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https://www.readbyqxmd.com/read/28214629/effects-of-metal-ion-replacement-on-pyrazinamidase-activity-a-quantum-mechanical-study
#1
Mahmoud Khadem-Maaref, Faramarz Mehrnejad, Arash Phirouznia
Pyrazinamidase (PZase), a metalloenzyme, is responsible for acidic modification of pyrazinamide (PZA), a drug used in tuberculosis treatment. The metal coordination site of the enzyme is able to coordinate various divalent metal cofactors. Previous experimental studies have demonstrated that metal ions, such as Co(2+), Mn(2+), and Zn(2+), are able to reactivate metal-depleted PZase, while others including Cu(2+), Fe(2+), and Mg(2+), cannot restore activity. In this study, we investigated binding of various metal ions to the metal coordination site (MCS) of the enzyme using quantum mechanical calculations...
February 2, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28214577/parafascicular-thalamic-nucleus-deep-brain-stimulation-decreases-nmda-receptor-glun1-subunit-gene-expression-in-the-prefrontal-cortex
#2
Mónica R Fernández-Cabrera, Abraham Selvas, Miguel Miguéns, Alejandro Higuera-Matas, Anna Vale-Martínez, Emilio Ambrosio, Margarita Martí-Nicolovius, Gemma Guillazo-Blanch
The rodent parafascicular nucleus (PFn) or the centromedian-parafascicular complex of primates is a posterior intralaminar nucleus of the thalamus related to cortical activation and maintenance of states of consciousness underlying attention, learning and memory. Deep brain stimulation (DBS) of the PFn has been proved to restore arousal and consciousness in humans and to enhance performance in learning and memory tasks in rats. The primary expected effect of PFn DBS is to induce plastic changes in target neurons of brain areas associated with cognitive function...
February 15, 2017: Neuroscience
https://www.readbyqxmd.com/read/28214358/the-n-terminus-of-cgas-de-oligomerizes-the-cgas-dna-complex-and-lifts-the-dna-size-restriction-of-core-cgas-activity
#3
Arum Lee, Eun-Byeol Park, Janghyun Lee, Byong-Seok Choi, Suk-Jo Kang
Cyclic GMP-AMP synthase (cGAS) is a DNA-sensing enzyme in the innate immune system. Recent studies using core-cGAS lacking the N-terminus investigated the mechanism for binding of double-stranded (ds) DNA and synthesis of 2',3'-cGAMP, a secondary messenger that ultimately induces type I interferons. However, the function of the N-terminus of cGAS remains largely unknown. Here, we found that the N-terminus enhanced the activity of core-cGAS in vivo. Importantly, the catalytic activity of core-cGAS decreased as the length of dsDNA increased, but the diminished activity was restored by addition of the N-terminus...
February 18, 2017: FEBS Letters
https://www.readbyqxmd.com/read/28214234/reablement-reactivation-rehabilitation-and-restorative-interventions-with-older-adults-in-receipt-of-home-care-a-systematic-review
#4
REVIEW
Joanie Sims-Gould, Catherine E Tong, Lutetia Wallis-Mayer, Maureen C Ashe
OBJECTIVE: To systematically review the impact of reablement, reactivation, rehabilitation, and restorative (4R) programs for older adults in receipt of home care services. DESIGN: Systematic review. DATA SOURCES: We searched the following electronic bibliographic databases: MEDLINE, EMBASE, PsycINFO, CINAHL (Cumulative Index to Nursing and Allied Health), SPORTDiscus and The Cochrane Library and reference lists. STUDY SELECTION: Randomized controlled trials that describe original data on the impact of home-based rehabilitative care and were written in English...
February 14, 2017: Journal of the American Medical Directors Association
https://www.readbyqxmd.com/read/28213976/enhancement-of-%C3%AE-globin-gene-expression-in-thalassemic-ivs2-654-induced-pluripotent-stem-cell-derived-erythroid-cells-by-modified-u7-snrna
#5
Phetcharat Phanthong, Suparerk Borwornpinyo, Narisorn Kitiyanant, Natee Jearawiriyapaisarn, Lalana Nuntakarn, Jirawat Saetan, Tiwaporn Nualkaew, Khanit Sa-Ngiamsuntorn, Usanarat Anurathapan, Andras Dinnyes, Yindee Kitiyanant, Suradej Hongeng
The therapeutic use of patient-specific induced pluripotent stem cells (iPSCs) is emerging as a potential treatment of β-thalassemia. Ideally, patient-specific iPSCs would be genetically corrected by various approaches to treat β-thalassemia including lentiviral gene transfer, lentivirus-delivered shRNA, and gene editing. These corrected iPSCs would be subsequently differentiated into hematopoietic stem cells and transplanted back into the same patient. In this article, we present a proof of principle study for disease modeling and screening using iPSCs to test the potential use of the modified U7 small nuclear (sn) RNA to correct a splice defect in IVS2-654 β-thalassemia...
