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Archive - Mar 8, 2017

Immune Response to Yeast & Increased Purine Metabolism May Exacerbate Crohn’s Disease

A new study reports that a strain of intestinal-dwelling yeast may exacerbate Crohn's disease, and blocking the fungus from causing problems in the gut could alleviate the symptoms of inflammatory bowel disorder in some patients. Approximately 1.6 million Americans currently live with inflammatory bowel disorders (IBD), and as many as 70,000 new cases are diagnosed every year. No cure exists for IBD, though many patients manage their symptoms with anti-inflammatory drugs. While several studies have illuminated links between intestinal bacteria and IBD, scant attention has been paid to the other types of microbes living in the gut, even though almost 70% of Crohn's disease patients are predisposed to mount immune reactions against yeast. In work that served as the cover story of the March 8, 2017 issue of Science Translational Medicine, Dr. Tyson Chiaro of the University of Utah School of Medicine and colleagues demonstrated that a strain of Saccharomyces cerevisiae aggravated intestinal damage in mouse models of colitis. The researchers determined that the yeast caused the rodents to produce elevated amounts of uric acid in their intestines. They gave yeast-colonized animals allopurinol (a clinical drug used to reduce uric acid), which reversed intestinal disease. To determine if yeast might cause similar effects in humans, the scientists examined serum from 168 healthy volunteers and observed a positive correlation between uric acid levels and circulating antibodies against S. cerevisiae. Testing Crohn’s disease patients for uric acid and immune responses to yeast could inform more targeted therapeutic interventions, the authors say. The open-access Science Translational Medicine article is titled “A Member of the Gut Mycobiota Modulates Host Purine Metabolism Exacerbating Colitis in Mice.”


“Jumping Genes” May Set Stage for Brain Cell Death in Alzheimer's & Other Neurodegenerative Diseases—“Alu Neurodegeneration Hypothesis” Expounded

The latest round of failed drug trials for Alzheimer's has researchers questioning the reigning approach to battling the disease, which focuses on preventing a sticky protein called amyloid from building up in the brain. Duke University scientists have identified a mechanism in the molecular machinery of the cell that could help explain how neurons begin to falter in the initial stages of Alzheimer's, even before amyloid clumps appear. This rethinking of the Alzheimer's process centers on human genes critical for the healthy functioning of mitochondria, the energy factories of the cell, which are riddled with mobile chunks of DNA called Alu elements. If these "jumping genes" lose their normal controls as a person ages, they could start to wreak havoc on the machinery that supplies energy to brain cells -- leading to a loss of neurons and ultimately dementia, the researchers say. And if this "Alu Neurodegeneration Hypothesis" holds up, it could help identify people at risk sooner, before they develop symptoms, or point to new ways to delay onset or slow progression of the disease, said study co-author Peter Larsen, Ph.D., Senior Research Scientist in co-author Biology Professor Anne Yoder's lab at Duke. The researchers describe the Alu neurodegeneration hypothesis in a paper published online on March 8, 2017 in Alzheimer's & Dementia: The Journal of the Alzheimer's Association. The open-access article is titled “The Alu Neurodegeneration Hypothesis: A Primate-Specific Mechanism for Neuronal Transcription Noise, Mitochondrial Dysfunction, and Manifestation of Neurodegenerative Disease.” The dominant idea guiding Alzheimer's research for 25 years has been that the disease results from the abnormal buildup of hard, waxy amyloid plaques in the parts of the brain that control memory.

