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metabolic flexibility

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https://www.readbyqxmd.com/read/28236238/flexible-backbone-methods-for-predicting-and-designing-peptide-specificity
#1
Noah Ollikainen
Protein-protein interactions play critical roles in essentially every cellular process. These interactions are often mediated by protein interaction domains that enable proteins to recognize their interaction partners, often by binding to short peptide motifs. For example, PDZ domains, which are among the most common protein interaction domains in the human proteome, recognize specific linear peptide sequences that are often at the C-terminus of other proteins. Determining the set of peptide sequences that a protein interaction domain binds, or it's "peptide specificity," is crucial for understanding its cellular function, and predicting how mutations impact peptide specificity is important for elucidating the mechanisms underlying human diseases...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28231413/metabolic-chemical-reporters-of-glycans-exhibit-cell-type-selective-metabolism-and-glycoprotein-labeling
#2
Anna R Batt, Balyn W Zaro, Marisol X Navarro, Matthew Robert Pratt
Since the pioneering work by Reutter and co-workers that demonstrated structural flexibility in the carbohydrate biosynthesis and glycosylation pathways, many different labs have used unnatural monosaccharide analogs to perform glycan engineering on the surface of living cells. A subset of these unnatural monosaccharides contain bioorthogonal groups that enable the selective installation of visualization or enrichment tags. These metabolic chemical reporters (MCRs) have proven to be powerful for the unbiased identification of glycoproteins; however they do have certain limitations...
February 23, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28230862/inactivation-of-lsd1-triggers-senescence-in-trophoblast-stem-cells-by-induction-of-sirt4
#3
Josefina Castex, Dominica Willmann, Toufike Kanouni, Laura Arrigoni, Yan Li, Marcel Friedrich, Michael Schleicher, Simon Wöhrle, Mark Pearson, Norbert Kraut, Michaël Méret, Thomas Manke, Eric Metzger, Roland Schüle, Thomas Günther
Coordination of energy metabolism is essential for homeostasis of stem cells, whereas an imbalance in energy homeostasis causes disease and accelerated aging. Here we show that deletion or enzymatic inactivation of lysine-specific demethylase 1 (Lsd1) triggers senescence in trophoblast stem cells (TSCs). Genome-wide transcriptional profiling of TSCs following Lsd1 inhibition shows gene set enrichment of aging and metabolic pathways. Consistently, global metabolomic and phenotypic analyses disclose an unbalanced redox status, decreased glutamine anaplerosis and mitochondrial function...
February 23, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28230167/cytotrophoblast-not-syncytiotrophoblast-dominates-glycolysis-and-oxidative-phosphorylation-in-human-term-placenta
#4
Kevin S Kolahi, Amy M Valent, Kent L Thornburg
The syncytiotrophoblast (SCT) at the maternal-fetal interface has been presumed to be the primary driver of placental metabolism, and the underlying progenitor cytotrophoblast cells (CTB) an insignificant contributor to placental metabolic activity. However, we now show that the metabolic rate of CTB is much greater than the SCT. The oxygen consumption and extracellular acidification rate, a measure of glycolysis, are both greater in CTB than in SCT in vitro (CTB: 96 ± 16 vs SCT: 46 ± 14 pmol O2 × min(-1) × 100 ng DNA(-1), p < 0...
February 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28220500/neuroplus-biofeedback-improves-attention-resilience-and-injury-prevention-in-elite-soccer-players
#5
Aiace Rusciano, Giuliano Corradini, Ivilin Stoianov
Performance and injury prevention in elite soccer players are typically investigated from physical-tactical, biomechanical, and metabolic perspectives. However, executive functions, visuospatial abilities, and psychophysiological adaptability or resilience are also fundamental for efficiency and well-being in sports. Based on previous research associating autonomic flexibility with prefrontal cortical control, we designed a novel integrated autonomic biofeedback training method called Neuroplus to improve resilience, visual attention, and injury prevention...
