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Metabolic genetics

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https://www.readbyqxmd.com/read/29454068/o-glcnacylation-of-rack1-promotes-hepatocellular-carcinogenesis
#1
Fangfang Duan, Hao Wu, Dongwei Jia, Weicheng Wu, Shifang Ren, Lan Wang, Shushu Song, Xinying Guo, Fenglin Liu, Yuanyuan Ruan, Jianxin Gu
BACKGROUND & AIMS: Aberrant oncogenic mRNA translation and protein O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) are general features during tumorigenesis. Nevertheless, whether and how these two pathways are interlinked remain unknown. Our previous study indicated that ribosomal RACK1 promoted the chemoresistance and growth in hepatocellular carcinoma (HCC). The aim of this study is to examine the role of RACK1 O-GlcNAcylation in oncogene translation and HCC carcinogenesis...
February 14, 2018: Journal of Hepatology
https://www.readbyqxmd.com/read/29454067/considering-our-methods-methodological-issues-with-rodent-models-of-appetite-and-obesity-research
#2
Thomas A Lutz
A large number of animal models are currently used in appetite and obesity research. Because the worldwide incidence of obesity continues to climb, it is imperative that animal models sharing characteristics of human obesity and its co-morbidities be used appropriately in the quest for novel preventions or treatments. There is probably no animal model, at least in rodents, that recapitulates all aspects of "common" human obesity and its comorbidities, but rodent models allow insight into specific mechanisms of disease or its consequences...
February 14, 2018: Physiology & Behavior
https://www.readbyqxmd.com/read/29453804/probiotics-affect-one-carbon-metabolites-and-catecholamines-in-a-genetic-rat-model-of-depression
#3
Sandra Tillmann, Hussain M Awwad, Amanda R Eskelund, Giulia Treccani, Juergen Geisel, Gregers Wegener, Rima Obeid
SCOPE: Probiotics may influence one-carbon (C1) metabolism, neurotransmitters, liver function markers, or behavior. METHODS AND RESULTS: Male adult Flinders Sensitive Line rats (model of depression, FSL; n = 22) received Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 (10 9 or 10 10 colony-forming units/d) or vehicle for 10 weeks. The controls, Flinders Resistant Line rats (FRL, n = 8), only received vehicle. C1-related metabolites were measured in plasma, urine, and different tissues...
February 17, 2018: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/29453510/next-generation-metabolic-screening-targeted-and-untargeted-metabolomics-for-the-diagnosis-of-inborn-errors-of-metabolism-in-individual-patients
#4
Karlien L M Coene, Leo A J Kluijtmans, Ed van der Heeft, Udo F H Engelke, Siebolt de Boer, Brechtje Hoegen, Hanneke J T Kwast, Maartje van de Vorst, Marleen C D G Huigen, Irene M L W Keularts, Michiel F Schreuder, Clara D M van Karnebeek, Saskia B Wortmann, Maaike C de Vries, Mirian C H Janssen, Christian Gilissen, Jasper Engel, Ron A Wevers
The implementation of whole-exome sequencing in clinical diagnostics has generated a need for functional evaluation of genetic variants. In the field of inborn errors of metabolism (IEM), a diverse spectrum of targeted biochemical assays is employed to analyze a limited amount of metabolites. We now present a single-platform, high-resolution liquid chromatography quadrupole time of flight (LC-QTOF) method that can be applied for holistic metabolic profiling in plasma of individual IEM-suspected patients. This method, which we termed "next-generation metabolic screening" (NGMS), can detect >10,000 features in each sample...
February 16, 2018: Journal of Inherited Metabolic Disease
https://www.readbyqxmd.com/read/29453413/depression-and-obesity-evidence-of-shared-biological-mechanisms
#5
REVIEW
Yuri Milaneschi, W Kyle Simmons, Elisabeth F C van Rossum, Brenda Wjh Penninx
Depression and obesity are common conditions with major public health implications that tend to co-occur within individuals. The relationship between these conditions is bidirectional: the presence of one increases the risk for developing the other. It has thus become crucial to gain a better understanding of the mechanisms responsible for the intertwined downward physiological spirals associated with both conditions. The present review focuses specifically on shared biological pathways that may mechanistically explain the depression-obesity link, including genetics, alterations in systems involved in homeostatic adjustments (HPA axis, immuno-inflammatory activation, neuroendocrine regulators of energy metabolism including leptin and insulin, and microbiome) and brain circuitries integrating homeostatic and mood regulatory responses...
