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critical transport

Sangyun Lee, Heather B Mayes, Jessica M J Swanson, Gregory A Voth
The ClC family of transmembrane proteins functions throughout nature to control the transport of Cl- ions across biological membranes. ClC-ec1 from Escherichia coli is an antiporter, coupling the transport of Cl- and H+ ions in opposite directions and driven by the concentration gradients of the ions. Despite keen interest in this protein, the molecular mechanism of the Cl-/H+ coupling has not been fully elucidated. Here, we have used multiscale simulation to help identify the essential mechanism of the Cl-/H+ coupling...
October 26, 2016: Journal of the American Chemical Society
Daniella Kovacsics, Izabel Patik, Csilla Özvegy-Laczka
The in vivo fate and effectiveness of a drug depends highly on its absorption, distribution, metabolism, excretion and toxicity (ADME-Tox). Organic anion transporting polypeptides (OATPs) are membrane proteins involved in the cellular uptake of various organic compounds, including clinically used drugs. Since OATPs are significant players in drug absorption and distribution, modulation of OATP function via pharmacotherapy with OATP substrates/inhibitors, or modulation of their expression, affects drug pharmacokinetics...
October 26, 2016: Expert Opinion on Drug Metabolism & Toxicology
Sutapa Roy, S Dietrich, Felix Höfling
The dynamic and static critical behavior of a family of binary Lennard-Jones liquid mixtures, close to their continuous demixing points (belonging to the so-called model H' dynamic universality class), are studied computationally by combining semi-grand canonical Monte Carlo simulations and large-scale molecular dynamics (MD) simulations, accelerated by graphic processing units (GPU). The symmetric binary liquid mixtures considered cover a variety of densities, a wide range of compressibilities, and various interactions between the unlike particles...
October 7, 2016: Journal of Chemical Physics
Jinwei Zhang, Geng Gao, Gulnaz Begum, Jinhua Wang, Arjun R Khanna, Boris E Shmukler, Gerrit M Daubner, Paola de Los Heros, Paul Davies, Joby Varghese, Mohammad Iqbal H Bhuiyan, Jinjing Duan, Jin Zhang, Daniel Duran, Seth L Alper, Dandan Sun, Stephen J Elledge, Dario R Alessi, Kristopher T Kahle
Cell volume homeostasis requires the dynamically regulated transport of ions across the plasmalemma. While the ensemble of ion transport proteins involved in cell volume regulation is well established, the molecular coordinators of their activities remain poorly characterized. We utilized a functional kinomics approach including a kinome-wide siRNA-phosphoproteomic screen, a high-content kinase inhibitor screen, and a kinase trapping-Orbitrap mass spectroscopy screen to systematically identify essential kinase regulators of KCC3 Thr(991)/Thr(1048) phosphorylation - a key signaling event in cell swelling-induced regulatory volume decrease (RVD)...
October 26, 2016: Scientific Reports
Durairaj Rajesh, Subramanian Muthukumar, Ganesan Saibaba, Durairaj Siva, Mohammad Abdulkader Akbarsha, Balázs Gulyás, Parasuraman Padmanabhan, Govindaraju Archunan
Transportation of pheromones bound with carrier proteins belonging to lipocalin superfamily is known to prolong chemo-signal communication between individuals belonging to the same species. Members of lipocalin family (MLF) proteins have three structurally conserved motifs for delivery of hydrophobic molecules to the specific recognizer. However, computational analyses are critically required to validate and emphasize the sequence and structural annotation of MLF. This study focused to elucidate the evolution, structural documentation, stability and binding efficiency of estrus urinary lipocalin protein (EULP) with endogenous pheromones adopting in-silico and fluorescence study...
October 26, 2016: Scientific Reports
K Yu Arutyunov, A Ramos-Álvarez, A V Semenov, Yu P Korneeva, P P An, A A Korneev, A Murphy, A Bezryadin, G N Gol'tsman
The topic of superconductivity in strongly disordered materials has attracted significant attention. These materials appear to be rather promising for fabrication of various nanoscale devices such as bolometers and transition edge sensors of electromagnetic radiation. The vividly debated subject of intrinsic spatial inhomogeneity responsible for the non-Bardeen-Cooper-Schrieffer relation between the superconducting gap and the pairing potential is crucial both for understanding the fundamental issues of superconductivity in highly disordered superconductors, and for the operation of corresponding nanoelectronic devices...
