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S Yesmin, M B Paget, H E Murray, R Downing
Cadaveric organ transplantation represents the definitive treatment option for end-stage disease but is restricted by the shortage of clinically-viable donor organs. This limitation has, in part, driven current research efforts for in vitro generation of transplantable tissue surrogates. Recent advances in organ reconstruction have been facilitated by the re-purposing of decellularized whole organs to serve as three-dimensional bio-scaffolds. Notably, studies in rodents indicate that such scaffolds retain native extracellular matrix components that provide appropriate biochemical, mechanical and physical stimuli for successful tissue/organ reconstruction...
September 12, 2017: Current Research in Translational Medicine
Fernanda Mendoza, José M Lluch, Laura Masgrau
Glycosyltransferases are enzymes that catalyze a monosaccharide transfer reaction from a donor to an acceptor substrate with the synthesis of a new glycosidic bond. They are highly substrate specific and regioselective, even though the acceptor substrate often presents multiple reactive groups. Currently, many efforts are dedicated to the development of biocatalysts for glycan synthesis and, therefore, a better understanding of how natural enzymes achieve this goal can be of valuable help. To gain a deeper insight into the catalytic strategies used by retaining glycosyltransferases, the wild type EXTL2 (CAZy family GT64) and four mutant forms (at positions 293 and 246) were studied using QM(DFT)/MM calculations and molecular dynamics simulations...
September 14, 2017: Organic & Biomolecular Chemistry
Timothy K Eitas, Wesley Stepp, Lucas Sjeklocha, Clayton Long, Caitlin Riley, James Callahan, Yolanda Sanchez, Peter Gough, Laquanda Knowlin, David van Duin, Shiara Ortiz-Pujols, Samuel Jones, Robert Maile, Zhi Hong, Scott Berger, Bruce Cairns
Burn patients suffer from immunological dysfunction for which there are currently no successful interventions. Similar to previous observations, we find that burn shock patients (≥15% Total Burn Surface Area (TBSA) injury) have elevated levels of the innate immune cytokines Interleukin-6 (IL-6) and Monocyte Chemoattractant Protein-1 (MCP-1)/CC-motif Chemokine Ligand 2(CCL2) early after hospital admission (0-48 Hours Post-hospital Admission (HPA). Functional immune assays with patient Peripheral Blood Mononuclear Cells (PBMCs) revealed that burn shock patients (≥15% TBSA) produced elevated levels of MCP-1/CCL2 after innate immune stimulation ex vivo relative to mild burn patients...
2017: PloS One
Vince Beachley, Garret Ma, Chris Papadimitriou, Matt Gibson, Michael Corvelli, Jennifer Elisseeff
Tissue extracellular matrix (ECM) is a complex material made up of fibrous proteins and ground substance (glycosaminoglycans, GAGs) that are secreted by cells. ECM contains important biological cues that modulate cell behaviors, and it also serves as a structural scaffold to which cells can adhere. For clinical applications, where immune rejection is a constraint, ECM can be processed using decellularization methods intended to remove cells and donor antigens from tissue or organs, while preserving native biological cues essential for cell growth and differentiation...
September 6, 2017: Journal of Biomedical Materials Research. Part A
Antony P McNamee, Jarod T Horobin, Geoff D Tansley, Michael J Simmonds
Patients receiving mechanical circulatory support often present with heightened inflammation and free radical production associated with pre-existing conditions in addition to that which is due to blood interactions with nonbiological surfaces. The aim of this experimental laboratory study was to assess the deformability of red blood cells (RBC) previously exposed to oxygen free radicals and determine the susceptibility of these cells to mechanical forces. In the present study, RBC from 15 healthy donors were washed and incubated for 60 min at 37°C with 50 µM phenazine methosulfate (PMS; an agent that generates superoxide within RBC)...
September 6, 2017: Artificial Organs
Albert John Roeland Heck, Sem Tamara, Richard Scheltema, Aneika C Leney
For many proteins phosphorylation regulates their interaction with other biomolecules. Here, we describe an unexpected phenomenon whereby within a binding interface phosphate groups transfer non-enzymatically from one interaction partner to the other upon activation in the gas-phase. Providing that a high affinity exists between the donor and acceptor sites, this phosphate transfer is very efficient and the phosphate groups only ligate to sites in proximity to the binding region. Consequently, such phosphate transfer reactions may define with high precision the binding site between a phosphoprotein and its binding partner, and in addition reveal that the binding site in this system is retained in the phase transfer from solution to the gas-phase...
September 4, 2017: Angewandte Chemie
I E Nifant'ev, A V Shlyakhtin, V V Bagrov, M E Minyaev, A V Churakov, S G Karchevsky, K P Birin, P V Ivchenko
Numerous heteroleptic 2,6-di-tert-butyl-4-methylphenolate (BHT) magnesium complexes have been synthesized by treatment of (BHT)MgBu(THF)2 with various alcohols. Molecular structures of the complexes have been determined by X-ray diffraction. The magnesium coordination number in [(BHT)Mg(μ-OBn)(THF)]2 (3) and [(BHT)Mg(μ-O-tert-BuC6H4)(THF)]2 (4) is equal to 4. Complexes formed from esters of glycolic and lactic acids, [(BHT)Mg(μ-OCH2COOEt)(THF)]2 (5) and [(BHT)Mg(μ-OCH(CH3)COOCH2COO(t)Bu)(THF)]2 (6) contain chelate fragments with pentacoordinated magnesium...