Exploring New Complication from an Emergent Tickborne Parasite—Asplenic Patients at Increased Risk of WAHA After Treatment for Babesiosis

Babesiosis is a rare, but increasingly common, disease spread by ticks. After a bite from an infected tick, microscopic malaria-like parasites are transmitted into the host where they can infect and destroy red blood cells, causing nonimmune hemolytic anemia. Treatment with antimicrobials usually clears the parasite and resolves the anemia. However, sporadic cases of warm-antibody autoimmune hemolytic anemia (WAHA) have been observed in patients after treatments for babesiosis. This autoimmune form of anemia occurs when the body attacks its own red blood cells, eliminating these cells from circulation. To better understand this complication, Brigham and Women’s Hospital (BWH) researchers led by Ann Wolley, M.D., and Francisco Marty, M.D., of the Division for Infectious Diseases at BWH conducted a retrospective analysis of patients who had been cared for at BWH from January 2009 through June 2016. Of 86 patients diagnosed with babesiosis during that time, six developed WAHA two to four weeks later, after the parasitic infection had been resolved. These six cases are presented in a study published online in the New England Journal of Medicine on March 9, 2017. The NEJM article is titled “Post-Babesiosis Warm Autoimmune Hemolytic Anemia.” In general, people who have weakened immune systems and those who have undergone splenectomy are at higher risk for severe and relapsing babesiosis, but WAHA after babesiosis in patients without history of autoimmune diseases had not been defined previously. All six babesiosis patients with WAHA were asplenic, meaning that their spleens had previously been removed. The researchers found that WAHA was much more common among asplenic patients with babesiosis, affecting as many as one in three of these patients. Many of these patients needed to receive immunosuppressive treatment to address WAHA.

New Centrifugal Microfluidic Platform (Exodisc) Enables Rapid, Size-Selective, and Efficient Isolation and Analysis of Nanoscale Extracellular Vesicles (EVs) from Raw Biological Samples; Utility in Cancer Diagnostics Seen

A team of researchers, led by Professor Yoon-Kyoung Cho of the School of Life Sciences at UNIST (Ulsan National Institute of Science and Technology in the Republic of Korea) has recently developed a new technique that effectively identifies cancer-causing substances in the urine or blood. In the study, Professor Cho, a group leader at the Institute for Basic Science (IBS) Research Center for Soft and Living Matter (CSLM) in the Republic of Korea, presented an integrated centrifugal microfluidic platform (Exodisc), a device that isolates extracellular vesicles (EVs) from urine. The results of the study were published (online on January 9, 2017) in the February 2017 issue of ACS Nano. The article is titled “Exodisc for Rapid, Size-Selective, and Efficient Isolation and Analysis of Nanoscale Extracellular Vesicles from Biological Samples.” The research team expects that this may be potentially useful in clinical settings to test urinary EV-based biomarkers for cancer diagnostics. Extracellular vesicles (EVs) are cell-derived nanovesicles (40-1,000 nm in size), present in almost all types of body fluids, which play a vital role in intercellular communication and are involved in the transport of biological signals for regulating diverse cellular functions. Despite the increasing clinical importance of EVs as potential biomarkers in the diagnosis and prognosis of various diseases, current methods of EV isolation and analysis suffer from complicated procedures with long processing times. For instance, even ultracentrifugation (UC), the most commonly used method for EV isolation, requires time-consuming steps involving centrifugation and acquisition of large sample volumes, and the results suffer from low yield and purity.

CRISPR-Cas9 Successfully Used to Modify Archaeal Species for First Time; Technique Allows Much More Rapid Generation of Mutants for Study; Utility Seen for Global Climate Change Studies

