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https://www.readbyqxmd.com/read/28524849/structural-basis-for-conductance-through-tric-cation-channels
#1
Min Su, Feng Gao, Qi Yuan, Yang Mao, De-Lin Li, Youzhong Guo, Cheng Yang, Xiao-Hui Wang, Renato Bruni, Brian Kloss, Hong Zhao, Yang Zeng, Fa-Ben Zhang, Andrew R Marks, Wayne A Hendrickson, Yu-Hang Chen
Mammalian TRICs function as K(+)-permeable cation channels that provide counter ions for Ca(2+) handling in intracellular stores. Here we describe the structures of two prokaryotic homologues, archaeal SaTRIC and bacterial CpTRIC, showing that TRIC channels are symmetrical trimers with transmembrane pores through each protomer. Each pore holds a string of water molecules centred at kinked helices in two inverted-repeat triple-helix bundles (THBs). The pores are locked in a closed state by a hydrogen bond network at the C terminus of the THBs, which is lost when the pores assume an open conformation...
May 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/28522750/inhibition-of-mitochondrial-matrix-chaperones-and-anti-apoptotic-bcl-2-family-proteins-empower-antitumor-therapeutic-responses
#2
Georg Karpel-Massler, Chiaki Tsuge Ishida, Elena Bianchetti, Chang Shu, Rolando Perez-Lorenzo, Basil Horst, Matei Banu, Kevin A Roth, Jeffrey N Bruce, Peter Canoll, Dario C Altieri, Markus D Siegelin
Rational therapeutic approaches based on synthetic lethality may improve cancer management. Based on a high-throughput drug screen, we provide preclinical proof of concept that targeting the mitochondrial Hsp90 chaperone network (mtHsp90) and inhibition of Bcl-2, Bcl-xL and Mcl-1 is sufficient to elicit synthetic lethality in tumors recalcitrant to therapy. Our analyses focused on BH3 mimetics that are broad acting (ABT263 and Obatoclax) or selective (ABT199, WEHI-539 and A1210477), along with the established mitochondrial matrix chaperone inhibitor Gamitrinib-TPP...
May 18, 2017: Cancer Research
https://www.readbyqxmd.com/read/28515050/the-mapping-of-predicted-triplex-dna-rna-in-the-drosophila-genome-reveals-a-prominent-location-in-development-and-morphogenesis-related-genes
#3
Claude Pasquier, Sandra Agnel, Alain Robichon
Double-stranded DNA is able to form triple-helical structures by accommodating a third nucleotide strand. A nucleic acid triplex occurs according to Hoogsteen rules that predict the stability and affinity of the third strand bound to the Watson-Crick duplex. The "triplex-forming oligonucleotide" (TFO) can be a short sequence of RNA that binds to the major groove of the targeted duplex only when this duplex presents a sequence of purine or pyrimidine bases in one of the DNA strands. Many nuclear proteins are known to bind triplex DNA or DNA:RNA, but their biological functions are unexplored...
May 17, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/28504127/complexation-of-%C3%AE%C2%BA-carrageenan-with-gelatin-in-the-aqueous-phase-analysed-by-1-h-nmr-kinetics-and-relaxation
#4
Nicolay G Voron'ko, Svetlana R Derkach, Mikhail A Vovk, Peter M Tolstoy
The (1)H NMR spectroscopy is used to study the kinetics of gelation in the aqueous mixtures of κ-carrageenan with gelatin. The time dependence of NMR signals intensities shows that the kinetics of gel formation consists of classical 'fast' (rate constant k≈6h(-1)) and 'slow' (k≈1h(-1)) periods, corresponding to a coil→helix transition and subsequent aggregation of helices. Upon increase of the κ-carrageenan/gelatin (w/w) ratio Z the rate of the fast process slows down by a factor of 1.6-2.4. Further analysis was done by studying the dependence of spin-spin relaxation times of protons of gelatin on Z in the aqueous phase...
August 1, 2017: Carbohydrate Polymers
https://www.readbyqxmd.com/read/28489820/discovery-of-nitrate-cpk-nlp-signalling-in-central-nutrient-growth-networks
#5
Kun-Hsiang Liu, Yajie Niu, Mineko Konishi, Yue Wu, Hao Du, Hoo Sun Chung, Lei Li, Marie Boudsocq, Matthew McCormack, Shugo Maekawa, Tetsuya Ishida, Chao Zhang, Kevan Shokat, Shuichi Yanagisawa, Jen Sheen
Nutrient signalling integrates and coordinates gene expression, metabolism and growth. However, its primary molecular mechanisms remain incompletely understood in plants and animals. Here we report unique Ca(2+) signalling triggered by nitrate with live imaging of an ultrasensitive biosensor in Arabidopsis leaves and roots. A nitrate-sensitized and targeted functional genomic screen identifies subgroup III Ca(2+)-sensor protein kinases (CPKs) as master regulators that orchestrate primary nitrate responses. A chemical switch with the engineered mutant CPK10(M141G) circumvents embryo lethality and enables conditional analyses of cpk10 cpk30 cpk32 triple mutants to define comprehensive nitrate-associated regulatory and developmental programs...