November 25, 2016: Nanotechnology
Christoph Bode, Franziska Richter, Christine Spröte, Tanja Brigadski, Anne Bauer, Simone Fietz, Jean-Marc Fritschy, Angelika Richter
GABAergic disinhibition has been suggested to play a critical role in the pathophysiology of several basal ganglia disorders, including dystonia, a common movement disorder. Previous studies have shown a deficit of striatal GABAergic interneurons (IN) in the dt(sz) mutant hamster, one of the few phenotypic animal models of dystonia. However, mechanisms underlying this deficit are largely unknown. In the present study, we investigated the migration and/or maturation of striatal IN during postnatal development (18days of age) and at age of highest severity of dystonia (33days of age) in this hamster model...
October 22, 2016: Experimental Neurology
Max Schelker, Caroline Maria Mair, Fabian Jolmes, Robert-William Welke, Edda Klipp, Andreas Herrmann, Max Flöttmann, Christian Sieben
After endocytic uptake, influenza viruses transit early endosomal compartments and eventually reach late endosomes. There, the viral glycoprotein hemagglutinin (HA) triggers fusion between endosomal and viral membrane, a critical step that leads to release of the viral segmented genome destined to reach the cell nucleus. Endosomal maturation is a complex process involving acidification of the endosomal lumen as well as endosome motility along microtubules. While the pH drop is clearly critical for the conformational change and membrane fusion activity of HA, the effect of intracellular transport dynamics on the progress of infection remains largely unclear...
October 2016: PLoS Computational Biology
Mohamed Osman, Rajesh Paleti, Sabyasachee Mishra, Mihalis M Golias
Work zones are critical parts of the transportation infrastructure renewal process consisting of rehabilitation of roadways, maintenance, and utility work. Given the specific nature of a work zone (complex arrangements of traffic control devices and signs, narrow lanes, duration) a number of crashes occur with varying severities involving different vehicle sizes. In this paper we attempt to investigate the causal factors contributing to injury severity of large truck crashes in work zones. Considering the discrete nature of injury severity categories, a number of comparable econometric models were developed including multinomial logit (MNL), nested logit (NL), ordered logit (ORL), and generalized ordered logit (GORL) models...
October 22, 2016: Accident; Analysis and Prevention
Hedwig Schroeck, Angela K Lyden, Wendy L Benedict, Satya Krishna Ramachandran
Background. Despite increasing adoption of active warming methods over the recent years, little is known about the effectiveness of these interventions on the occurrence of abnormal postoperative temperatures in sick infants. Methods. Preoperative and postoperative temperature readings, patient characteristics, and procedural factors of critically ill infants at a single institution were retrieved retrospectively from June 2006 until May 2014. The primary endpoints were the incidence and trend of postoperative hypothermia and hyperthermia on arrival at the intensive care units...
2016: Anesthesiology Research and Practice
Victoria L Ewing, Rachel Tolhurst, Andrew Kapinda, Esther Richards, Dianne J Terlouw, David G Lalloo
BACKGROUND: This study used qualitative methods to investigate the relationship between geographic access and gendered intra-household hierarchies and how these influence treatment-seeking decision-making for childhood fever within the Chikwawa district of Malawi. Previous cross-sectional survey findings in the district indicated that distance from facility and associated costs are important determinants of health facility attendance in the district. This paper uses qualitative data to add depth of understanding to these findings by exploring the relationship between distance from services, anticipated costs and cultural norms of intra-household decision-making, and to identify potential intervention opportunities to reduce challenges experienced by those in remote locations...
October 24, 2016: Malaria Journal
Yeomoon Sim, Gunhyuk Park, Hyeyoon Eo, Eugene Huh, Pil Sung Gu, Seon-Pyo Hong, Youngmi Kim Pak, Myung Sook Oh
Parkinson's disease (PD) is one of the progressive neurodegenerative diseases of whose condition is characterized by dopaminergic neuronal cell loss and dysfunction in the substantia nigra pars compacta (SNpc) and the striatum (ST). Recent studies have demonstrated that the nuclear receptor related-1 protein (Nurr1) is critical of dopaminergic phenotype induction in mesencephalic dopaminergic neurons. Further, Nurr1 engages in synthesizing and storing dopamine through regulating levels of tyrosine hydroxylase (TH), dopamine transporter (DAT) and vesicular monoamine transporter 2 (VMAT2)...
October 19, 2016: Neuroscience
Shady A Rehim, Stephanie DeMoor, Richard Olmsted, Daniel L Dent, Jessica Parker-Raley
BACKGROUND: Hospital action teams comprise interdisciplinary health care providers working simultaneously to treat critically ill patients. Assessments designed to evaluate communication effectiveness or "nontechnical" performance of these teams are essential to minimize medical errors and improve team productivity. Although multiple communication tools are available, the characteristics and psychometric validity of these instruments have yet to be systematically compared. OBJECTIVE: To identify assessments used to evaluate the communication or "nontechnical" performance of hospital action teams and summarize evidence to develop and validate these instruments...
