Restless Legs Syndrome Has Complex Genetic Involvement

A new study confirmed that a gene associated with restless legs syndrome (RLS) susceptibility is located on chromosome
12q and and also suggests that at least one other gene may be involved in restless leg syndrome, according to an article in
the April issue of the Archives of Neurology, one of the JAMA/Archives journals.


Restless legs syndrome is one of the leading causes of insomnia, affecting more than five to 10 percent of the white
population, according to background information in the article. Genetic contributions to restless legs syndrome have been
consistently supported by population, family and twin studies. To identify genetic risk factors, the current study used
information from French Canadian families, where, according to the researchers, prevalence of restless legs syndrome is
higher than in other populations.


Alex Desautels, Ph.D., of the University of Montreal, and colleagues examined the DNA of 19 multigenerational French Canadian
families with four to nine individuals who were affected (or possibly affected) by restless legs syndrome. The researchers
used statistical analysis of the genetic information to determine whether restless legs syndrome in each family was linked
with markers on the same location on chromosome 12q that had previously been associated with restless legs syndrome.


Two-hundred-seventy-six individuals were included in the study, including 146 affected individuals, 39 possibly affected
individuals and 91 unaffected family members. The researchers confirmed that the syndrome was consistent with linkage to
chromosome 12q within five families. Linkage to that location was formally excluded for six other families. The researchers
compared clinical features of the syndrome in affected individuals from the different families to see if those differences
correlated with the differences in linkage. They found that one feature, periodic leg movements during sleep, was
significantly greater for affected individuals from the linked families than for affected individuals from the unlinked
families.


"These results further support the involvement of an RLS-susceptibility locus [gene location] on chromosome 12q in the FC
[French Canadian] population and also provide evidence that there must be other loci involved in this common sleep disorder,"
the authors conclude. "Furthermore, our findings illustrate that extensive characterization of subclinical differences
represents a major tool in the identification of susceptibility loci for complex diseases ??? Although the background of RLS is
most likely complex, this finding may offer a new starting point for further dissecting the genetic cause of RLS."
(Arch Neurol. 2005;62:591-596.
Available post-embargo at archneurol)


This study was supported in part by research grants from the Canadian Institutes of Health Research (CIHR), Ottawa and from
the National Institutes of Health, Bethesda, Md. Dr. Desautels is a recipient of the CIHR studentship.


JAMA/Archives news release

Embryos Part-animal And Part-human Created

Embryos that are part-human and part-animal have been created by scientists at Newcastle University, UK. The scientists, who are researching into a range of illnesses, said the embryos survived for up to three days.


While religious leaders describe this development as monstrous, scientists and medical professionals hail the event as one step closer to understanding illnesses such as Alzheimer's and Parkinson's better, and ultimately being able to treat them. Members of the Catholic Church say these experiments are akin to those of Frankenstein.


Team leader, Dr. Lyle Armstrong, was granted a licence by HFEA (Human Fertilisation and Embryology Authority) to use animal eggs in research aimed at understanding how cells develop. Dr. Armstrong and team have been working on this project since the licence was granted and have made some very preliminary findings.


The hybrid embryos were created by injecting human skin cell DNA into eggs which were extracted from the ovaries of cows - the ovaries had had all their genetic material removed. According to the scientists, they used eggs from cow ovaries because eggs donated from humans are scarce.


Dr Armstrong is part of the North East England Stem Cell Institute (NESCI) and is based at the International Centre for Life in Newcastle.


The scientists stress that the hybrid embryos would never be allowed to survive beyond their 14th day. Their aim is to extract stem cells for research into a range of diseases, and eventually find ways of treating them.


"This is licensed work which has been carefully evaluated. This is a process in a dish, and we are dealing with a clump of cells which would never go on to develop. It's a laboratory process and these embryos would never be implanted into anyone. We now have preliminary data which looks promising but this is very much work in progress and the next step is to get the embryos to survive to around six days when we can hopefully derive stem cells from them," said Professor John Burn, Head of the Institute of Human Genetics, Newcastle University.


