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critical car

Sher Ali, Tao Xu, Xiaolan Xu
Ca(2+) release-activated Ca(2+) (CRAC) channels play an essential role in the immune system. The pore-forming subunit, Orai1, is an important pharmacological target. Here, we summarize the recent discoveries on the structure-function relationship of Orai1, as well as its interaction with the native channel opener STIM1 and chemical modulator 2-aminoethoxydiphenyl borate (2-APB). We first introduce the critical structural elements of Orai1, which include a Ca(2+) accumulating region (CAR), ion selectivity filter, hydrophobic centre, basic region, extended transmembrane orai1 N-terminal (ETON), transmembrane (TM) regions 2 and 3, P245 bend, (263) SHK(265) hinge linker and L273-L276 hydrophobic patch...
October 18, 2016: Journal of Physiology
Shiv Kumar Sarin, Ashok Choudhury
Acute-on-chronic liver failure (ACLF) is a distinct entity that differs from acute liver failure and decompensated cirrhosis in timing, presence of treatable acute precipitant, and course of disease, with a potential for self-recovery. The core concept is acute deterioration of existing liver function in a patient of chronic liver disease with or without cirrhosis in response to an acute insult. The insult should be a hepatic one and presentation in the form of liver failure (jaundice, encephalopathy, coagulopathy, ascites) with or without extrahepatic organ failure in a defined time frame...
December 2016: Current Gastroenterology Reports
Massimo Delogu, Francesco Del Pero, Lorenzo Berzi, Marco Pierini, Davide Bonaffini
The railway system represents one of the most resource-efficient answer to our ever-growing demand for transport service and the development trends for the following years forecast a substantial increase in this sector. Considering the European Union, rolling stock realizes a significant share of both goods and passengers carriage while it is responsible for a derisory quota of environmental impact and energy consumption involved by transportation. Contrary to the low environmental impact, the amount of End-of-Life (EoL) waste generated by rolling stocks in relation to the number of vehicles is notable, much greater than in the case of road vehicles...
October 7, 2016: Waste Management
Chris Neufeld, Stephanie E Kramer, Natalia Lapinskaya, Christopher C Heffner, Anton Malko, Ellen F Lau
A defining trait of linguistic competence is the ability to combine elements into increasingly complex structures to denote, and to comprehend, a potentially infinite number of meanings. Recent magnetoencephalography (MEG) work has investigated these processes by comparing the response to nouns in combinatorial (blue car) and non-combinatorial (rnsh car) contexts. In the current study we extended this paradigm using electroencephalography (EEG) to dissociate the role of semantic content from phonological well-formedness (yerl car)...
2016: PloS One
Jinling Xue, Jinshan Zhang, Bi Xu, Jiani Xie, Wenzhao Wu, Yun Lu
Use of reclaimed water for non potable uses requires consideration of potential adverse health effects. Considering that inhalation can be a significant transmission route of microorganisms and inflammatory agents, this study used a mouse model to test the possible adverse effects of reclaimed water use during car washing where aerosols are generated. Intensive innate immune responses were found in the lungs after acute exposure, and lavage polymorphonuclear cell proportion was the most sensitive endpoint. Four types of evidence are presented to demonstrate that the main risk factor initiating innate inflammation is the free endotoxin: 1) Small molecules (<10KD) cannot induce inflammation; 2) The endotoxin levels of 11 water samples from 5 different plants showed positive correlations with inflammatory responses; 3) Actual water samples showed similar activities with free endotoxins other than bacteria-bound endotoxins; and 4) Specific removal of endotoxins with polymyxin B affinity chromatography further confirmed the role of free endotoxins...
October 6, 2016: Environmental Science & Technology
Koki Wakunami, Po-Yuan Hsieh, Ryutaro Oi, Takanori Senoh, Hisayuki Sasaki, Yasuyuki Ichihashi, Makoto Okui, Yi-Pai Huang, Kenji Yamamoto
Owing to the limited spatio-temporal resolution of display devices, dynamic holographic three-dimensional displays suffer from a critical trade-off between the display size and the visual angle. Here we show a projection-type holographic three-dimensional display, in which a digitally designed holographic optical element and a digital holographic projection technique are combined to increase both factors at the same time. In the experiment, the enlarged holographic image, which is twice as large as the original display device, projected on the screen of the digitally designed holographic optical element was concentrated at the target observation area so as to increase the visual angle, which is six times as large as that for a general holographic display...
October 3, 2016: Nature Communications
Supriya R Kulkarni, Carol J Soroka, Lee R Hagey, James L Boyer
Sirtuin1 (Sirt1, mammalian homolog of S. Cerevisiae enzyme Sir2) is a transcriptional and transactivational regulator of murine Fxr, which is the primary bile acid (BA) sensor, and critical regulator of BA metabolism in physiological and pathophysiological conditions. Previous studies have suggested compromised Sirt1 expression in rodent models of cholestatic liver injury. We hypothesized that Sirt1 could be potentially targeted to alleviate cholestatic liver injury. In cultured primary human hepatocytes, SIRT1 mRNA was downregulated after GCA treatment, potentially via induction of miR-34a, whereas TUDCA induced SIRT1 expression without affecting miR-34a expression...