September 28, 2017: Dalton Transactions: An International Journal of Inorganic Chemistry
Michael L Freeman, Stephen R Morris, Michael M Lederman
BACKGROUND: Mucosa-associated invariant T (MAIT) cells are a recently identified class of innate-like T cells that are involved in the mucosal immune response. MAIT cells are characterized by expression of TCR Vα7.2 and CD161. In HIV infection, there is a profound early loss of MAIT cells from the circulation that never fully recovers, even after prolonged viral control with antiretroviral therapy (ART). METHODS: We analyzed PBMCs from fresh whole blood from HIV-negative or ART-treated HIV-positive donors with full (Immune Success) or impaired (Immune Failure) CD4(+) T- cell recovery by flow cytometry for T-cell markers, TCR Vα7...
2017: Pathogens & Immunity
Johanne Charbonneau, Marie-Soleil Cloutier, Balia Fainstein
BACKGROUND: The demand for therapeutic plasma-derived products poses a challenge to blood collection agencies (BCAs). In 2014-2015, the volume of plasma sent for fractionation met 17.7% of Quebec's needs for immunoglobulins. This article aims to offer an exploration of the paths blood donors follow in order to become plasma and platelet donors (PPDs). STUDY DESIGN AND METHOD: This analysis is based on semi-structured interviews with 50 PPDs in Quebec, Canada. Our analysis focused on the occurrence of events and the presence of contextual elements identified through: (1) factual data on PPDs; and (2) what PPDs identified as being an influence on their donation experience...
August 25, 2017: Journal of Clinical Apheresis
Sambuddha Sen, J A Cowan
Monothiol glutaredoxins (Grx) serve as intermediate cluster carriers in iron-sulfur cluster trafficking. The [2Fe-2S]-bound holo forms of Grx proteins display cysteinyl coordination from exogenous glutathione (GSH), in addition to contact from protein-derived Cys. Herein, we report mechanistic studies that investigate the role of exogenous glutathione in defining cluster chirality, ligand exchange, and the cluster transfer chemistry of Saccharomyces cerevisiae Grx3. Systematic perturbations were introduced to the glutathione-binding site by substitution of conserved charged amino acids that form crucial electrostatic contacts with the glutathione molecule...
August 23, 2017: Journal of Biological Inorganic Chemistry: JBIC
Patrick Rijkschroeff, Bruno G Loos, Elena A Nicu
Oral health is characterized by functional oral polymorphonuclear neutrophils (oPMNs). Edentulism might be associated with a loss of oPMNs because these cells enter the oral cavity primarily through the gingival crevices. The main aim of this study was to investigate the numbers of oPMNs in rinse samples obtained from edentulous (n = 21) and dentate (n = 20) subjects. A second study aim was to investigate possible differences between oPMNs and peripheral blood polymorphonuclear neutrophils (cPMNs). Apoptosis/necrosis and cell-activation markers (CD11b, CD63 and CD66b) were analyzed using flow cytometry...
August 19, 2017: European Journal of Oral Sciences
Panayiotis N Varelas, Paul Brady, Mohammed Rehman, Arash Afshinnik, Chandan Mehta, Tamer Abdelhak, Eelco F Wijdicks
BACKGROUND: Patients with primary posterior fossa catastrophic lesions may clinically meet brain death criteria, but may retain supratentorial brain function or blood flow. These patients could be declared brain-dead in the United Kingdom (UK), but not in the United States of America (USA). We report the outcome of adult patients with primary posterior fossa lesions without concurrent major supratentorial injury. METHODS: Henry Ford Hospital database was reviewed over a period of 88 months in order to identify all adult patients with isolated brainstem or posterior fossa lesions...
August 21, 2017: Neurocritical Care
Sara Alfieri, Maura Pozzi, Elena Marta, Vincenzo Saturni, Giovanni Aresi, Paolo Guiddi
BACKGROUND: The present work proposes to explore a phenomenon well known in the world of blood donation, but little explored by literature: multi-affiliations. By that term, in this paper we mean blood donors' engagement in multiple associations of various natures (donation, recreation, sports, etc.) simultaneously. The first objective proposes to explore the phenomenon of multi-affiliations in descriptive terms; the second is to look into the differences-in terms of motivations, family-work-volunteerism reconciliation, life satisfaction, and membership satisfaction-between those who "only" carry out blood donation activity and those who instead participate in multiple associative realities concurrently...
