illness with a genetic component. Dr. Lencz and his colleagues previously published the first “whole-genome” DNA microchip study in schizophrenia.

The study was funded by a private donation from the Donald and Barbara Zucker Foundation, an award from the KeySpan Corporation, and grants from the National Institute of Mental Health; NARSAD, the Mental Health Research Association (formerly known as National Alliance for Research on Schizophrenia and Depression); and the Stanley Medical Research Institute.

About The Feinstein Institute for Medical Research

Headquartered in Manhasset, NY, and part of the North Shore-LIJ Health System, The Feinstein Institute for Medical Research is among the top six percent of all institutions that receive funding from the National Institutes of Health. Building on its strengths in neurodegenerative and psychiatric disorders, genomics and human genetics, immunology and inflammation, and oncology and cell biology, its goal is to understand the biological processes that underlie various diseases and translate this knowledge into new tools for diagnosis and treatment. For more information, please visit the Feinstein blog.

Source: Jamie Talan

North Shore-Long Island Jewish (LIJ) Health System Continue reading →