February 18, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28213970/efficacy-and-safety-of-immuno-magnetically-sorted-smooth-muscle-progenitor-cells-derived-from-human-induced-pluripotent-stem-cells-for-restoring-urethral-sphincter-function
#6
Yanhui Li, Morgaine Green, Yan Wen, Yi Wei, Prachi Wani, Zhe Wang, Renee Reijo Pera, Bertha Chen
Human-induced pluripotent stem cells (hiPSCs)-based cell therapy holds promise for treating stress urinary incontinence (SUI). However, safety concerns, especially tumorgenic potential of residual undifferentiated cells in hiPSC derivatives, are major barriers for its clinical translation. An efficient, fast and clinical-scale strategy for purifying committed cells is also required. Our previous studies demonstrated the regenerative effects of hiPSC-derived smooth muscle progenitor cells (pSMCs) on the injured urethral sphincter in SUI, but the differentiation protocol required fluorescence-activated cell sorting (FACS) which is not practical for autologous clinical applications...
February 18, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28213953/the-effects-of-acl-graft-placement-on-in-vivo-knee-function-and-cartilage-thickness-distributions
#7
REVIEW
Louis E DeFrate
Injuries to the anterior cruciate ligament (ACL) frequently lead to early-onset osteoarthritis. Despite advancement in surgical techniques, ACL reconstruction has a limited ability to prevent these degenerative changes. While previous studies have investigated knee function after ACL reconstruction, in vivo investigations of the effects of graft placement on in vivo joint function and cartilage health are limited. This review presents a series of studies that used novel imaging and 3D modeling techniques to determine the in vivo placement of the ACL graft on the femur using two different ACL reconstruction techniques...
February 18, 2017: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
https://www.readbyqxmd.com/read/28213925/rotator-cuff-disease-opinion-regarding-surgical-criteria-and-likely-outcome
#8
Alison Thorpe, Mark Hurworth, Peter O'Sullivan, Tim Mitchell, Anne Smith
BACKGROUND: Clinical guidelines for the management of rotator cuff disease are not clear. Surgeon surveys in the USA and UK lack agreement regarding surgical indications. Physical examination tests aid surgical decision-making but also lack robust evidence. Study aims were to evaluate: Western Australian orthopaedic surgeons' perceptions about surgical indications; utility of physical examination tests; findings at surgery predictive of outcome and surgeon opinion of a successful surgical outcome...
February 17, 2017: ANZ Journal of Surgery
https://www.readbyqxmd.com/read/28213656/dual-functional-microrna-186-5p-targets-both-fgf2-and-rela-to-suppress-tumorigenesis-of-glioblastoma-multiforme
#9
Fachen Wang, Hui Jiang, Shanjun Wang, Bing Chen
Glioblastoma multiforme (GBM) is one of the most malignant cancers. MicroRNAs (miRs) were reported to play important roles in GBM recently. However, the role of a novel miR-186-5p in GBM tumorigenesis is still elusive. Using bioinformatics, miR-186-5p was identified as potential regulators of both fibroblast growth factor (FGF)-2 and NF-κB subunit RelA. Luciferase reporter assay was used to confirm the direct recognition FGF2 and RelA mRNAs by miR-186-5p. Invasion and migration assays were employed to study the effect of miR-186-5p on GBM cell growth in vitro...
February 17, 2017: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/28213542/plant-community-and-nitrogen-deposition-as-drivers-of-%C3%AE-and-%C3%AE-prokaryotic-diversity-in-reconstructed-oil-sands-soils-and-natural-boreal-forest-soils
#10
Jacynthe Masse, Cindy E Prescott, Sébastien Renaut, Yves Terrat, Sue J Grayston
The Athabasca Oil Sands deposit is one of the largest single oil deposits in the world. Following surface mining, companies are required to restore soil-like profiles that can support the previous land capabilities. The objective of this study was to assess if soil prokaryotic α- and β-diversity in oil-sands soils reconstructed 20-30 years previously, and planted to one of three vegetation types (coniferous or deciduous trees and grassland) were similar to those found in natural boreal-forest soils subject to wildfire disturbance...