February 16, 2018: Molecular Psychiatry
https://www.readbyqxmd.com/read/29453322/the-mtor-targets-4e-bp1-2-restrain-tumor-growth-and-promote-hypoxia-tolerance-in-pten-driven-prostate-cancer
#6
Mei Ding, Theodorus H van der Kwast, Ravi N Vellanki, Warren D Foltz, Trevor D McKee, Nahum Sonenberg, Pier Paolo Pandolfi, Marianne Koritzinsky, Bradly G Wouters
The mTOR signaling pathway is a central regulator of protein synthesis and cellular metabolism in response to the availability of energy, nutrients, oxygen, and growth factors. mTOR activation leads to phosphorylation of multiple downstream targets including the eukaryotic initiation factor 4E (eIF4E) binding proteins-1 and -2 (EIF4EBP1/4E-BP1 and EIF4EBP2/4E-BP2). These binding proteins inhibit protein synthesis, but are inactivated by mTOR to stimulate cell growth and metabolism. However, the role of these proteins in the context of aberrant activation of mTOR, which occurs frequently in cancers through loss of PTEN or mutational activation of the PI3K/AKT pathway, is unclear...
February 16, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29452643/combinatorial-crispr-cas9-metabolic-screens-reveal-critical-redox-control-points-dependent-on-the-keap1-nrf2-regulatory-axis
#7
Dongxin Zhao, Mehmet G Badur, Jens Luebeck, Jose H Magaña, Amanda Birmingham, Roman Sasik, Christopher S Ahn, Trey Ideker, Christian M Metallo, Prashant Mali
The metabolic pathways fueling tumor growth have been well characterized, but the specific impact of transforming events on network topology and enzyme essentiality remains poorly understood. To this end, we performed combinatorial CRISPR-Cas9 screens on a set of 51 carbohydrate metabolism genes that represent glycolysis and the pentose phosphate pathway (PPP). This high-throughput methodology enabled systems-level interrogation of metabolic gene dispensability, interactions, and compensation across multiple cell types...
February 15, 2018: Molecular Cell
https://www.readbyqxmd.com/read/29452640/serine-catabolism-by-shmt2-is-required-for-proper-mitochondrial-translation-initiation-and-maintenance-of-formylmethionyl-trnas
#8
Denise R Minton, Minwoo Nam, Daniel J McLaughlin, Jong Shin, Erol C Bayraktar, Samantha W Alvarez, Vladislav O Sviderskiy, Thales Papagiannakopoulos, David M Sabatini, Kıvanç Birsoy, Richard Possemato
Upon glucose restriction, eukaryotic cells upregulate oxidative metabolism to maintain homeostasis. Using genetic screens, we find that the mitochondrial serine hydroxymethyltransferase (SHMT2) is required for robust mitochondrial oxygen consumption and low glucose proliferation. SHMT2 catalyzes the first step in mitochondrial one-carbon metabolism, which, particularly in proliferating cells, produces tetrahydrofolate (THF)-conjugated one-carbon units used in cytoplasmic reactions despite the presence of a parallel cytoplasmic pathway...
February 15, 2018: Molecular Cell
https://www.readbyqxmd.com/read/29452420/gut-microbiomics-a-solution-to-unloose-the-gordian-knot-of-biological-effects-of-ionizing-radiation
#9
Amy Zhang, Tomoko Y Steen
The Chernobyl and Fukushima nuclear accidents have called forth a growing body of research on their biological aftermaths. A variety of wild organisms, including primates, birds, fish, insects, and worms are being studied in the affected areas, with emerging morphological, physiological, and genetic aberrations ascribed to ionizing radiation. Despite the effort in surveying Chernobyl and Fukushima wildlife, little is known about the microorganisms associated with these radiation-contaminated animals. The microbiota, especially the gut commensal, plays an important role in shaping the metabolic reservoir and immune system of the host, and is sensitive to a wide array of environmental factors, including ionizing radiation...
