Branching Off: New Insight Into Lysosomes As Tubular Organelles

Lysosomes are acidic, membrane-bound organelles that play essential roles in cellular quality control, metabolism, and signaling. The lysosomes of a cell are commonly depicted as vesicular organelles. Yet, lysosomes in fact show a high degree of ultrastructural heterogeneity. In some biological contexts, lysosome membranes naturally transform into tubular, non-vesicular morphologies. Though the purpose and regulation of tubular lysosomes has been historically understudied, emerging evidence suggests that tubular lysosomes may carry out unique activities, both degradative and non-degradative, that are critical to cell behavior, function, and viability. Here, we discuss recent advances in understanding the biological significance of tubular lysosomes in cellular physiology, and we highlight a growing number of examples that indicate the centrality of this special class of lysosomes to health and disease

Response to Aubin et al. (2017)

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138910/1/add13937.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138910/2/add13937_am.pd

Determination of Real-Time Efflux Phenotypes in Escherichia coli AcrB Binding Pocket Phenylalanine Mutants Using a 1,2′-Dinaphthylamine Efflux Assay

To evaluate the importance of phenylalanine residues for substrate transport in the Escherichia coli efflux pump protein AcrB, we subjected Phe-to-Ala binding pocket mutants to a real-time efflux assay with the novel near-infrared lipophilic membrane probe 1,2′-dinaphthylamine (1,2′-DNA). All mutations, with the exception of F617A, led to considerable retardation of efflux. F610A was the point mutation with the most pronounced impact, followed by F628A, F615A, F136A, and F178A. This is the first study to demonstrate the importance of single phenylalanine residues within the AcrB binding pocket for real-time substrate transport

Attitude Determination from Single-Antenna Carrier-Phase Measurements

A model of carrier phase measurement (as carried out by a satellite navigation receiver) is formulated based on electromagnetic theory. The model shows that the phase of the open-circuit voltage induced in the receiver antenna with respect to a local oscillator (in the receiver) depends on the relative orientation of the receiving and transmitting antennas. The model shows that using a {\it single} receiving antenna, and making carrier phase measurements to seven satellites, the 3-axis attitude of a user platform (in addition to its position and time) can be computed relative to an initial point. This measurement model can also be used to create high-fidelity satellite signal simulators that take into account the effect of platform rotation as well as translation.Comment: 12 pages, and one figure. Published in J. Appl. Phys. vol. 91, No. 7, April 1, 200

Detection and phylogenetic analysis of the membrane-bound nitrate reductase (Nar) in pure cultures and microbial communities from deep-sea hydrothermal vents

Over the past few years the relevance of nitrate respiration in microorganisms from deep-sea hydrothermal vents has become evident. In this study, we surveyed the membrane-bound nitrate reductase (Nar) encoding gene in three different deep-sea vent microbial communities from the East Pacific Rise and the Mid-Atlantic Ridge. Additionally, we tested pure cultures of vent strains for their ability to reduce nitrate and for the presence of the NarG-encoding gene in their genomes. By using the narG gene as a diagnostic marker for nitrate-reducing bacteria, we showed that nitrate reductases related to Gammaproteobacteria of the genus Marinobacter were numerically prevalent in the clone libraries derived from a black smoker and a diffuse flow vent. In contrast, NarG sequences retrieved from a community of filamentous bacteria located about 50 cm above a diffuse flow vent revealed the presence of a yet to be identified group of enzymes. 16S rRNA gene-inferred community compositions, in accordance with previous studies, showed a shift from Alpha- and Gammaproteobacteria to Epsilonproteobacteria as the vent fluids become warmer and more reducing. Based on these findings, we argue that Nar-catalyzed nitrate reduction is likely relevant in temperate and less reducing environments where Alpha- and Gammaproteobacteria are more abundant and where nitrate concentrations reflect that of background deep seawater. © 2013 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved

Degradative Tubular Lysosomes Link Pexophagy To Starvation And Early Aging In C. Elegans

Organelle-specific autophagy directs degradation of eukaryotic organelles under certain conditions. Like other organelles, peroxisomes are subject to autophagic turnover at lysosomes. However, peroxisome autophagy (pexophagy) has yet to be analyzed in a live-animal system, limiting knowledge on its regulation during an animal\u27s life. Here, we generated a tandem-fluorophore reporter that enabled real-time tracking of pexophagy in live Caenorhabditis elegans. We observed that pexophagy occurred at a population of non-canonical, tubular lysosomes specifically during starvation and aging. Remarkably, in these contexts, tubular lysosomes were the predominant type of lysosome in the intestine, transforming from vesicles. Though we found that peroxisomes were largely eliminated in early adulthood, they appeared restored in new generations. We identified peroxisomal genes that regulated age-dependent peroxisome loss and demonstrated that modifying this process altered animal lifespan. These findings reveal new facets of peroxisome homeostasis relevant to aging and challenge the prevailing perception of lysosome homogeneity in autophagy

Substance use disorders and the risk of suicide mortality among men and women in the US Veterans Health Administration

Background and AimsLimited information is available regarding links between specific substance use disorders (SUDs) and suicide mortality; however, the preliminary evidence that is available suggests that suicide risk associated with SUDs may differ for men and women. This study aimed to estimate associations between SUDs and suicide for men and women receiving Veterans Health Administration (VHA) care.DesignA cohort study using national administrative health records.SettingNational VHA system, USA.ParticipantsAll VHA users in fiscal year (FY) 2005 who were alive at the beginning of FY 2006 (n = 4 863 086).MeasurementsThe primary outcome of suicide mortality was assessed via FY 2006–2011 National Death Index (NDI) records. Current SUD diagnoses were the primary predictors of interest, and were assessed via FY 2004–2005 VHA National Patient Care Database (NPCD) records.FindingsIn unadjusted analyses, a diagnosis of any current SUD and the specific current diagnoses of alcohol, cocaine, cannabis, opioid, amphetamine and sedative use disorders were all associated significantly with increased risk of suicide for both males and females [hazard ratios (HRs)] ranging from 1.35 for cocaine use disorder to 4.74 for sedative use disorder for men, and 3.89 for cannabis use disorder to 11.36 for sedative use disorder for women]. Further, the HR estimates for the relations between any SUD, alcohol, cocaine and opioid use disorders and suicide were significantly stronger for women than men (P < 0.05). After adjustment for other factors, most notably comorbid psychiatric diagnoses, associations linking SUDs with suicide were attenuated markedly and the greater suicide risk among females was observed for only any SUD and opioid use disorder (P < 0.05).ConclusionsCurrent substance use disorders (SUDs) signal increased suicide risk, especially among women, and may be important markers to consider including in suicide risk assessment strategies. None the less, other co‐occurring psychiatric disorders may partially explain associations between SUDs and suicide, as well as the observed excess suicide risk associated with SUDs among women.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/137620/1/add13774.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137620/2/add13774_am.pd

Use of non‐pharmacological strategies for pain relief in addiction treatment patients with chronic pain

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138296/1/ajad12600_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138296/2/ajad12600.pd