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Julie J Miller, Wolfgang Wick
The majority of World Health Organization grade II and grade III gliomas harbor heterozygous mutations in the metabolic enzyme isocitrate dehydrogenase 1 (IDH1), and tumors with an IDH wild-type status show molecular features of a glioblastoma and simply may constitute a separate disease entity. This discovery has led to a profound shift in the way that gliomas are classified and, consequently, how treatment decisions are made. We will review the current understanding of IDH- mutant gliomagenesis and the preclinical models being used to investigate the underlying biology of these tumors and to explore new therapeutic options for these patients...
February 2018: Seminars in Neurology
Philipp Kickingereder, Ovidiu Cristian Andronesi
Magnetic resonance imaging plays a key role in diagnosis and treatment monitoring of brain tumors. Novel imaging techniques that specifically interrogate aspects of underlying tumor biology and biochemical pathways have great potential in neuro-oncology. This review focuses on the emerging role of 2-hydroxyglutarate-targeted magnetic resonance spectroscopy, as well as radiomics and radiogenomics in establishing diagnosis for isocitrate dehydrogenase mutant gliomas, and for monitoring treatment response and predicting prognosis of this group of brain tumor patients...
February 2018: Seminars in Neurology
Po-Han Chen, Jen-Tsan Chi, Michael Boyce
In metazoans, thousands of intracellular proteins are modified with O-linked β-N-acetylglucosamine (O-GlcNAc) in response to a wide range of stimuli and stresses. In particular, a complex and evolutionarily conserved interplay between O-GlcNAcylation and oxidative stress has emerged in recent years. Here, we review the current literature on the connections between O-GlcNAc and oxidative stress, with a particular emphasis on major signaling pathways, such as KEAP1/NRF2, FOXO, NFκB, p53 and cell metabolism...
March 14, 2018: Glycobiology
Shiqi Luo, Feng He, Junjie Luo, Shengqian Dou, Yirong Wang, Annan Guo, Jian Lu
Transfer RNA-derived small RNAs (tsRNAs) are an emerging class of small RNAs, yet their regulatory roles have not been well understood. Here we studied the molecular mechanisms and consequences of tsRNA-mediated regulation in Drosophila. By analyzing 495 public small RNA libraries, we demonstrate that most tsRNAs are conserved, prevalent and abundant in Drosophila. By carrying out mRNA sequencing and ribosome profiling of S2 cells transfected with single-stranded tsRNA mimics and mocks, we show that tsRNAs recognize target mRNAs through conserved complementary sequence matching and suppress target genes by translational inhibition...
March 14, 2018: Nucleic Acids Research
Brooke N Wolford, Cristen J Willer, Ida Surakka
The combination of Electronic Health Records (EHRs) with genetic data has ushered in the next wave of complex disease genetics. Population-based biobanks and other large cohorts provide sufficient sample sizes to identify novel genetic associations across the hundreds to thousands of phenotypes gleaned from EHRs. In this review we summarize the current state of these EHR-linked biobanks, explore ongoing methods development in the field, and highlight recent discoveries of genetic associations. We enumerate the many existing biobanks with EHRs linked to genetic data, many of which are available to researchers via application and contain sample sizes > 50,000...
March 14, 2018: Human Molecular Genetics
Rika Fukumori, Yoji Masuda, Ayaka Takeuchi, Rina Yanai, Khurchabiling Atchalalt, Borjigin Sarentonglaga, Kazuko Ogata, Mio Yamaguchi, Asuka Hara, Akane Sato, Toshihisa Sugino, Yoshikazu Nagao
The aim of this study was to investigate how intra-duodenal infusions of fatty acids (FA) affect appetite-related gut peptides such as glucagon-like peptide-1 (GLP-1) and ghrelin in sheep. We hypothesized that these peptides can be highly reactive to unsaturated long-chain FA, because they are well known to decrease DMI. Four ewes were fitted with a duodenal cannula and a jugular vein catheter for a 6-h duodenal infusion of the nine FA (C8:0, C10:0, C12:0, C14:0, C16:0, C18:0, C18:1, C18:2, C18:3) and water (control)...
March 14, 2018: Journal of Animal Science
Qiaozhen Meng, Zhenling Peng, Jianyi Yang
Motivation: Coenzyme A (CoA)-protein binding plays an important role in various cellular functions and metabolic pathways. However, no computational methods can be employed for CoA-binding residues prediction. Results: We developed three methods for the prediction of CoA- and CoA derivatives-binding residues, including an ab-initio method SVMpred, a template-based method TemPred, and a consensus-based method CoABind. In SVMpred, a comprehensive set of features are designed from two complementary sequence profiles and the predicted secondary structure and solvent accessibility...
