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Archive - Jul 29, 2015

High Circulating Levels of Four Specific Proteins Seem to Offer Protection Against Type 1 Diabetes

Patients with type 1 diabetes have significantly lower blood levels of four proteins that help protect their tissue from attack by their immune system, scientists report. Conversely, the patients’ first-degree relatives, who share some of the high-risk genes but do not have the disease, have high levels of these proteins circulating in their blood, said Dr. Jin-Xiong She, Director of the Center for Biotechnology and Genomic Medicine at the Medical College of Georgia (MCG) at Georgia Regents University. Healthy individuals without the risky genes also have higher levels of the four proteins, IL8, IL-1Ra, MCP-1, and MIP-1β, according to the study published online on July 9, 2015 in the Journal of Clinical Endocrinology & Metabolism. The article is titled “Large-Scale Discovery and Validation Studies Demonstrate Significant Reductions in Circulating Levels of IL8, IL-1Ra, MCP-1, and MIP-1 in Type-1 Diabetes Patients.” The findings point toward a sort of protein cocktail that could help at-risk children avoid disease development, as well as new biomarkers in the blood that could aid disease diagnosis, prognosis, and management, said Dr. She, Georgia Research Alliance Eminent Scholar in Genomic Medicine and the study's corresponding author. The scientists looked at a total of 13 cytokines and chemokines, which are cell signaling molecules involved in regulating the immune response. They first looked at blood samples from 697 children with type 1 diabetes and from 681 individuals without antibodies to insulin-producing pancreatic beta cells, a hallmark of this generarally autoimmune disease. The scientists then analyzed the blood of a second and larger set of individuals, which included 1,553 children with type 1 diabetes and 1,493 individuals without any sign of anti-beta-cell antibodies.

Yet Another CRISPR/Cas9 Advance; UCSF & UC-Berkeley Scientists Modify Approach to Edit T-Cells to Disable CXCR4 Receptor for HIV and Also Manage to Knock Out PD-1 Protein That Inhibits T-Cell Attack on Cancers

In a project spearheaded by investigators at the University of California (UC) San Francisco (UCSF), scientists and collaborators have devised a new strategy to precisely modify human T cells using the genome-editing system known as CRISPR/Cas9. Because these immune-system cells play important roles in a wide range of diseases, from diabetes to AIDS to cancer, the achievement provides a versatile new tool for research on T cell function, as well as a path toward CRISPR/Cas9-based therapies for many serious health problems. Using their novel approach, the scientists were able to disable a protein on the T-cell surface called CXCR4, which can be exploited by HIV when the virus infects T cells and causes AIDS. The group also successfully shut down PD-1, a protein that has attracted intense interest in the burgeoning field of cancer immunotherapy, as scientists have shown that using drugs to block PD-1 coaxes T cells to attack tumors. The CRISPR/Cas9 system has captured the imagination of both scientists and the general public, because it makes it possible to easily and inexpensively edit genetic information in virtually any organism. T cells, which circulate in the blood, are an obvious candidate for medical applications of the technology, as these cells not only stand at the center of many disease processes, but could be easily gathered from patients, edited with CRISPR/Cas9, then returned to the body to exert therapeutic effects. But in practice, editing T cell genomes with CRISPR/Cas9 has proved surprisingly difficult, said Alexander Marson, Ph.D., a UCSF Sandler Fellow, and senior and co-corresponding author of the new study. "Genome editing in human T cells has been a notable challenge for the field," Dr. Marson said.

Major European Study Seeks to Reveal the Roles of Mammalian Genes in Disease; Analysis of 320 Mouse Genes Reported; 90% of Mouse Genome Shared with Humans

The role of over 300 mammalian genes (mouse) has been revealed by scientists across Europe in a major initiative to understand the part they play in disease and biology. The results have were published online on July 27, 2015 in Nature Genetics. The article is titled “Deciphering Mammalian Gene Function through Broad-Based Phenotypic Screens across a Consortium of Mouse Clinics.” Because mice share 90 percent of our genes, they play an important role in understanding human genetics. The European Mouse Disease Clinic (EUMODIC) brought together scientists from across Europe to investigate the functions of 320 genes in mice. Over half of these genes had no previously known role, and the remaining genes were poorly understood. In order to study gene function, the EUMODIC consortium produced mouse lines which each had a single gene removed. These mouse lines were then analyzed in mouse clinics, where each line was assessed by a series of tests and investigations, allowing researchers to establish the role of the missing genes. Over 80 percent of the mouse lines assessed had a characteristic that provided a clue to what the missing gene’s role might be. If the mouse fails a hearing test, for example, it suggests the missing gene has a role in hearing. In total, the researchers carried out over 150 different tests on each mouse line. EUMODIC represents the first step towards the creation of a database of all mouse gene functions, a vision now being realized by the International Mouse Phenotyping Consortium (IMPC). The IMPC incorporates 20 centers from across the globe with the aim, over the next ten years, of uncovering the role of all 20,000 genes in the mouse genome.

Glioblastoma Spread Slowed in Mouse Model by Cutting Off Communication Mechanism of Cancer Cells; Gap Junction Targeting May Be Effective Approach to Treatment

The rapid spread of a common and deadly brain tumor has been slowed down significantly in a mouse model by cutting off the way some cancer cells communicate, according to a team of researchers that includes University of Florida (UF) Health faculty. The technique improved survival time by 50 percent when tested in a mouse model, said Loic P. Deleyrolle, Ph.D., a Research Assistant Professor of Neurosurgery in the UF College of Medicine. Researchers focused on disrupting the cell-to-cell communication that allows cancer stem cells to spread. To do that, they targeted a channel that cancer cells use to transfer molecules. By cutting off their communications pathway, it is possible to keep the deadly cells in check, Dr. Deleyrolle said. Eight UF Health researchers took part in the study, which was co-authored by Dr. Deleyrolle and published in an open-access article in the May 19, 2015 issue of Cell Reports. The article is titled “Differential Connexin Function Enhances Self-Renewal in Glioblastoma.” The UF scientists collaborated with researchers at the Cleveland Clinic and the University of California, Berkeley in this research effort. Glioblastoma is the most common brain tumor in adults and there is no effective long-term treatment. Patients usually live for just 12 to 15 months after diagnosis, according to the National Cancer Institute. Glioblastoma tumors, which are highly malignant, typically start in the largest part of the brain and can spread rapidly. The current research focused on connexin 46, a protein that is an essential component of cancer stem cells. Connexin 46 is part of intercellular channels known as a gap junctions. Those intercellular channels, which allow cells to exchange molecules and ions, are crucial to the growth of a glioblastoma tumor, researchers found.