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Archive - Jan 4, 2017

Researchers Discover New Mechanism for Type IV Pili Retraction in Vibrio cholerae

Type IV pili, essential for many pathogens to cause disease, are hair-like appendages that grow out of and are retracted back into bacteria cells, enabling them to move and adhere to surfaces. Although pathogenic bacteria often rely on a specialized molecular motor to retract their pili, a new study, published online on December 19, 2016 in PLOS Pathogens, reveals that a minor pilin protein elicits pilus retraction in the cholera bacterium, Vibrio cholerae. The open-access PLOS Pathogens article is titled “The Vibrio cholerae Minor Pilin TcpB Initiates Assembly and Retraction of the Toxin-Coregulated Pilus.” Bacteria utilize a number of highly sophisticated molecular tools to colonize their hosts. One of the most ubiquitous of these tools is a complex nanomachine called the Type IV pilus. This nanomachine has as few as 10 to as many as 30 molecular components, producing exquisitely thin filaments that extend from the bacterial surface and that can be several times the length of the bacterium itself. These pilus filaments have a remarkable array of functions that rely on their ability to (i) adhere to many substrates, including host cell surfaces, pili from nearby bacteria, DNA and bacterial viruses (bacteriophage), and (ii) to depolymerize or retract, which pulls the bacteria along mucosal surfaces, pulls them close together in protective aggregates, and can even draw in substrates like DNA and bacteriophage for nutrition and genetic variation. In collaboration with researchers from Dartmouth College and Simon Fraser University, Dr. Nicolas Biais, Assistant Professor of Biology at Brooklyn College, City University of New York (CUNY), developed an assay in his laboratory that revealed for the first time that the V.

Vaccine Shows Promising Results for Early-Stage Breast Cancer Patients: HER2-Targeted Dendritic Cell Vaccines Stimulate Immune Responses and Regression of HER2-Expressing Early-Stage Breast Tumors

Deregulation and inhibition of the immune system contributes to cancer development. Many therapeutic strategies aim to re-stimulate the immune system to recognize cancer cells and target them for destruction. Researchers from the Moffitt Cancer Center in Florida report that a dendritic cell vaccine that targets the HER2 protein on breast cancer cells is safe and effectively stimulates the immune system leading to regression of early-stage breast cancer. The HER2 protein is over-expressed in 20-25% of all breast cancer tumors and is associated with aggressive disease and poor prognosis. Researchers have previously shown that immune cells are less able to recognize and target cancer cells that express HER2 as breast cancer progresses into a more advanced and invasive stage. This suggests that strategies that can re-stimulate the immune system to recognize and target HER2 early during cancer development may be effective treatment options. The researchers previously developed a vaccine that helps the immune system recognize the HER2 protein on breast cancer cells. Their approach involves creating the vaccine from immune cells called dendritic cells that are harvested from each individual patient to create a personalized vaccine. In order to determine if the HER2-dendritic cell vaccine is safe and effective, the researchers performed a clinical trial in 54 women who have HER2-expressing early-stage breast cancer. The dendritic cell vaccines were prepared by isolating dendritic cells from each patients' blood and exposing them to fragments of the HER2 protein. Patients were injected with a dose of their personal dendritic cell vaccine once a week for six weeks into either a lymph node, the breast tumor, or into both sites.

Reduced Blood Flow in Broca’s Area of Brain Associated with Stuttering

A study led by researchers at Children's Hospital Los Angeles (CHLA) demonstrates what lead investigator Bradley Peterson, M.D., calls "a critical mass of evidence" of a common underlying lifelong vulnerability in both children and adults who stutter. The scientists discovered that regional cerebral blood flow is reduced in the Broca's area - the region in the frontal lobe of the brain linked to speech production - in persons who stutter. More severe stuttering is associated with even greater reductions in blood flow to this region. In addition, a greater abnormality of cerebral blood flow in the posterior language loop, associated with processing words that we hear, correlates with more severe stuttering. This finding suggests that a common pathophysiology throughout the neural "language" loop that connects the frontal and posterior temporal lobe likely contributes to stuttering severity. Dr. Peterson, who is Director of the Institute for the Developing Mind at CHLA and a professor of the Keck School of Medicine at the University of Southern California, says that such a study of resting blood flow, or perfusion, has never before been conducted in persons who stutter. His team also recently published a study using proton magnetic resonance spectroscopy to look at brain regions in both adults and children who stutter. Those findings demonstrated links between stuttering and changes in the brain circuits that control speech production, as well as those supporting attention and emotion. The present blood flow study adds significantly to the findings from that prior study and furthermore suggests that disturbances in the speech processing areas of the brain are likely of central importance as a cause of stuttering. According to Dr.

Promising New Small Molecule Stops Spread of Melanoma by Up to 90 Percent

Michigan State University (MSU) researchers have discovered that a chemical compound, and potential new drug, reduces the spread of melanoma cells by up to 90 percent. The man-made, small-molecule drug compound goes after a gene's ability to produce RNA molecules and certain proteins in melanoma tumors. This gene activity in melanoma causes the disease to spread but the compound can shut it down. Up until now, few other compounds of this kind have been able to accomplish this. "It's been a challenge developing small-molecule drugs that can block this gene activity that works as a signaling mechanism known to be important in melanoma progression," said Richard Neubig (photo), M.D., Ph.D., Pharmacology Professor, Chairperson of Pharmacology/Toxicology at MSU, and co-author of the study. "Our chemical compound is actually the same one that we've been working on to potentially treat the disease scleroderma, which now we've found works effectively on this type of cancer." Scleroderma is a rare and often fatal autoimmune disease that causes the hardening of skin tissue, as well as organs such as the lungs, heart and kidneys. The same mechanisms that produce fibrosis, or skin thickening, in scleroderma also contribute to the spread of cancer. Small-molecule drugs make up over 90 percent of the drugs on the market today and Dr. Neubig's co-author Dr. Kate Appleton, a postdoctoral student, said the findings are an early discovery that could be highly effective in battling the deadly skin cancer. It's estimated about 10,000 people die each year from the disease. The new findings have been published in the January 2017 issue of Molecular Cancer Therapeutics.