September 17, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
David B Kantor, Erik Su, Carly E Milliren, Thomas W Conlon
OBJECTIVE: Peripheral arterial catheterization is a common invasive procedure performed in critically ill children. However, the benefits of using ultrasound guidance for this procedure in critically ill children, especially when used by inexperienced trainees, are unclear. Our aims were to evaluate whether the use of ultrasound guidance for the placement of radial arterial catheters reduced time and improved success when compared with the palpation method and also to determine patient and trainee variables that influence procedure outcomes...
September 14, 2016: Pediatric Critical Care Medicine
Challice L Bonifant, Hollie J Jackson, Renier J Brentjens, Kevin J Curran
T cells can be genetically modified to target tumors through the expression of a chimeric antigen receptor (CAR). Most notably, CAR T cells have demonstrated clinical efficacy in hematologic malignancies with more modest responses when targeting solid tumors. However, CAR T cells also have the capacity to elicit expected and unexpected toxicities including: cytokine release syndrome, neurologic toxicity, "on target/off tumor" recognition, and anaphylaxis. Theoretical toxicities including clonal expansion secondary to insertional oncogenesis, graft versus host disease, and off-target antigen recognition have not been clinically evident...
2016: Molecular Therapy Oncolytics
Andre Monteiro da Rocha, Guadalupe Guerrero-Serna, Adam Helms, Carly Luzod, Sergey Mironov, Mark Russell, José Jalife, Sharlene M Day, Gary D Smith, Todd J Herron
AIMS: Mutations of cardiac sarcomere genes have been identified to cause HCM, but the molecular mechanisms that lead to cardiomyocyte hypertrophy and risk for sudden death are uncertain. The aim of this study was to examine HCM disease mechanisms at play during cardiac differentiation of human HCM specific pluripotent stem cells. METHODS AND RESULTS: We generated a human embryonic stem cell (hESC) line carrying a naturally occurring mutation of MYPBC3 (c.2905 +1 G >A) to study HCM pathogenesis during cardiac differentiation...
September 9, 2016: Journal of Molecular and Cellular Cardiology
Susan E Spratt, Katherine Pereira, Bradi B Granger, Bryan C Batch, Matthew Phelan, Michael Pencina, Marie Lynn Miranda, Ebony Boulware, Joseph E Lucas, Charlotte L Nelson, Benjamin Neely, Benjamin A Goldstein, Pamela Barth, Rachel L Richesson, Isaretta L Riley, Leonor Corsino, Eugenia R McPeek Hinz, Shelley Rusincovitch, Jennifer Green, Anna Beth Barton, Carly Kelley, Kristen Hyland, Monica Tang, Amanda Elliott, Ewa Ruel, Alexander Clark, Melanie Mabrey, Kay Lyn Morrissey, Jyothi Rao, Beatrice Hong, Marjorie Pierre-Louis, Katherine Kelly, Nicole Jelesoff
OBJECTIVE: We assessed the sensitivity and specificity of 8 electronic health record (EHR)-based phenotypes for diabetes mellitus against gold-standard American Diabetes Association (ADA) diagnostic criteria via chart review by clinical experts. MATERIALS AND METHODS: We identified EHR-based diabetes phenotype definitions that were developed for various purposes by a variety of users, including academic medical centers, Medicare, the New York City Health Department, and pharmacy benefit managers...
September 11, 2016: Journal of the American Medical Informatics Association: JAMIA
Xiaomeng Li, Xuedong Yan, Jiawei Wu, Essam Radwan, Yuting Zhang
Driver's collision avoidance performance has a direct link to the collision risk and crash severity. Previous studies demonstrated that the distracted driving, such as using a cell phone while driving, disrupted the driver's performance on road. This study aimed to investigate the manner and extent to which cell phone use and driver's gender affected driving performance and collision risk in a rear-end collision avoidance process. Forty-two licensed drivers completed the driving simulation experiment in three phone use conditions: no phone use, hands-free, and hand-held, in which the drivers drove in a car-following situation with potential rear-end collision risks caused by the leading vehicle's sudden deceleration...
August 23, 2016: Accident; Analysis and Prevention
J P Lozoya, F Teixeira de Mello, D Carrizo, F Weinstein, Y Olivera, F Cedrés, M Pereira, M Fossati
Beaches are social-ecological systems that provide several services improving human well-being. However, as one of the major coastal interfaces they are subject to plastic pollution, one of the most significant global environmental threats at present. For the first time for Uruguayan beaches, this study assessed and quantified the accumulation of plastic and microplastic debris on sandy beaches of the major touristic destination Punta del Este during the austral spring of 2013. Aiming to provide valuable information for decision-making, we performed a detailed analysis of plastic debris, their eventual transport pathways to the coast (from land and sea), and the associated persistent pollutants...
