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Jinny Robson, Parham Aram, Martyn P Nash, Chris P Bradley, Martin Hayward, David J Paterson, Peter Taggart, Richard H Clayton, Visakan Kadirkamanathan
In this paper, we present a novel approach to quantify the spatio-temporal organization of electrical activation during human ventricular fibrillation (VF). We propose three different methods based on correlation analysis, graph theoretical measures and hierarchical clustering. Using the proposed approach, we quantified the level of spatio-temporal organization during three episodes of VF in ten patients, recorded using multi-electrode epicardial recordings with 30 s coronary perfusion, 150 s global myocardial ischaemia and 30 s reflow...
March 15, 2018: Annals of Biomedical Engineering
Tie Li, Christopher D Cox, Byram Ozer, Nhung T Nguyen, Huytram N Nguyen, Thomas J Lai, Sichen Li, Fei Liu, Harley I Kornblum, Linda M Liau, Phioanh Leia Nghiemphu, Timothy F Cloughesy, Albert Lai
Mutant isocitrate dehydrogenase (IDH) 1/2 converts α-ketoglutarate (α-KG) to D-2 hydroxyglutarate (D-2-HG), a putative oncometabolite that can inhibit α-KG dependent enzymes, including ten-eleven translocation methylcytosine dioxygenase (TET) DNA demethylases. We recently established that miRNAs are components of the IDH1 mutant-associated glioma CpG island methylator phenotype (G-CIMP), and specifically identified MIR148A as a tumor-suppressive miRNA within G-CIMP. However, the precise mechanism by which mutant IDH induces hypermethylation of MIR148A and other G-CIMP promoters remains to be elucidated...
March 15, 2018: Molecular Cancer Research: MCR
Huisheng Wu, Chaoliang Tang, Lydia Wai Tai, Weifeng Yao, Peipei Guo, Junmou Hong, Xin Yang, Xinyi Li, Zhao Jin, Jianjuan Ke, Yanlin Wang
Background & Aims:  Ischemic stroke has been ranked the second cause of death in patients worldwide.Inflammation which is activated during cerebral ischemia/reperfusion is an important mechanism leading to brain injury. This study aimed to investigate the effect of flurbiprofen axetil on cerebral I/R injury and the role of inflammation in this process. Methods:  Rats were subjected to sham operation or global cerebral I/R with or without flurbiprofen axetil (5 mg/kg or 10 mg/kg). Global cerebral ischemia was achieved by occlusion of bilateral common carotid arteries combined with hypotension for 20 min followed by reperfusion for 72 h...
March 14, 2018: Bioscience Reports
Krzysztof Kucharz, Martin Lauritzen
Cortical spreading depolarization waves, the cause underlying migraine aura, are also the markers and mechanism of pathology in the acutely injured human brain. Propagation of spreading depolarization wave uniquely depends on the interaction between presynaptic and postsynaptic glutamate N-methyl-d-aspartate receptors (NMDARs). In the normally perfused brain, even a single wave causes a massive depolarization of neurons and glia, which results in transient loss of neuronal function and depression of the ongoing electrocorticographic activity...
March 12, 2018: Brain: a Journal of Neurology
Nishanth Makthal, Hackwon Do, Arica R VanderWal, Randall J Olsen, James M Musser, Muthiah Kumaraswami
Bacterial virulence factor production is a highly coordinated process. The temporal pattern of bacterial gene expression varies in different host anatomic sites to overcome niche-specific challenges. The human pathogen group A streptococcus (GAS) produces a potent secreted protease, SpeB, that is crucial for pathogenesis. Recently, we discovered that a quorum-sensing pathway comprised of a leaderless short peptide, SpeB-inducing peptide (SIP), and cytosolic global regulator, RopB, controls speB expression in concert with bacterial population density...
