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Archive - Aug 2017


August 2nd

Autism May Reflect Excitation-Inhibition Imbalance in Brain, Stanford Study Finds

A study by Stanford University investigators suggests that key features of autism reflect an imbalance in signaling from excitatory and inhibitory neurons in a portion of the forebrain, and that reversing the imbalance could alleviate some of its hallmark symptoms. In a series of experiments conducted on a mouse model of the disorder, the scientists showed that reducing the ratio of excitatory to inhibitory signaling countered hyperactivity and deficits in social ability, two classic symptoms of autism in humans. The study was published in the August 2, 2017 issue of Science Translational Medicine. Dr. Karl Deisseroth, Professor of Bioengineering and of Psychiatry and Behavioral Sciences, is the study's senior author. The lead author is former graduate student Aslihan Selimbeyoglu, PhD. The article is titled “Modulation of Prefrontal Cortex Excitation/Inhibition Balance Rescues Social Behavior In CNTNAP2-Deficient Mice.” In 2011, Dr. Deisseroth's group published a study in Nature showing that autism-like behavioral deficits could be induced in ordinary mice by elevating the ratio of excitatory to inhibitory neuronal firing patterns in the mice's medial prefrontal cortex. The new study shows that decreasing that ratio restores normal behavior patterns in a strain of lab mice bioengineered to mimic human autism. These mice carry a mutation equivalent to a corresponding mutation in humans that is associated with autism spectrum disorder. For reasons that are not understood, the incidence of autism spectrum disorder has increased steadily in recent years, said Dr. Deisseroth, a practicing psychiatrist. Approximately 1 in 80 American children may be diagnosed with the disorder, which is characterized by repetitive behaviors and difficulty with social interaction.

Gladstone Study Reveals How to Reprogram Cells in Our Immune System; Discovery Could Improve Treatments for Autoimmune Diseases and Cancer

When the immune system is imbalanced, either due to overly-active cells or cells that suppress its function, it causes a wide range of diseases, from psoriasis to cancer. By manipulating the function of certain immune cells, called T cells, researchers could help restore the system's balance and create new treatments to target these diseases. Scientists at the Gladstone Institutes in San Francisco revealed, for the first time, a method to reprogram specific T cells. More precisely, they discovered how to turn pro-inflammatory cells that boost the immune system into anti-inflammatory cells that suppress it, and vice versa. The researchers studied two types of cells called effector T cells, which activate the immune system to defend our body against different pathogens, and regulatory T cells, which help control the immune system and prevent it from attacking healthy parts of its environment. "Our findings could have a significant impact on the treatment of autoimmune diseases, as well as on stem cell and immuno-oncology therapies," said Gladstone Senior Investigator Sheng Ding, PhD, who is also a Professor of Pharmaceutical Chemistry at the University of California, San Francisco. By drawing on their expertise in drug discovery, Dr. Ding's team identified a small-molecule drug that can successfully reprogram effector T cells into regulatory T cells. Their study, published online on August 2, 2017 in Nature, describes, in detail, a metabolic mechanism that helps convert one cell type into another. The article is titled “Metabolic Control of TH17 and Induced Treg Cell Balance By An Epigenetic Mechanism.” This new approach to reprogram T cells could have several medical applications. For instance, in autoimmune disease, effector T cells are overly activated and cause damage to body.

Serum Exosomal miR-125b Is a Novel Prognostic Marker For Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide with high mortality. Circulating miRNA has been demonstrated as a novel noninvasive biomarker for many tumors. A new study by collaborators in China sought to investigate the potential of circulating miR-125b as a prognostic marker of HCC. In the work, exosomes were extracted from serum samples collected from two independent cohorts: cohort 1: HCC (n=30), chronic hepatitis B (CHB, n=30), liver cirrhosis (LC, n=30); cohort 2: HCC (n=128). The researchers found that miR-125b levels were remarkably increased in exosomes compared to those in serum from patients with CHB, LC, and HCC (P<0.01, respectively). However, miR-125b levels in exosomes and the serum from HCC patients were inferior to that of CHB (P<0.01 and P=0.06) and LC patients (P<0.01 for all). Additionally, miR-125b levels in exosomes were associated with tumor number (P=0.02), encapsulation (P<0.01), and TNM stage (P<0.01). In TMN, T describes the size of the original tumor and whether it has invaded nearby tissue; N describes nearby (regional) lymph nodes that are involved; and M describes distant metastasis. Kaplan–Meier analysis indicated that HCC patients with lower exosomal miR-125b levels showed reduced time to recurrence (TTR) (P<0.01) and overall survival (OS) (P<0.01). Furthermore, multivariate analysis revealed that miR-125b level in exosomes, but not in serum, was an independent predictive factor for TTR (P<0.001) and OS (P=0.011). Exosomal miR-125b levels predicted the recurrence and survival of HCC patients with an area under the ROC curve of 0.739 (83.0% sensitivity and 67.9% specificity) and 0.702 (82.5% sensitivity and 53.4% specificity). In conclusion, the researchers believe that exosomal miR-125b could serve as a promising prognostic marker for HCC.

