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Slow Pathway Modification

Stephanie Portillo-Ledesma, Lía M Randall, Derek Parsonage, Joaquín Dalla Rizza, P Andrew Karplus, Leslie B Poole, Ana Denicola, Gerardo Ferrer-Sueta
Two-cysteine peroxiredoxins (Prx) have a three-step catalytic cycle consisting of (1) reduction of peroxide and formation of sulfenic acid on the enzyme, (2) condensation of the sulfenic acid with a thiol to form disulfide, also known as resolution, and (3) reduction of the disulfide by a reductant protein. By following changes in protein fluorescence, we have studied the pH dependence of reaction 2 in human peroxiredoxins 1, 2 and 5, and in Salmonella typhimurium AhpC and obtained rate constants for the reaction and p Ka values of the thiol and sulfenic acid involved for each system...
March 19, 2018: Biochemistry
Huan Wang, Xiaoru Che
INTRODUCTION: Differentiation of wide QRS complex tachycardia required repeated electrophysiological stimuli and mapping. However, instability of tachycardia would increase the difficulty in differential diagnosis. SYMPTOMS AND CLINICAL FINDINGS: In this paper, we reported a wide QRS tachycardia following ablation of an atrioventricular reentrant tachycardia participated by a poster-septal accessory pathway. Limited differentiation strategy was performed because the wide QRS tachycardia was self-limited and with unstable hemodynamics...
March 2018: Medicine (Baltimore)
Janusz Sledz, Michal Labus, Mariusz Mazij, Monika Klank-Szafran, Dariusz Karbarz, Bartosz Ludwik, Jacek Kusa, Karol Deutsch, Leslaw Szydlowski, Adrian Mscisz, Jerzy Spikowski, Aleksandra Morka, Tomasz Kameczura, Aleksandra Swietoniowska-Mscisz, Sebastian Stec
PURPOSE: During incremental atrial pacing in patients with atrioventricular nodal reentrant tachycardia, the PR interval often exceeds the RR interval (PR > RR) during stable 1:1 AV conduction. However, the PR/RR ratio has never been evaluated in a large group of patients with pacing from the proximal coronary sinus and after isoproterenol challenge. Our study validates new site of pacing and easier method of identification of PR > RR. MATERIAL AND METHODS: A prospective protocol of incremental atrial pacing from the proximal coronary sinus was carried out in 398 patients (AVNRT-228 and control-170)...
February 10, 2018: Advances in Medical Sciences
Ioannis Papapetridis, Maaike Goudriaan, María Vázquez Vitali, Nikita A de Keijzer, Marcel van den Broek, Antonius J A van Maris, Jack T Pronk
Background: Reduction or elimination of by-product formation is of immediate economic relevance in fermentation processes for industrial bioethanol production with the yeast Saccharomyces cerevisiae. Anaerobic cultures of wild-type S. cerevisiae require formation of glycerol to maintain the intracellular NADH/NAD+ balance. Previously, functional expression of the Calvin-cycle enzymes ribulose-1,5-bisphosphate carboxylase (RuBisCO) and phosphoribulokinase (PRK) in S. cerevisiae was shown to enable reoxidation of NADH with CO2 as electron acceptor...
2018: Biotechnology for Biofuels
Ellen Kraig, Leslie A Linehan, Hanyu Liang, Terry Q Romo, Qianqian Liu, Yubo Wu, Adriana D Benavides, Tyler J Curiel, Martin A Javors, Nicolas Musi, Laura Chiodo, Wouter Koek, Jonathan A L Gelfond, Dean L Kellogg
Inhibition of the mechanistic target of rapamycin (mTOR) pathway by rapamycin (RAPA), an FDA-approved immunosuppressive drug used as a clinical therapy to prevent solid organ allograft rejection, enhances longevity in mice. Importantly, RAPA was efficacious even when initiated in relatively old animals, suggesting that mTOR inhibition could potentially slow the progression of aging-associated pathologies in older humans (Harrison et al., 2009; Miller et al., 2011). However, the safety and tolerability of RAPA in older human subjects have not yet been demonstrated...
February 3, 2018: Experimental Gerontology
Peter McCulloch, Joshua Feinberg, Yiannis Philippou, Angelos Kolias, Sean Kehoe, Gillian Lancaster, Jenny Donovan, Tatjana Petrinic, Riaz Agha, Christopher Pennell
The quality of clinical research in surgery has long attracted criticism. High-quality randomised trials have proved difficult to undertake in surgery, and many surgical treatments have therefore been adopted without adequate supporting evidence of efficacy and safety. This evidence deficit can adversely affect research funding and reimbursement decisions, lead to slow adoption of innovations, and permit widespread adoption of procedures that offer no benefit, or cause harm. Improvement in the quality of surgical evidence would therefore be valuable...