February 17, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28213521/signalling-adaptor-shcd-suppresses-erk-phosphorylation-distal-to-the-ret-and-trk-neurotrophic-receptors
#11
Melanie K B Wills, Ava Keyvani Chahi, Hayley R Lau, Manali Tilak, Brianna Guild, Laura A New, Peihua Lu, Keévin Jacquet, Susan O Meakin, Nicolas Bisson, Nina Jones
Proteins of the Shc family are typically involved in signal transduction events involving Ras/MAPK and PI3K/Akt pathways. In the nervous system, they function proximal to the neurotrophic factors that regulate cell survival, differentiation, and neuron-specific characteristics. The least-characterized homolog, ShcD, is robustly expressed in the developing and mature nervous system, but its contributions to neural cell circuitry are largely uncharted. We now report that ShcD binds to active Ret, TrkA, and TrkB neurotrophic factor receptors predominantly via its phosphotyrosine binding (PTB) domain...
February 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28213500/inducible-t-cell-kinase-regulates-the-acquisition-of-cytolytic-capacity-and-degranulation-in-cd8-ctls
#12
Senta M Kapnick, Jane C Stinchcombe, Gillian M Griffiths, Pamela L Schwartzberg
Patients with mutations in inducible T cell kinase (ITK) are susceptible to viral infections, particularly EBV, suggesting that these patients have defective function of CD8(+) CTLs. In this study, we evaluated the effects of ITK deficiency on cytolysis in murine CTLs deficient in ITK, and both human and murine cells treated with an ITK inhibitor. We find that ITK deficiency leads to a global defect in the cytolysis of multiple targets. The absence of ITK both affected CTL expansion and delayed the expression of cytolytic effectors during activation...
February 17, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28213190/n-acetylcysteine-for-treating-cocaine-addiction-a-systematic-review
#13
REVIEW
Marco Antonio Nocito Echevarria, Tassio Andrade Reis, Giulianno Ruffo Capatti, Victor Siciliano Soares, Dartiu Xavier da Silveira, Thiago Marques Fidalgo
The aim of this paper is to extensively review the current literature available on N-acetylcysteine (NAC) treatment for cocaine dependence (clinical and experimental studies). We screened all articles published before February 2016 reporting on the use of NAC as a pharmacological intervention for cocaine dependence or discussed its potential as a therapeutic approach for cocaine dependence. We described our results qualitatively. 21 studies matched our search criteria: 6 clinical trials and 15 animal studies...
February 11, 2017: Psychiatry Research
https://www.readbyqxmd.com/read/28212984/hiv-1-vpr-disrupts-mitochondria-axonal-transport-and-accelerates-neuronal-aging
#14
Ying Wang, Maryline Santerre, Italo Tempera, Kayla Martin, Ruma Mukerjee, Bassel E Sawaya
Disruption of mitochondria axonal transport, essential for the maintenance of synaptic and neuronal integrity and function, has been identified in neurodegenerative diseases. Whether HIV-1 viral proteins affect mitochondria axonal transport is unknown, albeit HIV-associated neurocognitive disorders occur in around half of the patients living with HIV. Therefore, we sought to examine the effect of HIV-1 viral protein R (Vpr) on mitochondria axonal transport. Using mice primary neuronal cultures, we demonstrated that 4-day Vpr treatment reduced the ratio of moving mitochondria associated with (i) less energy (ATP) supply, (ii) reduction in Miro-1 and (iii) increase of α-synuclein which led to loss of microtubule stability as demonstrated by inconsecutive distribution of acetylated α-tubulin along the axons...
February 14, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28212980/biofilm-formation-and-release-of-fluoride-from-dental-restorative-materials-in-relation-to-their-surface-properties
#15
Sebastian Hahnel, Andrei C Ionescu, Gloria Cazzaniga, Marco Ottobelli, Eugenio Brambilla
OBJECTIVES: To elucidate the impact of surface properties and the release of fluoride from different glass ionomer cements on biofilm formation. METHODS: Standardized specimens manufactured from various classes of glass ionomer cements (GICs), a resin-based composite (RBC), and human enamel were subjected to surface analyses. Subsequent to simulation of salivary pellicle formation, Streptococcus mutans biofilm formation was initiated using a drip flow reactor for 48h and 96h...
