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https://www.readbyqxmd.com/read/28213526/structural-and-mechanistic-insights-into-hemoglobin-catalyzed-hydrogen-sulfide-oxidation-and-the-fate-of-polysulfide-products
#1
Victor Vitvitsky, Pramod K Yadav, Sojin An, Javier Seravalli, Uhn-Soo Cho, Ruma Banerjee
Hydrogen sulfide is a cardioprotective signaling molecule but is toxic at elevated concentrations. Red blood cells can synthesize H2S but lacking organelles, cannot dispose off H2S via the mitochondrial sulfide oxidation pathway. We have recently shown that at high sulfide concentrations, ferric hemoglobin oxidizes H2S to a mixture of thiosulfate and iron-bound polysulfides in which the latter species predominates. Here, we report the crystal structure of human hemoglobin containing low-spin ferric sulfide, the first intermediate in heme-catalyzed sulfide oxidation...
February 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28198542/ceramide-synthase-2-facilitates-s1p-dependent-egress-of-thymocytes-into-the-circulation-in-mice
#2
Michael Rieck, Christiane Kremser, Katarzyna Jobin, Elisabeth Mettke, Christian Kurts, Markus Gräler, Klaus Willecke, Waldemar Kolanus
Well-defined gradients of the lipid mediator sphingosine-1-phosphate (S1P) direct chemotactic egress of mature thymocytes from the thymus into the circulation. Although it is known that these gradients result from low S1P levels in the thymic parenchyma and high S1P concentrations at the exit sites and in the plasma, the biochemical mechanisms that regulate these differential S1P levels remain unclear. Several studies demonstrated that ceramide synthase 2 (Cers2) regulates the levels of the S1P precursor sphingosine...
February 15, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28196470/proteasome-impairment-in-neural-cells-derived-from-hmsn-p-patient-ipscs
#3
Nagahisa Murakami, Keiko Imamura, Yuishin Izumi, Naohiro Egawa, Kayoko Tsukita, Takako Enami, Takuya Yamamoto, Toshitaka Kawarai, Ryuji Kaji, Haruhisa Inoue
Hereditary motor and sensory neuropathy with proximal dominant involvement (HMSN-P) is caused by a heterozygous mutation (P285L) in Tropomyosin-receptor kinase Fused Gene (TFG), histopathologically characterized by progressive spinal motor neuron loss with TFG cytosolic aggregates. Although the TFG protein, found as a type of fusion oncoprotein, is known to facilitate vesicle transport from endoplasmic reticulum (ER) to Golgi apparatus at ER exit site, it is unclear how mutant TFG causes motor neuron degeneration...
February 15, 2017: Molecular Brain
https://www.readbyqxmd.com/read/28193843/bound-substrate-in-the-structure-of-cyanobacterial-branching-enzyme-supports-a-new-mechanistic-model
#4
Mari Hayashi, Ryuichiro Suzuki, Christophe Colleoni, Steven G Ball, Naoko Fujita, Eiji Suzuki
Branching enzyme (BE) catalyzes the formation of α-1,6-glucosidic linkages in amylopectin and glycogen. The reaction products are variable depending on the organism sources, and the mechanistic basis for these different outcomes is unclear. Although most cyanobacteria have only one BE isoform belonging to glycoside hydrolase (GH) family 13, Cyanothece sp. ATCC 51142 has three isoforms (BE1, BE2, and BE3) with distinct enzymatic properties, suggesting that investigations of these enzymes might provide unique insights into this system...
February 13, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28191915/routes-and-mechanisms-of-post-endosomal-cholesterol-trafficking-a-story-that-never-ends
#5
REVIEW
Jie Luo, Luyi Jiang, Hongyuan Yang, Bao-Liang Song
Mammalian cells acquire most exogenous cholesterol through receptor-mediated endocytosis of low-density lipoproteins (LDLs). After internalization, LDL cholesteryl esters are hydrolyzed to release free cholesterol, which then translocates to late endosomes (LEs)/lysosomes (LYs) and incorporates into the membranes by coordinated actions of Niemann-Pick type C (NPC) 1 and NPC2 proteins. However, how cholesterol exits LEs/LYs and moves to other organelles remain largely unclear. Growing evidence has suggested that nonvesicular transport is critically involved in the post-endosomal cholesterol trafficking...