Legislation related to the creation of hybrid embryos


A bill which covers new legislation regarding the creation of hybrid embryos will be debated in parliament (UK) in May in the House of Commons. Prime Minister, Gordon Brown, had to give in to demands for a free vote (by parliamentarians) on this issue.


-- Hybrid Embryos - FAQs

-- Institute of Human Genetics

Altered DNA Allows Salmonella To Survive Better In Stomach

Since 1995 there has been a considerable increase in the number of infections with a specific type of Salmonella bacteria transmitted via food. This type, Salmonella serovar Typhimurium DT104, is resistant to at least five different antibiotics. Dutch researcher Armand Hermans found new genetic information in DNA of DT104 that might be involved in its survival and infection mechanism. This genetic information might also be involved in the increase in the number of infections caused by this pathogen.



By comparing the DNA of Salmonella serovar Typhimurium DT104 with the known DNA code of another Salmonella strain, Hermans found new DNA fragments in DT104. These pieces of DNA were found to contain genetic information that might play a role in the survival and infectiousness of this pathogen. The presence of such extra genetic characteristics can make the pathogen stronger and more infectious.



To examine how DT104 behaves to survive various "extreme" conditions, the switching on and off of 500 genetic characteristics was studied. This happened under different conditions such as in a hot, acid or oxygen-free environment. Almost all of the survival characteristics were found to be active under all conditions, whereas the pathogenic characteristics were only active under a few of the conditions. Therefore this pathogen always does everything it can to survive under all conditions, for example, during food conservation or in gastric acid. The pathogenic characteristics of DT104 on the other hand are only active in the intestines where the infection takes place.



Evolution of the pathogen



The DNA of the pathogen says something about how it survives and is transmitted. When a pathogen reproduces, the DNA can change a bit and this can lead to changes in the genetic characteristics. This can, for example, lead to antibiotic resistance but also heat or acid resistance. The pathogens with the best genetic characteristics can spread and survive better and are therefore more infectious: the evolution of a pathogen. Examining which genetic characteristics are present in an infectious Salmonella (in this case the DT104 type) can reveal how this pathogen has become stronger and caused more outbreaks. This information can also be used to make a less dangerous variant of this infectious Salmonella. Such a harmless variant can be used as a vaccine.



Salmonella serovar Typhimurium DT104 is an antibiotic-resistant pathogen that is transmitted via food and is considered to be dangerous for humans. In recent decades the number of infections with this variant has increased in many parts of the world. This research was funded by NWO and contributes to knowledge about the characteristics and behaviour of this dangerous Salmonella.







For further information please contact:
* Dr Armand Hermans



* The doctoral thesis was defended on 16 January 2007 at Wageningen University and Research Centre

* Supervisors Prof. T. Abee and Prof. M.H. Zwietering
* associate supervisor Dr H.J.M. Aarts



Contact: Dr Armand Hermans


Netherlands Organization for Scientific Research

New Drug Strategy Against Fragile X Syndrome

Researchers at Emory University School of Medicine have identified a potential new strategy for treating fragile X syndrome, the most common inherited cause of intellectual disability.



The researchers have found that a class of drugs called phosphoinositide-3 (PI3) kinase inhibitors can correct defects in the anatomy of neurons seen in a mouse model of fragile X syndrome. In experiments with cultured neurons from the hippocampus, a brain region involved in learning and memory, the drugs could restore normal appearance and levels of protein production at synapses, the junctions between cells where chemical communication occurs. The results, published online this week in the Journal of Neuroscience, suggest that PI3 kinase inhibitors could help improve learning and cognition in individuals with fragile X syndrome.



"This is an important first step toward having a new therapeutic strategy for fragile X syndrome that treats the underlying molecular defect, and it may be more broadly applicable to other forms of autism," says senior author Gary Bassell, professor of cell biology and neurology at Emory University School of Medicine. He adds that his group has recently begun experiments in the mouse model to assess PI3 kinase inhibitors' effects on behaviors associated with fragile X syndrome.



The first author of the paper is postdoctoral fellow Christina Gross. Collaborators included Keqiang Ye, PhD, associate professor of pathology and laboratory medicine, and Stephen Warren, PhD, professor and chairman of human genetics.