March 12, 2018: Infection and Immunity
Scott E Kasner, Pablo Lavados, Mukul Sharma, Yongjun Wang, Yilong Wang, Antoni Dávalos, Nikolay Shamalov, Luis Cunha, Arne Lindgren, Robert Mikulik, Antonio Arauz, Wilfried Lang, Anna Czlonkowska, Jens Eckstein, Rubens Gagliardi, Pierre Amarenco, Sebastián F Ameriso, Turgut Tatlisumak, Roland Veltkamp, Graeme J Hankey, Danilo S Toni, Daniel Bereczki, Shinichiro Uchiyama, George Ntaios, Byung-Woo Yoon, Raf Brouns, M M DeVries Basson, Matthias Endres, Keith Muir, Natan Bornstein, Serefnur Ozturk, Martin O'Donnell, Hardi Mundl, Calin Pater, Jeffrey Weitz, W Frank Peacock, Balakumar Swaminathan, Bodo Kirsch, Scott D Berkowitz, Gary Peters, Guillaume Pare, Ellison Themeles, Ashkan Shoamanesh, Stuart J Connolly, Robert G Hart
BACKGROUND: The New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial vs. ASA to Prevent Embolism in Embolic Stroke of Undetermined Source (NAVIGATE-ESUS) trial is a randomized phase-III trial comparing rivaroxaban versus aspirin in patients with recent ESUS. AIMS: We aimed to describe the baseline characteristics of this large ESUS cohort to explore relationships among key subgroups. METHODS: We enrolled 7213 patients at 459 sites in 31 countries...
March 7, 2018: Journal of Stroke and Cerebrovascular Diseases: the Official Journal of National Stroke Association
Aditi Jain, Jafar Hasan, Perumal Arumugam Desingu, Nagalingam R Sundaresan, Kaushik Chatterjee
Neonatal cardiomyocytes cultured on flat surfaces are commonly used as a model to study cardiac failure of diverse origin. A major drawback of such a system is that the cardiomyocytes do not exhibit alignment, organization and calcium transients, similar to the native heart. Therefore, there is a need to develop in vitro platforms that recapitulate the cellular microenvironment of the murine heart as organotypic models to study cardiovascular diseases. In this study, we report an engineered platform that mimics cardiac cell organization and function of the heart...
February 27, 2018: Colloids and Surfaces. B, Biointerfaces
Melisa Del Barrio, Matteo Sensi, Christophe Orain, Carole Baffert, Sébastien Dementin, Vincent Fourmond, Christophe Léger
Many enzymes that produce or transform small molecules such as O2 , H2 , and CO2 embed inorganic cofactors based on transition metals. Their active site, where the chemical reaction occurs, is buried in and protected by the protein matrix, and connected to the solvent in several ways: chains of redox cofactors mediate long-range electron transfer; static or dynamic tunnels guide the substrate, product and inhibitors; amino acids and water molecules transfer protons. The catalytic mechanism of these enzymes is therefore delocalized over the protein and involves many different steps, some of which determine the response of the enzyme under conditions of stress (extreme redox conditions, presence of inhibitors, light), the catalytic rates in the two directions of the reaction and their ratio (the "catalytic bias")...
March 8, 2018: Accounts of Chemical Research
Pierantonio Parmiani, Cristina Lucchetti, Gianfranco Franchi
Skilled reaching is a complex movement in which a forelimb is extended to grasp food for eating. Video-recordings analysis of control rats enables us to distinguish several components of skilled reaching: Orient, approaching the front wall of the reaching box and poking the nose into the slot to locate the food pellet; Transport, advancing the forelimb through the slot to reach-grasp the pellet; and Withdrawal of the grasped food to eat. Although food location and skilled reaching is guided by olfaction, the importance of whisker/nose tactile sense in rats suggests that this too could play a role in reaching behavior...