January 17, 2018: Lancet
Joshua R Elmore, Anna Furches, Gara N Wolff, Kent Gorday, Adam M Guss
Pseudomonas putida strains are highly robust bacteria known for their ability to efficiently utilize a variety of carbon sources, including aliphatic and aromatic hydrocarbons. Recently, P. putida has been engineered to valorize the lignin stream of a lignocellulosic biomass pretreatment process. Nonetheless, when compared to platform organisms such as Escherichia coli , the toolkit for engineering P. putida is underdeveloped. Heterologous gene expression in particular is problematic. Plasmid instability and copy number variance provide challenges for replicative plasmids, while use of homologous recombination for insertion of DNA into the chromosome is slow and laborious...
December 2017: Metabolic Engineering Communications
Sarah Bouhadoun, Chantal Guillard, Sébastien Sorgues, Alexandre Hérissan, Christophe Colbeau-Justin, Frederic Dapozze, Aurélie Habert, Vincent Maurel, Nathalie Herlin-Boime
Titanium dioxide nanoparticles were synthesized by laser pyrolysis, their surface and electronic properties were modified by gold and/or nitrogen. These materials were characterized by different techniques like X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS) and electron paramagnetic resonance (EPR). Time resolved conductivity (TRMC) was used to study the charge separation of electron/hole pairs. Altogether (XPS, EPR, TRMC), the physicochemical characterizations are well correlated with chemical photoactivity of the different samples...
2017: Science and Technology of Advanced Materials
Ying Dou, Logan C Macdonald, Yue Wu, David Fedida
Kv11.1 (hERG) is a voltage-gated potassium channel that shows very slow ionic current activation kinetics, and an unusual underlying biphasic gating charge movement with fast and slow components that differ greatly in time course. The structural basis and role of the fast component of gating charge (Qfast ) is unclear, and its relationship to the slow activation of hERG channels is not understood. In this study we have used the cut-open oocyte voltage-clamp technique to investigate the relationship of fast gating charge movement-to-residue interactions between D411 at the bottom of the S1, and lower S4 domain charged and uncharged residues...
November 7, 2017: Biophysical Journal
Catherine Wenhui Goh, Irene Chengjie Lee, Jeyapriya Rajameenakshi Sundaram, Simi Elizabeth George, Permeen Yusoff, Matthew Hayden Brush, Newman Siu Kwan Sze, Shirish Shenolikar
Oxidative and endoplasmic reticulum (ER) stresses are hallmarks of the pathophysiology of amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases. In these stresses, different kinases phosphorylate eukaryotic initiation factor eIF2α enabling the translation of stress response genes, among these is GADD34, the protein product of which recruits the α-isoform of protein phosphatase 1 catalytic subunit (PP1α) and eIF2α to assemble a phosphatase complex catalyzing eIF2α dephosphorylation and resumption of protein synthesis...
November 6, 2017: Journal of Biological Chemistry
Simone Bittencourt, Enéas Ferrazoli, Maria Fernanda Valente, Simone Romariz, Nilma R L L Janisset, Carlos Eduardo Macedo, Bruno de Brito Antonio, Vanessa Barros, Mayara Mundim, Marimélia Porcionatto, Mayra Consuelo Aarão, Maísa Ferreira Miranda, Antônio Márcio Rodrigues, Antônio-Carlos Guimarães de Almeida, Beatriz M Longo, Luiz E Mello
Brain injuries are often associated with the later development of epilepsy. Evidence suggests that morphological and functional changes occur in the remaining neural tissue during a silent (or latent) period in which no seizures are expressed. It is believed that this silent (reorganization) period may provide a therapeutic window for modifying the natural history of disease progression. Here we provide evidence that biperiden, a muscarinic anticholinergic agent, is able to alter disease progression in an animal model of epilepsy...
October 29, 2017: Epilepsy Research
Vicente Soriano
The huge success of current antiretroviral therapy is mediated by a triple effect: (i) Halting progression to AIDS in infected persons; (ii) reducing the risk of transmission to contacts (treatment as prevention); and (iii) minimizing the risk of HIV acquisition treating uninfected persons at risk (pre-exposure prophylaxis). However, UNAIDS has estimated that only 70% of infected people globally are diagnosed, only 53% are treated, and overall 44% have undetectable viral load, which is the necessary request for ensuring any antiretroviral benefit...
October 2017: AIDS Reviews
Hillary Miller, Marissa Fletcher, Melissa Primitivo, Alison Leonard, George L Sutphin, Nicholas Rintala, Matt Kaeberlein, Scott F Leiser
As in other poikilotherms, longevity in C. elegans varies inversely with temperature; worms are longer-lived at lower temperatures. While this observation may seem intuitive based on thermodynamics, the molecular and genetic basis for this phenomenon is not well understood. Several recent reports have argued that lifespan changes across temperatures are genetically controlled by temperature-specific gene regulation. Here, we provide data that both corroborate those studies and suggest that temperature-specific longevity is more the rule than the exception...