May 10, 2017: Nature
https://www.readbyqxmd.com/read/28485137/the-dielectric-relaxation-of-hydration-water-in-native-collagen-fibrils
#6
Yael Kurzweil-Segev, Ivan Popov, Inna Solomonov, Irit Sagit, Yuri Feldman
The dielectric relaxation of hydrated collagen powders was studied over a wide temperature and frequency range. We revealed two mechanisms of dielectric relaxation in hydration water that are driven by the migration of ionic and orientation defects. At high water fractions in powders (h>0.2), the hydration shell around the collagen triple helixes presents a spatial H-bonded network consisting of structural water bridges and cleft water channels. These two water phases provide the long-range paths for proton-hopping and orientation defect migration...
May 9, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28480496/preferential-hydration-fully-controls-the-renaturation-dynamics-of-collagen-in-water-glycerol-solvents
#7
O Ronsin, C Caroli, T Baumberger
Glycerol is one of the additives which stabilize collagen, as well as globular proteins, against thermally induced denaturation --an effect explained by preferential hydration, i.e. by the formation, in water/glycerol solvents, of a hydration layer whose entropic cost favors the more compact triple-helix native structure against the denatured one, gelatin. Quenching gelatin solutions promotes renaturation which, however, remains incomplete, as the formation of a gel network gives rise to growing topological constraints...
May 2017: European Physical Journal. E, Soft Matter
https://www.readbyqxmd.com/read/28470264/reconstruction-and-analysis-of-the-lncrna-mirna-mrna-network-based-on-competitive-endogenous-rna-reveal-functional-lncrnas-in-rheumatoid-arthritis
#8
Hui Jiang, Rong Ma, Shubiao Zou, Yongzhong Wang, Zhuqing Li, Weiping Li
Rheumatoid arthritis (RA) is an autoimmune disease with an unknown etiology, occurring in approximately 1.0% of general population. More and more studies have suggested that long non-coding RNAs (lncRNAs) could play important roles in various biological processes and be associated with the pathogenesis of different kinds of diseases including RA. Although a large number of lncRNAs have been found, our knowledge of their function and physiological/pathological significance is still in its infancy. In order to reveal functional lncRNAs and identify the key lncRNAs in RA, we reconstructed a global triple network based on the competitive endogenous RNA (ceRNA) theory using the data from National Center for Biotechnology Information Gene Expression Omnibus and our previous paper...
May 4, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28469138/ssga-and-msga-two-seed-growing-algorithms-for-constructing-collaborative-subnetworks
#9
Xiaohui Ji, Su Chen, Jun Cheng Li, Wenping Deng, Zhigang Wei, Hairong Wei
The establishment of a collaborative network of transcription factors (TFs) followed by decomposition and then construction of subnetworks is an effective way to obtain sets of collaborative TFs; each set controls a biological process or a complex trait. We previously developed eight gene association methods for genome-wide coexpression analysis between each TF and all other genomic genes and then constructing collaborative networks of TFs but only one algorithm, called Triple-Link Algorithm, for building collaborative subnetworks...
May 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28467815/epigenetic-silencing-of-triple-negative-breast-cancer-hallmarks-by-withaferin-a
#10
Katarzyna Szarc Vel Szic, Ken Declerck, René A J Crans, Jolien Diddens, David B Scherf, Clarissa Gerhäuser, Wim Vanden Berghe
Triple negative breast cancer (TNBC) is characterized by poor prognosis and a DNA hypomethylation profile. Withaferin A (WA) is a plant derived steroidal lactone which holds promise as a therapeutic agent for treatment of breast cancer (BC). We determined genome-wide DNA methylation changes in weakly-metastatic and aggressive, metastatic BC cell lines, following 72h treatment to a sub-cytotoxic concentration of WA. In contrast to the DNA demethylating agent 5-aza-2'-deoxycytidine (DAC), WA treatment of MDA-MB-231 cells rather tackles an epigenetic cancer network through gene-specific DNA hypermethylation of tumor promoting genes including ADAM metallopeptidase domain 8 (ADAM8), urokinase-type plasminogen activator (PLAU), tumor necrosis factor (ligand) superfamily, member 12 (TNFSF12), and genes related to detoxification (glutathione S-transferase mu 1, GSTM1), or mitochondrial metabolism (malic enzyme 3, ME3)...