March 14, 2018: Bioinformatics
Tristan Pascart, Frédéric Lioté
This review article summarizes the relevant English literature on gout from 2010 through April 2017. It emphasizes that the current epidemiology of gout indicates a rising prevalence worldwide, not only in Western countries but also in Southeast Asia, in close relationship with the obesity and metabolic syndrome epidemics. New pathogenic mechanisms of chronic hyperuricaemia focus on the gut (microbiota, ABCG2 expression) after the kidney. Cardiovascular and renal comorbidities are the key points to consider in terms of management...
March 13, 2018: Rheumatology
Kristel Ehala-Aleksejev, Margus Punab
This study aimed to determine the effect of metabolic syndrome (MS) on the reproductive function in fertile (FM) and male partners of infertile couples (MPIC). We performed a cross-sectional study formatting two study groups: partners of pregnant women (n = 238; mean age 32.0) as FM and male partners of infertile couples (n = 2642; mean age 32.6) as MPIC. A standard semen analysis was performed and clinical, laboratory and lifestyle data were analysed. The adapted NCEP-ATPIII criteria were used to define MS...
2018: PloS One
Mingfei Zeng, Huachuan Cao
Short chain fatty acids (SCFA) and ketone bodies recently emerged as important physiological relevant metabolites because of their association with microbiota, immunology, obesity and other metabolic states. They were commonly analyzed by GC-MS with long run time and laborious sample preparation. In this study we developed a novel LC-MS/MS method using fast derivatization coupled with liquid-liquid extraction to detect SCFA and ketone bodies in plasma and feces. Several different derivatization reagents were evaluated to compare the efficiency, the sensitivity and chromatographic separation of structural isomers...
March 8, 2018: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
Hilal Ahmad Parray, Jameel Lone, Jong Pil Park, Jang Won Choi, Jong Won Yun
OBJECTIVE: The aim of this study was to explore the browning and antioxidative effects of magnolol in 3T3-L1 adipocytes, as recruitment of beige-like adipocytes (browning) by natural compounds is being considered as a promising strategy to fight against obesity. METHODS: Magnolol-induced browning effect was evaluated by determining the expression levels of specific marker genes and proteins using real-time polymerase chain reaction and immunoblotting, respectively...
February 5, 2018: Nutrition
Sergio Polakof, Didier Rémond, Jérémie David, Dominique Dardevet, Isabelle Savary-Auzeloux
OBJECTIVES: High-fat high-sucrose diet (HFHS) overfeeding is one of the main factors responsible for the increased prevalence of metabolic disorders. Elevated levels of branched-chain amino acids (BCAAs) have been associated with metabolic dysfunctions, including insulin resistance (IR). The aim of this study was to elucidate whether elevated BCAA levels are the cause or the consequence of IR and to determine the mechanisms and tissues involved in such a phenotype. METHODS: We performed a 2-mo follow-up on minipigs overfed an HFHS diet and focused on kinetics fasting and postprandial (PP) BCAA levels and BCAA catabolism in key tissues...
November 27, 2017: Nutrition
Shelley HuaLei Zhang, Stephan E Maier, Lawrence P Panych
PURPOSE: Magnetic resonance spectroscopic imaging (MRSI), under low-spatial resolution settings, often suffers signal contamination from neighboring voxels due to ringing artifacts. Spatial localization can be improved by constraining the point-spread-function (PSF). Here the effectiveness of the two-dimensional PSF-Choice technique in providing improved spatial localization for MRSI is demonstrated. THEORY AND METHODS: The PSF-Choice technique constrains the PSF to a desired shape by manipulating the weighting of RF excitation pulse throughout phase-encode steps...
March 3, 2018: Journal of Magnetic Resonance
Laura Wallard, Sophie Boulet, Olivier Cornu, Jean-Emile Dubuc, Philippe Mahaudens, Didier Postlethwaite, Maïté Van Cauter, Christine Detrembleur
BACKGROUND: The gait mechanism requires an efficient intersegmental coordination in order to ensure the displacement of the body while simultaneously maintaining the postural stability. However, intersegmental coordination may be disrupted by neurological or orthopaedic involvement, this increasing the metabolic cost associated with excessive or prolonged muscle co-contraction. RESEARCH QUESTION: Our aim was to evaluate and to understand how hip OA affects lower limbs coordination during gait by using the kinematic segmental covariation law method and predict the energy expenditure...