2018: Frontiers in Behavioral Neuroscience
Tongtong Wang, Qian Du, Xingchen Wu, Yingying Niu, Lijuan Guan, Zhenyu Wang, Xiaomin Zhao, Shan-Lu Liu, Dewen Tong, Yong Huang
Porcine circovirus type 2 (PCV2) capsid protein (Cap) is a unique structure protein that plays pivotal roles in the process of viral replication and pathogenesis. Herein, we characterized putative porcine Makorin ring finger protein 1 variant (pMKRN1), a N-terminal-truncated variant of putative full-size porcine MKRN1, which is a unique expression pattern resulting from the porcine mkrn1 gene and interacts with PCV2 Cap. Domain mapping assay showed that the C terminus of pMKRN1 and the fragments (108-198 aa) of Cap are required for this interaction...
March 7, 2018: Journal of Virology
Felix Becker, Karl Wienand, Matthias Lechner, Erwin Frey, Heinrich Jung
Bacterial communities have rich social lives. A well-established interaction involves the exchange of a public good in Pseudomonas populations, where the iron-scavenging compound pyoverdine, synthesized by some cells, is shared with the rest. Pyoverdine thus mediates interactions between producers and non-producers and can constitute a public good. This interaction is often used to test game theoretical predictions on the "social dilemma" of producers. Such an approach, however, underestimates the impact of specific properties of the public good, for example consequences of its accumulation in the environment...
March 6, 2018: Scientific Reports
Fang Zhong, Haibing Chen, Yifan Xie, Evren U Azeloglu, Chengguo Wei, Weijia Zhang, Zhengzhe Li, Peter Y Chuang, Belinda Jim, Hong Li, Firas Elmastour, Jalish M Riyad, Thomas Weber, Hongyu Chen, Yongjun Wang, Aihua Zhang, Weiping Jia, Kyung Lee, John C He
Background Diabetic nephropathy (DN) is a leading cause of ESRD in the United States, but the molecular mechanisms mediating the early stages of DN are unclear. Methods To assess global changes that occur in early diabetic kidneys and to identify proteins potentially involved in pathogenic pathways in DN progression, we performed proteomic analysis of diabetic and nondiabetic rat glomeruli. Protein S (PS) among the highly upregulated proteins in the diabetic glomeruli. PS exerts multiple biologic effects through the Tyro3, Axl, and Mer (TAM) receptors...
March 6, 2018: Journal of the American Society of Nephrology: JASN
Anita R Iskandar, Florian Martin, Patrice Leroy, Walter K Schlage, Carole Mathis, Bjorn Titz, Kondylis Athanasios, Thomas Schneider, Grégory Vuillaume, Alain Sewer, Emmanuel Guedj, Keyur Trivedi, Ashraf Elamin, Stefan Frentzel, Nikolai V Ivanov, Manuel C Peitsch, Julia Hoeng
The biological impact of an aerosol of a potential modifiedrisk tobacco product, carbon heated tobacco product 1.2 (CHTP1.2), was comprehensively assessed for the first time in vitro using human small airway and nasal epithelial models following a systems toxicology approach. The potentially reduced effects of CHTP1.2 aerosol exposure were benchmarked against those of 3R4F cigarette smoke at similar nicotine concentrations. Experimental repetitions were conducted for which new batches of small airway and nasal cultures were exposed to CHTP1...
March 1, 2018: Food and Chemical Toxicology
Sayuri Suzuki, Annette Lis, Carsten Schmitz, Reinhold Penner, Andrea Fleig
The melastatin-related transient receptor potential member 7 (TRPM7) is a unique fusion protein with both ion channel function and enzymatic α-kinase activity. TRPM7 is essential for cellular systemic magnesium homeostasis and early embryogenesis; it promotes calcium transport during global brain ischemia and emerges as a key player in cancer growth. TRPM7 channels are negatively regulated through G-protein-coupled receptor-stimulation, either by reducing cellular cyclic adenosine monophosphate (cAMP) or depleting phosphatidylinositol bisphosphate (PIP2 ) levels in the plasma membrane...