April 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28466439/high-sensitivity-neuroimaging-biomarkers-for-the-identification-of-amnestic-mild-cognitive-impairment-based-on-resting-state-fmri-and-a-triple-network-model
#11
Enyan Yu, Zhengluan Liao, Yunfei Tan, Yaju Qiu, Junpeng Zhu, Zhang Han, Jue Wang, Xinwei Wang, Hong Wang, Yan Chen, Qi Zhang, Yumei Li, Dewang Mao, Zhongxiang Ding
Many functional magnetic resonance imaging (fMRI) studies have indicated that Granger causality analysis (GCA) is a suitable method for revealing causal effects between brain regions. The purpose of the present study was to identify neuroimaging biomarkers with a high sensitivity to amnestic mild cognitive impairment (aMCI). The resting-state fMRI data of 30 patients with Alzheimer's disease (AD), 14 patients with aMCI, and 18 healthy controls (HC) were evaluated using GCA. This study focused on the "triple networks" concept, a recently proposed higher-order functioning-related brain network model that includes the default-mode network (DMN), salience network (SN), and executive control network (ECN)...
May 3, 2017: Brain Imaging and Behavior
https://www.readbyqxmd.com/read/28463369/the-impact-of-thr91-mutation-on-c-src-resistance-to-um-164-molecular-dynamics-study-revealed-a-new-opportunity-for-drug-design
#12
Umar Ndagi, Ndumiso N Mhlongo, Mahmoud E Soliman
The emergence of a drug resistant non-receptor tyrosine kinase (c-Src) in triple-negative breast cancer (TNBC) remains a prime concern in relation to the burden of TNBC among people living with breast cancer and drug development. Thr91 mutation was found to induce a complete loss of protein conformation required for drug fitness. Herein, we provide the first account of the molecular impact of the Thr91 mutation on c-Src resistance to experimental drug UM-164 using various computational approaches, namely molecular dynamics simulation, principal component analysis (PCA), dynamic cross-correlation matrices (DCCM) analysis, hydrogen bond occupancy, thermodynamics calculation, ligand-residue interaction and residue interaction networks (RINs)...
May 2, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28463187/automatic-camera-calibration-using-multiple-sets-of-pairwise-correspondences
#13
Francisco Vasconcelos, Joao P Barreto, Edmond Boyer
We propose a new method to add an uncalibrated node into a network of calibrated cameras using only pairwise point correspondences. While previous methods perform this task using triple correspondences, these are often difficult to establish when there is limited overlap between different views. In such challenging cases we must rely on pairwise correspondences and our solution becomes more advantageous. Our method includes an 11-point minimal solution for the intrinsic and extrinsic calibration of a camera from pairwise correspondences with other two calibrated cameras, and a new inlier selection framework that extends the traditional RANSAC family of algorithms to sampling across multiple datasets...
April 28, 2017: IEEE Transactions on Pattern Analysis and Machine Intelligence
https://www.readbyqxmd.com/read/28462864/the-mechanical-importance-of-myelination-in-the-central-nervous-system
#14
Johannes Weickenmeier, Rijk de Rooij, Silvia Budday, Timothy C Ovaert, Ellen Kuhl
Neurons in the central nervous system are surrounded and cross-linked by myelin, a fatty white substance that wraps around axons to create an electrically insulating layer. The electrical function of myelin is widely recognized; yet, its mechanical importance remains underestimated. Here we combined nanoindentation testing and histological staining to correlate brain stiffness to the degree of myelination in immature, pre-natal brains and mature, post-natal brains. We found that both gray and white matter tissue stiffened significantly (p≪0...
April 19, 2017: Journal of the Mechanical Behavior of Biomedical Materials
https://www.readbyqxmd.com/read/28457807/safety-and-efficacy-of-anti-thrombotic-regimens-in-patients-with-percutaneous-coronary-intervention-requiring-oral-anticoagulation-a-traditional-and-network-meta-analysis
#15
REVIEW
Safi U Khan, Muhammad A Saleem, Amirahwaty Abdullah, Subash Ghimire, Manidhar Lekkala, Hammad Rahman, Ahmad N Lone, Edo Kaluski
BACKGROUND: Previous reports have been inconsistent in generating a consensus for optimal treatment strategy for patients with percutaneous coronary intervention (PCI) who also require oral anticoagulation (OAC). We conducted a traditional and network meta-analysis to evaluate the safety and efficacy of anti-thrombotic regimens in this subset of patients. METHODS: 30 articles were recovered through preferred reporting items for systematic reviews and meta-analyses (PRISMA) using MEDLINE, EMBASE and Cochrane Central Register of Controlled Clinical Trials (CENTRAL) from inception to December 2016...
