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Archive - Sep 24, 2015

Parasitic Worm That Causes Elephantiasis Releases Exosome-Like Vesicles Containing microRNAs That May Help Control Host Response

Lymphatic filariasis is a neglected tropical disease caused by three different species of parasitic worm, which are spread between human hosts by mosquitos. The molecular interactions between the worm, mosquito, and human are dynamic and delicately balanced, suggesting that disrupting these interactions might be an avenue for the development new therapeutic treatments. The worm Brugia malayi (image), one of the parasites that causes elephantiasis, develops as larvae inside the mosquito vector until it reaches the infective L3 stage at which point it is transmitted back into a human host when the mosquito takes a blood meal. The adult worms live and mate within the human lymphatic system while offspring are shed into the bloodstream to be picked up again by mosquitoes. While the life-cycle is well documented it has been difficult to define the exact molecules that the parasite uses to control its hosts. Research has traditionally searched for secreted proteins and, while there are several candidates, along with proteins expressed on the surface of the parasite that may play a part, recent research, carried out by scientists at Iowa State University, together with collaborators at Northewestern University, the University of Georgia, and the University of Wisconsin-Madison, has revealed that small non-coding RNAs carried in exosome-like vesicles (ELVs) may also be involved in controlling the host’s response to the parasite. This new research was published online on September 24, 2015 in the open-access journal PLOS Neglected Tropical Diseases.

Study Identifies Key Mechanism Connecting Stress Granules, Toxic Fibrils, and Degenerative Diseases Like ALS and FTD; Involvement of hnRNPA1 Protein and Its Long Disordered Tail Is Crucial; Results Suggest Benefit of Targeting Stress Granule Formation

St. Jude Children's Research Hospital scientists have discovered evidence of a mechanism at the heart of amyotrophic lateral sclerosis (ALS) and related degenerative diseases. The research appears in today's September 24, 2015 issue of Cell and highlights a possible new treatment strategy for the devastating disorders. The article is titled “Phase Separation by Low Complexity Domains Promotes Stress Granule Assembly and Drives Pathological Fibrillization.” The St. Jude’s study focused on usually short-lived compartments called stress granules that form in cells under stress. Stress granules are just one type of the membrane-less structures or organelles that assemble as needed to handle various cell functions and then rapidly disperse. Until now, however, the mechanism underlying stress granule formation was poorly understood. Stress granules are also tied to degenerative disorders such as ALS, which is also known as Lou Gehrig's disease. Genes encoding the protein components of stress granules are often mutated in patients with ALS and other diseases. These same proteins accumulate in thread-like deposits called amyloid fibrils in the nerve and muscle cells of patients with ALS, frontotemporal dementia (FTD), and inclusion body myopathy (IBM). But the unifying mechanism was a mystery. "This study provides the mechanism that links stress granules, toxic fibrils, and disease," said co-corresponding author J. Paul Taylor, M.D., Ph.D., a Howard Hughes Medical Institute (HHMI) Investigator and Chair of the St. Jude Department of Cell and Molecular Biology.

World Mitochondria Expert Douglas Wallace Publishes Provocative Piece in September 24 Issue of Cell; Argues That mtDNA Changes Enable More Rapid & Less Risky Adaptations to New Environments Than Do Changes to Genomic DNA

Mitochondria are not only the power plants of our cells, these tiny structures also play a central role in our physiology. Furthermore, by enabling flexible physiological responses to new environments, mitochondria have helped humans and other mammals to adapt and evolve throughout the history of life on earth. A pioneering scientist in mitochondrial biology and world-renowned expert on these critical organelles, Douglas C. Wallace, Ph.D., Director of the Center for Mitochondrial and Epigenomic Medicine at The Children's Hospital of Philadelphia (CHOP), synthesizes evidence for the importance of mitochondria in a provocative Perspective article published today, September 24, 2015, in the journal Cell. The Cell article is titled “Mitochondrial DNA Variation in Human Radiation and Disease." Residing in large numbers outside the nucleus of every cell, mitochondria contain their own DNA, with unique features that "may require a reassessment of some of our core assumptions about human genetics and evolutionary theory," concludes Dr. Wallace in his Cell article. Dr. Wallace has investigated mitochondria for more than 40 years. In 1988, he was the first to show that mutations in mitochondrial DNA (mtDNA) can cause inherited human disease. His body of research has focused on how mtDNA mutations contribute to both rare and common diseases by disrupting bioenergetics--chemical reactions that generate energy at the cellular level. Dr. Wallace and colleagues previously showed, in the late 1970s, that human mitochondrial DNA is inherited exclusively through the mother. They then used this knowledge to reconstruct the ancient migrations of women by comparing variation in mtDNA among populations throughout the world.

