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https://www.readbyqxmd.com/read/28630339/ucp1-deficiency-causes-brown-fat-respiratory-chain-depletion-and-sensitizes-mitochondria-to-calcium-overload-induced-dysfunction
#1
Lawrence Kazak, Edward T Chouchani, Irina G Stavrovskaya, Gina Z Lu, Mark P Jedrychowski, Daniel F Egan, Manju Kumari, Xingxing Kong, Brian K Erickson, John Szpyt, Evan D Rosen, Michael P Murphy, Bruce S Kristal, Steven P Gygi, Bruce M Spiegelman
Brown adipose tissue (BAT) mitochondria exhibit high oxidative capacity and abundant expression of both electron transport chain components and uncoupling protein 1 (UCP1). UCP1 dissipates the mitochondrial proton motive force (Δp) generated by the respiratory chain and increases thermogenesis. Here we find that in mice genetically lacking UCP1, cold-induced activation of metabolism triggers innate immune signaling and markers of cell death in BAT. Moreover, global proteomic analysis reveals that this cascade induced by UCP1 deletion is associated with a dramatic reduction in electron transport chain abundance...
June 19, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28621569/down-regulation-of-slcyp1-in-the-phloem-reduces-auxin-response-and-photosynthetic-rate-in-tomato-solanum-lycopersicum-plants
#2
Ziv Spiegelman, Amit Shahar, Shmuel Wolf
The tomato dgt mutant, containing a single mutation in the Cyclophilin1 (SlCyp1) gene, is auxin insensitive and exhibits a pleotropic phenotype that includes lack of lateral roots, malformed xylem structure and reduced root-to-shoot ratio. Recently, we found that the SlCyp1 protein is phloem-mobile and traffic from shoot to root to induce lateral root formation. These processes are achieved through activation of auxin-mediated developmental programs. Inhibition of the trafficked SlCyp1 activity at the target site resulted in inhibition of the auxin response, supporting the hypothesis that this protein is indeed a mobile signal...
June 16, 2017: Plant Signaling & Behavior
https://www.readbyqxmd.com/read/28590865/evaluating-public-health-interventions-6-modeling-ratios-or-differences-let-the-data-tell-us
#3
Donna Spiegelman, Tyler J VanderWeele
We provide an overview of the relative merits of ratio measures (relative risks, risk ratios, and rate ratios) compared with difference measures (risk and rate differences). We discuss evidence that the multiplicative model often fits the data well, so that rarely are interactions with other risk factors for the outcome observed when one uses a logistic, relative risk, or Cox regression model to estimate the intervention effect. As a consequence, additive models, which estimate the risk or rate difference, will often exhibit interactions...
July 2017: American Journal of Public Health
https://www.readbyqxmd.com/read/28559401/association-between-endometriosis-and-hypercholesterolemia-or-hypertension
#4
Fan Mu, Janet Rich-Edwards, Eric B Rimm, Donna Spiegelman, John P Forman, Stacey A Missmer
An altered hormonal or chronic systemic inflammatory milieu characterizing endometriosis may result in a higher risk of hypercholesterolemia and hypertension. Conversely, elevated low-density lipoprotein in hypercholesterolemia and chronic systemic inflammation resulting from hypertension may increase the risk of endometriosis. We assessed the association of laparoscopically confirmed endometriosis with hypercholesterolemia and hypertension in a large prospective cohort study. In 1989, 116 430 registered female nurses aged 25 to 42 completed the baseline questionnaire and were followed for 20 years...
July 2017: Hypertension
https://www.readbyqxmd.com/read/28459108/cachexia-brown-fat-a-burning-issue-in-cancer
#5
Serkan Kir, Bruce M Spiegelman
Cachexia, a progressive weight loss in cancer patients that results from tumor-induced energy wasting, is a serious problem that interferes with response to treatment and affects quality of life. Recent studies suggest that thermogenesis of adipose tissues is involved in energy wasting and also point to a link between the atrophy of fat and muscle. Tumor-derived PTHrP has emerged as a key molecule playing multiple roles in cachexia, from fat "browning" factor to potential therapeutic target.