In the United States, fragile X syndrome is the most common known one-gene cause of autism, accounting for between two and five percent of cases. Mutations in the PTEN gene and tuberous sclerosis genes, which in humans can lead to autism, also perturb the signaling of the PI3 kinase pathway, Bassell says. This connection suggests that PI3 kinase inhibition might be a viable strategy for treating individuals with mutations affecting this pathway.



While clinical trials in humans testing the effectiveness of another class of drugs, metabotropic glutamate receptor antagonists, against fragile X are well underway, Bassell says "the new approach may offer a different way to calm the overactive signaling, and also restore the glutamate receptor sensitivity that is lost in fragile X."



The genetic mutation responsible for fragile X prevents production of an RNA binding protein, FMRP, which regulates the production of many other proteins at synapses of brain cells. FMRP's absence leads to overactive signaling and protein production at synapses.



"The focus in the field has been on glutamate receptor antagonists," Bassell says. "The effects on glutamate receptor signaling are a big piece of fragile X, but they're not the only piece."



At their synapses, fragile X neurons produce proteins indiscriminately compared to unaffected neurons, he says. The "overexuberant" protein production leads to structural changes at their synapses, including a hyperabundance of dendritic spines. These spines are small protrusions that transmit electrical signals to adjacent neurons, and contribute to the communication between individual neurons in the brain.
















Gross and Bassell discovered that in cells from mice where the FMRP gene has been deleted, the PI3 kinase enzyme is three times more active. PI3 kinase regulates protein synthesis in response to the electrochemical signals neurons send each other. The authors showed that tamping down PI3 kinase activity in fragile X neurons can restore normal levels of both protein synthesis and dendritic spine density.



PI3 kinase inhibitors are already under investigation for their anti-cancer properties, and some drugs of this type, such as wortmannin, can be toxic to normal cells. Bassell notes that this type of drugs would need to be used at low doses to only dampen excess signaling of protein production caused by fragile x. The drugs his team tested were effective in correcting fragile X molecular defects at levels five times lower than those usually employed, and did not reduce protein production in normal cells.



Bassell anticipates that drugs that preferentially inhibit the subtype of PI3 kinase present only in neurons hold greater promise as a novel therapeutic strategy.



"A few of these subtype-specific drugs are already available for researchers, and we are involved in efforts to test these more specific drugs in the fragile x mouse model," he says.



"This is a really exciting time for fragile x research because progress is occurring at a fast pace," Gross says. "I look forward to testing our theory of this mechanistic link between fragile x and autism, which suggests that a specific drug treatment could be broadly applicable."



The research was supported by the National Institutes of Health and the National Fragile X Foundation.



Reference:
C. Gross, M. Nakamoto, X. Yao, C.B. Chan, S.Y. Yim, K. Ye, S.T. Warren and G.J. Bassell. Excess phosphoinositide 3-kinase subunit synthesis and activity as a novel therapeutic target in fragile X syndrome. J. Neurosci. 30: page #s (2010).



Source:

Jennifer Johnson

Emory University

Method By Which A Protein That Determines Cell Polarity Prevents Breast Cancer

In breast tissue, cells lining the breast's ducts have a certain shape that is required to maintain both organ structure and function. All breast cancers display a loss of this characteristic organization, but very little is known about the molecules and pathways that regulate tissue structure and the role they play during cancer.



A team of scientists at Cold Spring Harbor Laboratory (CSHL) has now discovered that a protein called Scribble, originally discovered as a cell-shape regulator in fruit flies and worms, is an important regulator of breast cancer. They report that normal function of Scribble protein allows breast epithelial cells to form duct-like structures and resist cancer formation. When Scribble stops functioning, the tissue loses its shape and cancers ensue.



A new approach to understanding how cancer begins



The discovery identifies "a new paradigm for understanding how cancer initiates," according to CSHL Professor Senthil Muthuswamy, Ph.D., who headed the team that conducted the research, published in Cell on Nov. 26. The results also constitute first steps toward identifying an entirely new class of molecules and pathways that can be targeted by anti-cancer therapies to prevent pre-cancerous lesions from turning into malignant tumors.