November 2016: Environmental Pollution
Wei-Wen Chen, Yung-Hsiang Yi, Cheng-Hao Chien, Kuei-Ching Hsiung, Tian-Hsiang Ma, Yi-Chun Lin, Szecheng J Lo, Ta-Chau Chang
Polyunsaturated fatty acids (PUFAs) exhibit critical functions in biological systems and their importance during animal oocyte maturation has been increasingly recognized. However, the detailed mechanism of lipid transportation for oocyte development remains largely unknown. In this study, the transportation of yolk lipoprotein (lipid carrier) and the rate of lipid delivery into oocytes in live C. elegans were examined for the first time by using coherent anti-Stokes Raman scattering (CARS) microscopy. The accumulation of secreted yolk lipoprotein in the pseudocoelom of live C...
2016: Scientific Reports
Milu T Cherian, Lei Yang, Sergio C Chai, Wenwei Lin, Taosheng Chen
The constitutive androstane receptor (CAR) regulates the expression of genes involved in drug metabolism and other processes. A specific inhibitor of CAR is critical for modulating constitutive CAR activity. We recently described a specific small-molecule inhibitor of CAR, CINPA1 (ethyl (5-(diethylglycyl)-10,11-dihydro-5H-dibenzo[b,f]azepin-3-yl)carbamate), which is capable of reducing CAR-mediated transcription by changing the coregulator recruitment pattern and reducing CAR occupancy at the promoter regions of its target genes...
November 2016: Drug Metabolism and Disposition: the Biological Fate of Chemicals
Carly Reagon, Nichola Gale, Stephanie Enright, Mala Mann, Robert van Deursen
OBJECTIVE: To investigate the effect of group singing on health related quality of life (HRQoL) for adult, amateur singers with chronic health conditions. METHODS: A literature search for experimental and observational studies and qualitative studies published before February 2014 was undertaken using the following databases: ASSIA (Proquest), CINAHL (Ebsco), EMBASE (OVID), HMIC (OVID), MEDLINE (OVID), MEDLINE in Process (OVID), OpenGrey, PsycINFO (OVID) and PubMed for Epub ahead of print studies...
August 2016: Complementary Therapies in Medicine
Fei Gao, Wahida Kihal, Nolwenn Le Meur, Marc Souris, Séverine Deguen
BACKGROUND: The evaluation of geographical healthcare accessibility in residential areas provides crucial information to public policy. Traditional methods - such as Physician Population Ratios (PPR) or shortest travel time - offer only a one-dimensional view of accessibility. This paper developed an improved indicator: the Index of Spatial Accessibility (ISA) to measure geographical healthcare accessibility at the smallest available infra-urban level, that is, the Îlot Regroupé pour des Indicateurs Statistiques...
2016: International Journal for Equity in Health
Ying-Yu Ma, Xiao-Jun Wang, Yong Han, Gang Li, Hui-Ju Wang, Shi-Bing Wang, Xiao-Yi Chen, Fan-Long Liu, Xiang-Lei He, Xiang-Min Tong, Xiao-Zhou Mou
The coxsackie and adenovirus receptor (CAR) is considered a tumor suppressor and critical factor for the efficacy of therapeutic strategies that employ the adenovirus. However, data on CAR expression levels in colorectal cancer are conflicting and its clinical relevance remains to be elucidated. Immunohistochemistry was performed on tissue microarrays containing 251 pairs of colon cancer and adjacent normal tissue samples from Chinese Han patients to assess the expression levels of CAR. Compared with healthy mucosa, decreased CAR expression (40...
September 2016: Molecular Medicine Reports
Josiah E Hardesty, Banrida Wahlang, K Cameron Falkner, Heather B Clair, Barbara J Clark, Brian P Ceresa, Russell A Prough, Matthew C Cave
1. Polychlorinated biphenyls (PCBs) are persistent environmental pollutants that disrupt hepatic xenobiotic and intermediary metabolism, leading to metabolic syndrome and nonalcoholic steatohepatitis (NASH). 2. Since phenobarbital indirectly activates Constitutive Androstane Receptor (CAR) by antagonizing growth factor binding to the epidermal growth factor receptor (EGFR), we hypothesised that PCBs may also diminish EGFR signaling. 3. The effects of the PCB mixture Aroclor 1260 on the protein phosphorylation cascade triggered by EGFR activation were determined in murine (in vitro and in vivo) and human models (in vitro)...
July 26, 2016: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
Ting-Min Hsieh, Tsung-Cheng Tsai, Yueh-Wei Liu, Ching-Hua Hsieh
BACKGROUND: High-grade blunt hepatic and/or splenic injuries (BHSI) remain a great challenge for trauma surgeons. The main aim of this study was to investigate the characteristics, mortality rates, and outcomes of high-grade BHSI in motorcyclists and car occupants hospitalized for treatment of traumatic injuries in a Level I trauma center in southern Taiwan. METHODS: High-grade BHSI are defined as grade III-VI blunt hepatic injuries and grade III-V blunt splenic injuries...
2016: International Journal of Environmental Research and Public Health
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