August 2nd

Scientists Uncover Secrets of Potent DNA Toxin

One of the most potent of known toxins acts by joining the two strands of the DNA double helix together in a unique fashion which foils the standard repair mechanisms cells use to protect their DNA. A team of Vanderbilt University researchers has worked out the molecular details that explain how this bacterial toxin -- yatakemycin (YTM) -- prevents DNA replication. The team’s results, described in a paper published online on July 24, 2017 in Nature Chemical Biology, explain YTM's extraordinary toxicity and could be used to fine-tune the compound's impressive antimicrobial and antifungal properties. The article is titled “Toxicity and Repair of DNA Adducts Produced by the Natural Product Yatakemycin.” YTM is produced by some members of the Streptomyces family of soil bacteria to kill competing strains of bacteria. It belongs to a class of bacterial compounds that are currently being tested for cancer chemotherapy because their toxicity is extremely effective against tumor cells. "In the past, we have thought about DNA repair in terms of protecting DNA against different kinds of chemical insults," said Professor of Biological Sciences Brandt Eichman. "Now, toxins like YTM are forcing us to consider their role as part of the ongoing chemical warfare that exists among bacteria, which can have important side effects on human health." Cells have developed several basic types of DNA repair, including base excision repair (BER) and nucleotide excision repair (NER). BER generally fixes small lesions and NER removes large, bulky lesions. A number of DNA toxins create bulky lesions that destabilize the double helix. However, some of the most toxic lesions bond to both strands of DNA, thereby preventing the cell's elaborate replication machinery from separating the DNA strands so they can be copied.

House Spider & Venomous Scorpion Share Common Ancestor; Genome Duplication Revealed by Genome Sequencing

In collaboration with scientists from the UK, Europe, Japan, and the United States, researchers at the Human Genome Sequencing Center at Baylor College of Medicine in Houston, Texas have discovered a whole genome duplication during the evolution of spiders and scorpions. The study was published online on July 31, 2017 in BMC Biology. The open-access article is titled “The House Spider Genome Reveals an Ancient Whole-Genome Duplication During Arachnid Evolution.” Researchers have long been studying spiders and scorpions for both applied reasons, such as studying venom components for pharmaceuticals and silks for materials science, and for basic questions such as the reasons for the evolution and to understand the development and ecological success of this diverse group of carnivorous organisms. As part of a pilot project for the i5K, a project to study the genomes of 5,000 arthropod species, the Human Genome Sequencing Center analyzed the genome of the house spider Parasteatoda tepidariorum - a model species studied in laboratories - and the Arizona bark scorpion Centruroides sculpturatus, - the most venomous scorpion in North America. Analysis of these genomes revealed that spiders and scorpions evolved from a shared ancestor more than 400 million years ago, which made new copies of all of the genes in its genome, a process called whole genome duplication. Such an event is one of the largest evolutionary changes that can happen to a genome and is relatively rare during animal evolution. Dr. Stephen Richards, Associate Professor in the Human Genome Sequencing Center, who led the genome sequencing at Baylor, said, "It is tremendously exciting to see rapid progress in our molecular understanding of a species that we coexist with on planet earth.

July 31st

History of Gum Disease Increases Cancer Risk in Older Women; New Study Is First to Report Association Between Periodontal Disease and Gallbladder Cancer Risk In Women or Men

Postmenopausal women who have a history of gum disease also have a higher risk of cancer, according to a new study of more than 65,000 women. The study, led by researchers at the University at Buffalo (UB) in New York, is the first national study of its kind involving U.S. women, and the first to focus specifically on older women. It's also the first study to find an association between periodontal disease and gallbladder cancer risk in women or men. The findings were published on August 1, 2017 in Cancer Epidemiology, Biomarkers & Prevention. "This study is the first national study focused on women, particularly older women," said Dr. Jean Wactawski-Wende, the study's senior author. "Our study was sufficiently large and detailed enough to examine not just overall risk of cancer among older women with periodontal disease, but also to provide useful information on a number of cancer-specific sites," added Dr. Wactawski-Wende, Dean of UB's School of Public Health and Health Professions and a Professor of Epidemiology and Environmental Health. The study included 65,869 postmenopausal women enrolled in the Women's Health Initiative, an ongoing national prospective study designed to investigate factors affecting disease and death risk in older American women. The average age of the participants was 68, and most were non-Hispanic white women. As part of a follow-up health questionnaire, participants were asked "Has a dentist or dental hygienist ever told you that you had periodontal or gum disease?" Women who reported a history of gum disease had a 14 percent increased risk of overall cancer. Of the 7,149 cancers that occurred in the study participants, the majority -- or 2,416 -- were breast cancer.