#Gene-analysis firms reach for the cloud For Chaim Jalas at the Center for Rare Jewish Genetic disorders in New york,
and identify mutations that might be causing the undiagnosed diseases that afflict his clients families.
And the cloud-based interfaces let him collaborate with doctors in Israel without worrying about repeatedly transferring data on slow Internet connections."
which will be touting for customers at a meeting of the American College of Medical Genetics and Genomics in Phoenix, Arizona, on 19-23 march.
as ever more affordable sequencing moves from academia into the clinic (see Nature 494,290-291; 2013).
) Doctors will increasingly want to use sequen#cing data to guide decisions about patient care, but might not necessarily want to invest in staff
and finds those most likely to cause disease. Personalis, down the road in Menlo Park, offers sequencing services and interpretation for clinicians and pharmaceutical and biotechnology companies.
to explore the variants roles in disease. The company will outsource the sequencing to Illumina,
and hospitals to analyse data. But one of the biggest questions will be how deeply analysis companies can reach into medical settings,
where privacy concerns are paramount. Hospitals can be fined if patient privacy is compromised, and clinical geneticists may be uneasy about uploading data to the cloud."
"It s your licence and your lab that go on the line when it comes to reporting a clinical result,
That is a large part of why many hospitals have chosen so far to build their own analysis infrastructure,
diseases and scavengers#but acknowledge that it might have been caused by behavioural changes, such as the birds learning to avoid cars.
but it would require surgery and would cover only a small fraction of the brain.
#Distinctive virus behind mystery horse disease For almost 100 years, veterinarians have puzzled over the cause of Theiler's disease,
a mysterious type of equine hepatitis that is linked to blood products and causes liver failure in up to 90%of afflicted animals.
A team of US scientists has discovered now that the disease is caused by a virus that shares just 35%of its amino acid sequences with its closest-known relative.
The team named it Theiler's disease-associated virus (TDAV), and published the discovery in the Proceedings of the National Academy of Sciences1.
Led by Amy Kistler at the Novartis Institutes for Biomedical Research in Emeryville California, the team responded to an outbreak of Theiler's disease at a farm in
which eight horses had developed suddenly hepatitis after being injected with an antitoxin to prevent them from developing botulism.
The researchers used next-generation sequencing to analyse RNA samples from the antitoxin and from two of the horses,
and assembled the complete genome of the new virus. The virus was found in every one of the eight horses,
as well as in the animal (from a different farm) that was the source of the contaminated antitoxin.#"
#"In the span of a few months, we were able to sequence and validate a virus that had gone undetected for almost a century,
the team inoculated four healthy horses with the contaminated antitoxin. Within ten weeks all of them carried TDAV in their bloodstream,
and one later showed rising levels of liver enzymes that suggested liver disease. Although the researchers did not purify the virus before injecting it into the horses, Pablo Murcia, a virologist from the University of Glasgow,
It is also possible that there is another unknown virus behind Theiler's disease. After all, human hepatitis can be caused by at least five viruses. TDAV belongs to the family Flaviviridae,
which includes the viruses behind yellow fever, dengue fever and hepatitis C. It is associated most closely with a genus of newly discovered viruses called Pegivirus,
and is the first of these to be linked convincingly to disease.""The challenges in culturing pegiviruses mean that we re only now getting an understanding of how widely distributed and significant they are,
says James wood, who studies animal infections at the University of Cambridge, UK. He hints that some studies on new pegiviruses may be published in the future u
#Obama to announce $2 billion plan to get US cars off gasoline An article by Scientific American.
This afternoon, President Barack Obama will ask Congress to direct our cars, trucks and buses to a realm that doesn t include gas stations.
and transmit thought commands collected from a brain implant. The researchers say that the wireless BCI is able to stream thought commands via its radio at a rate of 48 megabits per second, about the speed of a home Internet connection.
