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https://www.readbyqxmd.com/read/29161457/the-soluble-guanylate-cyclase-cyg12-is-required-for-the-acclimation-to-hypoxia-and-trophic-regimes-in-chlamydomonas-reinhardtii
#1
Melis Düner, Jan Lambertz, Carolin Mügge, Anja Hemschemeier
Oxygenic phototrophs frequently encounter environmental conditions that result in intracellular energy crises. Growth of the unicellular green alga Chlamydomonas reinhardtii in hypoxia in the light depends on acclimatory responses of which the induction of photosynthetic cyclic electron flow is essential. The microalga cannot grow in the absence of molecular oxygen (O2 ) in the dark, although it possesses an elaborate fermentation metabolism. Not much is known about how the microalga senses and signals the lack of O2 or about its survival strategies during energy crises...
November 21, 2017: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/29161034/dynamic-glycosylation-governs-the-vertebrate-copii-protein-trafficking-pathway
#2
Nathan J Cox, Gokhan Unlu, Brittany J Bisnett, Thomas R Meister, Brett Condon, Peter M Luo, Tim J Smith, Michael Hanna, Abhishek Chhetri, Erik J Soderblom, Anjon Audhya, Ela W Knapik, Michael Boyce
The COPII coat complex, which mediates secretory cargo trafficking from the endoplasmic reticulum, is a key control point for subcellular protein targeting. Because misdirected proteins cannot function, protein sorting by COPII is critical for establishing and maintaining normal cell and tissue homeostasis. Indeed, mutations in COPII genes cause a range of human pathologies, including cranio-lenticulo-sutural dysplasia (CLSD), which is characterized by collagen trafficking defects, craniofacial abnormalities and skeletal dysmorphology...
November 21, 2017: Biochemistry
https://www.readbyqxmd.com/read/29159981/understanding-the-metabolic-burden-of-recombinant-antibody-production-in-saccharomyces-cerevisiae-using-a-quantitative-metabolomics-approach
#3
Jorg C de Ruijter, Essi V Koskela, Jatin Nandania, Alexander D Frey, Vidya Velagapudi
The cellular changes induced by heterologous protein expression in the yeast Saccharomyces cerevisiae have been analyzed on many levels and found to be significant. However, even though high-level protein production poses a metabolic burden, evaluation of the expression host at the level of the metabolome has often been neglected. We present a comparison of metabolite profiles of a wild-type strain with those of three strains producing recombinant antibody variants of increasing size and complexity: a scFv fragment, a scFv-Fc fusion protein, and a full-length IgG molecule...
November 20, 2017: Yeast
https://www.readbyqxmd.com/read/29159769/diversity-effect-of-capsaicin-on-different-types-of-skeletal-muscle
#4
Gan Zhou, Lina Wang, Yaqiong Xu, Kelin Yang, Lv Luo, Leshan Wang, Yongxiang Li, Jiawen Wang, Gang Shu, Songbo Wang, Ping Gao, Xiaotong Zhu, Qianyun Xi, Jiajie Sun, Yongliang Zhang, Qingyan Jiang
Capsaicin is a major pungent content in green and red peppers which are widely used as spice, and capsaicin may activate different receptors. To determine whether capsaicin has different effects on different types of skeletal muscle, we applied different concentrations (0, 0.01, and 0.02%) of capsaicin in the normal diet and conducted a four-week experiment on Sprague-Dawley rats. The fiber type composition, glucose metabolism enzyme activity, and different signaling molecules' expressions of receptors were detected...
November 20, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/29159325/role-of-aramchol-in-steatohepatitis-and-fibrosis-in-mice
#5
Marta Iruarrizaga-Lejarreta, Marta Varela-Rey, David Fernández-Ramos, Ibon Martínez-Arranz, Teresa C Delgado, Jorge Simon, Virginia Gutiérrez-de Juan, Laura delaCruz-Villar, Mikel Azkargorta, José L Lavin, Rebeca Mayo, Sebastiaan M Van Liempd, Igor Aurrekoetxea, Xabier Buqué, Donatella Delle Cave, Arantza Peña, Juan Rodríguez-Cuesta, Ana M Aransay, Felix Elortza, Juan M Falcón-Pérez, Patricia Aspichueta, Liat Hayardeny, Mazen Noureddin, Arun J Sanyal, Cristina Alonso, Juan Anguita, María Luz Martínez-Chantar, Shelly C Lu, José M Mato
Nonalcoholic steatohepatitis (NASH) is the advanced form of nonalcoholic fatty liver disease (NAFLD) which sets the stage for further liver damage. The mechanism for the progression of NASH involves multiple parallel hits including oxidative stress, mitochondrial dysfunction, inflammation and others. Manipulation of any of these pathways may be an approach to prevent NASH development and progression. Aramchol (arachidyl-amido cholanoic acid) is presently in a phase IIb NASH study. The aim of this study was to investigate Aramchol's mechanism of action and its effect on fibrosis using the methionine- and choline-deficient (MCD) diet model of NASH...
