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Slow Pathway Modification

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https://www.readbyqxmd.com/read/29117522/the-fast-component-of-herg-gating-charge-an-interaction-between-d411-in-the-s1-and-s4-residues
#1
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
https://www.readbyqxmd.com/read/29109149/chronic-oxidative-stress-promotes-gadd34-mediated-phosphorylation-of-the-tar-dna-binding-protein-tdp-43-a-modification-linked-to-neurodegeneration
#2
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
https://www.readbyqxmd.com/read/29096134/modification-of-the-natural-progression-of-epileptogenesis-by-means-of-biperiden-in-the-pilocarpine-model-of-epilepsy
#3
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
https://www.readbyqxmd.com/read/29019352/hot-news-gene-therapy-with-crispr-cas9-coming-to-age-for-hiv-cure
#4
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
https://www.readbyqxmd.com/read/28940623/genetic-interaction-with-temperature-is-an-important-determinant-of-nematode-longevity
#5
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
https://www.readbyqxmd.com/read/28901528/beyond-symptomatic-effects-donepezil-s-potential-for-neuroprotection-and-disease-modification-in-alzheimer-s-disease
#6
REVIEW
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 (ChEIs) donepezil, galantamine, and rivastigmine and the N-methyl-D-aspartate-receptor antagonist memantine. Donepezil acts primarily on the cholinergic system as 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 a disease modifying effect of donepezil...
September 13, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28894268/recycling-of-a-selectable-marker-with-a-self-excisable-plasmid-in-pichia-pastoris
#7
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
https://www.readbyqxmd.com/read/28886254/the-research-progress-in-mechanism-and-influence-of-biosorption-between-lactic-acid-bacteria-and-pb-ii-a-review
#8
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
https://www.readbyqxmd.com/read/28883020/increased-gsnor-expression-during-aging-impairs-cognitive-function-and-decreases-s-nitrosation-of-camkii%C3%AE
#9
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
https://www.readbyqxmd.com/read/28810121/comparative-proteomic-and-transcriptomic-analysis-of-follistatin-induced-skeletal-muscle-hypertrophy
#10
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
https://www.readbyqxmd.com/read/28722113/specialized-stomatal-humidity-responses-underpin-ecological-diversity-in-c3-bromeliads
#11
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
https://www.readbyqxmd.com/read/28698388/delayed-cryptochrome-degradation-asymmetrically-alters-the-daily-rhythm-in-suprachiasmatic-clock-neuron-excitability
#12
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
https://www.readbyqxmd.com/read/28678862/pseudomonas-aeruginosa-cells-attached-to-a-surface-display-a-typical-proteome-early-as-20-minutes-of-incubation
#13
Marc Crouzet, Stéphane Claverol, Anne-Marie Lomenech, Caroline Le Sénéchal, Patricia Costaglioli, Christophe Barthe, Bertrand Garbay, Marc Bonneu, Sébastien Vilain
Biofilms are present in all environments and often result in negative effects due to properties of the biofilm lifestyle and especially antibiotics resistance. Biofilms are associated with chronic infections. Controlling bacterial attachment, the first step of biofilm formation, is crucial for fighting against biofilm and subsequently preventing the persistence of infection. Thus deciphering the underlying molecular mechanisms involved in attachment could allow discovering molecular targets from it would be possible to develop inhibitors against bacterial colonization and potentiate antibiotherapy...
2017: PloS One
https://www.readbyqxmd.com/read/28670495/bitterness-in-sugar-o-glcnacylation-aggravates-pre-b-acute-lymphocytic-leukemia-through-glycolysis-via-the-pi3k-akt-c-myc-pathway
#14
Bing Zhang, Panpan Zhou, Xue Li, Qing Shi, Dong Li, Xiuli Ju
Abnormal cellular energetics has emerged as a hallmark of cancer cells. Deregulating aerobic glycolysis can alter multiple metabolic and signaling pathways in cancer cells, and trigger unlimited growth and proliferation. Accumulating evidence suggests that elevated levels of protein modification with β-N-acetylglucosamine (O-GlcNAcylation) along with dysregulation of O-GlcNAc transferase (OGT) and/or O-GlcNAcase (OGA) levels may act as a nutrient sensor in cancer cells. However, the underlying mechanism of O-GlcNAcylation and the relationship between O-GlcNAcylation and glycolysis are largely unknown in pre-B acute lymphocytic leukemia (pre-B-ALL)...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/28641381/supraventricular-tachyarrhythmias-in-patients-with-a-persistent-left-superior-vena-cava
#15
Jongmin Hwang, Hyoung-Seob Park, Jun Kim, Jeong Su Kim, Jong Sung Park, Ki-Hun Kim, Myung Hwan Bae, Sang-Hee Lee, Young Soo Lee, Seongwook Han, Dae-Kyeong Kim, Tae-Joon Cha, Dong Gu Shin, Byung Chun Jung, Yoon-Nyun Kim
Aims: A persistent left superior vena cava (PLSVC) is the most common thoracic venous anomaly. This venous anomaly can impact the evaluation and treatment of supraventricular tachyarrhythmia (SVA). The aim of this study was to assess the proportion and characteristics of PLSVC in adult SVA patients. Methods and results: From July 2002 to July 2012, clinical and procedural data from databases of 10 cardiac electrophysiology laboratories in the Yeungnam region of the Republic of Korea were reviewed...