February 14, 2018: Journal of Heredity
https://www.readbyqxmd.com/read/29452355/culture-facilitated-comparative-genomics-of-the-facultative-symbiont-hamiltonella-defensa
#10
Germain Chevignon, Bret M Boyd, Jayce W Brandt, Kerry M Oliver, Michael R Strand
Many insects host facultative, bacterial symbionts that confer conditional fitness benefits to their hosts. Hamiltonella defensa is a common facultative symbiont of aphids that provides protection against parasitoid wasps. Protection levels vary among strains of H. defensa that are also differentially infected by bacteriophages named APSEs. However, little is known about trait variation among strains because only one isolate has been fully sequenced. Generating complete genomes for facultative symbionts is hindered by relatively large genome sizes but low abundances in hosts like aphids that are very small...
February 14, 2018: Genome Biology and Evolution
https://www.readbyqxmd.com/read/29451882/de-novo-transcriptomic-analysis-of-leaf-and-fruit-tissue-of-cornus-officinalis-using-illumina-platform
#11
Dian-Yun Hou, Lin-Chun Shi, Meng-Meng Yang, Jiong Li, Shuang Zhou, Hong-Xiao Zhang, Hua-Wei Xu
Cornus officinalis is one of the most widely used medicinal plants in China and other East Asian countries to cure diseases such as liver, kidney, cardiovascular diseases and frequent urination for thousands of years. It is a Level 3 protected species, and is one of the 42 national key protected wild species of animals and plants in China. However, the genetics and molecular biology of C. officinalis are poorly understood, which has hindered research on the molecular mechanism of its metabolism and utilization...
2018: PloS One
https://www.readbyqxmd.com/read/29451713/glucose-effectiveness-is-a-critical-pathogenic-factor-leading-to-the-emergence-of-glucose-intolerance-and-type-2-diabetes-mellitus-an-ignored-hypothesis
#12
F P Alford, J E Henriksen, C Rantzau, H Beck-Nielsen
BACKGROUND: Although the ability of glucose to mediate its own in vivo metabolism is long documented, the quantitative measurement of whole body glucose-mediated glucose disposal at basal insulin levels, [glucose effectiveness (GE)], followed the introduction of the Minimal Model IVGTT technique. METHODS: A literature review, combined with our own studies, of the role of GE in glucose metabolism in normal and "at risk" individuals, was undertaken to determine GE's contribution to glucose homeostasis...
February 16, 2018: Diabetes/metabolism Research and Reviews
https://www.readbyqxmd.com/read/29451525/-chronic-pancreatitis-new-definition-and-perspectives
#13
Maria Cristina Conti Bellocchi, Nicolò De Pretis, Antonio Amodio, Alessandro Zerbi, Luca Frulloni
Chronic pancreatitis has been considered over the past years as a single disease, alcohol-induced and different from acute pancreatitis, in terms of etiology and prognosis. Actually, the introduction of a new concept of chronic pancreatitis, now considered as a fibroinflammatory process caused by multiple factors (toxic-metabolic, genetic, immunologic, obstructive), allow to better understand the pathogenesis of this complex disease. Furthermore, the discover of peculiar forms of chronic pancreatitis (autoimmune, paraduodenal, associated to gene mutations), different in term of clinical aspects, findings at imaging, prognosis and therapy, radically changed the concept of the disease...
January 2018: Recenti Progressi in Medicina
https://www.readbyqxmd.com/read/29450776/modulatory-role-of-gstt1-and-gstm1-in-punjabi-agricultural-workers-exposed-to-pesticides
#14
Meenakshi Ahluwalia, Anupam Kaur
Glutathione S-transferases are important detoxification enzymes involved in the metabolism of endogenous as well as exogenous compounds. Individuals differ in metabolic capacity due to inherited genetic variations. Due to the polymorphism exhibited by GSTT1 and GSTM1 that results in the complete loss of function, the present study was aimed towards the determination of the frequency distribution of GSTT1 and GSTM1 in agricultural workers in Punjab, India. The study aimed to investigate their contribution in susceptibility to increased disease risk...
February 15, 2018: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/29450233/pharmacogenomics-guided-policy-in-opioid-use-disorder-oud-management-an-ethnically-diverse-case-based-approach
#15
Earl B Ettienne, Edwin Chapman, Mary Maneno, Adaku Ofoegbu, Bradford Wilson, Beverlyn Settles-Reaves, Melissa Clarke, Georgia Dunston, Kevin Rosenblatt
Introduction: Opioid use disorder (OUD) is characterized by a problematic pattern of opioid use leading to clinically-significant impairment or distress. Opioid agonist treatment is an integral component of OUD management, and buprenorphine is often utilized in OUD management due to strong clinical evidence for efficacy. However, interindividual genetic differences in buprenorphine metabolism may result in variable treatment response, leaving some patients undertreated and at increased risk for relapse...