February 21, 2017: Psychophysiology
https://www.readbyqxmd.com/read/28213330/drug-discovery-strategies-in-the-field-of-tumor-energy-metabolism-limitations-by-metabolic-flexibility-and-metabolic-resistance-to-chemotherapy
#6
REVIEW
N D Amoedo, E Obre, R Rossignol
The search for new drugs capable of blocking the metabolic vulnerabilities of human tumors has now entered the clinical evaluation stage, but several projects already failed in phase I or phase II. In particular, very promising in vitro studies could not be translated in vivo at preclinical stage and beyond. This was the case for most glycolysis inhibitors that demonstrated systemic toxicity. A more recent example is the inhibition of glutamine catabolism in lung adenocarcinoma that failed in vivo despite a strong addiction of several cancer cell lines to glutamine in vitro...
February 16, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28211258/effects-of-a-wide-range-of-dietary-nicotinamide-riboside-nr-concentrations-on-metabolic-flexibility-and-white-adipose-tissue-wat-of-mice-fed-a-mildly-obesogenic-diet
#7
Wenbiao Shi, Maria A Hegeman, Dorien A M van Dartel, Jing Tang, Manuel Suarez, Hans Swarts, Bart van der Hee, Lluis Arola, Jaap Keijer
SCOPE: Metabolic flexibility is the ability to switch metabolism between carbohydrate oxidation (CHO) and fatty acid oxidation (FAO) and is a biomarker for metabolic health. The effect on metabolic health of nicotinamide riboside (NR) as an exclusive source of vitamin B3 is unknown and is examined here for a wide range of NR. DESIGN AND METHODS: Nine-week-old male C57BL/6JRcc mice received a semi-purified mildly obesogenic (40 en% fat) diet containing 0.14% L-tryptophan and either 5, 15, 30, 180 or 900 mg NR per kg diet for 15 weeks...
February 16, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/28211128/staged-intraperitoneal-brachytherapy-and-hyperthermic-intraperitoneal-chemotherapy-in-an-adolescent-novel-anesthetic-challenges-for-pediatric-anesthetists
#8
Andrew D Weatherall, Tristan R Bennett, Mark Lovell, Winnie Fung, Jonathan de Lima
Newer techniques that have found a place in cancer management in adults are offered far less commonly in pediatric patients. We present a case of a patient with recurrent Wilms' tumor managed with a novel combination of cytoreductive surgery, intraperitoneal brachytherapy, and subsequent hyperthermic intraperitoneal chemotherapy. Each stage presents challenges that the pediatric anesthetist is unlikely to have faced before. Such cases require flexibility and thorough planning to manage the combination of major surgery, remote anesthesia with brachytherapy and hyperthermic chemotherapy with its potential for metabolic derangement, significant fluid shifts, analgesic care, and potential exposure of staff to cytotoxic agents...
February 17, 2017: Paediatric Anaesthesia
https://www.readbyqxmd.com/read/28209135/marv-a-tool-for-genome-wide-multi-phenotype-analysis-of-rare-variants
#9
Marika Kaakinen, Reedik Mägi, Krista Fischer, Jani Heikkinen, Marjo-Riitta Järvelin, Andrew P Morris, Inga Prokopenko
BACKGROUND: Genome-wide association studies have enabled identification of thousands of loci for hundreds of traits. Yet, for most human traits a substantial part of the estimated heritability is unexplained. This and recent advances in technology to produce high-dimensional data cost-effectively have led to method development beyond standard common variant analysis, including single-phenotype rare variant and multi-phenotype common variant analysis, with the latter increasing power for locus discovery and providing suggestions of pleiotropic effects...
February 16, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/28196863/conformational-changes-in-the-activation-loop-of-mitochondrial-glutaminase-c-a-direct-fluorescence-read-out-that-distinguishes-the-binding-of-allosteric-inhibitors-from-activators
#10
Clint A Stalnecker, Jon W Erickson, Richard A Cerione
The first step in glutamine catabolism is catalyzed by the mitochondrial enzyme glutaminase, with a specific isoform, glutaminase C (GAC), being highly expressed in cancer cells. GAC activation requires the formation of homo-tetramers, promoted by anionic allosteric activators such as inorganic phosphate. This leads to the proper orientation of a flexible loop proximal to the dimer-dimer interface that is essential for catalysis (i.e. the activation loop). A major class of allosteric inhibitors of GAC, with the prototype being BPTES (bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl)ethyl sulfide), and the related molecule CB-839, binds to the activation loop and induces the formation of an inactive tetramer (2 inhibitors bound per active tetramer)...