December 2017: Aging Cell
Seung Hyun Kim, Nagaendran Kandiah, Jung-Lung Hsu, Chuthamanee Suthisisang, Chesda Udommongkol, Amitabh Dash
Alzheimer's disease (AD) is associated with neurodegenerative changes resulting clinically in progressive cognitive and functional deficits. The only therapies are the cholinesterase inhibitors donepezil, galantamine and rivastigmine and the N-methyl-D-aspartate-receptor antagonist memantine. Donepezil acts primarily on the cholinergic system as a symptomatic treatment, but it also has potential for disease modification and may reduce the rate of progression of AD. This review explores the potential for disease modifying effects of donepezil...
December 2017: British Journal of Pharmacology
Cheng Li, Ying Lin, Xueyun Zheng, Qingyan Yuan, Nuo Pang, Xihao Liao, Yuanyuan Huang, Xinying Zhang, Shuli Liang
Pichia pastoris is a widely used heterologous protein production workhorse. However, with its multiple genetic modifications to solve bottlenecks for heterologous protein productivity, P. pastoris lacks selectable markers. Existing selectable marker recycling plasmids have drawbacks (e.g., slow growth and conditional lethality). Here, zeocin-resistance marker recycling vectors were constructed using the Cre/loxP recombination system. The vectors were used to (i) knock in heterologous phytase, xylanase and lipase expression cassettes, (ii) increase the phytase, xylanase and lipase gene copy number to 13, 5, and 5, respectively, with vector introduction and (iii) engineer the secretion pathway by co-overexpressing secretion helper factors (Sly1p and Sec1p) without introducing selectable markers, giving a phytase field of 0...
September 11, 2017: Scientific Reports
Derong Lin, Ran Ji, Dan Wang, Mengshi Xiao, Jingjing Zhao, Jinpeng Zou, Yutong Li, Tao Qin, Baoshan Xing, Yuan Chen, Peng Liu, Zhijun Wu, Lilin Wang, Qing Zhang, Hong Chen, Wen Qin, Dingtao Wu, Yuntao Liu, Yaowen Liu, Suqing Li
Currently, due to high surface to volume ratio; large availability, rapid kinetics of adsorption and desorption and low cost, the exploitation of microbial biosorption of heavy metals is regarded as a reliable alternative compared to the conventional bioremediation approaches. In parallel with the increasing attractiveness of biosorption research, its pace of advance is also boosted. The barrier that prevent biosorption as an effective method from being applied into wastewater purification is listed, (1) There is not enough data on multi-component biosorption, (2) It remains to be seen that physical-chemical characteristics of different biomasses...
September 8, 2017: Critical Reviews in Food Science and Nutrition
Yuying Zhang, Kaiyuan Wu, Wenting Su, Deng-Feng Zhang, Ping Wang, Xinhua Qiao, Qin Yao, Zengqiang Yuan, Yong-Gang Yao, Guanghui Liu, Chen Zhang, Limin Liu, Chang Chen
As the population ages, an increasing number of people suffer from age-related cognitive impairment. However, the mechanisms underlying this process remain unclear. Here, we found that S-nitrosoglutathione reductase (GSNOR), the key enzyme that metabolizes intracellular nitric oxide (NO) and regulates S-nitrosation, was significantly increased in the hippocampus of both aging humans and mice. Transgenic mice overexpressing GSNOR exclusively in neurons showed cognitive impairment in behavioral tests, including the Morris water maze, fear conditioning, and the Y-maze test...
October 4, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Caroline Barbé, Fabrice Bray, Marine Gueugneau, Stéphanie Devassine, Pascale Lause, Caroline Tokarski, Christian Rolando, Jean-Paul Thissen
Skeletal muscle, the most abundant body tissue, plays vital roles in locomotion and metabolism. Myostatin is a negative regulator of skeletal muscle mass. In addition to increasing muscle mass, Myostatin inhibition impacts muscle contractility and energy metabolism. To decipher the mechanisms of action of the Myostatin inhibitors, we used proteomic and transcriptomic approaches to investigate the changes induced in skeletal muscles of transgenic mice overexpressing Follistatin, a physiological Myostatin inhibitor...
October 6, 2017: Journal of Proteome Research
Jamie Males, Howard Griffiths
The Neotropical Bromeliaceae display an extraordinary level of ecological variety, with species differing widely in habit, photosynthetic pathway and growth form. Divergences in stomatal structure and function, hitherto understudied in treatments of bromeliad evolutionary physiology, could have been critical to the generation of variety in ecophysiological strategies among the bromeliads. Because humidity is a key factor in bromeliad niches, we focussed on stomatal responses to vapour pressure deficit (VPD)...
July 19, 2017: Plant, Cell & Environment
Sven Wegner, Mino D C Belle, Alun T L Hughes, Casey O Diekman, Hugh D Piggins
Suprachiasmatic nuclei (SCN) neurons contain an intracellular molecular circadian clock and the Cryptochromes (CRY1/2), key transcriptional repressors of this molecular apparatus, are subject to post-translational modification through ubiquitination and targeting for proteosomal degradation by the ubiquitin E3 ligase complex. Loss-of-function point mutations in a component of this ligase complex, Fbxl3, delay CRY1/2 degradation, reduce circadian rhythm strength, and lengthen the circadian period by ∼2.5 h...
August 16, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
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