December 2017: Addictive Behaviors Reports
https://www.readbyqxmd.com/read/29449715/leptin-and-brain-adipose-crosstalks
#16
REVIEW
Alexandre Caron, Syann Lee, Joel K Elmquist, Laurent Gautron
Interactions between the brain and distinct adipose depots have a key role in maintaining energy balance, thereby promoting survival in response to metabolic challenges such as cold exposure and starvation. Recently, there has been renewed interest in the specific central neuronal circuits that regulate adipose depots. Here, we review anatomical, genetic and pharmacological studies on the neural regulation of adipose function, including lipolysis, non-shivering thermogenesis, browning and leptin secretion. In particular, we emphasize the role of leptin-sensitive neurons and the sympathetic nervous system in modulating the activity of brown, white and beige adipose tissues...
February 16, 2018: Nature Reviews. Neuroscience
https://www.readbyqxmd.com/read/29449058/-epidemiology-of-lower-extremity-artery-disease
#17
Victor Aboyans, Marie-Antoinette Sevestre, Ileana Désormais, Philippe Lacroix, Gerry Fowkes, Michael H Criqui
It is estimated that more than 200 million individuals are affected by lower extremity artery disease (LEAD) worldwide. This prevalence has increased between 2000 and 2010 by 25%, especially in low/middle income countries. In France, about one million people are affected by this condition. Almost two-thirds of patients with LEAD are asymptomatic. This explains the interest of the measurement of the ankle-brachial index (ABI), an objective and harmless diagnostic tool. An ABI≤0.90 is considered as diagnostic for LEAD...
February 12, 2018: La Presse Médicale
https://www.readbyqxmd.com/read/29448931/effects-of-different-extracts-of-curcumin-on-tpc1-papillary-thyroid-cancer-cell-line
#18
Angelica Perna, Antonio De Luca, Laura Adelfi, Tammaro Pasquale, Bruno Varriale, Teresa Esposito
BACKGROUND: The thyroid gland is one of the largest endocrine glands in the body. The vast majority of TCs (> 90%) originate from follicular cells and are defined as differentiated thyroid cancers (DTC) and the two histological subtypes are the papillary TC with its variants and the follicular TC. Curcumin possesses a wide variety of biological functions, and thanks to its properties, it has gained considerable attention due to its profound medicinal values (Prasad, Gupta, Tyagi, and Aggarwal, Biotechnol Adv 32:1053-1064, 2014)...
February 15, 2018: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/29448188/genotype-phenotype-and-in-silico-pathogenicity-analysis-of-hexb-mutations-panel-based-sequencing-for-differential-diagnosis-of-gangliosidosis
#19
Nejat Mahdieh, Sahar Mikaeeli, Ali Reza Tavasoli, Zahra Rezaei, Majid Maleki, Bahareh Rabbani
OBJECTIVES: Gangliosidosis is an inherited metabolic disorder causing neurodegeneration and motor regression. Preventive diagnosis is the first choice for the affected families due to lack of straightforward therapy. Genetic studies could confirm the diagnosis and help families for carrier screening and prenatal diagnosis. An update of HEXB gene variants concerning genotype, phenotype and in silico analysis are presented. PATIENTS AND METHODS: Panel based next generation sequencing and direct sequencing of four cases were performed to confirm the clinical diagnosis and for reproductive planning...
February 8, 2018: Clinical Neurology and Neurosurgery
https://www.readbyqxmd.com/read/29447918/chemical-genetics-in-tumor-lipogenesis
#20
REVIEW
Simone Braig
Since cancer cells depend on de novo lipogenesis for energy supply, highly active membrane biosynthesis and signaling, enhanced fatty acid synthesis is a crucial characteristic of cancer cells. Hence, targeting lipogenic enzymes and signaling cascades is a very promising approach in developing innovative therapeutic agents for the fight against cancer. This review summarizes main aspects of altered fatty acid synthesis in cancer cells and emphasizes the power of chemical genetic approaches in identifying and analyzing novel anti-cancer drug candidates interfering with lipid metabolism...
February 12, 2018: Biotechnology Advances
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