November 2017: Hepatol Commun
https://www.readbyqxmd.com/read/29158827/long-term-effect-of-biomineralized-insulin-nanoparticles-on-type-2-diabetes-treatment
#6
Yun Xiao, Xiaoyu Wang, Ben Wang, Xueyao Liu, Xurong Xu, Ruikang Tang
Intracellular insulin may exhibit a long-term effect in regulating protein synthesis, DNA synthesis, and gene transcription. However, the intracellular delivery of insulin is a great challenge. Here, we describe how a simple biomineralization modification of insulin can transport it into intact cells on a large scale, leading to a long-term therapeutic effect on diabetes mellitus. Using insulin-resistant HepG2 cell and diabetic KKAy mice as models, in vitro and in vivo assessments have demonstrated that biomineralized insulin nanoparticles can trigger glucose metabolism, and this improvement extends after the treatment...
2017: Theranostics
https://www.readbyqxmd.com/read/29158770/does-the-enterolactone-enl-affect-fatty-acid-transporters-and-lipid-metabolism-in-liver
#7
Krzysztof Drygalski, Klaudia Berk, Tomasz Charytoniuk, Nicoletta Iłowska, Bartłomiej Łukaszuk, Adrian Chabowski, Karolina Konstantynowicz-Nowicka
Background: NAFLD as a result of inappropriate diet and obesity, may progress to sever conditions such as: type 2 diabetes mellitus or steatohepatitis, and has recently become a prevalent topic of numerous investigations. Due to its dangerous aftermaths, finding new substances, such as polyphenols and their derivatives, which might reduce liver steatosis is the main target of research into NAFLD treatment. Hence, the aim of the present study was to evaluate the effect(s) of enterolactone (ENL), a metabolite of secoisolariciresinol (SECO), on lipid metabolism together with changes in the expression of fatty acid transporters in fatty liver...
2017: Nutrition & Metabolism
https://www.readbyqxmd.com/read/29158619/the-effect-of-mineral-based-alkaline-water-on-hydration-status-and-the-metabolic-response-to-short-term-anaerobic-exercise
#8
Jakub Chycki, Tomasz Zając, Adam Maszczyk, Anna Kurylas
Previously it was demonstrated that mineralization and alkalization properties of mineral water are important factors influencing acid-base balance and hydration in athletes. The purpose of this study was to investigate the effects of drinking different types of water on urine pH, specific urine gravity, and post-exercise lactate utilization in response to strenuous exercise. Thirty-six male soccer players were divided into three intervention groups, consuming around 4.0 l/day of different types of water for 7 days: HM (n=12; highly mineralized water), LM (n=12; low mineralized water), and CON (n=12; table water)...
September 2017: Biology of Sport
https://www.readbyqxmd.com/read/29158350/cell-fate-decisions-emerging-roles-for-metabolic-signals-and-cell-morphology
#9
REVIEW
Sumitra Tatapudy, Francesca Aloisio, Diane Barber, Todd Nystul
Understanding how cell fate decisions are regulated is a fundamental goal of developmental and stem cell biology. Most studies on the control of cell fate decisions address the contributions of changes in transcriptional programming, epigenetic modifications, and biochemical differentiation cues. However, recent studies have found that other aspects of cell biology also make important contributions to regulating cell fate decisions. These cues can have a permissive or instructive role and are integrated into the larger network of signaling, functioning both upstream and downstream of developmental signaling pathways...
November 20, 2017: EMBO Reports
https://www.readbyqxmd.com/read/29158345/stable-oxidative-cytosine-modifications-accumulate-in-cardiac-mesenchymal-cells-from-type2-diabetes-patients-rescue-by-alpha-ketoglutarate-and-tet-tdg-functional-reactivation
#10
Francesco Spallotta, Chiara Cencioni, Sandra Atlante, Davide Garella, Mattia Cocco, Mattia Mori, Raffaella Mastrocola, Carsten Künne, Stefan Günther, Simona Nanni, Valerio Azzimato, Sven Zukunft, Angela Kornberger, Duran Sueruen, Frank Schnutgen, Harald von Melchner, Antonella Di Stilo, Manuela Aragno, Maarten Braspenning, Wim Van Criekinge, Miles J De Blasio, Rebecca H Ritchie, Germana Zaccagnini, Fabio Martelli, Antonella Farsetti, Ingrid Fleming, Thomas Braun, Andres Beiras-Fernandez, Bruno Botta, Massimo Collino, Massimo Bertinaria, Andreas M Zeiher, Carlo Gaetano
Rationale: Human cardiac mesenchymal cells (CMSCs) are a therapeutically-relevant primary cell population. Diabetes compromises CMSC function as consequence of metabolic alterations and incorporation of stable epigenetic changes. Objective: To investigate the role of α-ketoglutarate (αKG) in the epi-metabolic control of DNA demethylation in CMSCs. Methods and Results: Quantitative global analysis, methylated and hydroxymethylated DNA sequencing and gene specific GC methylation detection revealed an accumulation of 5mC, 5hmC and 5fC in the genomic DNA of human CMSCs isolated from diabetic (D) donors (D-CMSCs)...