October 19, 2016: Journal of Surgical Education
Ying Zhang, Qinqin Yu, Nan Jiang, Xu Yan, Chao Wang, Qingmei Wang, Jianzhong Liu, Muyuan Zhu, Sebastian Y Bednarek, Jian Xu, Jianwei Pan
Phototropism is the process by which plants grow towards light in order to maximize the capture of light for photosynthesis, which is particularly important for germinating seedlings. In Arabidopsis, hypocotyl phototropism is predominantly triggered by blue light (BL), which has a profound effect on the establishment of asymmetric auxin distribution, essential for hypocotyl phototropism. Two auxin efflux transporters ATP-BINDING CASSETTE B19 (ABCB19) and PIN-FORMED 3 (PIN3), are known to mediate the effect of BL on auxin distribution in the hypocotyl, but the details for how BL triggers PIN3 lateralization remain poorly understood...
October 22, 2016: Plant, Cell & Environment
Sylvia Neumann, Romain Chassefeyre, George E Campbell, Sandra E Encalada
In axons, proper localization of proteins, vesicles, organelles, and other cargoes is accomplished by the highly regulated coordination of kinesins and dyneins, molecular motors that bind to cargoes and translocate them along microtubule (MT) tracks. Impairment of axonal transport is implicated in the pathogenesis of multiple neurodegenerative disorders including Alzheimer's and Huntington's diseases. To understand how MT-based cargo motility is regulated and to delineate its role in neurodegeneration, it is critical to analyze the detailed dynamics of moving cargoes inside axons...
October 22, 2016: Traffic
Michael L Schulte, Matthew R Hight, Gregory D Ayers, Qi Liu, Yu Shyr, M Kay Washington, H Charles Manning
PURPOSE: This study aimed to study whether cancer cells possess distinguishing metabolic features compared with surrounding normal cells, such as increased glutamine uptake. Given this, quantitative measures of glutamine uptake may reflect critical processes in oncology. Approximately, 10 % of patients with colorectal cancer (CRC) express BRAF (V600E) , which may be actionable with selective BRAF inhibitors or in combination with inhibitors of complementary signaling axes. Non-invasive and quantitative predictive measures of response to these targeted therapies remain poorly developed in this setting...
October 21, 2016: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
Daniel Kolinsky, Samuel M Keim, Brian G Cohn, Evan S Schwarz, Donald M Yealy
BACKGROUND: The current standards for domestic emergency medical services suggest that all patients suspected of opioid overdose be transported to the emergency department for evaluation and treatment. This includes patients who improve after naloxone administration in the field because of concerns for rebound toxicity. However, various emergency medical services systems release such patients at the scene after a 15- to 20-min observation period as long as they return to their baseline...
October 18, 2016: Journal of Emergency Medicine
Angkana Sommanustweechai, Weerasak Putthasri, Mya Lay Nwe, Saw Thetlya Aung, Mya Min Theint, Viroj Tangcharoensathien, San Shway Wynn
BACKGROUND: Myanmar is classified as critical shortage of health workforce. In responses to limited number of trained health workforce in the hard-to-reach and remote areas, the MOH trained the Community Health Worker (CHW) as health volunteers serving these communities on a pro bono basis. This study aimed to assess the socio-economic profiles, contributions of CHW to primary health care services and their needs for supports to maintain their quality contributions in rural hard to reach areas in Myanmar...
October 21, 2016: Human Resources for Health
Travis L Goron, Manish N Raizada
BACKGROUND: The amino acid glutamine (Gln) is a primary transport form of nitrogen in vasculature following root uptake, critical for the location/timing of growth in maize and other cereals. Analytical chemistry methods do not permit in situ analysis of Gln, including visualization within the vascular network. Their cost and tissue requirement are barriers to exploring the complexity of Gln dynamics. We previously reported a biosensor, GlnLux, which can measure relative Gln levels inexpensively with tiny amounts of tissue...
October 21, 2016: BMC Plant Biology
Narges Abdali, Jerry Matthew Parks, Keith Haynes, Julie L Chaney, Adam T Green, David Wolloscheck, John K Walker, Valentin V Rybenkov, Jerome Yves Baudry, Jeremy C Smith, Helen I Zgurskaya
Antibiotic resistance is a major threat to human welfare. Inhibitors of multidrug efflux pumps (EPIs) are promising alternative therapeutics that could revive activities of antibiotics and reduce bacterial virulence. Identification of new druggable sites for inhibition is critical for development of effective EPIs, especially in light of constantly emerging resistance. Here, we describe EPIs that interact with periplasmic membrane fusion proteins, critical components of efflux pumps that are responsible for the activation of the transporter and the recruitment of the outer-membrane channel...
October 21, 2016: ACS Infectious Diseases
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