September 2016: Trends in Cancer
https://www.readbyqxmd.com/read/28406396/sirt6-regulates-ras-related-protein-r-ras2-by-lysine-defatty-acylation
#6
Xiaoyu Zhang, Nicole A Spiegelman, Ornella D Nelson, Hui Jing, Hening Lin
The Ras family of GTPases are important in cell signaling and frequently mutated in human tumors. Understanding their regulation is thus important for studying biology and human diseases. Here, we report that a novel posttranslational mechanism, reversible lysine fatty acylation, regulates R-Ras2, a member of the Ras family. SIRT6, a sirtuin with established tumor suppressor function, regulates the lysine fatty acylation of R-Ras2. In mouse embryonic fibroblasts (MEFs), Sirt6 knockout (KO) increased R-Ras2 lysine fatty acylation...
April 13, 2017: ELife
https://www.readbyqxmd.com/read/28402488/evaluation-of-the-24-hour-recall-as-a-reference-instrument-for-calibrating-other-self-report-instruments-in-nutritional-cohort-studies-evidence-from-the-validation-studies-pooling-project
#7
Laurence S Freedman, John M Commins, Walter Willett, Lesley F Tinker, Donna Spiegelman, Donna Rhodes, Nancy Potischman, Marian L Neuhouser, Alanna J Moshfegh, Victor Kipnis, David J Baer, Lenore Arab, Ross L Prentice, Amy F Subar
Calibrating dietary self-report instruments is recommended as a way to adjust for measurement error when estimating diet-disease associations. Because biomarkers available for calibration are limited, most investigators use self-reports (e.g., 24-hour recalls (24HRs)) as the reference instrument. We evaluated the performance of 24HRs as reference instruments for calibrating food frequency questionnaires (FFQs), using data from the Validation Studies Pooling Project, comprising 5 large validation studies using recovery biomarkers...
April 10, 2017: American Journal of Epidemiology
https://www.readbyqxmd.com/read/28387836/switching-to-second-line-art-in-relation-to-mortality-in-a-large-tanzanian-hiv-cohort
#8
Claudia Hawkins, Ellen Hertzmark, Donna Spiegelman, Aisa Muya, Nzovu Ulenga, Sehee Kim, Polyna Khudyakov, Beatrice Christian, David Sando, Eric Aris, Wafaie Fawzi
Objectives: In a large cohort of HIV-infected Tanzanians, we assessed: (i) rates of first-line treatment failure and switches to second-line ART; (ii) the effect of switching to second-line ART on death and loss to follow-up; and (iii) treatment outcomes on second-line ART by regimen. Methods: HIV-1-infected adults (≥15 years) initiated on first-line ART between November 2004 and September 2012, and who remained on initial therapy for at least 24 weeks before switching, were studied...
April 6, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28380374/mitochondrial-patch-clamp-of-beige-adipocytes-reveals-ucp1-positive-and-ucp1-negative-cells-both-exhibiting-futile-creatine-cycling
#9
Ambre M Bertholet, Lawrence Kazak, Edward T Chouchani, Marta G Bogaczyńska, Ishan Paranjpe, Gabrielle L Wainwright, Alexandre Bétourné, Shingo Kajimura, Bruce M Spiegelman, Yuriy Kirichok
Cold and other environmental factors induce "browning" of white fat depots-development of beige adipocytes with morphological and functional resemblance to brown fat. Similar to brown fat, beige adipocytes are assumed to express mitochondrial uncoupling protein 1 (UCP1) and are thermogenic due to the UCP1-mediated H(+) leak across the inner mitochondrial membrane. However, this assumption has never been tested directly. Herein we patch clamped the inner mitochondrial membrane of beige and brown fat to provide a direct comparison of their thermogenic H(+) leak (IH)...
April 4, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28379291/heterozygous-pink1-p-g411s-in-rapid-eye-movement-sleep-behaviour-disorder
#10
Ziv Gan-Or, Jennifer A Ruskey, Dan Spiegelman, Isabelle Arnulf, Yves Dauvilliers, Birgit Högl, Christelle Monaca-Charley, Ronald B Postuma, Jacques Y Montplaisir, Guy A Rouleau
No abstract text is available yet for this article.