April 22, 2017: Cardiovascular Revascularization Medicine: Including Molecular Interventions
https://www.readbyqxmd.com/read/28454466/identification-of-molecular-characteristics-induced-by-radiotherapy-in-rectal-cancer-based-on-microarray-data
#16
Chang Ge, Mengxia Wu, Guifang Chen, Guanying Yu, Dehui Ji, Shaozhao Wang
The present study aimed to reveal the molecular characteristics induced by radiotherapy in rectal cancer at the transcriptome level. Microarray data (ID, GSE26027) downloaded from the Gene Expression Omnibus database were re-analyzed to identify differentially expressed genes (DEGs) between rectal cancer tissues during and prior to radiotherapy. The DEGs were then inputted into the database for annotation, visualization and integrated discovery, an online tool to perform enrichment analyses, and into the search tool for the retrieval of interacting genes/proteins database to identify protein-protein interactions (PPIs)...
April 2017: Oncology Letters
https://www.readbyqxmd.com/read/28451115/stretchable-supramolecular-hydrogels-with-triple-shape-memory-effect
#17
Xiaoxia Le, Wei Lu, Jing Zheng, Dingyi Tong, Ning Zhao, Chunxin Ma, He Xiao, Jiawei Zhang, Youju Huang, Tao Chen
Shape memory polymers based on reversible supramolecular interactions have invoked growing research interest, but still suffer from limitations such as poor mechanical strength and finite shape memory performance. Here, we present a novel mechanical stretchable supramolecular hydrogel with a triple shape memory effect at the macro/micro scale. The introduction of a double network concept into supramolecular shape memory hydrogels endows them with excellent mechanical properties. The design of two non-interfering supramolecular interaction systems of both dynamic phenylboronic (PBA)-diol ester bonds and the chelation of alginate with Ca(2+) endues the hydrogel with outstanding triple shape memory functionalities...
November 1, 2016: Chemical Science
https://www.readbyqxmd.com/read/28443878/influence-of-high-energy-electron-irradiation-on-the-network-structure-of-gelatin-hydrogels-as-investigated-by-small-angle-x-ray-scattering-saxs
#18
Emilia I Wisotzki, Paolo Tempesti, Emiliano Fratini, Stefan G Mayr
The impact of high energy crosslinking on the network structure of gelatin hydrogels was investigated in comparison to physically entangled gels by small-angle X-ray scattering (SAXS). Physically entangled gelatin of increasing concentration exhibited a nearly constant correlation length of several nanometers. These gels had scattering behavior close to that of polymer coils swollen in a good solvent, as evidenced by the Porod exponent of 1.8. The mass fractal dimension decreased towards 1, indicating increased formation of semiflexible gelatin triple helices and rod-like structures as a function of the gelatin concentration...
May 17, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28441676/transitioning-from-volume-to-value-one-academic-medical-center-s-approach-to-improving-population-health
#19
Stephanie A C Halvorson, Mary E Tanski, Thomas R Yackel
PROBLEM: The U.S. health care system is undergoing a major transformation. Clinical delivery systems are now being paid according to the value of the care they provide, in accordance with the Triple Aim, which incorporates improving the quality and cost of care and the patient experience. Increasingly, financial risk is being transferred from insurers to clinical delivery systems that become responsible for both episode-based clinical care and the longitudinal care of patients. Thus, these delivery systems need to develop strategies to manage the health of populations...
May 2017: Academic Medicine: Journal of the Association of American Medical Colleges
https://www.readbyqxmd.com/read/28433163/fabrication-of-schizophyllan-hydrogel-via-orthogonal-thiol-ene-photopolymerization
#20
Sora Lee, Hyunhyuk Tae, Chang Seok Ki
Schizophyllan (SPG) is a water soluble β-glucan, which is obtained from Schizophyllum commune. SPG has been widely explored with its unique properties such as triple helical structure, immune-modulation, and anti-tumoral activity. In this study, we tried to fabricate SPG hydrogel via thiol-ene photopolymerization. SPG-norbornene and SPG-thiol were synthesized from ultrasonicated SPG. Two types of SPG hydrogels (SPG and PEG/SPG hybrid) were formed via thiol-ene photo-click reaction. By controlling the SPG content and stoichiometric balance of norbornene and thiol groups, swelling ratio and shear elastic modulus of SPG hydrogel could be controlled in the range of 20-60 and 0...
July 1, 2017: Carbohydrate Polymers
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