Study pinpoints cell type and brain region affected by gene mutations in autism
|
A team led by UC San Francisco scientists has identified the disruption of a single type of cell - in a particular brain region and at a particular time in brain development - as a significant factor in the emergence of autism.
The finding, reported in the November 21, 2013 issue of Cell, was made with techniques developed only within the last few years, and marks a turning point in autism spectrum disorders (ASDs) research.
Large-scale gene sequencing projects are revealing hundreds of autism-associated genes, and scientists have begun to leverage new methods to decipher how mutations in these disparate genes might converge to exert their effects in the developing brain.
The new research focused on just nine genes, those most strongly associated with autism in recent sequencing studies, and investigated their effects using precise maps of gene expression during human brain development.
Researchers from Braunschweig describe new possibilities of the CRISPR-Cas-system
|
Viruses cannot only cause illnesses in humans, they also infect bacteria. Those protect themselves with a kind of ‘immune system’ which - simply put - consists of specific sequences in the genetic material of the bacteria and a suitable enzyme. It detects foreign DNA, which may originate from a virus, cuts it up and thus makes the invaders harmless. Scientists from the Helmholtz Centre for Infection Research (HZI) in Braunschweig have now shown that the dual-RNA guided enzyme Cas9 which is involved in the process has developed independently in various strains of bacteria. This enhances the potential of exploiting the bacterial immune system for genome engineering.
Even though it has only been discovered in recent years the immune system with the cryptic name ‘CRISPR-Cas’ has been attracting attention of geneticists and biotechnologists as it is a promising tool for genetic engineering. CRISPR is short for Clustered Regularly Interspaced Palindromic Repeats, whereas Cas simply stands for the CRISPR-associated protein. Throughout evolution, this molecule has developed independently in numerous strains of bacteria. This is now shown by Prof Emmanuelle Charpentier and her colleagues at the Helmholtz Centre for Infection Research (HZI) who published their finding in the international open access journal Nucleic Acids Research.
The CRISPR-Cas-system is not only valuable for bacteria but also for working in the laboratory. It detects a specific sequence of letters in the genetic code and cuts the DNA at this point. Thus, scientists can either remove or add genes at the interface. By this, for instance, plants can be cultivated which are resistant against vermins or fungi. Existing technologies doing the same thing are often expensive, time consuming or less accurate. In contrast to them the new method is faster, more precise and cheaper, as fewer components are needed and it can target longer gene sequences.
Optimal site for cell transplantation to treat spinal cord injury investigated
|
It is known that transplanting neural stem/progenitor cells (NS/PCs) into the spinal cord promotes functional recovery after spinal cord injury (SCI). However, which transplantation sites provide optimal benefit? This question was investigated by a Japanese research team and their findings will be published in a future issue of Cell Transplantation, but are currently freely available on-line as an unedited early e-pub at http://url.health.am/1326/.
“It is critical to determine the optimal transplantation site for NS/PCs aimed at treating SCI,” said Dr. Masaya Nakamura of the Department of Orthopedic Surgery at the Keio University School of Medicine.
Previous work by the same research team revealed that NS/PCs injected into non-injury sites such as by intravenous or intrathecal administration did not engraft to the injury site in sufficient numbers, but instead were often “trapped” in the lungs and kidneys. They concluded that intralesional application might be the most effective and reliable method for transplanting NS/PCs. This study, also using laboratory mice with SCI, sought to determine how effective intralesional injection might be. NS/PCs were obtained from mice transgenic for Venus and luciferase fusion protein, which allowed the cells to be tracked by bioluminescence imaging (BLI) after transplantation.
“Wild-type mice were given a contusive spinal cord injury at the T10 level,” explained Dr. Nakamura. “Low and high doses of NS/PCs derived from fetal transgenic mice were injected into four groups of mice at either the lesion epicenter (E) or at rostral and caudal sites (RC) with neural stem/progenitor cells derived from fetal transgenic mice while a fifth group of controls was injected with phosphate buffered saline at E.”
Fungus-fighting drug may make mild flu meaner
|
Mice given a drug commonly used in patients to fight systemic fungal infections more often succumb to what would otherwise be a mild case of the flu. The evidence reported in the Cell Press journal Cell Reports on November 21st shows that the drug called Amphotericin B, which has an estimated $330 million in sales around the world each year, can render a protein important for antiviral defense ineffective in both cells and mice.
The findings suggest that patients receiving the antifungal therapy may be functionally immunocompromised and more vulnerable to influenza and other viral infections, the researchers said.
“Many critically ill cancer and bone marrow transplant patients are treated with Amphotericin B-based therapies each year,” said Abraham Brass of the University of Massachusetts Medical School (UMMS). “Given these results in cells and mice, it may be worthwhile to consider that patients receiving, or who may receive, Amphotericin B-based therapies be appropriately vaccinated against influenza virus. Also, clinical consideration may be given to close monitoring of patients receiving Amphotericin B-based therapies for any symptoms suggestive of flu so that they might be considered for the early administration of an antiflu therapy.”