Braingate was among the first to place implants in the brains of paralyzed people and show that electrical signals emitted by neurons inside the cortex could be recorded,
#MIT's multifunctional fiber implant could revolutionize neural prosthetics Today cutting edge neural implants can passively read brain activity,
these fiber based neural implants are much more flexible than the current industry standard, multielectrode arrays and hooked eedlestyle stimulators.
so harder implants that don bend with their surrounding biological environment can easily shift and move to a different area than they were implanted,
The most exciting thing about these new fibers is undoubtedly the ability to bundle together different functionalities in the same implant,
to have an implant with electrodes paired with drug delivery pumps that could sense an oncoming epileptic seizure
what theye created to build whatever kind of neural implants they can dream up. And people say we aren living in the future
simulate lesion dynamics or implement network analysis functions from a library of graph theoretic measures. Within the immersive mixed/virtual reality space of Brainx3 users can explore and analysis dynamical activity patterns of brain networks
or for discovering of signaling pathways associated to brain function and/or dysfunction or as a tool for virtual neurosurgery.
Knowledge of brain activity in these various states is clinically relevant for assessing levels of consciousness in patients with severe brain injury y
which could revolutionize drug discovery and personalized medicine. In a laboratory first, Duke researchers have grown human skeletal muscle that contracts
and study diseases in functioning human muscle outside of the human body. The study was led by Nenad Bursac, associate professor of biomedical engineering at Duke university
and those that make taking muscle biopsies difficult. Bursac and Madden started with a small sample of human cells that had progressed already beyond stem cells
To see if the muscle could be used as a proxy for medical tests, Bursac and Madden studied its response to a variety of drugs,
showing the lab-grown muscle was giving a truly human response. ne of our goals is to use this method to provide personalized medicine to patients,
said Bursac. e can take a biopsy from each patient, grow many new muscles to use as test samples
Bursac group is also trying to grow contracting human muscles using induced pluripotent stem cells instead of biopsied cells. here are a some diseases, like Duchenne Muscular dystrophy for example,
that make taking muscle biopsies difficult, said Bursac. f we could grow working, testable muscles from induced pluripotent stem cells,
and William Krauss, professor of biomedical engineering, medicine and nursing at Duke university. The research was supported by NIH Grants R01ar055226 and R01ar065873 from the National Institute of Arthritis and Musculoskeletal and Skin disease and UH2TR000505 from the NIH Common Fund for the Microphysiological Systems Initiative.
Bioengineered human myobundles mimic clinical responses of skeletal muscle to drugs Existing in vitro models of human skeletal muscle cannot recapitulate the organization and function of native muscle
myobundles undergo dose-dependent hypertrophy or toxic myopathy similar to clinical outcomes. Human myobundles provide an enabling platform for predictive drug
and toxicology screening and development of novel therapeutics for muscle-related disorders. ioengineered human myobundles mimic clinical responses of skeletal muscle to drugsby Lauran Madden, Mark Juhas, William
#Researchers Identify Important Control Mechanisms for Walking Even after complete spinal paralysis, the human spinal cord is able to trigger activity in the leg muscles using electrical pulses from an implanted stimulator.
Now, as part of a joint international project, a team of young researchers at the Center for Medical Physics and Biomedical engineering at Meduni Vienna has succeeded in identifying the mechanisms the spinal cord uses to control this muscle activity.
even if the neural pathways from the brain are interrupted physically as the result of a spinal cord injury.
This is the first time throughout the world that the spinal-cord activation patterns for walking have been decoded Paraplegics still have neural connections (so-called locomotion centers) below the site of the injury
explains study author Simon Danner, from the Center for Medical Physics and Biomedical engineering of Meduni Vienna.
New possibilities for rehabilitation following spinal paralysis These new findings relating to the basic patterns for triggering
and the resulting paralysis by stimulating them electrically. This opens the way to new therapeutic options for helping paraplegics to at least partially regain lost rhythmic movements.
Exactly how the neural networks need to be stimulated depends upon the patient individual injury profile and is the subject of further studies.