February 13, 2017: Traffic
https://www.readbyqxmd.com/read/28183985/characterization-of-pph3-mediated-dephosphorylation-of-rad53-during-methyl-methanesulfonate-induced-dna-damage-repair-in-candida-albicans
#6
Guangyin Yao, Junhua Wan, Qizheng Liu, Chunhua Mu, Yue Wang, Jianli Sang
Genotoxic stress causes DNA damage or stalled DNA replication and filamentous growth in the pathogenic fungus Candida albicans The DNA checkpoint kinase Rad53 critically regulates by phosphorylation effectors that execute the stress response. Rad53 itself is activated by phosphorylation and inactivated by dephosphorylation. Previous studies have suggested that the phosphatase Pph3 dephosphorylates Rad53. Here, we used mass spectrometry and mutagenesis to identify Pph3 dephosphorylation sites on Rad53 in C. albicans We found that serine residues 351, 461, and 477, which were dephosphorylated in wild-type cells during the recovery from DNA damage caused by methyl methanesulfonate (MMS), remained phosphorylated in pph3Δ/Δ cells...
February 9, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28183858/comparison-of-topical-chlorhexidine-and-mupirocin-for-the-prevention-of-exit-site-infection-in-incident-peritoneal-dialysis-patients
#7
Htay Htay, David W Johnson, Sin Yan Wu, Elizabeth L Oei, Marjorie Wai Yin Foo, Jason C Choo
♦ Objective: Prevention of exit-site infection (ESI) is of paramount importance to peritoneal dialysis (PD) patients. The aim of this study was to evaluate the effectiveness of chlorhexidine in the prevention of ESI in incident PD patients compared with mupirocin. ♦ Methods: This retrospective, pre-test/post-test observational study included all incident PD patients at Singapore General Hospital from 2012 to 2015. Patients received daily topical exit-site application of either mupirocin (2012 - 2013) or chlorhexidine (2014 - 2015) in addition to routine exit-site cleaning with 10% povidone-iodine...
February 9, 2017: Peritoneal Dialysis International: Journal of the International Society for Peritoneal Dialysis
https://www.readbyqxmd.com/read/28169832/interface-between-40s-exit-channel-protein-us7-rps5-and-eif2%C3%AE-modulates-start-codon-recognition-in-vivo
#8
Jyothsna Visweswaraiah, Alan G Hinnebusch
The eukaryotic pre-initiation complex (PIC) bearing the eIF2•GTP•Met-tRNAi(Met) ternary complex (TC) scans the mRNA for an AUG codon in favorable context. AUG recognition evokes rearrangement of the PIC from an open, scanning to a closed, arrested conformation. Cryo-EM reconstructions of yeast PICs suggest remodeling of the interface between 40S protein Rps5/uS7 and eIF2α between open and closed states; however, its importance was unknown. uS7 substitutions disrupting eIF2α contacts favored in the open complex increase initiation at suboptimal sites, and uS7-S223D stabilizes TC binding to PICs reconstituted with a UUG start codon, indicating inappropriate rearrangement to the closed state...
February 7, 2017: ELife
https://www.readbyqxmd.com/read/28167077/electrocardiographic-localization-of-ventricular-tachycardia-in-patients-with-structural-heart-disease
#9
REVIEW
John M Miller, Rahul Jain, Gopi Dandamudi, Thomas R Kambur
The 12-lead electrocardiogram (ECG) during ventricular tachycardia (VT) in patients with structural heart disease contains information that helps to narrow the electrophysiologist's search for target sites for ablation. Although replacement of myocardium by scar might be expected to produce variability in the spread of activation during VT, nonetheless reasonably consistent ECG patterns exist that can regionalize exit sites from VT circuits in up to 75% of cases. Most experience with this comes from patients with prior myocardial infarction, but a growing body of data exists concerning patients with nonischemic cardiomyopathies...
March 2017: Cardiac Electrophysiology Clinics
https://www.readbyqxmd.com/read/28160489/sec16-in-conventional-and-unconventional-exocytosis-working-at-the-interface-of-membrane-traffic-and-secretory-autophagy
#10
REVIEW
Bor Luen Tang
Sec16 is classically perceived to be a scaffolding protein localized to the transitional endoplasmic reticulum (tER) or the ER exit sites (ERES), and has a conserved function in facilitating coat protein II (COPII) complex-mediated ER exit. Recent findings have however pointed towards a role for Sec16 in unconventional exocytosis of certain membrane proteins, such as the Cystic fibrosis transmembrane conductance regulator (CFTR) in mammalian cells, and possibly also α-integrin in certain contexts of Drosophila development...