The researchers showed that Amphotericin-B prevents the antiviral protein in cells known as IFITM3 from fending off influenza A virus.
Stanford scientists think mysterious virus could be a signal of a weak immune system
|
More than 260,000 Americans are alive today thanks to transplant operations that have replaced their failing kidneys, hearts, lungs or livers with healthy organs donated by volunteers or accident victims.
But treatment doesn’t end with surgery. Transplant recipients follow strict drug regimens designed to suppress their immune systems just enough to prevent rejection of the donated organ, but not so much as to leave them prone to infection.
Until now, maintaining this delicate balance has been something of a medical guessing game. But in a study to be published Nov. 21 in Cell, Stanford University scientists report the discovery of what may be a barometer of immune system strength: a little-known virus that proliferates as the medications suppress the immune system.
The work was led by senior author Stephen Quake, PhD, the Lee Otterson Professor in the School of Engineering and professor of bioengineering and of applied physics.
Intestinal bacteria influence food transit through the gut
|
Food transit through the small intestine affects the body’s absorption of nutrients and, consequently, our health. The discovery that food transit time is regulated by a hormone indicates new ways to increase the intestinal absorption of nutrients, and thus potentially treat malnutrition.
One of the tasks of the gut microbiota is to break down essential nutrients from our diet to provide a usable energy source in the colon.
Researchers at the Sahlgrenska Academy, University of Gothenburg, Sweden, have now shown that lack of energy in the colon leads to increased release of a hormone primarily associated with appetite control and insulin secretion, GLP-1.
Importantly, they also showed that the released GLP-1 regulates how quickly food passes through the small intestine. These findings may open up new possibilities to treat malnutrition and malnutrition-related diseases.
Stanford research upends understanding of how humans perceive sound
|
A key piece of the scientific model used for the past 30 years to help explain how humans perceive sound is wrong, according to a new study by researchers at the Stanford University School of Medicine.
The long-held theory helped to explain a part of the hearing process called “adaptation,” or how humans can hear everything from the drop of a pin to a jet engine blast with high acuity, without pain or damage to the ear. Its overturning could have significant impact on future research for treating hearing loss, said Anthony Ricci, PhD, the Edward C. and Amy H. Sewall Professor of Otolaryngology and senior author of the study.
“I would argue that adaptation is probably the most important step in the hearing process, and this study shows we have no idea how it works,” Ricci said. “Hearing damage caused by noise and by aging can target this particular molecular process. We need to know how it works if we are going to be able to fix it.”
The study will be published Nov. 20 in Neuron. The lead author is postdoctoral scholar Anthony Peng, PhD.
Long-term unemployment may accelerate aging in men
|
|
Men who are unemployed for more than two years show signs of faster ageing in their DNA, a new study has found.
Researchers at Imperial College London and the University of Oulu, Finland studied DNA samples from 5,620 men and women born in Finland in 1966.
They measured structures called telomeres, which lie at the ends of chromosomes and protect the genetic code from being degraded. Telomeres become shorter over a person’s lifetime, and their length is considered a marker for biological ageing. Short telomeres are linked to higher risk of age-related diseases such as type 2 diabetes and heart disease.
The researchers looked at telomere length in blood cells from samples collected in 1997, when the participants were all 31 years old. The study, funded by the Wellcome Trust, found that men who had been unemployed for more than two of the preceding three years were more than twice as likely to have short telomeres compared to men who were continuously employed.
Reducing the salt in bread without losing saltiness, thanks to a texture trick
|
|
Want to make bread taste pleasantly salty without adding more salt? Change the bread’s texture so it is less dense, say scientists. They report in ACS’ Journal of Agricultural and Food Chemistry that simply making the pores, or holes, larger can make people perceive bread as having saltier taste. The process could become a new strategy for reducing salt intake, which is a risk factor for high blood pressure and heart disease.
Peter Koehler and colleagues explain that every day, people in industrialized countries consume, on average, twice as much salt as the World Health Organization recommends. Much of that salt - 35 percent in the United Kingdom and about 25 percent in Germany - comes from bread, which for millennia has ranked as one of the world’s most ubiquitous foods. Cutting dietary salt would reduce people’s risk for developing high blood pressure, which has been diagnosed in 40 percent of adults aged 25 and older worldwide, and heart disease, which was the cause of 30 percent of all deaths in 2008. But the big question is how to do it in a palatable way. Researchers have tried different methods, such as using salt substitutes, but only to limited effect. Studies on cheese and gels has shown that changing texture can make a product taste salty even if salt content is reduced, so Koehler’s team decided to see if this would work with bread.
To alter the texture of bread for the study, they baked bread using different proofing times. Proofing is when a baker lets the dough rise. Longer proofing times lead to softer breads with larger pores. The subjects in the study rated the fluffier bread with the longest proofing time as noticeably more salty, even though each bite actually contained less salt. “Appropriate modification of crumb texture thus leads to enhanced saltiness, suggesting a new strategy for salt reduction in bread,” say the researchers.