March 7, 2018: Gait & Posture
Qiushi Li, Jihui Wang, Xuteng Xing, Wenbin Hu
The corrosion behavior of X65 steel was investigated in the seawater inoculated with sulfate reducing bacteria (SRB) under the aerobic environment by electrochemical impedance techniques and immersion tests. The corroded morphologies and the composition of the corrosion products were investigated. The variation of the solution parameters including the bacterium number, the pH value and the soluble iron concentration were also investigated. The results indicated that in the SRB-containing system, the impedance responses presented a depressed semi-circle in the initial period, which then turned into the blocked electrode characteristic during the later immersion...
March 11, 2018: Bioelectrochemistry
Annarita Falanga, Flavia A Mercurio, Antonietta Siciliano, Lucia Lombardi, Stefania Galdiero, Marco Guida, Giovanni Libralato, Marilisa Leone, Emilia Galdiero
This study evaluated the effect of QDs functionalized with the antimicrobial peptide indolicidin on oxidative stress and metabolomics profiles of Daphnia magna across three generations (F0, F1, and F2). Exposing D. magna to sub-lethal concentrations of the complex QDs-indolicidin, a normal survival of daphnids was observed from F0 to F2, but a delay of first brood, fewer broods per female, a decrease of length of about 50% compared to control. In addition, QDs-indolicidin induced a significantly higher production of reactive oxygen species (ROS) gradually in each generation and an impairment of enzymes response to oxidative stress such as superoxide dismutase (SOD), catalase (CAT) and glutathione transferase (GST)...
March 8, 2018: Aquatic Toxicology
Jared T Hammill, Deepak Bhasin, Daniel C Scott, Jaeki Min, Yizhe Chen, Yan Lu, Lei Yang, Ho Shin Kim, Michele C Connelly, Courtney Hammill, Gloria Holbrook, Cynthia Jeffries, Bhuvanesh Singh, Brenda A Schulman, R Kiplin Guy
We previously reported the discovery, validation, and structure-activity relationships of a series of piperidinyl ureas that potently inhibit the DCN1-UBE2M interaction. We demonstrated that compound 7 inhibits both the DCN1-UBE2M protein-protein interaction and DCN1-mediated cullin neddylation in biochemical assays and reduces levels of steady-state cullin neddylation in a squamous carcinoma cell line harboring DCN1 amplification. Although compound 7 exhibits good solubility and permeability, it is rapidly metabolized in microsomal models (CLint = 170 mL/min/kg)...
March 16, 2018: Journal of Medicinal Chemistry
Christelle Sanchez, Gabriel Mazzucchelli, Cécile Lambert, Fanny Comblain, Edwin DePauw, Yves Henrotin
OBJECTIVE: Osteoarthritis (OA) is characterized by cartilage degradation but also by other joint tissues modifications like subchondral bone sclerosis. In this study, we used a proteomic approach to compare secretome of osteoblast isolated from sclerotic (SC) or non sclerotic (NSC) area of OA subchondral bone. DESIGN: Secretome was analyzed using differential quantitative and relative label free analysis on nanoUPLC G2 HDMS system. mRNA of the more differentially secreted proteins were quantified by RT-PCR in cell culture from 5 other patients...
2018: PloS One
Nasir Mehmood, Ranim Alayoubi, Eric Husson, Cédric Jacquard, Jochen Büchs, Catherine Sarazin, Isabelle Gosselin
Imidazolium ionic liquids (ILs) are promising solvents for lignocellulosic biomass (LCB) pretreatment and allow the achievement of higher ethanolic yields after enzymatic hydrolysis and ethanolic fermentation. However, residual ILs entrapped in pretreated biomass are often toxic for fermentative microorganisms, but interaction mechanisms between ILs and cells are still unknown. Here we studied the effects of 1-ethyl-3-methylimidazolium acetate [Emim][OAc] and 1-ethyl-3-methylimidazolium methylphosphonate [Emim][MeO(H)PO₂] on Kluyveromyces marxianus , a thermotolerant ethanologenic yeast...
March 16, 2018: International Journal of Molecular Sciences
Huaqi Zhang, Song Lin, Tianlin Gao, Feng Zhong, Jing Cai, Yongye Sun, Aiguo Ma
The associations between sarcopenia and metabolic syndrome (MetS) in non-obese middle-aged and older adults remain controversial. Thus, this meta-analysis aimed to evaluate the overall prevalence of MetS and the correlations between sarcopenia and MetS in middle-aged and older non-obese adults. We performed a systematic searched strategy using PUBMED, EMBASE and Web of Science databases for relevant observational studies investigating sarcopenia and MetS up to 11 May 2017. The polled prevalence of MetS and odds ratios with 95% confidence intervals (CI), as well as subgroup analyses were calculated using a random effects model...
March 16, 2018: Nutrients
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