February 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28195990/improvements-in-health-related-quality-of-life-cardio-metabolic-health-and-fitness-in-postmenopausal-women-after-a-supervised-multicomponent-adapted-exercise-program-in-a-suited-health-promotion-intervention-a-multigroup-study
#11
Débora Godoy-Izquierdo, Nicolás Mendoza Ladrón de Guevara, Mercedes Vélez Toral, Carlos de Teresa Galván, Alberto Salamanca Ballesteros, Juan F Godoy García
OBJECTIVES: This study explored the multidimensional outcomes that resulted from the adherence to regular exercise among previously sedentary postmenopausal women. The exercise was managed through a supervised, multicomponent, adapted approximately 20-week program in a suited health promotion intervention. METHODS: A multigroup, mixed-design study with between-group (intervention, sedentary, and active women) and within-subject measures (baseline, postintervention, and 3- and 12-month follow-ups) was conducted using intention-to-treat methodology...
February 13, 2017: Menopause: the Journal of the North American Menopause Society
https://www.readbyqxmd.com/read/28194237/the-impact-of-micronutrient-status-on-health-correlation-network-analysis-to-understand-the-role-of-micronutrients-in-metabolic-inflammatory-processes-regulating-homeostasis-and-phenotypic-flexibility
#12
Tim J van den Broek, Bas H A Kremer, Marisa Marcondes Rezende, Femke P M Hoevenaars, Peter Weber, Ulrich Hoeller, Ben van Ommen, Suzan Wopereis
BACKGROUND: Vitamins and carotenoids are key micronutrients facilitating the maintenance of health, as evidenced by the increased risk of disease with low intake. Optimal phenotypic flexibility, i.e., the ability to respond to a physiological challenge, is an essential indicator of health status. Therefore, health can be measured by applying a challenge test and monitoring the response of relevant phenotypic processes. In this study, we assessed the correlation of three fat-soluble vitamins, (i...
2017: Genes & Nutrition
https://www.readbyqxmd.com/read/28192772/direct-3d-bioprinting-of-prevascularized-tissue-constructs-with-complex-microarchitecture
#13
Wei Zhu, Xin Qu, Jie Zhu, Xuanyi Ma, Sherrina Patel, Justin Liu, Pengrui Wang, Cheuk Sun Edwin Lai, Maling Gou, Yang Xu, Kang Zhang, Shaochen Chen
Living tissues rely heavily on vascular networks to transport nutrients, oxygen and metabolic waste. However, there still remains a need for a simple and efficient approach to engineer vascularized tissues. Here, we created prevascularized tissues with complex three-dimensional (3D) microarchitectures using a rapid bioprinting method - microscale continuous optical bioprinting (μCOB). Multiple cell types mimicking the native vascular cell composition were encapsulated directly into hydrogels with precisely controlled distribution without the need of sacrificial materials or perfusion...
February 2, 2017: Biomaterials
https://www.readbyqxmd.com/read/28192103/endoscopic-bariatric-and-metabolic-therapies-new-and-emerging-technologies
#14
Shelby Sullivan, Steven A Edmundowicz, Christopher C Thompson
Endoscopic Bariatric and Metabolic Therapies (EBMT) are a new addition to the treatment arsenal for obesity. These include devices which are placed or removed via flexible endoscopy, and procedures which utilize instruments that require flexible endoscopy for the indications of weight loss or treatment of glucose intolerance (from pre-diabetes to diabetes). The EBMTs are generally divided into gastric and small bowel categories, and although individual EBMTs may have unique mechanisms of action, similar themes in proposed mechanism of action are seen in the gastric and small bowel EBMTs respectively...
February 9, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28188340/development-and-validation-of-a-new-dynamic-in-vitro-model-of-the-piglet-colon-pigutivm-application-to-the-study-of-probiotics
#15
Mickaël Alain Fleury, Olivier Le Goff, Sylvain Denis, Frédérique Chaucheyras-Durand, Eric Jouy, Isabelle Kempf, Monique Alric, Stéphanie Blanquet-Diot
For ethical, technical, regulatory, and cost reasons, in vitro methods are increasingly used as an alternative to in vivo experimentations. The aim of the present study was to validate, according to in vivo data in living animals, a new in vitro model of the piglet colon, the PigutIVM, under both control conditions and antibiotic disturbance by the widely used colistin. The PigutIVM reproduces the main biotic and abiotic parameters of the piglet colon: temperature, pH, retention time, supply of ileal effluents, complex, and metabolically active microbiota and self-maintained anaerobiosis...
