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Science Round up- Top Recent Research Findings

Feb 05, 2016

Welcome to the first in a new monthly series on the blog where we highlight the latest research findings in key research areas along with other interesting science news. Happy reading!


Gene therapy for treating amyotrophic lateral sclerosis (ALS)

It wasn’t too long ago that people were pouring cold water on top of their heads to raise awareness of and funding for ALS. The fatal neuromuscular disorder is characterized by deterioration of motor neurons leading to muscle weakness and eventually paralysis and death. A recent study by Jara et al. at Northwestern University Feinberg School of Medicine demonstrated the effectiveness of gene therapy for treating this devastating disease. Using an adeno-associated virus (AAV), the authors successfully delivered genes to corticospinal motor neurons (CSMNs), allowing specific modification of gene expression without affecting other neurons. This study sets the stage for CSMN gene therapy in ALS.

Jara JH et al. (2016). Healthy and diseased corticospinal motor neurons are selectively transduced upon direct AAV2-2 injection into the motor cortex. Gene Ther doi: 10.1038/gt.2015.112 [Epub ahead of print]


The genetic basis of pediatric low-grade gliomas identified

A collaborative team of researchers at University of Pennsylvania, The Children’s Hospital of Philadelphia and the Dana Farber Cancer Institute set out to identify the genomic abnormalities underlying the most common childhood brain cancer called angiocentric glioma, a subset of pediatric low-grade gliomas (PLGGs). Through genomic analysis of 249 cases of PLGG, the authors determined that the most common genetic alteration involved the transcription factor growth gene MYB, which contained deleted chromosomal DNA causing a fusion to a separate gene called QKI. This MYB-QKI gene rearrangement was shown to significantly contribute to tumor formation through three unique mechanisms. 

Bandopadhayay P et al. (2016). MYB-QKI rearrangements in angiocentric glioma drive tumorigenicity through a tripartite mechanism. Nat Genet doi: 10.1038/ng.3500. [Epub ahead of print]


Central tolerance in polyclonal CD4+ T cells reclassified 

Development of T cell tolerance to self antigens is a necessary process initially occurring in the thymus. Tolerance mechanisms have evolved to limit T cells that demonstrate high-affinity interactions to self epitopes from the immune repertoire, since this can lead to autoimmunity. Using transgenic mouse strains, prominent researchers in the field of immunology at the University of Minnesota Medical School and University of California San Francisco demonstrate that tolerance in the normally diverse CD4+ T cell repertoire can be attributed to one of three mechanisms depending on the expression pattern of the self epitope. This finding emphasizes which mechanisms operate in the normal repertoire and could impact cancer therapy that aims to use T cells that recognize mutated antigens to combat tumor growth.

Malhotra D et al. (2016). Tolerance is established in polyclonal CD4+ T cells by distinct mechanisms, according to self-peptide expression patterns. Nat Immunol 17, 187-195.

Millar DG and Ohashi PS (2016). Central Tolerance: what you see is what you don’t get! Nat Immunol 17, 115-116. 

Veterinary Research

Immune evasion by an economical porcine virus is further characterized

Porcine reproductive and respiratory syndrome virus (PRRSV) is an economically important virus that affects pigs causing what has been described as the blue-ear pig disease. PRRSV causes reproductive failure in breeding stock pigs and respiratory tract illness in young pigs. The virus has evolved mechanisms to evade host IFN-I responses and researchers at China Agricultural University and North Carolina State University have determined that a host micro-RNA, miR-30c, helps the virus infect pigs. The authors show that mIR-30c is a negative regulator of IFN-I signaling via targeting of JAK1, which leads to enhanced PRRSV infection. This finding highlights a new strategy used by PRRSV to escape host immune responses and could lead to future work identifying a treatment for this costly porcine pathogen.

Zhang Q et al. (2016).  MicroRNA-30c modulates type I IFN responses to facilitate porcine reproductive and respiratory syndrome virus infection by targeting JAK1. J Immunol pii: 1502006. [Epub ahead of print]

Cell Biology

Modest changes in autophagy impact the fate of stem cells

The process of autophagy is a key mechanism utilized by cells to maintain homeostasis and normal cellular function. Its mechanism of action is widely studied, but little is known about how autophagy impacts normal physiology. Researchers at the University of Cambridge and Washington University School of Medicine in St. Louis have demonstrated for the first time that autophagy impacts stem cell differentiation. Using a mouse model with a mutation in the key autophagy gene Atg, they show that autophagy regulates the Notch pathway, which is important in both disease and development. Consequently, since this pathway regulates neural stem cells and neuronal development, autophagy induced degradation of Notch-1 led to impaired neural stem cell development. This study shows that autophagy can impact stem cell fate, which may also be relevant for disease conditions such as Alzheimer’s disease or Crohn’s disease.

Wu X et al. (2016). Autophagy regulates Notch degradation and modulates stem cell development and neurogenesis. Nat Commun 7, 10533 doi: 10.1038/ncomms10533.

Infectious Diseases

Helminths can enhance the severity of tuberculosis

Parasitic helminth worms, such as Schistosoma mansoni, are typically endemic in regions with high incidence of tuberculosis. Using a mouse model of Mycobacterium tuberculosis infection, researchers at Washington University in St. Louis and Children’s Hospital of Pittsburgh determined that co-infection with S. mansoni reversibly impairs M. tuberculosis specific T helper type 1 responses and lung inflammation. The exacerbated lung inflammation observed was associated with the accumulation of arginase-1 positive macrophages in the lungs. The study concludes that helminth co-infection or exposure to helminth antigens increases susceptibility to tuberculosis as well as disease severity, thus providing a biological basis for the initial epidemiological observation.

Monin L et al. (2015). Helminth-induced arginase-1 exacerbates lung inflammation and disease severity in tuberculosis. J Clin Invest 125, 4699-4713.

Fehervari Z (2016). Coinfection enhances inflammation. Nat Immunol 17, 121.

Science News

Basic science research is declining in medical journals 

Basic science research is focused on examining cells and molecules to better understand the causes and mechanisms of disease. In contrast, clinical research involves clinical trials of drugs and epidemiological studies. A team of researchers at the University of Toronto and St. Michael’s Hospital searched the medical research database, PubMed, to find articles published between 1994 and 2013 in top tier clinical journals in cardiology, endocrinology, gastroenterology, infectious diseases, nephrology, oncology and pulmonology. They found that in six of the eight journals examined, the number of basic science articles published decreased by 40¬—60% over the years. However, there was no decline in basic science articles in well-known non-clinical journals, specifically Journal of Biological Chemistry, Journal of Clinical Investigation and Cell. While clinical research is of particular interest to physicians, basic science is critical for understanding the mechanisms of disease and treatment, which significantly impacts clinical practice. Therefore, the decline in basic science research in clinical journals could have negative effects on patient care… unless physicians develop an interest in basic science research journals.

Steinberg BE et al. (2016). Is basic science disappearing from medicine? The decline of biomedical research in the medical literature. FASEB J 30, 515-518. 

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