To help with this, the scientists at Meduni Vienna have developed a unique, noninvasive method for stimulating the spinal cord,
which involves attaching electrodes to the surface of the skin. his method allows easy access to the neural connections in the spinal cord below a spinal injury
#Genetic Brain disorders Converge at the Synapse Several genetic disorders cause intellectual disability and autism. Historically, these genetic brain diseases were viewed as untreatable.
However, in recent years neuroscientists have shown in animal models that it is possible to reverse the debilitating effects of these gene mutations.
a treatment developed for one genetic cause of autism and intellectual disability might be useful for many others.
In a paper published today in the online edition of Nature Neuroscience, a research team led by Mark Bear,
the Picower Professor of Neuroscience in MIT Picower Institute for Learning and Memory, showed that two very different genetic causes of autism
and intellectual disability disrupt protein synthesis at synapses, and that a treatment developed for one disease produced a cognitive benefit in the other.
The research was performed by postdoc and lead author Di Tian, graduate student Laura Stoppel, and research scientist Arnold Heynen, in collaboration with scientists at Cold Spring Harbor Laboratory and Roche pharmaceuticals.
Researching the role of fragile X syndrome One heritable cause of intellectual disability and autism is fragile X syndrome,
which arises when a single gene on the X chromosome, called FMR1, is turned off during brain development.
that too much protein synthesis downstream of mglur5 activation gives rise to many of the psychiatric and neurological symptoms of fragile X. Bear lab tested this idea in mice,
Different genes, same consequences Another cause of autism and intellectual disability is the loss of a series of genes on human chromosome 16,
Some of the 27 affected genes play a role in protein synthesis regulation, leading Bear and colleagues to wonder if 16p11.2 microdeletion syndrome and fragile X syndrome affect synapses in the same way.
similar to fragile X. Restoring brain function after disease onset These findings encouraged the MIT researchers to attempt to improve memory function in the 16p11.2 mice with the same approach that has worked in fragile X mice.
The implication, according to Bear, is that ome cognitive aspects of this disease, previously believed to be an intractable consequence of altered early brain development,
Current research indicates that well over 100 distinct gene mutations can manifest as intellectual disability and autism.
as they indicate not only that drug therapies might be effective to improve cognition and behavior in affected individuals,
Studies at other institutions have identified mutations in the gene for Syngap associated with autism and intellectual disability.
All three of the disability-associated mutations showed similar effects: Compared to normal neurons, there was less Syngap in synapses
Biomedical Research, the UCSF Diabetes Center Obesity Pilot program, and the National institutes of health b
#New ALS Gene and Signaling Pathways Identified Using advanced DNA sequencing methods, researchers have identified a new gene that is associated with sporadic amyotrophic lateral sclerosis (ALS),
or Lou Gehrig disease. ALS is a devastating neurodegenerative disorder that results in the loss of all voluntary movement
and is fatal in the majority of cases. The next-generation genetic sequencing of the exomes (protein-coding portions) of 2, 874 ALS patients and 6,
inflammation (a reaction to injury or infection) and autophagy (a cellular process involved in the removal of damaged cellular components.
The study, conducted by an international ALS consortium that includes scientists and clinicians from Columbia University Medical center (CUMC), Biogen idec,
especially since the inflammatory and autophagy pathways have been implicated previously in the disease, said Lucie Bruijn, Phd,
Chief Scientist for The ALS Association. he fact that TBK1 accounts for one percent of ALS adds significantly to our growing understanding of the genetic underpinnings of the disease.
said study co-leader David B. Goldstein, Phd, professor of genetics and development and director of the new Institute for Genomic Medicine at CUMC.