"Thinking about cancer as a disease that results only due to an increase in cell numbers is too simplistic," according to Muthuswamy. He points out that proteins that control cell number and regulate cell structure are both critical in cancer development. He therefore proposes that carcinomas--cancers derived from epithelial cells in organs such as breast, ovary, prostate, lung and pancreas--should be approached as a problem of "deregulated morphogenic processes and not just as a disease of increased cell number."



Seeing cells in three dimensions



Many studies aimed at unraveling cancer's molecular mechanisms use cells cultured on plastic dishes as an experimental platform. "Such models have been quite satisfactory in allowing scientists to analyze mechanisms involved in cell growth" says Muthuswamy. But they don't allow scientists to capture the three-dimensional organization of cells seen in tissue, including their polarity. A major enabler for Muthuswamy's current work is an experimental model system that enables him to grow breast cells in three-dimensional cultures to allow them to form structures similar to those seen in breast ducts and lobules.



On Muthuswamy's novel test bed, cells undergo morphogenesis -- a growth/death cycle that expands and shapes tissue. Such cells give rise to what looks like a hollow ball of cells. The polarity protein Scribble lines the sides of each cell, lending to each a specific orientation.



What happens when Scribble is missing?



In breast epithelial cells grown in this new experimental culture system, when the Scribble protein is missing, cells were observed by Muthuswamy's team to radically change their character and behavior. They lost their orientation -- an effect one might have predicted since Scribble regulates polarity -- and started to fill the hollow ball.. The team hypothesized that the filling-in of the "ball" was akin to the process, in living creatures, by which a breast epithelial tumor would form.
















To test this notion, the experiment was moved from a cell-culture dish to living animals. Mouse breasts were generated using genetically engineered cells that had stopped producing the Scribble protein. In such mice, the researchers found that breast ducts were deformed and tumors typically developed after about one year's time. This dramatic result pointed to Scribble, a cell shape regulator, as a tumor suppressor in breast epithelial cells.



The targets of tumor suppressors are usually cancer-causing genes, or oncogenes, such as Myc, which past research has shown to be overexpressed, i.e., present in abnormal quantity, in human breast cancer. Myc is known to activate pathways of both growth and death in breast epithelial cells. In fact, the only way that cancer can occur when Myc is overexpressed is if some other mechanism blocks its propensity to induce abnormal cells to commit suicide, a process called apoptosis. Muthuswamy and colleagues now identify this "other mechanism" as the loss of the Scribble protein, which thus is revealed to be a tumor suppressor protein.



Cells engineered by the CSHL team to lack Scribble and overexpress Myc not only stayed alive, but also went into a growth overdrive. The combined effect of polarity loss and Myc overactivation was the formation of unusually large and fast-growing breast epithelial tumors.



The CSHL team worked out the molecular players and specific intracellular pathway controlled by Scribble to initiate cell death. This revealed that Scribble only works as a cancer deflector when it finds itself in the right location--within the junctions between cells. Cellular disorientation occurs when mutations in the gene that orders Scribble to be produced in a cell either prevents its expression or causes it to be expressed in the wrong location within the cell. In either case, the same severe consequence ensues: cancer progression.



How Scribble gets deregulated in cancer remains a mystery. The CSHL team is now addressing the question of how the deregulated Scribble pathway can be targeted for diagnosis and treatment.







"Deregulation of Scribble promotes mammary tumorigenesis and reveals a role for cell polarity in carcinoma" appears in the November 2008 issue of Cell. The full citation is: Lixing Zhan, Avi Rosenberg, Kenneth C. Bergami, Min Yu, Zhenyu Xuan, Aron B. Jaffe, Craig Allred, and Senthil K. Muthuswamy. The paper appears online at cell/ on Nov 26th 2008.



Cold Spring Harbor Laboratory (CSHL) is a private, not-for-profit research and education institution at the forefront of efforts in molecular biology and genetics to generate knowledge that will yield better diagnostics and treatments for cancer, neurological diseases and other major causes of human suffering.



