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Silmara Montalvão, Priscila Soares Elídio, Sabrina da Silva Saraiva, Bruna de Moraes Mazetto, Marina Pereira Colella, Erich Vinícius de Paula, Simone Appenzeller, Joyce Annichino-Bizzacchi, Fernanda Andrade Orsi
INTRODUCTION: Antibodies directed against domain 1 of β2 glycoprotein 1 (aβ2GP1-Dm1) have been involved in the immunopathogenesis of antiphospholipid syndrome (APS). However, the clinical relevance of aβ2GP1-Dm1 in thrombotic APS has not yet been fully explored. OBJECTIVES: To determine the frequency of aβ2GP1-Dm1 in a cohort of patients with thrombotic APS, and to evaluate whether testing for aβ2GP1-Dm1 could have a clinical impact upon the risk assessment of the disease...
October 4, 2016: Thrombosis Research
Agnieszka Fiszer, Marianna E Ellison-Klimontowicz, Wlodzimierz J Krzyzosiak
Polyglutamine (polyQ) diseases comprise a group of nine genetic disorders that are caused by the expansion of the CAG triplet repeat, which encodes glutamine, in unrelated single genes. Various oligonucleotide (ON)-based therapeutic approaches have been considered for polyQ diseases. The very attractive CAG repeat-targeting strategy offers selective silencing of the mutant allele by directly targeting the mutation site. CAG repeat-targeting miRNA-like siRNAs have been shown to specifically inhibit the mutant gene expression, and their characteristic feature is the formation of mismatches in their interactions with the target site...
October 21, 2016: Acta Biochimica Polonica
Zhen Lei, Abdul Sami Shaikh, Wenshuai Zheng, Xiao Yu, Jingui Yu, Jingxin Li
Itch, the unpleasant sensation that evokes a desire to scratch, accompanies numerous skin and nervous system disorders. However, the molecular mechanisms of itch are unclear. Acid sensing ion channel 3 (ASIC3) is a sensor of acidic and primary inflammatory pain. The whole-cell patch-clamp technique was used to determine the effect of Chloroquine (CQ)on ASICs currents in primary sensory neurons or the Chinese hamster ovary (CHO) cells transfected with rat-ASIC1a or- ASIC3. Site-directed mutagenesis of plasmid was performed...
October 22, 2016: Journal of Neurochemistry
David P Hickey
Enzymatic glucose biosensors and biofuel cells make use of the electrochemical transduction between an oxidoreductase enzyme, such as glucose oxidase (GOx), and an electrode to either quantify the amount of glucose in a solution or generate electrical energy. However, many enzymes including GOx are not able to electrochemically interact with an electrode surface directly, but require an external electrochemical relay to shuttle electrons to the electrode. Ferrocene-modified linear poly(ethylenimine) (Fc-LPEI) redox polymers have been designed to simultaneously immobilize glucose oxidase (GOx) at an electrode and mediate electron transfer from their flavin adenine dinucleotide (FAD) active site to the electrode surface...
2017: Methods in Molecular Biology
Andriy Bilichak, Igor Kovalchuk
DNA strand breaks arise from normal cellular processes such as replication, transcription, and DNA repair as well as spontaneous DNA damage caused by cell metabolic activities. In addition, strand breaks occur due to direct or indirect DNA damage produced by various abiotic and biotic stresses. Strand breaks are among the most problematic DNA lesions because unrepaired strand breaks may lead to cell cycle arrest, gross chromosome rearrangements, or even cell death. Thus, the measurement of the relative number of strand breaks can provide an informative picture of genome stability of a given cell, tissue, or organism...
2017: Methods in Molecular Biology
Zhenglin Chi, Peng Yang, Dajiang Song, Zan Li, Liang Tang, Weiyang Gao, Yonghuan Song, Tingang Chu
INTRODUCTION: To investigate the results of resurfacing completely degloved digits using bilobed innervated radial artery superficial palmar branch (RASPB) perforator flap in a spiral fashion. METHODS: A detailed anatomic study on 30 adult fresh frozen cadavers preinjected with silicone rubber compound to demarcate arterial anatomy documented locations, numbers, and diameters of arteries and skin perforators with surrounding nerves. The flap-raising procedure was performed using four fresh cadaver specimen...