July 25, 2017: Transfusion and Apheresis Science
Rabia U Malik, Matthew Dysthe, Michael Ritt, Roger K Sunahara, Sivaraj Sivaramakrishnan
FRET and BRET approaches are well established for detecting ligand induced GPCR-G protein interactions in cells. Currently, FRET/BRET assays rely on co-expression of GPCR and G protein, and hence depend on the stoichiometry and expression levels of the donor and acceptor probes. On the other hand, GPCR-G protein fusions have been used extensively to understand the selectivity of GPCR signaling pathways. However, the signaling properties of fusion proteins are not consistent across GPCRs. In this study, we describe and characterize novel sensors based on the Systematic Protein Affinity Strength Modulation (SPASM) technique...
August 10, 2017: Scientific Reports
Charles A Mkony, Ephata E Kaaya, Alex J Goodell, Sarah B Macfarlane
Background Faced with one of the lowest physician-to-population ratios in the world, the Government of Tanzania is urging its medical schools to train more physicians. The annual number of medical students admitted across the country rose from 55 in the 1990s to 1,680 approved places for the 2015/16 academic year. These escalating numbers strain existing faculty. Objective To describe the availability of faculty in medical schools in Tanzania. Design We identified faculty lists published on the Internet by five Tanzanian medical schools for the 2011/12 academic year and analyzed the appointment status, rank, discipline, and qualifications of faculty members...
December 2016: Global Health Action
Wenhu Zhou, Jinsong Ding, Juewen Liu
Recently, a few Na(+)-specific RNA-cleaving DNAzymes have been reported, and a Na(+) aptamer was identified from the NaA43 and Ce13d DNAzymes. These DNAzymes and the embedded aptamer have been used for Na(+) detection. In this work, we studied the Na(+)-dependent folding of the Ce13d DNAzyme using fluorescence resonance energy transfer (FRET). When a FRET donor and an acceptor were respectively labeled at the ends of the DNAzyme, Na(+) failed to induce an obvious end-to-end distance change, suggesting a rigid global structure...
August 23, 2017: Organic & Biomolecular Chemistry
Jyung Mean Son, Ehab H Sarsour, Anurag Kakkerla Balaraju, Jenna Fussell, Amanda L Kalen, Brett A Wagner, Garry R Buettner, Prabhat C Goswami
Replicative and chronological lifespan are two different modes of cellular aging. Chronological lifespan is defined as the duration during which quiescent normal cells retain their capacity to re-enter the proliferative cycle. This study investigated whether changes in metabolism occur during aging of quiescent normal human fibroblasts (NHFs) and the mechanisms that regulate these changes. Bioenergetics measurements were taken in quiescent NHFs from younger (newborn, 3-day, 5-month, and 1-year) and older (58-, 61-, 63-, 68-, and 70-year) healthy donors as well as NHFs from the same individual at different ages (29, 36, and 46 years)...
October 2017: Aging Cell
Qian Li, Ying-Ying Huang, Louis Patrick Conway, Meng He, Shuang Wei, Kun Huang, Xu-Chu Duan, Sabine L Flitsch, Josef Voglmeir
A glucose-1-phosphate nucleotidyltransferase (TiGPNT) was cloned and biochemically characterized from the deep sea bacterium Thermodesulfatator indicus. TiGPNT was recombinantly expressed under the control of the T7 promoter in Escherichia coli and could be successfully enriched by heat treatment at 80°C for 30 min. The obtained enzyme worked best at pH 7.5 and the optimum reaction temperature was determined to be 50°C. Interestingly, TiGPNT could fully retain its activity even after extended incubation periods at temperatures of up to 80°C...
July 24, 2017: Protein and Peptide Letters
Leslie C Sutherland, Philippe Thibault, Mathieu Durand, Elvy Lapointe, Jose M Knee, Ariane Beauvais, Irina Kalatskaya, Sarah C Hunt, Julie J Loiselle, Justin G Roy, Sarah J Tessier, Gustavo Ybazeta, Lincoln Stein, Rashmi Kothary, Roscoe Klinck, Benoit Chabot
BACKGROUND: RBM10 is an RNA binding protein involved in message stabilization and alternative splicing regulation. The objective of the research described herein was to identify novel targets of RBM10-regulated splicing. To accomplish this, we downregulated RBM10 in human cell lines, using small interfering RNAs, then monitored alternative splicing, using a reverse transcription-PCR screening platform. RESULTS: RBM10 knockdown (KD) provoked alterations in splicing events in 10-20% of the pre-mRNAs, most of which had not been previously identified as RBM10 targets...
July 20, 2017: BMC Molecular Biology
Oliver Hallich
Sperm donation is an increasingly common method of assisted reproduction. In the debate on sperm donation, the right to privacy - construed as a right that refers to the limits of the realm of information to which others have access - plays a pivotal role with regard to two questions. The first question is whether the sperm donor's right to privacy implies his right to retain his anonymity, the second is whether the gamete recipients' right to privacy entitles them to withhold information about the circumstances of their conception from their donor-conceived offspring...
July 20, 2017: New Bioethics: a Multidisciplinary Journal of Biotechnology and the Body
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