For more information please visit cshl.edu/.



Source: Hema Bashyam


Cold Spring Harbor Laboratory

Errors In Cilia Transmission Result In Major Childhood Diseases And Defects

Johns Hopkins researchers say they have figured out how human and all animal cells tune in to a key signal, one that literally transmits the instructions that shape their final bodies. It turns out the cells assemble their own little radio antenna on their surfaces to help them relay the proper signal to the developmental proteins "listening" on the inside of the cell.



The transmitters are primary cilia, relatively rigid, hairlike "tails" that respond to specialized signals from a host of proteins, including a key family of proteins known as Wnts. The Wnts in turn trigger a cascade of shape-making decisions that guide cells to take specific shapes, like curved eyelid cells or vibrating hair cells in the ear, and even make sure that arms and legs emerge at the right spots.



"Our experiments go to the heart of the development and maintenance of our body tissue," says Johns Hopkins geneticist Nicholas Katsanis, Ph.D., associate professor at the McKusick-Nathans Institute for Genetic Medicine. "Any miscues with the Wnt signaling pathway," says Katsanis, "and you're looking at major childhood diseases and defects."



In a report published in Nature Genetics, Katsanis and his team used a small transparent fish, zebrafish, to literally watch what happened if they chemically blocked the production of three proteins that are required for primary cilia function during the period when a fish egg develops into a grown up, fully-finned fish.



The more they blocked, the more developmental errors -- for example, the growing fish would not properly extend their tails -- they were able to track to defective Wnt signaling.



Katsanis notes that once inside a cell, the Wnt pathway splits into two branches that need to be balanced depending on the needs of each cell: the so-called canonical branch, which typically drives cells to multiply, and the non-canonical branch, which controls messages to refine cell shape and growth. The errors seen in the fish pointed to an imbalance where canonical signaling predominated.



A series of biochemical studies revealed that cilia normally help a cell keep the right balance by selectively destroying proteins in the canonical branch to prevent excess growth. Defective ciliary function therefore leads to defective destruction of key proteins, which then causes problems in interpreting the Wnt signal.



"We thought that the key to the balancing act occurred inside the cell, but it now seems clear that the cilia are the main relay stations," Katsanis says. "We've just reset a huge volume of literature under a new light."







The research was funded by the National Institute of Child Health and Development, the National Institute of Diabetes, Digestive and Kidney Disorders, the National Institute for Arthritis and Musculoskeletal Disorders, the German Academic Exchange Service, and the Medical Research Council.



Authors on the paper are Philip Beachy of Stanford School of Medicine; Philip Beales of University College London; George DeMartino from UT Southwestern; and Jantje M. Gerdes, Norann Zaghloul, Carmen Leitch, Shaneka S. Lawson, Masaki Kato, Shannon Fisher and Katsanis of Johns Hopkins.



On the Web:

katsanis.igm.jhmi.edu/


nature/ng



Source: Nick Zagorski


Johns Hopkins Medical Institutions

Successful Initial Safety Tests For Genetically-modified Rice That Fights Allergy - Journal Of Agricultural And Food Chemistry

In a first-of-its-kind advance toward the next generation of genetically modified foods - intended to improve consumers' health - researchers in Japan are reporting that a new transgenic rice designed to fight a common pollen allergy appears safe in animal studies. Their report is in the current issue of ACS' Journal of Agricultural and Food Chemistry, a bi-weekly publication.



Fumio Takaiwa and colleagues note that the first generation of genetically-modified crops was designed to help keep crops weed and insect free. The next generation of transgenic crops is being developed to directly benefit human health. This includes veggies and grains that produce higher levels of nutrients, such as vitamins and minerals, or even medicines and vaccines. Like the first generation of transgenic foods, however, researchers are anxiously trying to determine whether foods produced from these "biopharmaceutical" crops will be safe for humans and the environment.



The scientists describe development of a transgenic rice plant that has been genetically- engineered to fight allergies to Japanese cedar pollen, a growing public health problem in Japan that affects about 20 percent of the population. In laboratory studies, the researchers fed a steamed version of the transgenic rice and a non-transgenic version to a group of monkeys everyday for 26 weeks. At the end of the study period, the test animals did not show any health problems, in an initial demonstration that the allergy-fighting rice may be safe for consumption, the researchers say.


