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Ariane Nunes-Alves, Daniel M Zuckerman, Guilherme Menegon Arantes
The T4 lysozyme L99A mutant is often used as a model system to study small-molecule binding to proteins, but pathways for ligand entry and exit from the buried binding site and the associated protein conformational changes have not been fully resolved. Here, molecular dynamics simulations were employed to model benzene exit from its binding cavity using the weighted ensemble (WE) approach to enhance sampling of low-probability unbinding trajectories. Independent WE simulations revealed four pathways for benzene exit, which correspond to transient tunnels spontaneously formed in previous simulations of apo T4 lysozyme...
March 13, 2018: Biophysical Journal
Cher-Pheng Ooi, Terry K Smith, Eva Gluenz, Nadina Vasileva Wand, Sue Vaughan, Gloria Rudenko
The predominant secretory cargo of bloodstream form Trypanosoma brucei is Variant Surface Glycoprotein (VSG), comprising ~10% total protein and forming a dense protective layer. Blocking VSG translation using Morpholino oligonucleotides triggered a precise pre-cytokinesis arrest. We investigated the effect of blocking VSG synthesis on the secretory pathway. The number of Golgi decreased, particularly in post-mitotic cells, from 3.5 ± 0.6 to 2.0 ± 0.04 per cell. Similarly, the number of ER exit sites (ERES) in post-mitotic cells dropped from (3...
March 13, 2018: Traffic
Joseph J Kavolus, David Sia, Hollis G Potter, David E Attarian, Paul F Lachiewicz
BACKGROUND: Surgeon-performed periarticular injections and anesthesiologist-performed femoral nerve or adductor canal blocks with local anesthetic are in common use as part of multimodal pain management regimens for patients undergoing TKA. However, femoral nerve blocks risk causing quadriceps weakness and falls, and anesthesiologist-performed adductor canal blocks are costly in time and resources and may be unreliable. We investigated the feasibility of a surgeon-performed saphenous nerve ("adductor canal") block from within the knee at the time of TKA...
January 2018: Clinical Orthopaedics and related Research
Anthony Li, Joseph Samuel Davis, Alexander Grimster, Jeremiah Wierwille, Keith Herold, Dennis Morgan, Elijah R Behr, Stephen Shorofsky, Magdi Saba
Aims: To determine if a software algorithm can use an individualized distance-morphology difference model, built from three initial pacemaps, to prospectively locate the exit site (ES) of ventricular arrhythmias (VA). Methods and results: Consecutive patients undergoing ablation of VA from a single centre were recruited. During mapping, three initial pacing points were collected in the chamber of interest and the navigation algorithm applied to predict the ES, which was corroborated by conventional mapping techniques...
March 8, 2018: Europace: European Pacing, Arrhythmias, and Cardiac Electrophysiology
Navroop K Dhaliwal, Kamelia Miri, Scott Davidson, Hala Tamim El Jarkass, Jennifer A Mitchell
Cooperative action of a transcription factor complex containing OCT4, SOX2, NANOG, and KLF4 maintains the naive pluripotent state; however, less is known about the mechanisms that disrupt this complex, initiating exit from pluripotency. We show that, as embryonic stem cells (ESCs) exit pluripotency, KLF4 protein is exported from the nucleus causing rapid decline in Nanog and Klf4 transcription; as a result, KLF4 is the first pluripotency transcription factor removed from transcription-associated complexes during differentiation...
March 1, 2018: Stem Cell Reports
Christine C Lee, Bing Li, Hongtao Yu, Michael J Matunis
The Anaphase Promoting Complex/Cyclosome (APC/C) is a ubiquitin E3 ligase that functions as the gatekeeper to mitotic exit. APC/C activity is controlled by an interplay of multiple pathways during mitosis, including the spindle assembly checkpoint (SAC), that are not yet fully understood. Here, we show that sumoylation of the APC4 subunit of the APC/C peaks during mitosis and is critical for timely APC/C activation and anaphase onset. We have also identified a functionally important SUMO interacting motif in the cullin-homology domain of APC2 located near the APC4 sumoylation sites and APC/C catalytic core...
March 8, 2018: ELife
Neha Vithani, Pravin Kumar Ankush Jagtap, Sunil Kumar Verma, Ravi Tripathi, Shalini Awasthi, Nisanth N Nair, Balaji Prakash
The nucleotidyl transfer reaction, catalyzed by sugar nucleotidyltransferases (SNTs), is assisted by two active site Mg2+ ions. While studying this reaction using X-ray crystallography, we captured snapshots of the pyrophosphate (product) as it exits along a pocket. Surprisingly, one of the active site Mg2+ ions remains coordinated to the exiting pyrophosphate. This hints at the participation of Mg2+ in the process of product release, besides its role in catalyzing nucleotidyl transfer. These observations are further supported by enhanced sampling molecular dynamics simulations...
