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Sabine Nafzger, Jean-Sebastien Rougier
AIM: The L-type voltage-gated calcium channel Cav1.2 mediates the calcium influx into cells upon membrane depolarization. The list of cardiopathies associated to Cav1.2 dysfunctions highlights the importance of this channel in cardiac physiology. Calcium/calmodulin-dependent serine protein kinase (CASK), expressed in cardiac cells, has been identified as a regulator of Cav2.2 channels in neurons, but no experiments have been performed to investigate its role in Cav1.2 regulation. METHODS AND RESULTS: Full length or the distal C-terminal truncated of the pore-forming Cav1...
October 5, 2016: Cell Calcium
Robyn Johnston, Julia Stafford, Hannah Pierce, Mike Daube
INTRODUCTION AND AIMS: In Australia, most alcohol is sold as packaged liquor from off-premises retailers, a market increasingly dominated by supermarket chains. Competition between retailers may encourage marketing approaches, for example, discounting, that evidence indicates contribute to alcohol-related harms. This research documented the nature and variety of promotional methods used by two major supermarket retailers to promote alcohol products in their supermarket catalogues. DESIGN AND METHODS: Weekly catalogues from the two largest Australian supermarket chains were reviewed for alcohol-related content over 12 months...
September 28, 2016: Drug and Alcohol Review
Hsiao-Tang Hu, Hisashi Umemori, Yi-Ping Hsueh
Functional synapse formation requires tight coordination between pre- and post-synaptic termini. Previous studies have shown that postsynaptic expression of heparan sulfate proteoglycan syndecan-2 (SDC2) induces dendritic spinogenesis. Those SDC2-induced dendritic spines are frequently associated with presynaptic termini. However, how postsynaptic SDC2 accelerates maturation of corresponding presynaptic termini is unknown. Because fibroblast growth factor 22 (FGF22), a heparan sulfate binding growth factor, has been shown to act as a presynaptic organizer released from the postsynaptic site, it seems possible that postsynaptic SDC2 presents FGF22 to the presynaptic FGF receptor to promote presynaptic differentiation...
2016: Scientific Reports
Minmin Jiang, Juhui Qiu, Lingling Zhang, Dongyuan Lü, Mian Long, Li Chen, Xiangdong Luo
Wound healing is a complicated but highly organized process in which cell migration and proliferation are actively involved. However, the process by which mechanical stretch regulates the proliferation and migration of human skin fibroblasts (HFs) and keratinocytes is poorly understood. Using a house built mechanical stretch device, we examined the HFs extracellular matrix (ECM) components changes under non-stretch, static stretch or cyclic stretch conditions. We further investigated the changes in ECM component protein expression levels in keratinocytes and analyzed the effects of individual ECM component on keratinocyte proliferation and migration...
September 2016: Experimental and Therapeutic Medicine
Ekaterina Smirnova, Jamie J Kwan, Ryan Siu, Xin Gao, Georg Zoidl, Borries Demeler, Vivian Saridakis, Logan W Donaldson
BACKGROUND: CASKIN2 is a homolog of CASKIN1, a scaffolding protein that participates in a signaling network with CASK (calcium/calmodulin-dependent serine kinase). Despite a high level of homology between CASKIN2 and CASKIN1, CASKIN2 cannot bind CASK due to the absence of a CASK Interaction Domain and consequently, may have evolved undiscovered structural and functional distinctions. RESULTS: We demonstrate that the crystal structure of the Sterile Alpha Motif (SAM) domain tandem (SAM1-SAM2) oligomer from CASKIN2 is different than CASKIN1, with the minimal repeating unit being a dimer, rather than a monomer...
2016: Cell Communication and Signaling: CCS
Sara Esther Diomandé, Bénédicte Doublet, Florian Vasaï, Marie-Hélène Guinebretière, Véronique Broussolle, Julien Brillard
Two-component systems (TCS) allow a cell to elaborate a variety of adaptive responses to environment changes. The recently discovered CasK/R TCS plays a role in the optimal unsaturation of fatty acids necessary for cold adaptation of the foodborne-pathogen Bacillus cereus Here, we showed that the promoter activity of the operon encoding this TCS was repressed during growth at low temperature in the stationary phase in the parental strain when compared to the casK/R mutant, suggesting that CasR negatively regulates the activity of its own promoter in these conditions...
August 2016: FEMS Microbiology Letters
José Manuel Serrano-Morales, María Dolores Vázquez-Carretero, María José Peral, Anunciacion Ana Ilundáin, Pablo García-Miranda
Reelin is an extracellular matrix protein that plays a critical role in neuronal migration. Here we show that the mucosa of human colon expresses reelin, its receptors ApoER2 and VLDLR, and its effector protein Dab1. Immunohistochemical analyses reveal that reelin expression is restricted to pericryptal myofibroblasts; Dab1 is detected at myofibroblasts, the apical domain of surface epithelial and crypt cells, and a strong linear staining is observed at the basement membrane; VLDLR and ApoER2 are in the cytoplasm of surface epithelium and myofibroblasts, and VLDLR is also detected in the cytoplasm of the crypt cells...
July 19, 2016: Molecular Carcinogenesis
Catherine A Eichel, Adeline Beuriot, Morgan Y E Chevalier, Jean-Sébastien Rougier, Florent Louault, Gilles Dilanian, Julien Amour, Alain Coulombe, Hugues Abriel, Stéphane N Hatem, Elise Balse
RATIONALE: Mechanisms underlying membrane protein localization are crucial in the proper function of cardiac myocytes. The main cardiac sodium channel, NaV1.5, carries the sodium current (INa) that provides a rapid depolarizing current during the upstroke of the action potential. Although enriched in the intercalated disc, NaV1.5 is present in different membrane domains in myocytes and interacts with several partners. OBJECTIVE: To test the hypothesis that the MAGUK (membrane-associated guanylate kinase) protein CASK (calcium/calmodulin-dependent serine protein kinase) interacts with and regulates NaV1...