"26-Week Oral Safety Study in macaques for Transgenic Rice Containing major Human T-Cell Epitope Peptides from Japanese Cedar Pollen Allergens"



Source

American Chemical Society

Researcher Collaborates To Identify New Gene Associated With ALS

A collaborative research effort spanning nearly a decade between researchers at Massachusetts General Hospital (MGH), MIT, the Broad Institute, King's College London (KCL) and other institutions has identified a novel gene for inherited amyotrophic lateral sclerosis (ALS, also known as Lou Gehrig's disease). This is the fourth gene associated with familial forms of the devastating neurological disorder. Two papers, published in the February 27 edition of Science, report mutations in FUS/TLS, a gene known to play a role in DNA repair and the regulation of gene expression. The mutations affect the behavior of the FUS/TLS protein within cells and lead to deposits of abnormal protein within motor neurons.


Nobel laureate H. Robert Horvitz, an investigator in the McGovern Institute for Brain Research at MIT and the Howard Hughes Medical Institute, collaborated on one of the studies led by researchers at MGH. The second study was conducted at King's College London.


The MGH-led team found a series of mutations in a gene that interacts with biological pathways already implicated in ALS and other neurological diseases, resulting in familial ALS of differing inheritance patterns and varying severity. "This puts us closer to identifying the link between inherited and sporadic ALS as well as to new targets for drug design," said Thomas Kwiatkowski, MD, PhD, of the MassGeneral Institute for Neurodegenerative Disease (MGH-MIND), lead author of the report. MGH neurologist Robert Brown, MD, PhD, a long-term collaborator with Horvitz on ALS, was senior author.


ALS is a progressive neurodegenerative disease affecting motor neurons in the brain and spinal cord. Death of these nerve cells stops the transmission of neural impulses to muscle fibers, leading to weakness, paralysis and usually death from respiratory failure. Most cases of ALS are sporadic, with no evidence of inheritance, but 10 percent of cases appear to be inherited.


The current findings began when the MGH-led team analyzed a family from the Cape Verde islands in which four individuals developed a form of ALS primarily affecting their arms and legs but not their respiratory system. The patients' maternal grandparents were first cousins, and the fact that many Cape Verde residents in small communities are closely related to each other increased the possibility that the disorder was caused by a recessive mutation inherited from both parents. The researchers screened affected and unaffected members of the family for instances in which both copies of a chromosomal region were identical. Affected family members were found to have such an area in a segment of chromosome 16, which previous studies by both groups had suggested might harbor an ALS gene.















Detailed sequencing of several candidate genes in that region identified an ALS-associated mutation in FUS/TLS, two copies of which were present in all four affected family members. Some apparently unaffected family members who also had two mutated copies had not reached the age where ALS symptoms typically appear. Several unaffected family members had a single copy of the variant, which was also seen in one unrelated Cape Verdean but not in a control group of 1,446 North American individuals.


The researchers then fully sequenced the protein-coding regions of FUS/TLS in two families that previous research had implicated as having an ALS-associated gene on chromosome 16 and found distinct FUS/TLS mutations in affected members of both families. Analysis of the gene in 81 unrelated familial ALS cases and almost 300 sporadic cases led to finding a total of 13 different FUS/TLS mutations in 17 familial ALS families, but no mutations were found in the sporadic cases or the control group.


The researchers sought to validate their early data implicating FUS/TLS mutations by asking researchers at King's College London, led by Christopher Shaw, MBChB, MD, to screen the families they had been studying. As described in their Science paper, the KCL team reported three mutations in eight apparently unrelated families and went on to characterize the effect of the mutations in cultured cells. They also identified deposits of FUS/TLS protein in motor neurons of three patients with FUS/TLS mutations, deposits absent from patients with SOD1 mutations or sporadic ALS.