U.S. FDA panel backs BioMarin’s Morquio A Syndrome drug
|
|
An experimental drug to treat Morquio A Syndrome, a rare genetic disorder that causes skeletal malformation and a variety of related lung, eye, ear and heart problems, should be approved, an advisory panel to the U.S. Food and Drug Administration concluded on Tuesday.
The 21-member panel voted overwhelmingly in favor of approval, saying the benefits of the drug, Vimizim, which is made by BioMarin Pharmaceutical Inc, outweigh its risks. The FDA is not obliged to follow the recommendations of its advisory panels but typically does so.
Morquio A Syndrome is characterized by a deficiency of an enzyme known as N-acetylgalactosamine-6-sulfatase, which causes excessive storage in the body of long chains of sugars known as glycosaminoglycans.
This build-up can lead to short stature and joint abnormalities that limit mobility and endurance. The disease can also cause hearing loss, eye problems and heart disease. Symptoms often appear before the age of five.
About 70 taken ill after California chemical plant leak
|
|
About 70 people were taken ill after a sulphuric acid leak at a chemical company in California late on Monday, Los Angeles County Fire Department officials said.
People in the Carson area complained of throat and nose irritation and vomiting after being exposed to an “apparent sulphuric acid release in the air from a neighboring business,” Los Angeles County Fire Department spokesman Robert Diaz said.
Thirteen people were treated at local hospitals and later released, Fire Department official Phil Ulloa said. Others were treated at the scene.
Ulloa said the leak was caused by a scrubber machine malfunctioning at the Solvay chemical plant.
EU clears Roche drugs after probe into lax safety reports
|
|
Europe’s main drugs regulator has found no new safety issues linked to Roche medicines after an investigation into the Swiss drugmaker, which was rapped last year for lax drug-safety reporting.
The European Medicines Agency (EMA) launched a probe into Roche in June 2012 after a routine inspection found it had failed to properly assess tens of thousands of cases of possible adverse drug reactions.
The investigation included 19 centrally approved drugs, several of which were for cancer. Roche is the world’s largest maker of cancer medicines, as well as producing drugs for viral infections and inflammatory diseases.
Without Sufficient Support, Community Health Centers Will Drop 1 Million Patients
|
|
A new report by the Geiger Gibson/RCHN Community Health Foundation Research Collaborative at the George Washington University School of Public Health and Health Services (SPHHS) examines the impact of federal and state policy decisions on community health centers (CHCs) and their ability to continue providing primary care to the nation’s poorest residents. The report, “How Medicaid Expansions and Future Community Health Center Funding Will Shape Capacity to Meet the Nation’s Primary Care Needs,” estimates that under a worst-case scenario, the nation’s health centers would be forced to contract, leaving an estimated 1 million low-income people without access to health care services by the year 2020.
“Without continued support, community health centers will not be able to meet the rising demand for primary care in underserved parts of the United States,” said the lead author of the report, Leighton Ku, PhD, MPH, a professor of health policy and director of the Center for Health Policy Research at SPHHS. “Unless policymakers act now to support these centers, many low-income Americans will be left without the high-quality care that can prevent many expensive health conditions from developing in the first place.”
The authors analyzed two key policy issues - the level of federal grant funding and the expansion of Medicaid eligibility under the Affordable Care Act (ACA) - and examined the impact of various levels of support on health center capacity. The researchers found that with sufficient federal funding and Medicaid expansion in all states, health centers could nearly double their capacity by 2020. In contrast, health centers would have to curtail services and turn away patients if grant funding is limited, and Medicaid expansion is not broadened.
Innovative Experiment Aims to Boost Lung Transplants
|
|
The pair of lungs sits inside a clear dome, gently inflating as doctors measure how well they’ll breathe if implanted into a patient who desperately needs a new set.
It’s a little-known twist of nature - your lungs can live on for a while after you die. The air left inside keeps them from deteriorating right away as other organs do.
An innovative experiment now aims to use that hour or more window of time to boost lung transplants by allowing donations from people who suddenly collapse and die at home instead of in a hospital.
“There aren’t enough lungs. We’re burying them,” said Dr. Thomas Egan of the University of North Carolina, Chapel Hill, who is leading the project. “It turns out your lungs don’t die when you do.”
Method to estimate LDL-C may provide more accurate risk classification
|
|
Seth S. Martin, M.D., of the Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, and colleagues developed a method for estimating low-density lipoprotein cholesterol (LDL-C) levels that is more accurate than the standard measure.
Low-density lipoprotein cholesterol is the primary target for treatment in national and international clinical practice guidelines. Conventionally, LDL-C is estimated by the Friedewald equation, which estimates LDL-C as (total cholesterol) - (high-density lipoprotein cholesterol [HDL-C]) - (triglycerides/5) in mg/dL. The final term assumes a fixed ratio of triglyceride levels to very low-density lipoprotein cholesterol (TG:VLDL-C) of 5:1. “Applying a factor of 5 to every individual patient is problematic given variance in the TG:VLDL-C ratio across the range of triglyceride and non-HDL-C levels,” according to background information in the study.
The researchers used a sample of lipid profiles obtained from 2009 through 2011 from 1,350,908 children, adolescents, and adults in the United States.