February 4, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28153969/outcomes-of-pd-patients-at-6-months
#11
William Hoffman, Heena Sheth, Filitsa Bender, Beth Piraino
The peritoneal dialysis (PD) patient population has grown rapidly in the past few years with concern over poor early outcomes. We report 6-month outcomes of incident PD patients in an experienced program with a strong focus on quality care. We analyzed data from an Institutional Review Board (IRB)- approved registry of all incident PD patients from January 1, 1991, to December 31, 2013, with follow-up to June 30, 2014. Time at risk began on the first day of training. Age, gender, race, diabetes mellitus (DM), Charlson comorbidity index (CCI), and albumin were collected at PD start...
January 2017: Peritoneal Dialysis International: Journal of the International Society for Peritoneal Dialysis
https://www.readbyqxmd.com/read/28153191/peritoneal-dialysis-catheter-insertion
#12
REVIEW
John H Crabtree, Kai-Ming Chow
The success of peritoneal dialysis as renal-replacement therapy depends on a well-functioning peritoneal catheter. Knowledge of best practices in catheter insertion can minimize the risk of catheter complications that lead to peritoneal dialysis failure. The catheter placement procedure begins with preoperative assessment of the patient to determine the most appropriate catheter type, insertion site, and exit site location. Preoperative preparation of the patient is an instrumental step in facilitating the performance of the procedure, avoiding untoward events, and promoting the desired outcome...
January 2017: Seminars in Nephrology
https://www.readbyqxmd.com/read/28147279/endothelial-basement-membrane-laminin-511-contributes-to-endothelial-junctional-tightness-and-thereby-inhibits-leukocyte-transmigration
#13
Jian Song, Xueli Zhang, Konrad Buscher, Ying Wang, Huiyu Wang, Jacopo Di Russo, Lixia Li, Stefan Lütke-Enking, Alexander Zarbock, Anika Stadtmann, Paul Striewski, Benedikt Wirth, Ivan Kuzmanov, Heinz Wiendl, Dörte Schulte, Dietmar Vestweber, Lydia Sorokin
Endothelial basement membranes constitute barriers to extravasating leukocytes during inflammation, a process where laminin isoforms define sites of leukocyte exit; however, how this occurs is poorly understood. In addition to a direct effect on leukocyte transmigration, we show that laminin 511 affects endothelial barrier function by stabilizing VE-cadherin at junctions and downregulating expression of CD99L2, correlating with reduced neutrophil extravasation. Binding of endothelial cells to laminin 511, but not laminin 411 or non-endothelial laminin 111, enhanced transendothelial cell electrical resistance (TEER) and inhibited neutrophil transmigration...
January 31, 2017: Cell Reports
https://www.readbyqxmd.com/read/28142500/hyaluronic-acid-collagen-hydrogel-as-an-alternative-to-alginate-for-long-term-immunoprotected-islet-transplantation
#14
Stephen Harrington, S Janette Williams, Sonia Rawal, Karthik Ramachandran, Lisa Stehno-Bittel
Alginate has long been the material of choice for immunoprotection of islets for its low cost and ability to easily form microspheres. Unfortunately, this seaweed-derived material is notoriously prone to fibrotic overgrowth in vivo, resulting in premature graft failure. The purpose of this study was to test an alternative, hyaluronic acid (HA-COL), for in vitro function, viability and allogeneic islet transplant outcomes in diabetic rats. In vitro studies indicated that the HA-COL gel had diffusion characteristics that would allow small molecules like glucose and insulin to enter and exit the gel, while larger molecules (70 and 500kD dextrans) were impeded from diffusing past the gel edge in 24 hours...
January 31, 2017: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/28139383/olecranon-physeal-nonunion-in-the-adolescent-athlete-identification-of-two-patterns
#15
Rachel M Frank, Brett A Lenart, Mark S Cohen
BACKGROUND: This study aimed to present the outcomes of patients undergoing surgical management of persistent, symptomatic olecranon physes. METHODS: Consecutive patients undergoing surgical management for symptomatic persistent olecranon physeal abnormalities were reviewed. Preoperative data, intraoperative findings, and postoperative clinical outcomes including physical examination findings, radiographs, complications, and reoperations were analyzed. RESULTS: A total of 13 elbows in 12 patients (100% male; average age, 18 ± 4 years) were identified...