February 14, 2017: Journal of Dentistry
https://www.readbyqxmd.com/read/28212569/mir-124-acts-as-a-tumor-suppressor-by-inhibiting-the-expression-of-sphingosine-kinase-1-and-its-downstream-signaling-in-head-and-neck-squamous-cell-carcinoma
#16
Yuan Zhao, Zhiqiang Ling, Yubin Hao, Xiaowu Pang, Xianlin Han, Joseph A Califano, Liang Shan, Xinbin Gu
By analyzing the expression profile of microRNAs in head and neck squamous cell carcinomas (HNSCC), we found that the expression level of miR-124 was 4.59-fold lower in tumors than in normal tissues. To understand its functions, we generated a miR-124-expressing subline (JHU-22miR124) and a mock vector-transfected subline (JHU-22vec) by transfecting the mimic of miR-124 into JHU-22 cancer cells. Restored expression of miR-124 in JHU-22miR124 cells led to reduced cell proliferation, delayed colony formation, and decreased tumor growth, indicating a tumor-suppressive effect of miR-124...
February 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28212538/sevoflurane-preconditioning-induced-endogenous-neurogenesis-against-ischemic-brain-injury-by-promoting-microglial-activation
#17
Li Li, Hexige Saiyin, Jingmo Xie, Lixiang Ma, Lei Xue, Wei Wang, Weimin Liang, Qiong Yu
Brain ischemia causes irreversible damage to functional neurons in cases of infarct. Promoting endogenous neurogenesis to replace necrotic neurons is a promising therapeutic strategy for ischemia patients. The neuroprotective role of sevoflurane preconditioning implies that it might also enhance endogenous neurogenesis and functional restoration in the infarct region. By using a transient middle cerebral artery occlusion (tMCAO) model, we discovered that endogenous neurogenesis was enhanced by sevoflurane preconditioning...
February 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28212523/redox-regulation-in-metabolic-programming-and-inflammation
#18
REVIEW
Helen R Griffiths, Dan Gao, Chathyan Pararasa
Energy metabolism and redox state are intrinsically linked. In order to mount an adequate immune response, cells must have an adequate and rapidly available energy resource to migrate to the inflammatory site, to generate reactive oxygen species using NADPH as a cofactor and to engulf bacteria or damaged tissue. The first responder cells of the innate immune response, neutrophils, are largely dependent on glycolysis. Neutrophils are relatively short-lived, dying via apoptosis in the process of bacterial killing through production of hypochlorous acid and release of extracellular NETs...
February 12, 2017: Redox Biology
https://www.readbyqxmd.com/read/28212454/clinical-comparison-of-screw-retained-and-screwless-morse-taper-implant-abutment-connections-one-year-postloading-results
#19
Esma Geckili, Onur Geckili, Hakan Bilhan, Omer Kutay, Tayfun Bilgin
PURPOSE: The purpose of this study was to clinically evaluate the screwless Morse taper implant-abutment connection type, in which the retention screw is totally eliminated, in terms of stability, success, periodontal parameters, and marginal bone levels after 1 year of function by comparing it with a passive fit internal implant-abutment connection, wherein a space exists between the matching components. MATERIALS AND METHODS: Each edentulous subject received an implant with a screwless Morse taper connection (MT) in the left canine area of the mandible and an implant with a screw-retained implant-abutment connection (SR) in the right canine area of the mandible...
February 17, 2017: International Journal of Oral & Maxillofacial Implants
https://www.readbyqxmd.com/read/28212417/splitax-a-novel-method-to-assess-the-function-of-engineered-nucleases
#20
Richard A Axton, Sharmin S Haideri, Martha Lopez-Yrigoyen, Helen A Taylor, Lesley M Forrester
Engineered nucleases have been used to generate knockout or reporter cell lines and a range of animal models for human disease. These new technologies also hold great promise for therapeutic genome editing. Current methods to evaluate the activity of these nucleases are time consuming, require extensive optimization and are hampered by readouts with low signals and high background. We have developed a simple and easy to perform method (SplitAx) that largely addresses these issues and provides a readout of nuclease activity...
2017: PloS One
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