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Slow Pathway Modification

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https://www.readbyqxmd.com/read/29722617/cheap-labor-myosin-fiber-type-expression-and-enzyme-activity-in-the-forelimb-musculature-of-sloths-pilosa-xenarthra
#1
Kyle B Spainhower, Rebecca N Cliffe, Allan K Metz, Ernest M Barkett, Paije M Kiraly, Dylan R Thomas, Sarah J Kennedy, Judy Avey-Arroyo, Michael T Butcher
Sloths are canopy-dwelling inhabitants of American neotropical rainforests that exhibit suspensory behaviors. These abilities require both strength and muscular endurance to hang for extended periods of time; however, the skeletal muscle mass of sloths is reduced, thus requiring modifications to muscle architecture and leverage for large joint torque. We hypothesize that intrinsic muscle properties also are modified for fatigue resistance and predict a heterogeneous expression of slow/fast myosin heavy chain (MHC) fibers that utilize oxidative metabolic pathways for economic force production...
May 3, 2018: Journal of Applied Physiology
https://www.readbyqxmd.com/read/29710783/targeting-epigenetic-aberrations-in-pancreatic-cancer-a-new-path-to-improve-patient-outcomes
#2
REVIEW
Brooke D Paradise, Whitney Barham, Martín E Fernandez-Zapico
Pancreatic cancer has one of the highest mortality rates among all types of cancers. The disease is highly aggressive and typically diagnosed in late stage making it difficult to treat. Currently, the vast majority of therapeutic regimens have only modest curative effects, and most of them are in the surgical/neo-adjuvant setting. There is a great need for new and more effective treatment strategies in common clinical practice. Previously, pathogenesis of pancreatic cancer was attributed solely to genetic mutations; however, recent advancements in the field have demonstrated that aberrant activation of epigenetic pathways contributes significantly to the pathogenesis of the disease...
April 28, 2018: Cancers
https://www.readbyqxmd.com/read/29707483/slow-pathway-modification-for-treatment-of-pseudo-pacemaker-syndrome-due-to-first-degree-atrioventricular-block-with-dual-atrioventricular-nodal-physiology
#3
Joshua M Lader, David Park, Anthony Aizer, Douglas Holmes, Larry A Chinitz, Chirag R Barbhaiya
No abstract text is available yet for this article.
March 2018: HeartRhythm Case Reports
https://www.readbyqxmd.com/read/29704474/new-insights-about-the-peculiar-role-of-the-28-38-c-terminal-segment-and-some-selected-residues-in-pacap-for-signaling-and-neuroprotection
#4
Mathilde Poujol de Molliens, Myriam Létourneau, Dominic Devost, Terence E Hébert, Alain Fournier, David Chatenet
The pituitary adenylate cyclase-activating polypeptide (PACAP), which exists in two isoforms of 27 and 38 amino acids, can induce neuronal protection in vitro and in vivo following the activation of PAC1, a class B G protein-coupled receptor (GPCR). With its potent neuroprotective and anti-inflammatory effects, this peptide represents a promising avenue for the development of therapeutic strategies to potentially cure or at least slow the progression of neurodegenerative disorders. Beyond the canonical G protein signal effectors, GPCRs are also coupled to a multitude of intracellular signaling pathways that can be independently activated by biased ligands, thereby expanding vastly the potential for discovering new drugs...
April 25, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29664676/a-mathematical-analysis-of-adaptations-to-the-metabolic-fate-of-fructose-in-essential-fructosuria-subjects
#5
R J Allen, Cynthia J Musante
Fructose is a major component of Western diets and is implicated in the pathogenesis of obesity and type 2 diabetes. In response to an oral challenge, the majority of fructose is cleared during "first-pass" liver metabolism, primarily via phosphorylation by ketohexokinase (KHK). A rare benign genetic deficiency in KHK, called essential fructosuria (EF), leads to altered fructose metabolism. The only reported symptom of EF is the appearance of fructose in the urine following either oral or intravenous fructose administration...
April 17, 2018: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29661146/slow-darkening-of-pinto-bean-seed-coat-is-associated-with-significant-metabolite-and-transcript-differences-related-to-proanthocyanidin-biosynthesis
#6
Kishor Duwadi, Ryan S Austin, Hemanta R Mainali, Kirstin Bett, Frédéric Marsolais, Sangeeta Dhaubhadel
BACKGROUND: Postharvest seed coat darkening in pinto bean is an undesirable trait resulting in a loss in the economic value of the crop. The extent of darkening varies between the bean cultivars and their storage conditions. RESULTS: Metabolite analysis revealed that the majority of flavonoids including proanthocyanidin monomer catechin accumulated at higher level in a regular darkening (RD) pinto line CDC Pintium than in a slow darkening (SD) line 1533-15. A transcriptome analysis was conducted to compare gene expression between CDC Pintium and 1533-15 and identify the gene (s) that may play a role in slow darkening processes in 1533-15 pinto...