June 20, 2017: Europace: European Pacing, Arrhythmias, and Cardiac Electrophysiology
https://www.readbyqxmd.com/read/28640638/enzyme-mediated-conversion-of-flavin-adenine-dinucleotide-fad-to-8-formyl-fad-in-formate-oxidase-results-in-a-modified-cofactor-with-enhanced-catalytic-properties
#16
John M Robbins, Michael G Souffrant, Donald Hamelberg, Giovanni Gadda, Andreas S Bommarius
Flavins, including flavin adenine dinucleotide (FAD), are fundamental catalytic cofactors that are responsible for the redox functionality of a diverse set of proteins. Alternatively, modified flavin analogues are rarely found in nature as their incorporation typically results in inactivation of flavoproteins, thus leading to the disruption of important cellular pathways. Here, we report that the fungal flavoenzyme formate oxidase (FOX) catalyzes the slow conversion of noncovalently bound FAD to 8-formyl FAD and that this conversion results in a nearly 10-fold increase in formate oxidase activity...
July 25, 2017: Biochemistry
https://www.readbyqxmd.com/read/28622913/targeting-urate-to-reduce-oxidative-stress-in-parkinson-disease
#17
REVIEW
Grace F Crotty, Alberto Ascherio, Michael A Schwarzschild
Oxidative stress has been implicated as a core contributor to the initiation and progression of multiple neurological diseases. Genetic and environmental factors can produce oxidative stress through mitochondrial dysfunction leading to the degeneration of dopaminergic and other neurons underlying Parkinson disease (PD). Although clinical trials of antioxidants have thus far failed to demonstrate slowed progression of PD, oxidative stress remains a compelling target. Rather than prompting abandonment of antioxidant strategies, these failures have raised the bar for justifying drug and dosing selections and for improving study designs to test for disease modification by antioxidants...
December 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28593442/remodeling-of-heterochromatin-structure-slows-neuropathological-progression-and-prolongs-survival-in-an-animal-model-of-huntington-s-disease
#18
Junghee Lee, Yu Jin Hwang, Yunha Kim, Min Young Lee, Seung Jae Hyeon, Soojin Lee, Dong Hyun Kim, Sung Jae Jang, Hyoenjoo Im, Sun-Joon Min, Hyunah Choo, Ae Nim Pae, Dong Jin Kim, Kyung Sang Cho, Neil W Kowall, Hoon Ryu
Huntington's disease (HD) is an autosomal-dominant inherited neurological disorder caused by expanded CAG repeats in exon 1 of the Huntingtin (HTT) gene. Altered histone modifications and epigenetic mechanisms are closely associated with HD suggesting that transcriptional repression may play a pathogenic role. Epigenetic compounds have significant therapeutic effects in cellular and animal models of HD, but they have not been successful in clinical trials. Herein, we report that dSETDB1/ESET, a histone methyltransferase (HMT), is a mediator of mutant HTT-induced degeneration in a fly HD model...
June 7, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28556588/effects-of-dna-methylation-on-progression-to-interstitial-fibrosis-and-tubular-atrophy-in-renal-allograft-biopsies-a-multi-omics-approach
#19
S V Bontha, D G Maluf, K J Archer, C I Dumur, M G Dozmorov, A L King, E Akalin, T F Mueller, L Gallon, V R Mas
Progressive fibrosis of the interstitium is the dominant final pathway in renal destruction in native and transplanted kidneys. Over time, the continuum of molecular events following immunological and nonimmunological insults lead to interstitial fibrosis and tubular atrophy and culminate in kidney failure. We hypothesize that these insults trigger changes in DNA methylation (DNAm) patterns, which in turn could exacerbate injury and slow down the regeneration processes, leading to fibrosis development and graft dysfunction...
December 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28450734/modulation-of-gene-expression-dynamics-by-co-transcriptional-histone-methylations
#20
REVIEW
Hyeonju Woo, So Dam Ha, Sung Bae Lee, Stephen Buratowski, TaeSoo Kim
Co-transcriptional methylations of histone H3 at lysines 4 and 36, highly conserved methyl marks from yeast to humans, have profound roles in regulation of histone acetylation. These modifications function to recruit and/or activate distinct histone acetyltransferases (HATs) or histone deacetylases (HDACs). Whereas H3K4me3 increases acetylation at promoters via multiple HATs, H3K4me2 targets Set3 HDAC to deacetylate histones in 5' transcribed regions. In 3' regions of genes, H3K36me2/3 facilitates deacetylation by Rpd3S HDAC and slows elongation...
April 28, 2017: Experimental & Molecular Medicine
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