March 2, 2018: Cellular and Molecular Life Sciences: CMLS
Kendra A Bussey, Ulrike Lau, Sophie Schumann, Antonio Gallo, Lisa Osbelt, Markus Stempel, Christine Arnold, Josef Wissing, Hans Henrik Gad, Rune Hartmann, Wolfram Brune, Lothar Jänsch, Adrian Whitehouse, Melanie M Brinkmann
Kaposi's sarcoma-associated herpesvirus (KSHV) is one of the few oncogenic human viruses known to date. Its large genome encodes more than 85 proteins and includes both unique viral proteins as well as proteins conserved amongst herpesviruses. KSHV ORF20 is a member of the herpesviral core UL24 family, but the function of ORF20 and its role in the viral life cycle is not well understood. ORF20 encodes three largely uncharacterized isoforms, which we found were localized predominantly in the nuclei and nucleoli...
March 2, 2018: PLoS Pathogens
Sandra Schlee, Thomas Klein, Magdalena Schumacher, Julian Nazet, Rainer Merkl, Heinz-Juergen Steinhoff, Reinhard Sterner
It is important to understand how the catalytic activity of enzymes is related to their conformational flexibility. We have studied this activity-flexibility correlation using the example of indole-glycerol-phosphate synthase from Sulfolobus solfataricus (ssIGPS), which catalyzes the fifth step in the biosynthesis of tryptophan. ssIGPS is a thermostable representative of enzymes with the frequently encountered and catalytically versatile (βα)8 -barrel fold. Four activated variants of ssIGPS with increased catalytic turnover numbers were analyzed by transient kinetics at 25°C, and wild-type ssIGPS was likewise analyzed both at 25°C and at 60°C...
March 2, 2018: Biochemistry
Denys Fontaine, Serena Santucci, Michel Lanteri-Minet
Cluster headache (CH) is a primary headache and considered as one of the worst pains known to man. The sphenopalatine ganglion (SPG) plays a pivotal role in cranial autonomic symptoms associated with pain. Lesioning procedures involving the SPG and experimental acute SPG stimulation have shown some degree of efficacy with regard to CH. A neuromodulation device, chronically implanted in the pterygopalatine fossa, has been specifically designed for acute on-demand SPG stimulation. In a pilot placebo-controlled study in 28 patients suffering from refractory chronic CH, alleviation of pain was achieved in 67...
2018: Journal of Pain Research
Sophie E Irving, Rebecca M Corrigan
The stringent response is a conserved bacterial stress response mechanism that allows bacteria to respond to nutritional challenges. It is mediated by the alarmones pppGpp and ppGpp, nucleotides that are synthesized and hydrolyzed by members of the RSH superfamily. Whilst there are key differences in the binding targets for (p)ppGpp between Gram-negative and Gram-positive bacterial species, the transient accumulation of (p)ppGpp caused by nutritional stresses results in a global change in gene expression in all species...
March 2018: Microbiology
José L Jara, Nazia P Saeed, Ronney B Panerai, Thompson G Robinson
OBJECTIVE: To devise an appropriate measure of the quality of a magnetic resonance imaging (MRI) signal for the assessment of dynamic cerebral autoregulation, and propose simple strategies to improve its quality. MATERIALS AND METHODS: Magnetic resonance images of 11 healthy subjects were scanned during a transient decrease in arterial blood pressure (BP). Mean signals were extracted from non-overlapping brain regions for each image. An ad-hoc contrast-to-noise ratio (CNR) was used to evaluate the quality of these regional signals...
2018: Acta Neurochirurgica. Supplement
Cristina Carrasco, Mustafa Naziroǧlu, Ana B Rodríguez, José A Pariente
Currently, neuropathic pain is an underestimated socioeconomic health problem affecting millions of people worldwide, which incidence may increase in the next years due to chronification of several diseases, such as cancer and diabetes. Growing evidence links neuropathic pain present in several disorders [i.e., spinal cord injury (SCI), cancer, diabetes and alcoholism] to central sensitization, as a global result of mitochondrial dysfunction induced by oxidative and nitrosative stress. Additionally, inflammatory signals and the overload in intracellular calcium ion could be also implicated in this complex network that has not yet been elucidated...
2018: Frontiers in Physiology
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