June 1, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28338828/validity-of-a-dietary-questionnaire-assessed-by-comparison-with-multiple-weighed-dietary-records-or-24-hour-recalls
#11
COMPARATIVE STUDY
Changzheng Yuan, Donna Spiegelman, Eric B Rimm, Bernard A Rosner, Meir J Stampfer, Junaidah B Barnett, Jorge E Chavarro, Amy F Subar, Laura K Sampson, Walter C Willett
The authors evaluated the validity of a 152-item semiquantitative food frequency questionnaire (SFFQ) by comparing it with two 7-day dietary records (7DDRs) or up to 4 automated self-administered 24-hour recalls (ASA24s) over a 1-year period in the women's Lifestyle Validation Study (2010-2012), conducted among subgroups of the Nurses' Health Studies. Intakes of energy and 44 nutrients were assessed using the 3 methods among 632 US women. Compared with the 7DDRs, SFFQ responses tended to underestimate sodium intake but overestimate intakes of energy, macronutrients, and several nutrients in fruits and vegetables, such as carotenoids...
April 1, 2017: American Journal of Epidemiology
https://www.readbyqxmd.com/read/28291481/self-reported-visual-quality-of-life-after-combat-ocular-trauma
#12
Andrew McLaughlin, Marcus H Colyer, Denise S Ryan, Rose K Sia, Eric D Weichel, Andrew Spiegelman, S G Eaddy, Robert A Mazzoli, Kraig S Bower
OBJECTIVES: To describe the visual outlook and quality of life of service members after combat ocular trauma. METHODS: In a single-center, prospective observational study of service members sustaining ocular trauma, participants underwent a series of ocular examinations and noninvasive tests, including the National Eye Institute Visual Functioning Questionnaire (VFQ-25). RESULTS: Of the 165 enrolled participants, 137 completed the VFQ-25. The mean VFQ-25 composite score was 74...
March 2017: Military Medicine
https://www.readbyqxmd.com/read/28276201/rare-deleterious-variants-in-grhl3-are-associated-with-human-spina-bifida
#13
Philippe Lemay, Patrizia De Marco, Alexandre Emond, Dan Spiegelman, Alexandre Dionne-Laporte, Sandra Laurent, Elisa Merello, Andrea Accogli, Guy A Rouleau, Valeria Capra, Zoha Kibar
Neural tube defects, including spina bifida, are among the most common birth defects caused by failure of neural tube closure during development. They have a complex etiology involving largely undetermined environmental and genetic factors. Previous studies in mouse models have implicated the transcription factor Grhl3 as an important factor in the pathogenesis of spina bifida. In the present study, we conducted a resequencing analysis of GRHL3 in a cohort of 233 familial and sporadic cases of spina bifida...
June 2017: Human Mutation
https://www.readbyqxmd.com/read/28249003/the-prospective-impact-of-food-pricing-on-improving-dietary-consumption-a-systematic-review-and-meta-analysis
#14
Ashkan Afshin, José L Peñalvo, Liana Del Gobbo, Jose Silva, Melody Michaelson, Martin O'Flaherty, Simon Capewell, Donna Spiegelman, Goodarz Danaei, Dariush Mozaffarian
BACKGROUND: While food pricing is a promising strategy to improve diet, the prospective impact of food pricing on diet has not been systematically quantified. OBJECTIVE: To quantify the prospective effect of changes in food prices on dietary consumption. DESIGN: We systematically searched online databases for interventional or prospective observational studies of price change and diet; we also searched for studies evaluating adiposity as a secondary outcome...
2017: PloS One
https://www.readbyqxmd.com/read/28236510/a-strategy-for-dual-inhibition-of-the-proteasome-and-fatty-acid-synthase-with-belactosin-c-orlistat-hybrids
#15
Mingzhao Zhu, Wayne D Harshbarger, Omar Robles, Joanna Krysiak, Kenneth G Hull, Sung Wook Cho, Robyn D Richardson, Yanyan Yang, Andres Garcia, Lindsey Spiegelman, Bianca Ramirez, Christopher T Wilson, Ju Anne Yau, James T Moore, Caitlen B Walker, James C Sacchettini, Wenshe R Liu, Stephan A Sieber, Jeffrey W Smith, Daniel Romo
The proteasome, a validated cellular target for cancer, is central for maintaining cellular homeostasis, while fatty acid synthase (FAS), a novel target for numerous cancers, is responsible for palmitic acid biosynthesis. Perturbation of either enzymatic machine results in decreased proliferation and ultimately cellular apoptosis. Based on structural similarities, we hypothesized that hybrid molecules of belactosin C, a known proteasome inhibitor, and orlistat, a known inhibitor of the thioesterase domain of FAS, could inhibit both enzymes...