November 20, 2017: Circulation Research
https://www.readbyqxmd.com/read/29157600/receptor-structure-based-discovery-of-non-metabolite-agonists-for-the-succinate-receptor-gpr91
#11
Mette Trauelsen, Elisabeth Rexen Ulven, Siv A Hjorth, Matjaz Brvar, Claudia Monaco, Thomas M Frimurer, Thue W Schwartz
OBJECTIVE: Besides functioning as an intracellular metabolite, succinate acts as a stress-induced extracellular signal through activation of GPR91 (SUCNR1) for which we lack suitable pharmacological tools. METHODS AND RESULTS: Here we first determined that the cis conformation of the succinate backbone is preferred and that certain backbone modifications are allowed for GPR91 activation. Through receptor modeling over the X-ray structure of the closely related P2Y1 receptor, we discovered that the binding pocket is partly occupied by a segment of an extracellular loop and that succinate therefore binds in a very different mode than generally believed...
December 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/29157236/monitoring-of-nutrient-limitation-in-growing-e-coli-a-mathematical-model-of-a-ppgpp-based-biosensor
#12
Alexandra Pokhilko
BACKGROUND: E. coli can be used as bacterial cell factories for production of biofuels and other useful compounds. The efficient production of the desired products requires careful monitoring of growth conditions and the optimization of metabolic fluxes. To avoid nutrient depletion and maximize product yields we suggest using a natural mechanism for sensing nutrient limitation, related to biosynthesis of an intracellular messenger - guanosine tetraphosphate (ppGpp). RESULTS: We propose a design for a biosensor, which monitors changes in the intracellular concentration of ppGpp by coupling it to a fluorescent output...
November 21, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/29157227/metabolic-adaptation-of-two-in-silico-mutants-of-mycobacterium-tuberculosis-during-infection
#13
Víctor A López-Agudelo, Andres Baena, Howard Ramirez-Malule, Silvia Ochoa, Luis F Barrera, Rigoberto Ríos-Estepa
BACKGROUND: Up to date, Mycobacterium tuberculosis (Mtb) remains as the worst intracellular killer pathogen. To establish infection, inside the granuloma, Mtb reprograms its metabolism to support both growth and survival, keeping a balance between catabolism, anabolism and energy supply. Mtb knockouts with the faculty of being essential on a wide range of nutritional conditions are deemed as target candidates for tuberculosis (TB) treatment. Constraint-based genome-scale modeling is considered as a promising tool for evaluating genetic and nutritional perturbations on Mtb metabolic reprogramming...
November 21, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/29156912/genetic-biomarkers-associated-with-pain-flare-and-dexamethasone-response-following-palliative-radiotherapy-in-patients-with-painful-bone-metastases
#14
Anthony Furfari, Bo Angela Wan, Keyue Ding, Andrew Wong, Liting Zhu, Andrea Bezjak, Rebecca Wong, Carolyn F Wilson, Carlo DeAngelis, Azar Azad, Edward Chow, George S Charames
BACKGROUND: In patients who receive palliative radiation therapy (RT) for painful bone metastases, 40% experience a transient increase in pain known as a pain flare. Prophylactic dexamethasone has been shown to reduce pain flare incidence to 25%. We aimed to identify DNA biomarkers associated with pain flare and dexamethasone response. METHODS: Daily pain levels were recorded by 81 patients who received a single 8 Gy RT for painful bone metastases, of which 50 also received prophylactic dexamethasone...
September 20, 2017: Annals of Palliative Medicine
https://www.readbyqxmd.com/read/29156431/pathway-of-oxfendazole-from-the-host-into-the-worm-trichuris-suis-in-pigs
#15
Tina V A Hansen, Andrew R Williams, Matthew Denwood, Peter Nejsum, Stig M Thamsborg, Christian Friis
It is well known that the efficacy of a single oral dose of benzimidazoles against Trichuris spp. infections in humans and animals is poor, but is currently still used in control programmes against human trichuriasis. However, the route of the benzimidazoles from the treated host to Trichuris remains unknown. As parts of adult Trichuris are situated intracellularly in the caecum, they might be exposed to anthelmintic drugs in the intestinal content as well as the mucosa. In this study, the pathway of oxfendazole and its metabolites was explored using a T...