LS is an incredibly diverse disease, caused by dozens of different genetic mutations, which wee only beginning to discover.
the better we can deciphernd influencehe pathways that lead to disease. The other co-leaders of the study are Richard M. Myers, Phd, president and scientific director of Hudsonalpha,
and Tim Harris, Phd, DSC, Senior vice president, Technology and Translational Sciences, Biogen idec. hese findings demonstrate the power of exome sequencing in the search for rare variants that predispose individuals to disease and in identifying potential
focused collaborations with the best academic scientists to advance our understanding of the molecular pathology of disease.
especially in the context of precision medicine and whole-genome sequencing.""Industry and academia often do things together,
The combination of those groups with a large number of the clinical collaborators who have been seeing patients with this disease for many years and providing clinical information
TBK1 mutations appeared in about 1 percent of the ALS patients large proportion in the context of a complex disease with multiple genetic components, according to Dr. Goldstein.
may actually be a major player in the disease. emarkably, the TBK1 protein and optineurin, which is encoded by the OPTN gene,
and mouse models with mutations in TBK1 or OPTN to study ALS disease mechanisms and to screen for drug candidates.
Several compounds that affect TBK1 signaling have already been developed for use in cancer, where the gene is thought to play a role in tumor-cell survival. his is a great example of the potential of precision medicine,
said Tom Maniatis, Phd, the Isidore S. Edelman Professor, chair of biochemistry and molecular biophysics,
and director of Columbia university-wide precision medicine initiative. t now seems clear that future ALS treatments will not be equally effective for all patients because of the disease genetic diversity.
as candidate therapies become available, we hope to be able to use the genetic data from each ALS patient to direct that person to the most appropriate clinical trials and,
senior researcher at the Department of Medical Biochemistry and Biophysics. ut in recent years wee developed much more sensitive methods of analysis that allow us to see which genes are active in individual cells.
protect against infection and supply nerve cells with nutrients. With the help of this detailed map, the scientists were able to identify hitherto unknown cell types,
The new knowledge the project has generated can shed more light on diseases that affect the myelin
such as multiple sclerosis (MS). e could also confirm previous findings, such as that the pyramidal cells of the cerebral cortex are organised functionally in layers,
This gives science a new tool for studying these cell types in disease models and helps us to understand better how brain cell respond to disease and injury.
There are estimated to be 100 million cells in a mouse brain and 65 billion in a human brain.
The study was carried out by Sten Linnarsson and Jens Hjerling-Leffler research groups at the department of medical biochemistry and biophysics, in particular by Amit Zeisel and Ana Muños Manchado.
It also involved researchers from Karolinska Institutet Department of Oncology-Pathology, and Uppsala University. The study was financed with grants from several bodies,
including the European Research Council, the Swedish Research Council, the Swedish Cancer Society, the EU Seventh Framework Programme, the Swedish Society of Medicine, the Swedish Brain Fund, Karolinska Institutet strategic programme for neuroscience (Stratneuro), the Human Frontier Science Program
, the Åke Wiberg Foundation and the Clas Groschinsky Memorial Fund s
#Molecular Inhibitor Breaks Cycle That Leads to Alzheimer's A molecular chaperone has been found to inhibit a key stage in the development of Alzheimer disease and break the toxic chain reaction that leads to the death of brain cells, a new study shows.
The research provides an effective basis for searching for candidate molecules that could be used to treat the condition.
A molecule that can block the progress of Alzheimer disease at a crucial stage in its development has been identified by researchers in a new study,
breaking the cycle of events that scientists believe leads to the disease. Specifically, the molecule, called Brichos, sticks to threads made up of malfunctioning proteins, called amyloid fibrils,
which are the hallmark of the disease. By doing so, it stops these threads from coming into contact with other proteins,
thereby helping to avoid the formation of highly toxic clusters that enable the condition to proliferate in the brain.
This step where fibrils made up of malfunctioning proteins assist in the formation of toxic clusters is considered to be one of the most critical stages in the development of Alzheimer in sufferers.
scientists have moved closer to identifying a substance that could eventually be used to treat the disease.
great deal of work in this field has gone into understanding which microscopic processes are important in the development of Alzheimer disease;
so we can prevent the toxic effects of protein aggregation that are associated with this terrible condition.