January 27, 2017: Journal of Shoulder and Elbow Surgery
https://www.readbyqxmd.com/read/28137908/the-pp2a-b56-phosphatase-opposes-cyclin-e-autocatalytic-degradation-via-site-specific-dephosphorylation
#16
Ryan J Davis, Jherek Swanger, Bridget T Hughes, Bruce E Clurman
Cyclin E, in conjunction with its catalytic partner cyclin-dependent kinase 2 (CDK2), regulates cell cycle progression as cells exit quiescence and enter S-phase. Multiple mechanisms control cyclin E periodicity during the cell cycle, including phosphorylation-dependent cyclin E ubiquitylation by the SCF(Fbw7) ubiquitin ligase. Serine 384 (S384) is the critical cyclin E phosphorylation site that stimulates Fbw7 binding and cyclin E ubiquitylation and degradation. Because S384 is autophosphorylated by bound CDK2, this presents a paradox as to how cyclin E can evade autocatalytically induced degradation in order to phosphorylate its other substrates...
January 30, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28125841/clearance-kinetics-and-clearance-routes-of-molecules-from-the-suprachoroidal-space-after-microneedle-injection
#17
Bryce Chiang, Ke Wang, C Ross Ethier, Mark R Prausnitz
Purpose: To determine clearance kinetics and routes of clearance of molecules from the suprachoroidal space (SCS) of live New Zealand White rabbits. Methods: Suprachoroidal space collapse rate and pressure changes after microneedle injection into SCS were determined. Fluorescent fundus images were acquired to determine clearance rates of molecules ranging in size from 332 Da to 2 MDa. Microneedle injections of fluorescein were performed, and samples were taken from various sites over time to determine amount of fluorescein exiting the eye...
January 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28122398/comparison-between-types-of-dressing-following-catheter-insertion-and-early-exit-site-infection-in-peritoneal-dialysis
#18
Ana Elizabeth Figueiredo, Carolina de Mattos, Cristine Saraiva, Marcia Olandoski, Pasqual Barretti, Roberto Pecoits Filho, Thyago Proença de Moraes
AIM: To investigate whether the type of dressing used (occlusive vs semi-occlusive) impacts on exit-site infection (ESI). BACKGROUND: Exit-site infections are a major predisposing factor for peritoneal dialysis (PD)-related peritonitis, the main cause of technique failure and an important cause of mortality. Care taken in exit-site dressing is considered an important procedure for the prevention of trauma and contamination of this area. Nevertheless, to our knowledge, no study has yet analyzed the impact of different dressing types on early ESI (up to 2 months after catheter insertion)...
January 25, 2017: Journal of Clinical Nursing
https://www.readbyqxmd.com/read/28120237/hibernating-substrate-of-ventricular-tachycardia-a-three-dimensional-metabolic-and-electro-anatomic-assessment
#19
Ayman A Hussein, Michelle Niekoop, Vasken Dilsizian, Yousra Ghzally, Mohammed Abdulghani, Ramazan Asoglu, Wengen Chen, Mark Smith, Vincent See, Stephen R Shorofsky, Timm-Michael Dickfeld
PURPOSE: Hibernating myocardium (HM) is associated with sudden cardiac death (SCD). Little is known about the electrophysiological properties of HM and the basis of its association with SCD. We aimed to electrophysiologically characterize HM in patients with ventricular tachycardia (VT). METHODS: Endocardial voltage mapping, metabolic (18)FDG-positron emission tomography (PET) and perfusion (82)Rb, (201)Tl, or (99m)Tc scans were performed in 61 ischemic heart disease patients with VT...
January 25, 2017: Journal of Interventional Cardiac Electrophysiology: An International Journal of Arrhythmias and Pacing
https://www.readbyqxmd.com/read/28119406/closing-the-gap-in-paediatric-ventricular-assist-device-therapy-with-the-berlin-heart-excor%C3%A2-15-ml-pump%C3%A2
#20
Fabrizio De Rita, Massimo Griselli, Eugen Sandica, Oliver Miera, Ann Karimova, Yves d'Udekem, Ranny Goldwasser, Katarzyna Januszewska, Antonio Amodeo, Nadine Jurrmann, Simon Ersel, Ares K Menon
OBJECTIVES: The Berlin Heart EXCOR(®) (EXCOR) paediatric ventricular assist device is used worldwide for mechanical support of infants and small children with end-stage heart failure. A clinically important gap between the smallest EXCOR blood pump (10 ml) and the next larger size (25 ml) limited the choice of pump size in patients with a body surface area (BSA) between 0.33 and 0.5 m(2) We present the first clinical experience from the early product surveillance (EPS) of the new EXCOR 15-ml blood pump...
January 23, 2017: Interactive Cardiovascular and Thoracic Surgery
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