March 6, 2018: Structure
Fadia Ibrahim, Manolis Maragkakis, Panagiotis Alexiou, Zissimos Mourelatos
mRNAs transmit the genetic information that dictates protein production and are a nexus for numerous pathways that regulate gene expression. The prevailing view of canonical mRNA decay is that it is mediated by deadenylation and decapping followed by exonucleolysis from the 3' and 5' ends. By developing Akron-seq, a novel approach that captures the native 3' and 5' ends of capped and polyadenylated RNAs, respectively, we show that canonical human mRNAs are subject to repeated cotranslational and ribosome-phased endonucleolytic cuts at the exit site of the mRNA ribosome channel, in a process that we term ribothrypsis...
March 5, 2018: Nature Structural & Molecular Biology
Xieyang Guo, Alexander G Myasnikov, James Chen, Corinne Crucifix, Gabor Papai, Maria Takacs, Patrick Schultz, Albert Weixlbaumer
Transcriptional pausing by RNA polymerases (RNAPs) is a key mechanism to regulate gene expression in all kingdoms of life and is a prerequisite for transcription termination. The essential bacterial transcription factor NusA stimulates both pausing and termination of transcription, thus playing a central role. Here, we report single-particle electron cryo-microscopy reconstructions of NusA bound to paused E. coli RNAP elongation complexes with and without a pause-enhancing hairpin in the RNA exit channel...
March 1, 2018: Molecular Cell
Anil K Tyor, Kanika Pahwa
River Yamuna is under constant menace due to pollution levels beyond limit, ensuing chronic poisoning of aquatic biota. Induction of oxidative stress and cellular deformities is a common effect in fish. The present study aimed in assessing impact of environmental pollutants on gonad (testis) of Clarias gariepinus from Wazirabad barrage (entry site) and Okhla barrage (exit site) of river Yamuna in Delhi segment. Antioxidant enzymes assays viz. Super oxide dismutase (SOD), catalase (CAT) and ferric reducing antioxidant power (FRAP); thiobarbituric acid reactive substance assay (TBARS) for determining level of lipid peroxidation and histology for analysis of degenerative changes were employed as biomarkers...
March 1, 2018: Bulletin of Environmental Contamination and Toxicology
Kieran D James, William E Jenkinson, Graham Anderson
T-cells bearing the αβTCR play a vital role in defending the host against foreign pathogens and malignant transformation of self. Importantly, T-cells are required to remain tolerant to the host's own cells and tissues in order to prevent self-reactive responses that can lead to autoimmune disease. T-cells achieve the capacity for self/nonself discrimination by undergoing a highly selective and rigorous developmental program during their maturation in the thymus. This organ is unique in its ability to support a program of T-cell development that ensures the establishment of a functionally diverse αβTCR repertoire within the peripheral T-cell pool...
February 27, 2018: Journal of Leukocyte Biology
Sarah J Swartz, Alicia Neu, Amy Skversky Mason, Troy Richardson, Jonathan Rodean, John Lawlor, Bradley Warady, Michael J G Somers
BACKGROUND: The Standardizing Care to Improve Outcomes in Pediatric End Stage Renal Disease (SCOPE) Collaborative is a quality improvement initiative to reduce dialysis-associated infections. The frequency of peritoneal dialysis (PD) catheter exit site infection (ESI) and variables influencing its development and end result are unclear. We sought to determine ESI rates, to elucidate the epidemiology, risk factors, and outcomes for ESI, and to assess for association between provider compliance with care bundles and ESI risk...
February 26, 2018: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
Tracy N Zembles, Linda S Flannery, Anna R Huppler
PURPOSE: The development and implementation of an antimicrobial lock therapy guideline at a large pediatric hospital are described. SUMMARY: Central venous access devices (CVADs) are essential in the medical management of patients requiring long-term total parenteral nutrition, chemotherapy, or hemodialysis. However, the use of a CVAD carries a significant risk of the development of central line-associated bloodstream infection (CLABSI). Antimicrobial lock therapy is indicated for patients with CLABSIs who have no signs of exit site or tunnel infection and for whom catheter salvage is a goal...