Alzheimer disease is one of a number of conditions caused by naturally occurring protein molecules folding into the wrong shape
however a second critical step in the disease development. After amyloid fibrils first form from misfolded proteins, they help other proteins
These oligomers are highly toxic to nerve cells and are thought now to be responsible for the devastating effects of Alzheimer disease.
This second stage, known as secondary nucleation, sets off a chain reaction which creates many more toxic oligomers
and ultimately amyloid fibrils, generating the toxic effects that eventually manifest themselves as Alzheimer. Without the secondary nucleation process, single molecules would have to misfold and form toxic clusters unaided,
which is a much slower and far less devastating process. By studying the molecular processes by
which each of these steps takes effect, the research team assembled a wealth of data that enabled them to model not only
what happens during the progression of Alzheimer disease, but also what might happen if one stage in the process was switched somehow off. e had reached a stage where we knew what the data should look like
and nucleating into toxic oligomers. The research team then carried out further tests in which living mouse brain tissue was exposed to amyloid-beta, the specific protein that forms the amyloid fibrils in Alzheimer disease.
Allowing the amyloid-beta to misfold and form amyloids increased toxicity in the tissue significantly.
When this happened in the presence of the molecular chaperone however, amyloid fibrils still formed but the toxicity did not develop in the brain tissue,
confirming that the molecule had suppressed the chain reaction from secondary nucleation that feeds the catastrophic production of oligomers leading to Alzheimer disease.
By modelling what might happen if secondary nucleation is switched off and then finding a molecule that performs that function,
if these can be used as the starting point for developing a future therapy. e
#Tau Associated MAPT Gene Increases Risk for Alzheimer's disease A international team of scientists, led by researchers at the University of California,
San diego School of medicine, has identified the microtubule associated-protein protein tau (MAPT) gene as increasing the risk for developing Alzheimer disease (AD).
The MAPT gene encodes the tau protein, which is involved with a number of neurodegenerative disorders, including Parkinson disease (PD) and AD.
These findings provide novel insight into Alzheimer neurodegeneration, possibly opening the door for improved clinical diagnosis and treatment.
The findings are published in the February 18 online issue of Molecular Psychiatry. Alzheimer disease, which afflicts an estimated 5 million Americans,
is characterized typically by progressive decline in cognitive skills, such as memory and language and behavioral changes.
While some recent AD genome-wide association studies (GWAS), which search the entire human genome for small variations,
have suggested that MAPT is associated with increased risk for AD, other studies have found no association.
In comparison, a number of studies have found a strong association between MAPT and other neurodegenerative disorders,
such as PD. hough a tremendous amount of work has been conducted showing the involvement of the tau protein in Alzheimer disease,
the role of the tau-associated MAPT gene is said still unclear Rahul S. Desikan, MD,
Phd, research fellow and radiology resident at the UC San diego School of medicine and the study first author.
Microscopic image depicting plaques and tangles characteristic of Alzheimer disease. Image credit: Tom Deerinck, NCMIR, UC San diego. In the new Molecular Psychiatry paper, conducted with collaborators across the country and world,
Desikan and colleagues narrowed their search. Rather than looking at all possible loci (specific gene locations),
and more likely to experience increased brain atrophy than non-carriers. his study demonstrates that tau deposits in the brains of Alzheimer disease subjects are not just a consequence of the disease,
and progression of the disease, said Gerard Schellenberg, Phd, professor of pathology and laboratory medicine at the University of Pennsylvania,
principal investigator of the Alzheimer Disease Genetics Consortium and a study co-author. n important aspect was the collaborative nature of this work.