A new study by Dr. Bill Metcalfe, G. William Arends Professor of Microbiology at the University of Illinois, and his postdoctoral Fellow Dr. Dipti Nayak, has documented the use of CRISPR-Cas9-mediated genome editing in the third domain of life, Archaea, for the first time. The ground-breaking work, reported online on March 6, 2017 in PNAS, has the potential to vastly accelerate future studies of these organisms, with implications for research including global climate change. Dr. Metcalf and Dr. Nayak are members of the Carl R. Woese Institute for Genomic Biology at Illinois. The PNAS article is titled “Cas9-Mediated Genome Editing in the Methanogenic Archaeon Methanosarcina acetivorans.” "Under most circumstances, our model archaeon, Methanosarcina acetivorans, has a doubling time of 8 to 10 hours, as compared to E. coli, which can double in about 30 minutes. What that means is that doing genetics, getting a mutant, can take months--the same thing would take three days in E. coli," explains Dr. Nayak. "What CRISPR-Cas9 enables us to do, at a very basic level, is speed up the whole process. It removes a major bottleneck... in doing genetics research with this archaeon.” "Even more," continues Dr. Nayak, "with our previous techniques, mutations had to be introduced one step at a time. Using this new technology, we can introduce multiple mutations at the same time. We can scale up the process of mutant generation exponentially with CRISPR." CRISPR, short for Clustered Regularly Interspaced Short Palindromic Repeats, began as an immune defense system in archaea and bacteria. By identifying and storing short fragments of foreign DNA, Cas (CRISPR-associated system) proteins are able to quickly identify that DNA in the future, so that it can then quickly be destroyed, protecting the organism from viral invasion.

American Society of Human Genetics (ASHG) Opposes H.R.1313 “Preserving Employee Wellness Programs Act”--Bill Would Undermine Genetic Privacy Protections, ASHG Maintains

In a March 8, 2017 press release, the American Society of Human Genetics (ASHG) announced that it opposes H.R.1313, the Preserving Employee Wellness Programs Act, introduced on March 2,2017 and scheduled for markup by the House Education and the Workforce Committee on March 8, 2017. If enacted, this bill would fundamentally undermine the privacy provisions of the Genetic Information Nondiscrimination Act (GINA) and the Americans with Disabilities Act (ADA), the ASHG maintains. “We urge the Committee not to move forward with consideration of this bill,” said ASHG President Nancy J. Cox, Ph.D. “As longtime advocates of genetic privacy, we instead encourage the Committee to pursue ways to foster workplace wellness and employee health without infringing upon the civil rights afforded by ADA and GINA.” According to the ASHG, a key component of the ADA and GINA Acts is that they prevent workers and their families from being coerced into sharing sensitive medical or genetic information with their employer. For GINA, genetic information encompasses not only employees’ genetic test results, but also their family medical histories. H.R.1313 would effectively repeal these protections by allowing employers to ask employees invasive questions about their and their families’ health, including genetic tests they, their spouses, and their children may have undergone, the ASHG maintains. GINA’s requirement that employees’ genetic information collected through a workplace wellness program only be shared with health care professionals would no longer apply. The ASHG said that the bill would also allow employers to impose financial penalties of up to 30 percent of the total cost the employee’s health insurance on employees who choose to keep such information private.

Study Finds 63 Alterations in Human Genome That Modestly Increase Risk of Premature Male-Pattern Baldness; Short Stature Among Associations Implicated; Link with Prostate Cancer Confirmed

Short men may have an increased risk of becoming bald prematurely. An international genetic study under the leadership of the University of Bonn at least points in this direction. During the study, the scientists investigated the genetic material of more than 20,000 men. Their data show that premature hair loss is linked to a range of various physical characteristics and illnesses. The work was published online on March 8, 2017 in Nature Communications. The open-access article is titled “Meta-Analysis Identifies Novel Risk Loci and Yields Systematic Insights into the Biology of Male-Pattern Baldness.” It has already long been known that men with premature hair loss suffer from heart diseases and prostate cancer somewhat more often. The new genetic data now confirm suspicions that there are further connections to other characteristics and illnesses. In their study, the researchers analyzed genetic data from approximately 11,000 men with premature baldness. Approximately12,000 men with no hair loss served as a control. The participants came from seven different countries. “We were thus able to identify 63 alterations in the human genome that increase the risk of premature hair loss,” explains Dr. Stefanie Heilmann-Heimbach. The human geneticist at the University of Bonn is one of the lead authors of the international study. “Some of these alterations were also found in connection with other characteristics and illnesses, such as reduced body size, earlier occurrence of puberty, and various cancers.” The genetic findings also confirm the link between hair loss and an increased risk of prostate cancer. The link with heart disease is much more complicated. Genes that reduce the risk were found along with genes that increase the risk.