February 10, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28187134/metabolic-regulation-is-sufficient-for-global-and-robust-coordination-of-glucose-uptake-catabolism-energy-production-and-growth-in-escherichia-coli
#16
Pierre Millard, Kieran Smallbone, Pedro Mendes
The metabolism of microorganisms is regulated through two main mechanisms: changes of enzyme capacities as a consequence of gene expression modulation ("hierarchical control") and changes of enzyme activities through metabolite-enzyme interactions. An increasing body of evidence indicates that hierarchical control is insufficient to explain metabolic behaviors, but the system-wide impact of metabolic regulation remains largely uncharacterized. To clarify its role, we developed and validated a detailed kinetic model of Escherichia coli central metabolism that links growth to environment...
February 10, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28182651/a-comprehensive-software-suite-for-protein-family-construction-and-functional-site-prediction
#17
David Renfrew Haft, Daniel H Haft
In functionally diverse protein families, conservation in short signature regions may outperform full-length sequence comparisons for identifying proteins that belong to a subgroup within which one specific aspect of their function is conserved. The SIMBAL workflow (Sites Inferred by Metabolic Background Assertion Labeling) is a data-mining procedure for finding such signature regions. It begins by using clues from genomic context, such as co-occurrence or conserved gene neighborhoods, to build a useful training set from a large number of uncharacterized but mutually homologous proteins...
2017: PloS One
https://www.readbyqxmd.com/read/28179229/exogenous-amino-acids-suppress-glucose-oxidation-and-potentiate-hepatic-glucose-production-in-late-gestation-fetal-sheep
#18
Laura D Brown, Jaden R Kohn, Paul J Rozance, William W Hay, Stephanie R Wesolowski
Acute amino acid (AA) infusion increases AA oxidation rates in normal late gestation fetal sheep. Because fetal oxygen consumption rate does not change with increased AA oxidation, we hypothesized that AA infusion would suppress glucose oxidation pathways and that the additional carbon supply from AA would activate hepatic glucose production. To test this, late gestation fetal sheep were infused intravenously for 3h with saline or exogenous AA (AA). Glucose tracer metabolic studies were performed and skeletal muscle and liver tissues samples were collected...
February 8, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/28178355/effects-of-exercise-training-on-circulating-levels-of-dickkpof-1-and-secreted-frizzled-related-protein-1-in-breast-cancer-survivors-a-pilot-single-blind-randomized-controlled-trial
#19
Tae Ho Kim, Jae Seung Chang, Kyu-Sang Park, Jeeyeon Park, Nahyun Kim, Jong In Lee, In Deok Kong
BACKGROUND: Wingless and integration site growth factor (Wnt) signaling is a tumorigenesis-related signaling pathway. Dickkpof-1 (DKK1) and secreted frizzled-related protein-1 (SFRP1) are endogenous negative regulators of Wnt/β-catenin signaling. Accumulating evidence indicates that higher serum levels of DKK1 are correlated with poor prognosis of various types of cancer. Here, we investigated whether exercise training causes changes in the serum levels of DKK1 and SFRP1 in patients with breast cancer...
2017: PloS One
https://www.readbyqxmd.com/read/28174563/metabolic-flexibility-of-yarrowia-lipolytica-growing-on-glycerol
#20
Michael Egermeier, Hannes Russmayer, Michael Sauer, Hans Marx
The yeast Yarrowia lipolytica is a fascinating microorganism with an amazing metabolic flexibility. This yeast grows very well on a wide variety of carbon sources from alkanes over lipids, to sugars and glycerol. Y. lipolytica accumulates a wide array of industrially relevant metabolites. It is very tolerant to many environmental factors, above all the pH value. It grows perfectly well over a wide pH range, but it has been described, that the pH has a decisive influence on the metabolite pattern accumulated by this yeast...
2017: Frontiers in Microbiology
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