SIRT3 as a regulator of hepatic autophagy

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138374/1/hep29271.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138374/2/hep29271_am.pd

Sestrins are evolutionarily conserved mediators of exercise benefits.

Exercise is among the most effective interventions for age-associated mobility decline and metabolic dysregulation. Although long-term endurance exercise promotes insulin sensitivity and expands respiratory capacity, genetic components and pathways mediating the metabolic benefits of exercise have remained elusive. Here, we show that Sestrins, a family of evolutionarily conserved exercise-inducible proteins, are critical mediators of exercise benefits. In both fly and mouse models, genetic ablation of Sestrins prevents organisms from acquiring metabolic benefits of exercise and improving their endurance through training. Conversely, Sestrin upregulation mimics both molecular and physiological effects of exercise, suggesting that it could be a major effector of exercise metabolism. Among the various targets modulated by Sestrin in response to exercise, AKT and PGC1α are critical for the Sestrin effects in extending endurance. These results indicate that Sestrin is a key integrating factor that drives the benefits of chronic exercise to metabolism and physical endurance

Complete genome sequence of Mycobacterium tuberculosis K from a Korean high school outbreak, belonging to the Beijing family

Mycobacterium tuberculosis K, a member of the Beijing family, was first identified in 1999 as the most prevalent genotype in South Korea among clinical isolates of M. tuberculosis from high school outbreaks. M. tuberculosis K is an aerobic, non-motile, Gram-positive, and non-spore-forming rod-shaped bacillus. A transmission electron microscopy analysis displayed an abundance of lipid bodies in the cytosol. The genome of the M. tuberculosis K strain was sequenced using two independent sequencing methods (Sanger and Illumina). Here, we present the genomic features of the 4,385,518-bp-long complete genome sequence of M. tuberculosis K (one chromosome, no plasmid, and 65.59 % G + C content) and its annotation, which consists of 4194 genes (3447 genes with predicted functions), 48 RNA genes (3 rRNA and 45 tRNA) and 261 genes with peptide signals.

Janus-faced Sestrin2 controls ROS and mTOR signalling through two separate functional domains

Sestrins are stress-inducible metabolic regulators with two seemingly unrelated but physiologically important functions: reduction of reactive oxygen species (ROS) and inhibition of the mechanistic target of rapamycin complex 1 (mTORC1). How Sestrins fulfil this dual role has remained elusive so far. Here we report the crystal structure of human Sestrin2 (hSesn2), and show that hSesn2 is twofold pseudo-symmetric with two globular subdomains, which are structurally similar but functionally distinct from each other. While the N-terminal domain (Sesn-A) reduces alkylhydroperoxide radicals through its helix–turn–helix oxidoreductase motif, the C-terminal domain (Sesn-C) modified this motif to accommodate physical interaction with GATOR2 and subsequent inhibition of mTORC1. These findings clarify the molecular mechanism of how Sestrins can attenuate degenerative processes such as aging and diabetes by acting as a simultaneous inhibitor of ROS accumulation and mTORC1 activation

Quantitative agreement of Dzyaloshinskii-Moriya interactions for domain-wall motion and spin-wave propagation

The magnetic exchange interaction is the one of the key factors governing the basic characteristics of magnetic systems. Unlike the symmetric nature of the Heisenberg exchange interaction, the interfacial Dzyaloshinskii-Moriya interaction (DMI) generates an antisymmetric exchange interaction which offers challenging opportunities in spintronics with intriguing antisymmetric phenomena. The role of the DMI, however, is still being debated, largely because distinct strengths of DMI have been measured for different magnetic objects, particularly chiral magnetic domain walls (DWs) and non-reciprocal spin waves (SWs). In this paper, we show that, after careful data analysis, both the DWs and SWs experience the same strength of DMI. This was confirmed by spin-torque efficiency measurement for the DWs, and Brillouin light scattering measurement for the SWs. This observation, therefore, indicates the unique role of the DMI on the magnetic DW and SW dynamics and also guarantees the compatibility of several DMI-measurement schemes recently proposed.Comment: 24 pages, 5 figure

Lipotoxicity induces hepatic protein inclusions through TANK binding kinase 1â mediated p62/sequestosome 1 phosphorylation

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146331/1/hep29742.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146331/2/hep29742_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146331/3/hep29742-sup-0011-suppinfo.pd

Comparative Genomic Analysis of the 2016 Vibrio cholerae Outbreak in South Korea

In August 2016, South Korea experienced a cholera outbreak that caused acute watery diarrhea in three patients. This outbreak was the first time in 15 years that an outbreak was not linked to an overseas source. To identify the cause and to study the epidemiological implications of this outbreak, we sequenced the whole genome of Vibrio cholerae isolates; three from each patient and one from a seawater sample. Herein we present comparative genomic data which reveals that the genome sequences of these four isolates are very similar. Interestingly, these isolates form a monophyletic Glade with V. cholerae strains that caused an outbreak in the Philippines in 2011. The V. cholerae strains responsible for the Korean and Philippines outbreaks have almost identical genomes in which two unique genomic islands are shared, and they both lack SXT elements. Furthermore, we confirm that seawater is the likely source of this outbreak, which suggests the necessity for future routine surveillance of South Korea's seashore.

Dysregulated Amino Acid Sensing Drives Colorectal Cancer Growth and Metabolic Reprogramming Leading to Chemoresistance

BACKGROUND & AIMS: Colorectal cancer (CRC) is a devastating disease that is highly modulated by dietary nutrients. Mechanistic target of rapamycin complex 1 (mTORC1) contributes to tumor growth and limits therapy responses. Growth factor signaling is a major mechanism of mTORC1 activation. However, compensatory pathways exist to sustain mTORC1 activity after therapies that target oncogenic growth factor signaling. Amino acids potently activate mTORC1 via amino acid-sensing GTPase activity towards Rags (GATOR). The role of amino acid-sensing pathways in CRC is unclear. METHODS: Human colon cancer cell lines, preclinical intestinal epithelial-specific GATOR1 and GATOR2 knockout mice subjected to colitis-induced or sporadic colon tumor models, small interfering RNA screening targeting regulators of mTORC1, and tissues of patients with CRC were used to assess the role of amino acid sensing in CRC. RESULTS: We identified loss-of-function mutations of the GATOR1 complex in CRC and showed that altered expression of amino acid-sensing pathways predicted poor patient outcomes. We showed that dysregulated amino acid-sensing induced mTORC1 activation drives colon tumorigenesis in multiple mouse models. We found amino acid-sensing pathways to be essential in the cellular reprogramming of chemoresistance, and chemotherapeutic-resistant patients with colon cancer exhibited de-regulated amino acid sensing. Limiting amino acids in in vitro and in vivo models (low-protein diet) reverted drug resistance, revealing a metabolic vulnerability. CONCLUSIONS: Our findings suggest a critical role for amino acid-sensing pathways in driving CRC and highlight the translational implications of dietary protein intervention in CRC