The MGH-led team then analyzed brain tissue from one of its patient and also found abnormal deposits of the FUS/TLS protein in the nucleus of both neuronal and non-neuronal cells, along with degenerative changes typical of ALS. "Finding genes for rare and rapidly fatal diseases is extremely challenging I can't stress enough how important it has been to have this international collaboration involving so many dedicated scientists and physicians on both sides of the Atlantic," said Kwiatkowski, an instructor in Neurology at Harvard Medical School.


"We've just begun to look at how these apparent FUS/TLS aggregates relate to the disease process whether they contribute to neuronal damage or protect against it," he continued. "We're also developing a genetic test for mutations in this gene, which could help screen at-risk individuals and aid clinicians in diagnosis. It's been wonderful working together to try to solve ALS, and I hope our continued cooperation will make even greater strides."


Brown added, "This discovery identifies new pathways implicated in ALS and will almost certainly lead to new animal- and cell-based models for this disease, which should accelerate efforts to find a therapy for ALS."


The MGH-based study was supported by grants from the National Institutes of Health, the Angel Fund, the ALS Therapy Alliance, the ALS Association, Project ALS, the Al-Athel ALS Research Foundation, the Pierre de Bourgknecht ALS Research Foundation and other funders. Kwiatkowski and Brown have applied for a patent covering FUS/TLS mutations in ALS, and Brown is a co-founder of AviTx Inc., a company working to develop ALS therapies.


Additional co-authors of the MGH Science paper are E. Tamrazian, A. Davis, B. Hosler, Diane McKenna-Yasek, Peter Sapp, and Charles Venderburg, PhD, MGH-MIND; Daryl Bosco, PhD, A. LeClerc, and John Landers, PhD, UMass School of Medicine; Carsten Russ, PhD, Broad Institute; James Gilchrist, MD, Rhode Island Hospital; Edward J. Kasarskis, MD, PhD, University of Kentucky; Theodore Munsat, MD, Tufts Medical Center; Paul Vladmanis and Guy Rouleau, MD, PhD, University of Montreal; Pietro Cortelli, MD, PhD, University of Bologna; Pieter de Jong, PhD, and Y. Yoshinaga, Children's Hospital Oakland Research Institute; Jonathan Haines, PhD, Vanderbilt University; Margaret Pericak-Vance, PhD, Miami Institute of Human Genetics; Jianhua Yan and Teepu Siddique, MD, Northwestern Feinberg School of Medicine; and N. Ticozza, University of Milan.


About Massachusetts General Hospital


Massachusetts General Hospital, established in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of more than $500 million and major research centers in AIDS, cardiovascular research, cancer, computational and integrative biology, cutaneous biology, human genetics, medical imaging, neurodegenerative disorders, regenerative medicine, systems biology, transplantation biology and photomedicine.


About the McGovern Institute


The McGovern Institute for Brain Research at MIT is led by a team of world-renowned neuroscientists committed to meeting two great challenges of modern science: understanding how the brain works and discovering new ways to prevent or treat brain disorders. The McGovern Institute was established in 2000 by Patrick J. McGovern and Lore Harp McGovern, who are committed to improving human welfare, communication and understanding through their support for neuroscience research. The director is Robert Desimone, formerly the head of intramural research at the National Institute of Mental Health. Further information is available at: web.mit.edu/mcgovern


McGovern Institute for Brain Research

Bldg. 46-3160, 77 Massachusetts Ave.

Cambridge

MA 02139

United States

web.mit.edu/mcgovern

Diagnosis Is The Key To Fighting The Spread Of Food Poisoning

A Queensland University of Technology researcher has developed a new technique that can help scientists and clinicians quickly and cheaply diagnose the bacteria which causes the most common bout of food poisoning in Australia.



Erin Price, from QUT's Faculty of Science, has developed a novel set of methods that uses genetic markers to pinpoint the bacteria Campylobacter jejuni.



"Campylobacter jejuni is the commonest cause of bacterial food-borne gastroenteritis in westernised countries," Ms Price said.



"It is more common than salmonella, yet most people have never heard of it."



Ms Price said although there were about 20,000 registered cases of the disease in Australia each year, scientists believed the real rate could be 10 times higher.



