Clock-related regulation of mitochondrial physiology in skeletal muscle

Biological rhythms regulate numerous functional processes within organisms, including the expression of peroxisome proliferator-activated receptor-y coactivator 1-a (PGC-1a), a potent regulator of mitochondrial biogenesis. Homozygous Clock mutant mice are characterized by arrhythmic and suppressed expression of circadian genes within skeletal muscle, including PGC-1a. The present study sought to investigate mitochondrial physiology within these mutant animals, and to assess their adaptability to a chronic voluntary endurance training protocol. Our results indicate that Clock mutant mice exhibit decreased mitochondrial content, and this contributes to exercise intolerance in these mutant animals. Interestingly, endurance training ameliorates the decrement in mitochondrial content, as well as restores exercise capacity to levels evident in the wildtype mice. Thus, a functional CLOCK protein is necessary for optimal mitochondrial physiology, however Clock mutant mice retain the ability to adapt to chronic exercise

The RNA-Recognition Motifs of TAR DNA-Binding Protein 43 May Play a Role in the Aberrant Self-Assembly of the Protein

The TAR DNA-binding protein 43 (TDP-43) is a nucleic acid-binding protein implicated in gene regulation and RNA processing and shuffling. It is a ribonuclear protein that carries out most of its functions by binding specific nucleic acid sequences with its two RNA-recognition motifs, RRM1 and RRM2. TDP-43 has been identified in toxic cytosolic inclusions in neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U). The unstructured C-terminus has prion-like behavior and has been considered the driver of the aberrant self-assembly of TDP-43. In this work, we set out to test the hypothesis that the RNA-binding domains could also play a role in protein aggregation. This knowledge could be of important value for understanding TDP-43 aberrant, disease-leading behavior and, in the future, inform the design of small molecules that could prevent or slow down protein aggregation by exploiting the RNA-binding properties of the protein. We investigated the behavior of the two tandem RRM domains separately and linked together and studied their self-assembly properties and RNA-binding ability with a number of biophysical techniques. The picture that emerges from our study suggests that this region of the protein plays an important and so far unexplored role in the aggregation of this protein

Bounding Anomalous Gauge-Boson Couplings

In this version we have corrected some minor errors in the tables, corrected typos, and added a reference. We have also updated our comparison with earlier workers. Figures are now included as uuencoded compressed tar files.Comment: 32 page

US Cosmic Visions: New Ideas in Dark Matter 2017: Community Report

This white paper summarizes the workshop "U.S. Cosmic Visions: New Ideas in Dark Matter" held at University of Maryland on March 23-25, 2017.Comment: 102 pages + reference