Description: The 16.5 kb human mitochondrial genome encodes for 13 polypeptides, 22 tRNAs and 2 rRNAs involved in oxidative phosphorylation. Mitochondrial DNA (mtDNA), unlike its nuclear counterpart, is not packaged into nucleosomes and is more prone to the adverse effects of reactive oxygen species (ROS) generated during oxidative phosphorylation. The past few decades have witnessed an increase in the number of proteins observed to translocate to the mitochondria for the purposes of mitochondrial genome maintenance. The mtDNA damage produced by ROS, if not properly repaired, leads to instability and can ultimately manifest in mitochondrial dysfunction and disease. The base excision repair (BER) pathway is employed for the removal and consequently the repair of deaminated, oxidized, and alkylated DNA bases. Specialized enzymes called DNA glycosylases, which locate and cleave the damaged base, catalyze the first step of this highly coordinated repair pathway. This review focuses on members of the four human BER DNA glycosylase superfamilies and their subcellular localization in the mitochondria and/or the nucleus, as well as summarizes their structural features, biochemical properties, and functional role in the excision of damaged bases. This article is protected by copyright. All rights reserved

Description: Hepatic steatosis is defined by the accumulation of lipid droplets (LDs). Once thought to be only inert energy storage depots, LDs are increasingly recognized as organelles that have important functions in hepatocytes beyond lipid storage. The lipid and protein composition of LDs is highly dynamic and influences their intrinsic metabolism and signaling properties, which ultimately links them to the changes in hepatic function. This concise review will highlight recent discoveries in LD biology and highlight unique aspects of hepatic LDs and their role in liver disease. This article is protected by copyright. All rights reserved.

Description: Background: Smokeless tobacco is consumed in most countries in the world. In view of its widespread use and increasing awareness of the associated risks, there is a need for a detailed assessment of its impact on health. We present the first global estimates of the burden of disease due to consumption of smokeless tobacco by adults. Methods: The burden attributable to smokeless tobacco use in adults was estimated as a proportion of the disability-adjusted life-years (DALYs) lost and deaths reported in the 2010 Global Burden of Disease study. We used the comparative risk assessment method, which evaluates changes in population health that result from modifying a population’s exposure to a risk factor. Population exposure was extrapolated from country-specific prevalence of smokeless tobacco consumption, and changes in population health were estimated using disease-specific risk estimates (relative risks/odds ratios) associated with it. Country-specific prevalence estimates were obtained through systematically searching for all relevant studies. Disease-specific risks were estimated by conducting systematic reviews and meta-analyses based on epidemiological studies. Results: We found adult smokeless tobacco consumption figures for 115 countries and estimated burden of disease figures for 113 of these countries. Our estimates indicate that in 2010, smokeless tobacco use led to 1.7 million DALYs lost and 62,283 deaths due to cancers of mouth, pharynx and oesophagus and, based on data from the benchmark 52 country INTERHEART study, 4.7 million DALYs lost and 204,309 deaths from ischaemic heart disease. Over 85 % of this burden was in South-East Asia. Conclusions: Smokeless tobacco results in considerable, potentially preventable, global morbidity and mortality from cancer; estimates in relation to ischaemic heart disease need to be interpreted with more caution, but nonetheless suggest that the likely burden of disease is also substantial. The World Health Organization needs to consider incorporating regulation of smokeless tobacco into its Framework Convention for Tobacco Control.

Description: Author(s): Yang Wang, Xianli Zhang, Theodore A. Corcovilos, Aishwarya Kumar, and David S. Weiss Researchers manipulate atomic qubits individually in a three-dimensional optical lattice. [Phys. Rev. Lett. 115, 043003] Published Thu Jul 23, 2015

Description: Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer fatalities in Western societies, characterized by high metastatic potential and resistance to chemotherapy. Critical molecular mechanisms of these phenotypical features still remain unknown, thus hampering the development of effective prognostic and therapeutic measures in PDAC. Here, we show that transcriptional co-factor Transducin beta-like (TBL) 1 was over-expressed in both human and murine PDAC. Inactivation of TBL1 in human and mouse pancreatic cancer cells reduced cellular proliferation and invasiveness, correlating with diminished glucose uptake, glycolytic flux, and oncogenic PI3 kinase signaling which in turn could rescue TBL1 deficiency-dependent phenotypes. TBL1 deficiency both prevented and reversed pancreatic tumor growth, mediated transcriptional PI3 kinase inhibition, and increased chemosensitivity of PDAC cells in vivo . As TBL1 mRNA levels were also found to correlate with PI3 kinase levels and overall survival in a cohort of human PDAC patients, TBL1 was identified as a checkpoint in the malignant behavior of pancreatic cancer and its expression may serve as a novel molecular target in the treatment of human PDAC. The transcriptional co-factor TBL1, with known functions in liver and adipose tissue, is shown to be an oncogenic driver in pancreatic cancer. TBL1 inactivation curbs cancer growth and aggressiveness and regulates PI3 kinase in vitro and in vivo .

Description: This study uses more than a decade’s worth of data across Arizona to characterize the spatiotemporal distribution, frequency, and source of extreme aerosol events, defined as when the concentration of a species on a particular day exceeds that of the average plus two standard deviations for that given month. Depending on which of eight sites studied, between 5% and 7% of the total days exhibited an extreme aerosol event due to either extreme levels of PM10, PM2.5, and/or fine soil. Grand Canyon exhibited the most extreme event days (120, i.e., 7% of its total days). Fine soil is the pollutant type that most frequently impacted multiple sites at once at an extreme level. PM10, PM2.5, fine soil, non-Asian dust, and Elemental Carbon extreme events occurred most frequently in August. Nearly all Asian dust extreme events occurred between March and June. Extreme Elemental Carbon events have decreased as a function of time with statistical significance, while other pollutant categories did not show any significant change. Extreme events were most frequent for the various pollutant categories on either Wednesday or Thursday, but there was no statistically significant difference in the number of events on any particular day or on weekends versus weekdays.