Rapamycin Prevents Parkinson’s Disease in Mouse Model; New Understanding of Parkin Role in Cellular Dynamics Also Gained—Parkin Finding Challenges Current PD Dogma and Suggests New Directions for Drug Discovery

Rapamycin, an FDA-approved drug that extends lifespan in several species, prevented Parkinson's disease (PD) in middle-age mice that were genetically fated to develop the incurable neurodegenerative motor disease that affects as many as one million Americans. While the rapamycin did great things for the mice, scientists in the Andersen lab at the Buck Institute for Research on Aging in Novato, California, also got an unexpected dividend from the research - a new understanding of the role the parkin protein (image) plays in cellular dynamics, one that challenges the current dogma in PD research and presents new opportunities for drug discovery. The Buck Institute study was published in the September 16, 2015 issue of The Journal of Neuroscience. The article is titled “Mitochondrial Quality Control via the PGC1alpha-TFEB Signaling Pathway Is Compromised by Parkin Q311X Mutation, But Independently Restored by Rapamycin.” "Given its side effects as an immunosuppressant, there are issues with long-term use of rapamycin, but the results of our study suggest that use of derivatives of rapamycin, or other agents with similar biological properties, may constitute novel therapeutics for the disorder," said senior scientist and Buck faculty member Julie Andersen, Ph.D. "Our discoveries regarding parkin may provide an even more important therapeutic target for PD." Parkin is a protein encoded by the PARK2 gene in humans. Mutations in PARK2 are most commonly linked to both sporadic and familial forms of PD; they diminish the cell's ability to recycle its internal garbage. PD is characterized by the accumulation of damaged proteins and mitochondria in the area of the brain where the neurotransmitter dopamine is produced. Rapamycin prevented PD symptoms from occurring in middle-aged mice who had a human mutation in the PARK2 gene.

Corneal Surfaces of 23 Orders of Insects Completely Fit Mathematician Alan Turing’s Model for Formation of Complex Patterns; New Russian Study Focuses on Anti-Reflective 3D Nanocoating of Insect Eyes; First-Ever Biological Example of Turing Nanopatterns

In 1952, the legendary British mathematician and cryptographer Alan Turing proposed a model, which assumes formation of complex patterns through chemical interaction of two diffusing reagents. Russian scientists have recently managed to prove that the corneal surface nanopatterns in 23 insect orders completely fit into this model. Their work was published in the September 22, 2015 issue of PNAS. The article is titled “Diverse Set of Turing Nanopatterns Coat Corneae Across Insect Lineages.” The author state that to their knowledge this is the first-ever biological example of Turing nanopatterns. The study was performed by a team working in the Institute of Protein Research of the Russian Academy of Sciences (Pushchino, Russia) and the Department of Entomology at the Faculty of Biology of the Lomonosov Moscow State University. It was supervised by Professor Vladimir Katanaev, who also leads a lab at the University of Lausanne, Switzerland. Dr. Artem Blagodatskiy and Dr. Mikhail Kryuchkov performed the choice and preparation of insect corneal samples and analyzed the data. Dr. Yulia Lopatina from the Lomonosov Moscow State University played the role of expert entomologist, while Dr. Anton Sergeev performed the atomic force microscopy. The initial goal of the study was to characterize the anti-reflective three-dimensional nanopatterns covering insect eye cornea, with respect to the taxonomy of studied insects and to gain insight into their possible evolution path. The result was surprising as the pattern morphology did not correlate with insect position on the evolutionary tree. Instead, Russian scientists have characterized four main morphological corneal nanopatterns, as well as transition forms between them, omnipresent among the insect class.