"The reason the rate is so low is that it rarely kills people and is self-resolving, so in many cases it is not diagnosed," she said.



"Symptoms include diarrhoea which can last anywhere from two days to two weeks."



Ms Price said despite the high rates of infection, it was still unknown exactly how the bacteria was transmitted to humans.



"We think that it is mainly transmitted in foodstuffs, and predominantly from improperly handled and undercooked poultry, although there are potentially many other sources of infection," she said.



"One hampering factor in detecting Campylobacter jejuni is the lack of standardised, routine, simple and cost-effective methods of fingerprinting or identifying the bacteria.



"What I have done is develop a systematic and novel genotyping method to be used by clinicians and scientists, which essentially creates a fingerprint of the bacteria using genetic markers.



"This fingerprint can then be used to characterise the bacterial strain present."



Ms Price's novel genotyping methods rely on software developed at QUT which identified genetic targets.



She said that by improving methods for characterising Campylobacter jejuni strains, clinicians and scientists were better able to monitor and understand the transmission of these bacteria to humans.



"If we can figure out where the bacteria is coming from we can look for ways of preventing its spread."



Ms Price, who has almost completed her PhD, said her study paved the way for improved diagnosis of Campylobacter jejuni as well as many other clinically significant infectious agents.







Source: Sandra Hutchinson


Queensland University of Technology
Queensland University of Technology

Pre-operative Genetic Testing May Improve Treatment For Thyroid Cancer Patients, Pitt Study Finds

Knowing prior to surgery whether a patient's thyroid cancer harbors a specific gene mutation leads to tailored treatments and improved outcomes, according to researchers at the University of Pittsburgh School of Medicine. Results of the study were presented today at the American Association of Endocrine Surgeons annual meeting in Madison, Wisconsin.


According to Linwah Yip, M.D., a surgical oncologist at the University of Pittsburgh Medical Center's (UPMC) Multidisciplinary Thyroid Center, malignant thyroid tumors can contain a mutation in a gene known as BRAF, and BRAF-positive cancers are more likely to recur.


"For that reason, using genetic testing to establish BRAF status prior to surgery has important implications for the type and extent of surgery the patients need," she explained. "BRAF-positive thyroid cancer patients should have the entire thyroid gland removed instead of having a partial thyroidectomy."


Dr. Yip and her colleagues reviewed 206 papillary thyroid cancer cases of which 106 were BRAF-positive and 100 were BRAF-negative. In 19 percent of the cases, the surgical plan would have changed if BRAF status had been determined prior to surgery.


Papillary thyroid cancer is one of the most common forms of the disease, and it is considered very treatable. Approximately 37,000 people are diagnosed with the disease each year. Dr. Yip said patients with a BRAF mutation face a more aggressive disease, which is why testing the tumor for gene mutations is important.


"In the past, we've proven that this mutation is 100 percent predictive of thyroid cancer. Through genetic testing, we can ensure patients receive the right operation the first time, reducing recurrences and additional surgeries," said Dr. Yip. "The UPMC Multidisciplinary Thyroid Center routinely conducts BRAF testing on all of our patients in order to streamline their treatment."


As one of the nation's leading academic centers for biomedical research, the University of Pittsburgh School of Medicine integrates advanced technology with basic science across a broad range of disciplines in a continuous quest to harness the power of new knowledge and improve the human condition. Driven mainly by the School of Medicine and its affiliates, Pitt has ranked among the top 10 recipients of funding from the National Institutes of Health since 1997 and now ranks fifth in the nation, according to preliminary data for fiscal year 2008. Likewise, the School of Medicine is equally committed to advancing the quality and strength of its medical and graduate education programs, for which it is recognized as an innovative leader, and to training highly skilled, compassionate clinicians and creative scientists well-equipped to engage in world-class research. The School of Medicine is the academic partner of UPMC, which has collaborated with the University to raise the standard of medical excellence in Pittsburgh and to position health care as a driving force behind the region's economy. For more information about the School of Medicine, see medschool.pitt.edu.



Source
The University of Pittsburgh School of Medicine