October 21, 2016: Surgical and Radiologic Anatomy: SRA
Jamie L Burgess, R Alan Burgess, Yalemi Morales, Jenna M Bouvang, Sean J Johnson, Nicholas E Dickenson
Like many Gram-negative pathogens, Shigella rely on a complex type three secretion system (T3SS) to inject effector proteins into host cells, take over host functions, and ultimately establish infection. Despite these critical roles, the energetics and regulatory mechanisms controlling the T3SS and pathogen virulence remain largely unclear. In this study, we present a series of high-resolution crystal structures of Spa47 and use the structures to model an activated Spa47 oligomer, finding that ATP hydrolysis may be supported by specific sidechain contributions from adjacent protomers within the complex...
October 21, 2016: Journal of Biological Chemistry
Dennis Walczyk, Markus Gößringer, Walter Rossmanith, Timofei S Zatsepin, Tatiana S Oretskaya, Roland K Hartmann
Ribonuclease P (RNase P) is the enzyme that endonucleolytically removes 5'-precursor sequences from tRNA transcripts in all domains of life. RNase P activities are either ribonucleoprotein (RNP) or protein-only (PRORP) enzymes, raising the question about the mechanistic strategies utilized by these architecturally different enzyme classes to catalyze the same type of reaction. Here we analyzed the kinetics and cleavage-site selection by PRORP3 from Arabidopsis thaliana (AtPRORP3) using precursor tRNAs (pre-tRNAs) with individual modifications at the canonical cleavage site, either Rp- or Sp-phosphorothioate, or 2'-deoxy, 2'-fluoro, 2'-amino or 2'-O-methyl substitutions...
October 18, 2016: Journal of Molecular Biology
Chao-Ming Hung, Ying-Chao Lin, Liang-Chih Liu, Sheng-Chu Kuo, Chi-Tang Ho, Tzong-Der Way
CWF-145, a synthetic 2-phenyl-4-quinolone derivative exerted potent cytotoxicity against prostate cancer. CWF-145 inhibited prostate cancer cell lines PC-3, DU-145 and LNCap. It had a very low IC50 about 200 nM against castrate-resistant prostate cancer (CRPC) PC-3. We found that CWF-145 had a similar effect to clinical trial antimitotic agents in cancer cells and normal cells. CWF-145 arrested cell cycle at G2/M phase by binding to the β-tubulin at the colchicine-binding site then disrupted microtubule polymerization...
October 18, 2016: Chemico-biological Interactions
F Lucernoni, L Capelli, S Sironi
The aim of this study is related to the assessment of odour emissions from landfill surfaces. Up to now, there is not a widely accepted method to quantify odour emissions from this particular kind of source. Five different methods were developed and investigated. These methods can be considered as based on three distinct approaches, both experimental and computational. The first approach provides to use models for the estimation the landfill gas production, whereby the second and the third approach are based on direct measurement campaigns on the landfill surface: for the determination of the methane concentration or for the direct measurement of the odour concentration, respectively...
October 18, 2016: Waste Management
Jie Gao, Narasimha Midde, Jun Zhu, Alvin V Terry, Campbell McInnes, James M Chapman
Using molecular modeling and rationally designed structural modifications, the multi-target structure-activity relationship for a series of ranitidine analogs has been investigated. Incorporation of a variety of isosteric groups indicated that appropriate aromatic moieties provide optimal interactions with the hydrophobic and π-π interactions with the peripheral anionic site of the AChE active site. The SAR of a series of cyclic imides demonstrated that AChE inhibition is increased by additional aromatic rings, where 1,8-naphthalimide derivatives were the most potent analogs and other key determinants were revealed...
October 6, 2016: Bioorganic & Medicinal Chemistry Letters
A Ulges, E Schmitt, C Becker, T Bopp
The immune system has evolved to defend the organism against an almost infinite number of pathogens in a locally confined and antigen-specific manner while at the same time preserving tolerance to harmless antigens and self. Regulatory T (Treg) cells essentially contribute to an immunoregulatory network preventing excessive immune responses and immunopathology. There is emerging evidence that Treg cells not only operate in secondary lymphoid tissue but also regulate immune responses directly at the site of inflammation...
2016: Advances in Immunology
Michelle Gray, Anne Malott, Beth Murray Davis, Christine Sandor
BACKGROUND: contemporary knowledge related to the experiences of new midwifery practitioners is limited to countries that run hospital-based transition to practice programmes within an employment contract arrangement, such as the United Kingdom, and Australia. Less is known of the experiences of New Midwifery Practitioners (NMPs) who transition into autonomous private practice in New Zealand, Canada and the Netherlands. PURPOSE: the purpose of this paper is to report on a scoping review of the way NMPs are transitioned to practice in the first year of registered practice across the selected countries...