March 1, 2018: American Journal of Health-system Pharmacy: AJHP
Jamal Saleh Al Wakeel, Mohammed A Al Ghonaim, Abdullah Aldohayan, Saira Usama, Saad Al Obaili, Ahmad R Tarakji, Mohammad Alkhowaiter
Our objective is to study the outcomes and complications of peritoneal dialysis (PD) including comparison of self-care PD with home-care assisted PD during a five-year period. A retrospective study of PD data at King Saud University-affiliated hospital in Riyadh from January 1, 2009, to December 31, 2013. One hundred and eleven patients were included (female 55%). The average age was 47.4 (1-83) years. Twenty-one (18.91%) patients were on continuous ambulatory PD and 90 (81.08%) on automated PD. The mean time on PD was 23...
January 2018: Saudi Journal of Kidney Diseases and Transplantation
Abhilash Koratala, Michael J Casey, Amir Kazory
No abstract text is available yet for this article.
February 16, 2018: Blood Purification
Laurel H Messer, Gregory P Forlenza, Jennifer L Sherr, R Paul Wadwa, Bruce A Buckingham, Stuart A Weinzimer, David M Maahs, Robert H Slover
OBJECTIVE: The MiniMed 670G System is the first commercial hybrid closed-loop (HCL) system for management of type 1 diabetes. Using data from adolescent and young adult participants, we compared insulin delivery patterns and time-in-range metrics in HCL (Auto Mode) and open-loop (OL). System alerts, usage profiles, and operational parameters were examined to provide suggestions for optimal clinical use of the system. RESEARCH DESIGN AND METHODS: Data from 31 adolescent and young adult participants (14-26 years old) at three clinical sites in the 670G pivotal trial were analyzed...
February 14, 2018: Diabetes Care
XingRong Shen, Manman Lu, Rui Feng, Jing Cheng, Jing Chai, Maomao Xie, Xuemeng Dong, Tao Jiang, Debin Wang
BACKGROUND: Excessive use of antibiotics is very common worldwide, especially in rural China; various measures that have been used in curbing the problem have shown only marginal effects. OBJECTIVE: The objective of this study was to test an innovative intervention that provided just-in-time information and feedback (JITIF) to village doctors on care of common infectious diseases. METHODS: The information component of JITIF consisted of a set of theory or evidence-based ingredients, including operation guideline, public commitment, and takeaway information, whereas the feedback component tells each participating doctor about his or her performance scores and percentages of antibiotic prescriptions...
February 14, 2018: Journal of Medical Internet Research
Mohammad Reza Keramati, Ali Abbaszadeh-Kasbi, Amir Keshvari
BACKGROUND: Prophylactic laparoscopic omentopexy is a safe technique to prevent peritoneal dialysis (PD) catheter obstruction. For the first time, we would like to describe a surgical technique in which the omentopexy is done using a single PD port which is used for the omentopexy, PD catheter insertion, and the rectus sheath tunneling of the catheter. METHODS: The surgical method of the omentopexy using the PD port (US Patent 20170119430) will be thoroughly described...
February 7, 2018: Peritoneal Dialysis International: Journal of the International Society for Peritoneal Dialysis
Verena Kriechbaumer, Lilly Maneta-Peyret, Laetitia Fouillen, Stanley W Botchway, Jessica Upson, Louise Hughes, Jake Richardson, Maike Kittelmann, Patrick Moreau, Chris Hawes
Reticulons are integral ER membrane proteins characterised by a reticulon homology domain comprising four transmembrane domains which results in the proteins sitting in the membrane in a W-topology. Here we report on a novel subgroup of reticulons with an extended N-terminal domain and in particular on arabidopsis reticulon 20. Using high resolution confocal microscopy we show that reticulon 20 is located in a unique punctate pattern on the ER membrane. Its closest homologue reticulon 19 labels the whole ER...
February 2, 2018: Scientific Reports
K Shivanand Nayak, Sreepada V Subhramanyam, Navva Pavankumar, Sinoj Antony, M A Sarfaraz Khan
BACKGROUND/AIMS: Initiating renal replacement therapy in late referred patients with central venous catheter (CVC) hemodialysis (HD) causes serious complications. In urgent start peritoneal dialysis, initiating peritoneal dialysis (PD) within 14 days of catheter insertion still needs HD with CVC. We initiated Emergent start PD (ESPD) with Automated PD (APD) at our center within 48 h from the time of presentation. METHODS: A prospective, case-controlled, intention-to-treat study with 56 patients was conducted between March 2016 and August 2017...
January 30, 2018: Blood Purification
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