April 16, 2018: BMC Genomics
https://www.readbyqxmd.com/read/29656472/in-vitro-and-in-vivo-characterization-of-an-interleukin-15-antagonist-peptide-by-metabolic-stability-99m-tc-labeling-and-biological-activity-assays
#7
Yunier Rodríguez-Álvarez, Ania Cabrales-Rico, Alejandro Perera-Pintado, Anais Prats-Capote, Hilda E Garay-Pérez, Osvaldo Reyes-Acosta, Erik Pérez-García, Araceli Chico-Capote, Alicia Santos-Savio
Interleukin (IL)-15 is an inflammatory cytokine that constitutes a validated therapeutic target in some immunopathologies, including rheumatoid arthritis (RA). Previously, we identified an IL-15 antagonist peptide named [K6T]P8, with potential therapeutic application in RA. In the current work, the metabolic stability of this peptide in synovial fluids from RA patients was studied. Moreover, [K6T]P8 peptide was labeled with 99m Tc to investigate its stability in human plasma and its biodistribution pattern in healthy rats...
April 15, 2018: Journal of Peptide Science: An Official Publication of the European Peptide Society
https://www.readbyqxmd.com/read/29644751/disease-modification-in-parkinson-s-disease-current-approaches-challenges-and-future-considerations
#8
REVIEW
Anthony E Lang, Alberto J Espay
The greatest unmet therapeutic need in Parkinson's disease is the development of treatment that slows the relentless progression of the neurodegenerative process. The concept of "disease modification" encompasses intervention types ranging from those designed to slow the underlying degeneration to treatments directed at regenerating or replacing lost neurons. To date all attempts to develop effective disease-modifying therapy have failed. Many reasons have been proposed for these failures including our rudimentary understanding of disease pathogenesis and the assumption that each targeted mechanisms of disease apply to most patients with the same clinical diagnosis...
April 11, 2018: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/29593032/extracellular-conformational-changes-in-the-capsid-of-human-papillomaviruses-contribute-to-asynchronous-uptake-into-host-cells
#9
Miriam Becker, Lilo Greune, M Alexander Schmidt, Mario Schelhaas
The human papillomavirus type 16 (HPV16) is the leading cause of cervical cancer. For initial infection, HPV16 utilizes a novel endocytic pathway for host cell entry. Unique amongst viruses, uptake occurs asynchronously over a protracted period of time with half-times between 9-12 h. To trigger endocytic uptake, the virus particles need to undergo a series of structural modifications after initial binding to heparan sulfate proteoglycans (HSPG). These changes involve proteolytic cleavage of the major capsid protein L1 by kallikrein-8 (KLK8), exposure of the N-terminus of the minor capsid protein L2 by cyclophilins, and cleavage of this N-terminus by furin...
March 28, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29553725/differential-kinetics-of-two-cysteine-peroxiredoxin-disulfide-formation-reveal-a-novel-model-for-peroxide-sensing
#10
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
https://www.readbyqxmd.com/read/29538207/case-report-an-unstable-wide-qrs-complexes-tachycardia-after-ablation-of-a-poster-septal-accessory-pathway-what-is-the-mechanism
#11
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)
https://www.readbyqxmd.com/read/29433068/a-simplified-approach-for-evaluating-sustained-slow-pathway-conduction-for-diagnosis-and-treatment-of-atrioventricular-nodal-reentry-tachycardia-in-children-and-adults
#12
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
https://www.readbyqxmd.com/read/29416562/optimizing-anaerobic-growth-rate-and-fermentation-kinetics-in-saccharomyces-cerevisiae-strains-expressing-calvin-cycle-enzymes-for-improved-ethanol-yield
#13
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
https://www.readbyqxmd.com/read/29408453/a-randomized-control-trial-to-establish-the-feasibility-and-safety-of-rapamycin-treatment-in-an-older-human-cohort-immunological-physical-performance-and-cognitive-effects
#14
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...
May 2018: Experimental Gerontology
https://www.readbyqxmd.com/read/29361334/progress-in-clinical-research-in-surgery-and-ideal
#15
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
https://www.readbyqxmd.com/read/29188179/development-of-a-high-efficiency-integration-system-and-promoter-library-for-rapid-modification-of-pseudomonas-putida-kt2440
#16
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
https://www.readbyqxmd.com/read/29152015/laser-synthesized-tio-2-based-nanoparticles-and-their-efficiency-in-the-photocatalytic-degradation-of-linear-carboxylic-acids
#17
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
https://www.readbyqxmd.com/read/29117522/the-fast-component-of-herg-gating-charge-an-interaction-between-d411-in-the-s1-and-s4-residues
#18
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
#19
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 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...
January 5, 2018: 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
#20
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
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