Thanks to our collaborators from the Consortium, the International Parkinson Disease Genetics Consortium, the Genetic and Environmental Risk in Alzheimer Disease, the Cohorts for Heart and Aging research in Genomic Epidemiology, decode Genetics and the Demgene cohort,
professor of biological psychiatry at the University of Oslo and a senior co-author. Sudha Seshadri, MD, professor of neurology at the Boston University School of medicine, the principal investigator of the Neurology Working group within the Cohorts for Heart and Aging research in Genomic Epidemiology consortium and a study co-author added:
lthough it has been known since Alois Alzheimer time that both plaques (with amyloid) and tangles (of tau) are key features of Alzheimer pathology,
attempts to prevent or slow down clinical disease progression have focused on the amyloid pathway. Until this year no one had shown convincingly that the MAPT (tau) gene altered the risk of AD and this,
combined with the greater ease of imaging amyloid in life, lead some researchers to postulate that tau changes were secondary to amyloid changes.
These findings underscore the importance of using a multi-modal and multi-disciplinary approach to evaluating Alzheimer neurodegeneration. hese findings suggest that the combination of genetic,
and quantifying the biochemical effects of therapeutic interventions, said Anders M. Dale, Phd, professor of neurosciences and radiology and director of the Center for Translational Imaging and Precision Medicine at UC San diego and the study senior author e
#What Autism Can Teach Us About Brain Cancer Both disorders involve faults in the same protein.
Applying lessons learned from autism to brain cancer, researchers at The Johns hopkins university have discovered why elevated levels of the protein NHE9 add to the lethality of the most common and aggressive form of brain cancer, glioblastoma.
Their discovery suggests that drugs designed to target NHE9 could help to successfully fight the deadly disease.
A summary of their work in human tumor cells and mice will be published on Feb 9 in the journal Nature Communications. y laboratory research on cargo transport inside the cells of patients with autism has led to a new strategy
for treating a deadly brain cancer says Rajini Rao, Ph d, . a professor of physiology at the Johns hopkins university School of medicine. his is a great example of the unexpected good that can come from going wherever the science takes us.
All animal and human cells contain many argo packagessurrounded by membranes. These so-called endosomes carry newly minted proteins to specific destinations throughout the cell
and haul away old proteins for destruction. Key to their hipping speedis the level of acidity inside the endosomes.
Rao research group previously showed that autism-associated defects in the protein NHE9 are harmful
Teaming up with Alfredo Quinones-Hinojosa, M d.,a professor of neurosurgery at Johns Hopkins, the researchers examined NHE9 in tumor cells from several patients.
Cells with low levels of NHE9 grew the slowest, the team found, and those with the highest levels grew fastest.
And this was confirmed when the tumor cells, which were manipulated to have high or low NHE9, were transplanted into the brains of mice.
Based on their autism research, the team suspected that the boost NHE9 gave to glioblastomas was explained by abnormal endosome acidity.
Further studies revealed that, in contrast to autism, NHE9 is overactive in brain cancer, causing endosomes to leak too many protons
and become too alkaline. This slows down the hipping rateof cancer-promoting cargo and leaves them on the cell surface for too long.
Research from other laboratories suggested that one such cargo protein is EGFR, which maintains cancer-promoting signals at the cell surface
and helps tumors become more robust so they grow and move faster. It is also found at elevated levels in more than one-half of patients with glioblastomas.
Drugs targeting EGFR in these patients are sometimes effective. As they suspected, the team found that alkaline endosomes slow down the removal of EGFR from cell surfaces.
Lab-grown tumor cells were killed more readily when treated with both a drug countering NHE proteins
so that hopefully we can make this disease less aggressive and less devastating. About this genetics research Other authors of the report include Kalyan Kondapalli, Jose Llongueras, Vivian Capilla-Gonzalez, Hari Prasad, Anniesha Hack, Christopher Smith and Hugo Guerrero
This work was supported by grants from the National Institute of Neurological disorders and Stroke (NS070024), the National Institute of Diabetes and Digestive and Kidney diseases (DK054214
the National Institute of General Medical sciences (GM62142), the American Heart Association (11post7380034), the Johns Hopkins Post-Baccalaureate Research Education Program, the International Fulbright Science and Technology Award,
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