January 19, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28196865/s-palmitoylation-of-junctional-adhesion-molecule-c-regulates-its-tight-junction-localization-and-cell-migration
#16
Pornpun Aramsangtienchai, Nicole A Spiegelman, Ji Cao, Hening Lin
Junctional adhesion molecule C (JAM-C) is an immunoglobulin superfamily protein expressed in epithelial cells, endothelial cells, and leukocytes. JAM-C has been implicated in leukocyte transendothelial migration, angiogenesis, cell adhesion, cell polarity, spermatogenesis, and metastasis. Here, we show that JAM-C undergoes S-palmitoylation on two juxtamembrane cysteine residues, Cys-264 and Cys-265. We have identified DHHC7 as a JAM-C palmitoylating enzyme by screening all known palmitoyltransferases (DHHCs)...
March 31, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28158909/teneurin-transmembrane-protein-4-is-not-a-cause-for-essential-tremor-in-a-canadian-population
#17
Gabrielle Houle, Jean-François Schmouth, Claire S Leblond, Amirthagowri Ambalavanan, Dan Spiegelman, Sandra B Laurent, Cynthia V Bourassa, Michel Panisset, Sylvain Chouinard, Nicolas Dupré, Carles Vilariño-Güell, Alex Rajput, Patrick A Dion, Guy A Rouleau
INTRODUCTION: Mutations in teneurin transmembrane protein 4 were reported to be a risk factor for essential tremor, but the relevance of this across different population remains to be examined. The aim of this study was to determine the frequency and spectrum of variations in teneurin transmembrane protein 4 in a cohort of Canadian essential tremor cases. METHODS: The coding portion of teneurin transmembrane protein 4 was sequenced in 269 unrelated essential tremor cases and 288 matched control individuals using a targeted and high-throughput sequencing approach...
February 2017: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/28115667/vitamin-a-and-zinc-supplementation-among-pregnant-women-to-prevent-placental-malaria-a-randomized-double-blind-placebo-controlled-trial-in-tanzania
#18
Anne Marie Darling, Ferdinand M Mugusi, Analee J Etheredge, Nilupa S Gunaratna, Ajibola Ibraheem Abioye, Said Aboud, Christopher Duggan, Robert Mongi, Donna Spiegelman, Drucilla Roberts, Davidson H Hamer, Kevin C Kain, Wafaie W Fawzi
AbstractVitamin A and zinc are important for immune function and may improve host defense against malaria and reduce the risk of adverse pregnancy outcomes. Our objective was to determine whether daily oral supplementation with either or both nutrients starting in the first trimester reduces the risk of placental malaria and adverse pregnancy outcomes. We undertook a randomized, double-blind placebo-controlled trial with a factorial design among 2,500 human immunodeficiency virus-negative primigravid or secundigravid pregnant women in their first trimester of pregnancy in Dar es Salaam, Tanzania...
April 2017: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/28093263/-cross-sectional-stepped-wedge-designs-always-reduce-the-required-sample-size-when-there-is-no-time-effect
#19
LETTER
Xin Zhou, Xiaomei Liao, Donna Spiegelman
No abstract text is available yet for this article.
January 16, 2017: Journal of Clinical Epidemiology
https://www.readbyqxmd.com/read/28053189/function-of-cyclophilin1-as-a-long-distance-signal-molecule-in-the-phloem-of-tomato-plants
#20
Ziv Spiegelman, Sumita Omer, Ben N Mansfeld, Shmuel Wolf
Tomato (Solanum lycopersicum) diageotropica (dgt) mutants, containing a single mutation in the Cyclophilin1 (SlCyp1) gene, are auxin-insensitive, exhibiting a pleiotropic phenotype including lack of geotropism, abnormal xylem structure, lack of lateral roots (LRs), and elevated shoot-to-root ratio. SlCyp1 is a putative peptidyl-prolyl isomerase that can traffic from shoot to root, where it induces changes in auxin response, LR formation, and xylem development, suggesting it has a role as a long-distance signaling molecule...
February 1, 2017: Journal of Experimental Botany
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