September 28, 2016: Midwifery
Camilla Hardeland, Kjetil Sunde, Helge Ramsdal, Susan R Hebbert, Linda Soilammi, Fredrik Westmark, Fredrik Nordum, Andreas E Hansen, Jon E Steen-Hansen, Theresa M Olasveengen
AIM: Explore, understand and address issues that impact upon timely and adequate allocation of prehospital medical assistance and resources to out-of-hospital cardiac arrest (OHCA) patients. METHODS: Mixed-methods: design obtaining data for one year in three emergency medical communication centres (EMCC); Oslo-Akershus (OA), Vestfold-Telemark (VT) and Østfold (Ø). Data collection included quantitative data from analysis of dispatch logs, ambulance records and audio files...
October 18, 2016: Resuscitation
Anders J Davidson, Lucas P Neff, Joseph J DuBose, James B Sampson, Christopher M Abbot, Timothy K Williams
Peripheral vascular injuries carry significant risk for permanent functional impairment, limb loss, and death. Definitive correction of these injuries requires significant operative time and has traditionally been resource and skill set intensive. In the initial surgical treatment of the physiologically depleted trauma patient, faster techniques may prove more appropriate. Damage control techniques, including vascular shunting, rapidly restore distal flow but require additional vascular intervention and risk shunt thrombosis with prolonged use...
November 2016: Journal of Trauma and Acute Care Surgery
Eric B Loucks, Yen-Tsung Huang, Golareh Agha, Su Chu, Charles B Eaton, Stephen E Gilman, Stephen L Buka, Karl T Kelsey
OBJECTIVE: Childhood socioeconomic disadvantage is associated with adulthood obesity risk; however, epigenetic mechanisms are poorly understood. This work's objective was to evaluate whether associations of childhood socioeconomic disadvantage with adulthood body mass index (BMI) are mediated by DNA methylation. METHODS: Participants were 141 men and women from the New England Family Study, prospectively followed prenatally through a mean age of 47 years. Epigenomewide DNA methylation was evaluated in peripheral blood and adipose tissue obtained at adulthood, using the Infinium HumanMethylation450K BeadChip...
October 20, 2016: Psychosomatic Medicine
Kristin Bösch, Lamprinos Frantzeskakis, Miroslav Vraneš, Jörg Kämper, Kerstin Schipper, Vera Göhre
Gene deletion plays an important role in the analysis of gene function. One of the most efficient methods to disrupt genes in a targeted manner is the replacement of the entire gene with a selectable marker via homologous recombination. During homologous recombination, exchange of DNA takes place between sequences with high similarity. Therefore, linear genomic sequences flanking a target gene can be used to specifically direct a selectable marker to the desired integration site. Blunt ends of the deletion construct activate the cell's DNA repair systems and thereby promote integration of the construct either via homologous recombination or by non-homologous-end-joining...
September 30, 2016: Journal of Visualized Experiments: JoVE
Gayathri Sivakumar, Marie-Louise Mares
How do patients respond when advice on health websites differs from advice given by a doctor? To test effects of advice concordance, 418 participants 25-80 years old were randomly assigned to read real websites that varied in quality of information about diabetes: high (medically accurate and complete), medium (accurate but incomplete), and low (inaccurate). The control group read travel sites. Participants then watched a video of a physician making treatment recommendations for a diabetic patient, and indicated how they would respond if they were the patient...
October 21, 2016: Health Communication
Gil Henkin, Daniel Berard, Francis Stabile, Marjan Shayegan, Jason S Leith, Sabrina R Leslie
We present a dynamically adjustable nanofluidic platform for formatting the conformations of and visualizing the interaction kinetics between biomolecules in solution, offering new time resolution and control of the reaction processes. This platform extends Convex Lens-induced Confinement (CLiC), a technique for imaging molecules under confinement, by introducing a system for in-situ modification of the chemical environment; this system uses a deep microchannel to diffusively exchange reagents within the nanoscale imaging region, whose height is fixed by a nanopost array...
October 21, 2016: Analytical Chemistry
Pierre E Affaticati, Shao-Bo Dai, Panwajee Payongsri, Helen C Hailes, Kai Tittmann, Paul A Dalby
The S385Y/D469T/R520Q variant of E. coli transketolase was evolved previously with three successive smart libraries, each guided by different structural, bioinformatical or computational methods. Substrate-walking progressively shifted the target acceptor substrate from phosphorylated aldehydes, towards a non-phosphorylated polar aldehyde, a non-polar aliphatic aldehyde, and finally a non-polar aromatic aldehyde. Kinetic evaluations on three benzaldehyde derivatives, suggested that their active-site binding was differentially sensitive to the S385Y mutation...
October 21, 2016: Scientific Reports
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