In the United States, a research team led by the La Jolla Institute for Allergy & Immunology has identified the specific gene that triggers the body to produce disease-fighting antibodies a seminal finding that clarifies the exact molecular steps taken by the body to mount an antibody defence against viruses and other pathogens. The finding has major implications for the development of new and more effective vaccines.

The La Jolla Institutes Dr. Shane Crotty was the lead researcher on the team, which also included scientists from Yale University led by Dr. Joseph Craft. The finding is important because it identified the molecular switch that tells the body to create antibodies. Antibody production is a multi-step process that involves interactions between many cellular players; key among them the CD4 helper T cells, which are disease-fighting white blood cells. There were different types of these CD4 helper T cells and, for many years the scientists had thought that one of the four varieties of CD4 helper type 2 cells (known as TH-2 cells) triggered the antibody process. But about a decade ago, they realized that there was a fifth variety of CD4 helper T cell that initiated antibody production. They named the cell TFH.

Studying the workings of the TFH pathway, Dr. Crottys team conclusively proved that the BCL6 gene was a master regulator in the process. If this gene is turned on, more TFH type cells are produced, and these cells signal the B cells to produce antibodies. The more TFH cells produced, the greater the antibody response.
Source: www.biocetera.com

Researchers in the Heart Institute at Cincinnati Childrens Hospital Medical Centre, the United States, have discovered a novel gene responsible for heart muscle disease and chronic heart failure in some children and adults with dilated cardiomyopathy (DCM). Their study found that mutations in the ANKRD1 a gene that encodes a protein that plays a role in the structure and functional ability of the heart would cause DCM, which is the most common cause of chronic heart failure in young people.

Our study indicates that variants in ANKRD1 result in dysfunction of the contraction apparatus and signalling machinery of the heart, the method by which cells communicate to influence heart function, says Dr. Jeffrey Towbin, Co-Director of the Heart Institute and Director of Cardiology at Cincinnati Childrens. This clarifies the mechanisms by which these inherited mutations cause disease in a subset of DCM patients.

Dr. Towbins team screened 208 patients, mostly children and young adults, with DCM for gene mutations. They found three, disease-associated variants of the ANKRD1 gene. All four patients carrying the variants were male. This prevalence rate is consistent with prevalence data for most of the other known genes associated with DCM.
Source: www.sciencedaily.com

A study at the Pennsylvania State University, the United States, provides new information about the genes that are involved in a mammals early brain development, including those that contribute to neurological disorders. The study is the first to use high-throughput sequencing to uncover active genes in developing brains. The results of the research, which was led by Distinguished Professor of Biology Dr. Hong Ma and Associate Professor of Biology Dr. Gong Chen, one day could lead to the development of drugs or gene therapies that treat neurological disorders such as autism and mental retardation.

The scientists sequenced millions of messenger-RNA molecules, which carry genetic information from DNA molecules to protein molecules. They obtained the RNA from the brains of mice, and found that over 16,000 genes more than half of the mouses entire set of known genes are involved in the brains development and functions. They focused on two critical times during the development of brain: embryonic day 18 (E18) and post-natal day 7 (P7): two time points that represent major milestones during brain formation. Brain development in an 18-day-old embryo involves a significant amount of brain cells, or neurons. In contrast, brain development in a 7-day-old infant involves the formation of numerous connections between these neurons. Our goal was to determine which genes are active during these two critical times, said Dr. Ma.

The scientists examined genes that correspond to the RNA molecules from the cortex responsible for most cognitive and sensory abilities. They found that over 3,700 of the 16,000 genes identified have different levels of activity between the E18 and P7 time points. Some of the genes that the researchers found in mice are known to be matched to the human genes that are involved in neurological disorders, such as Alzheimers disease and autism. Our results can help pinpoint the specific time during brain development when the genes related to certain diseases are active, said Dr. Ma. This could help other scientists to develop drugs or gene therapies that can treat the diseases.
Source: www.sciencedaily.com

In the United States, a University of California Irvine (UCI) study has found that a gene called TOMM40 appears twice as often in people with Alzheimers disease than in those without it. The harmful form of TOMM40 significantly increases ones susceptibility when other risk factors such as having a gene called ApoE-4 are present, the study reports. People with ApoE-4 are three to eight times more likely to develop Alzheimers.

The TOMM40 gene influences the ease with which molecules can get in and out of mitochondria, the energy production centre and stress mediator of cells. TOMM40 also processes materials that form amyloid plaque, a hallmark of Alzheimers, said Dr. Steven Potkin, lead author of the study and UCI Professor of Psychiatry & Human Behaviour. With aging, the number and function of mitochondria decrease, accompanied by a parallel increased risk of developing Alzheimers, he said. This study points to the use of therapies based on mitochondria for treating the disease.
Source: www.sciencedaily.com

Scientists at Stanford University, the United States, have identified a gene that may play a role in the development of type 1 diabetes. The study team, led by Dr. C. Garrison Fathman, examined genes from mice that develop a type 1 diabetes-like disease. The investigators found that cells in the pancreatic lymph nodes of mice make two forms of the same gene called deformed epidermal autoregulatory factor 1 (Deaf1). One form is full-length and functional and the other is a shorter, non-functional variant. The full-length Deaf1 controls the production of molecules needed to eliminate immune cells that can destroy insulin-producing cells. The presence of the Deaf1 variant was found to prevent the full-length Deaf1 protein from functioning normally. Further experiments showed that the variant form blocked the genes needed to produce certain molecules involved in immune regulation.

When the researchers measured the levels of these two forms in people with type 1 diabetes and in healthy individuals, levels of the variant form were found to be higher in people with type 1 diabetes compared with those in healthy controls. In addition, the variant form, as in mice, inhibited the full-length form from functioning normally.

The researchers propose that the development of type 1 diabetes may in part be due to increased levels of the Deaf1 variant protein in pancreatic lymph nodes of people with this disease. Higher levels of Deaf1 variant may, in turn, lead to reduced production of molecules that are required to educate the immune system not to attack the bodys own cells, including the insulin-producing cells of the pancreas. These results show that Deaf1 variant form is a risk factor for type 1 diabetes and provide a target for drug development to combat the disease.
Source: www.physorg.com

Researchers at the University of Oklahoma Health Sciences Centre, the United States, have shown the first link between a newly discovered anti-aging gene and hypertension. Led by principal investigator Dr. Zhongjie Sun, the researchers tested the effect of the anti-aging gene called klotho on reducing hypertension. They found that by increasing the expression of the gene in laboratory models, they not only stopped blood pressure from continuing to rise, but also succeeded in lowering it. The most impressive result was the complete reversal of kidney damage, which is associated with prolonged high blood pressure. Scientists have been working with the klotho gene and its link to aging since 1997 when it was discovered by Japanese scientists.

The researchers used one injection of the klotho gene in hypertensive research models and were able to markedly reduce blood pressure by the second week. It continued to decline steadily for the length of the project 12 weeks. The klotho gene was delivered with a safe viral vector that is currently used for gene therapy. Researchers are studying the genes effect for longer periods to test its ability to return blood pressure levels to normal.
Source: www.redorbit.com