November 9, 2017: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/29155247/cells-have-sex-chromosomes-and-circadian-clocks-implications-for-organismal-level-functions
#16
Rae Silver
A great number of stakeholders have a keen interest in issues surrounding sex differences. These participants in the discourse often use the same evidence to draw opposite conclusions, with implications for individuals and society as a whole. One part of the maelstrom and associated emotionality derives from confounds between the concepts of "sex" vs. "gender", even among professionals. Here, the oft-repeated point is made that evidence for gender differences can't be derived from the animal research, once the generally accepted conception of gender as a process unique to humans, is acknowledged...
November 15, 2017: Physiology & Behavior
https://www.readbyqxmd.com/read/29155147/selective-and-membrane-permeable-small-molecule-inhibitors-of-nicotinamide-n-methyltransferase-reverse-high-fat-diet-induced-obesity-in-mice
#17
Harshini Neelakantan, Virginia Vance, Michael D Wetzel, Hua-Yu Leo Wang, Stanton F McHardy, Celeste C Finnerty, Jonathan D Hommel, Stanley J Watowich
There is a critical need for new mechanism-of-action drugs that reduce the burden of obesity and associated chronic metabolic comorbidities. A potentially novel target to treat obesity and type 2 diabetes is nicotinamide-N-methyltransferase (NNMT), a cytosolic enzyme with newly identified roles in cellular metabolism and energy homeostasis. To validate NNMT as an anti-obesity drug target, we investigated the permeability, selectivity, mechanistic, and physiological properties of a series of small molecule NNMT inhibitors...
November 15, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29154757/macrophage-polarization-and-meta-inflammation
#18
REVIEW
Chuan Li, Maria M Xu, Kepeng Wang, Adam J Adler, Anthony T Vella, Beiyan Zhou
Chronic overnutrition and obesity induces low-grade inflammation throughout the body. Termed "meta-inflammation," this chronic state of inflammation is mediated by macrophages located within the colon, liver, muscle, and adipose tissue. A sentinel orchestrator of immune activity and homeostasis, macrophages adopt variable states of activation as a function of time and environmental cues. Meta-inflammation phenotypically skews these polarization states and has been linked to numerous metabolic disorders. The past decade has revealed several key regulators of macrophage polarization, including the signal transducer and activator of transcription family, the peroxisome proliferator-activated receptor gamma, the CCAAT-enhancer-binding proteins (C/EBP) family, and the interferon regulatory factors...
November 3, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/29154687/pyruvate-enhancement-of-cardiac-performance-cellular-mechanisms-and-clinical-application
#19
Robert T Mallet, Albert H Olivencia-Yurvati, Rolf Bünger
Cardiac contractile function is adenosine-5'-triphosphate (ATP)-intensive, and the myocardium's high demand for oxygen and energy substrates leaves it acutely vulnerable to interruptions in its blood supply. The myriad cardioprotective properties of the natural intermediary metabolite pyruvate make it a potentially powerful intervention against the complex injury cascade ignited by myocardial ischemia-reperfusion. A readily oxidized metabolic substrate, pyruvate augments myocardial free energy of ATP hydrolysis to a greater extent than the physiological fuels glucose, lactate and fatty acids, particularly when it is provided at supra-physiological plasma concentrations...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/29154213/liposomally-formulated-phospholipid-conjugated-novel-near-infrared-fluorescence-probe-for-particle-size-effect-on-cellular-uptake-and-biodistribution-in-vivo
#20
Jing Xing, Dong Liu, Gaoxin Zhou, Yuan Li, Peng Wang, Ke Hu, Ning Gu, Min Ji
Lipid based nanoparticles (LBNs) with excellent biocompatibility and versatility have received much attention from the drug delivery community recently. A detailed understanding of in vitro and vivo fate of LBNs is important for developing different types of LBNs with improved selectivity and low cytotoxicity. We developed a novel near-infrared (NIR) probe with high fluorescence, designated as DSPE-ir623 (iDSPE). Then, we prepared iDSPE-embeded liposomes (iLPs) with two different hydrodynamic sizes (∼100nm and ∼400nm) to evaluate the effect of particle size on cellular uptake and biodistribution of nanoliposomes in vivo...
November 16, 2017: Colloids and Surfaces. B, Biointerfaces
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