August 5, 2016: Circulation Research
Ernestas Narkunas, Arturas Smaizys, Povilas Poskas, Valdas Ragaisis
Existing interim spent nuclear fuel storage facility (SNFSF) at Ignalina nuclear power plant in Lithuania is fully loaded with CASTOR(®)RBMK-1500 and CONSTOR(®)RBMK-1500 storage casks. The planned lifetime of these casks is 50 years and the first loaded cask was moved to the SNFSF in 1999. The start of operation of disposal facility in Lithuania is foreseen later than the planned interim storage ends. So, the possibilities to extend the storage period over 50 years should be considered. Therefore, the casks decommissioning issues should be taken into account, as due to prolonged neutron irradiation casks materials could became activated...
September 2016: Applied Radiation and Isotopes
Bo Pang, Frank Becker
Albedo neutron dosemeter is the German official personal neutron dosemeter in mixed radiation fields where neutrons contribute to personal dose. In deep geological repositories for high-level nuclear waste, where neutrons can dominate the radiation field, it is of interest to investigate the performance of albedo neutron dosemeter in such facilities. In this study, the deep geological repository is represented by a shielding cask loaded with spent nuclear fuel placed inside a rock salt emplacement drift. Due to the backscattering of neutrons in the drift, issues concerning calibration of the dosemeter arise...
June 24, 2016: Radiation Protection Dosimetry
Stine Ninel Hansen, Natasja Spring Ehlers, Shida Zhu, Mathilde Borg Houlberg Thomsen, Rikke Linnemann Nielsen, Dongbing Liu, Guangbiao Wang, Yong Hou, Xiuqing Zhang, Xun Xu, Lars Bolund, Huanming Yang, Jun Wang, Jose Moreira, Henrik J Ditzel, Nils Brünner, Anne-Sofie Schrohl, Jan Stenvang, Ramneek Gupta
BACKGROUND: Resistance to taxane-based therapy in breast cancer patients is a major clinical problem that may be addressed through insight of the genomic alterations leading to taxane resistance in breast cancer cells. In the current study we used whole exome sequencing to discover somatic genomic alterations, evolving across evolutionary stages during the acquisition of docetaxel resistance in breast cancer cell lines. RESULTS: Two human breast cancer in vitro models (MCF-7 and MDA-MB-231) of the step-wise acquisition of docetaxel resistance were developed by exposing cells to 18 gradually increasing concentrations of docetaxel...
2016: BMC Genomics
Heng Jiang, Sarah Callinan, Michael Livingston, Robin Room
INTRODUCTION AND AIMS: To delineate what type and how much alcohol is purchased from different types of off-licence premises and how this varies across demographic sub-groups, as a basis for public debate and decisions on pricing and planning policies to reduce alcohol-related harm in Australia. DESIGN AND METHODS: The data on alcohol purchasing from off-licence premises are taken from the Australian Alcohol Consumption and Purchasing survey-a nationally representative landline and mobile telephone survey in 2013 on the experiences with alcohol consumption and purchasing of 2020 Australians aged 16+...
May 24, 2016: Drug and Alcohol Review
Tanja Bele, Elsa Fabbretti
P2X3 receptors, gated by extracellular ATP, are expressed by sensory neurons and are involved in peripheral nociception and pain sensitization. The ability of P2X3 receptors to transduce extracellular stimuli into neuronal signals critically depends on the dynamic molecular partnership with the calcium/calmodulin-dependent serine protein kinase (CASK). The present work used trigeminal sensory neurons to study the impact that activation of P2X3 receptors (evoked by the agonist α,β-meATP) has on the release of endogenous ATP and how CASK modulates this phenomenon...
August 2016: Journal of Neurochemistry
Eyal Reinstein, Shay Tzur, Concetta Bormans, Doron M Behar
Whole-exome sequencing for clinical applications is now an integral part of medical genetics practice. Though most studies are performed in order to establish diagnoses in individuals with rare and clinically unrecognizable disorders, due to the constantly decreasing costs and commercial availability, whole-exome sequencing has gradually become the initial tool to study patients with clinically recognized disorders when more than one gene is responsible for the phenotype or in complex phenotypes, when variants in more than one gene can be the cause for the disease...
2016: Genetics Research
Gong-Her Wu, Muniesh Muthaiyan Shanmugam, Prerana Bhan, Yu-Hsin Huang, Oliver Ingvar Wagner
Kinesin-3 UNC-104(KIF1A) is the major axonal transporter of synaptic vesicles. Employing yeast two-hybrid and co-immunoprecipitation (Co-IP) assays, we characterized a LIN-2(CASK) binding site overlapping with that of reported UNC-104 activator protein SYD-2(Liprin-α) on the motor's stalk domain. We identified the L27 and GUK domains of LIN-2 to be the most critical interaction domains for UNC-104. Further, we demonstrated that the L27 domain interacts with the sterile alpha motifs (SAM) domains of SYD-2, while the GUK domain is able to interact with both the coiled coils and SAM domains of SYD-2...
August 2016: Traffic
Heng Jiang, Michael Livingston, Robin Room, Sarah Callinan
BACKGROUND: Understanding how price policies will affect alcohol consumption requires estimates of the impact of price on consumption among different types of drinkers and across different consumption settings. This study aims to estimate how changes in price could affect alcohol demand across different beverages, different settings (on-premise, e.g., bars, restaurants and off-premise, e.g., liquor stores, supermarkets), and different levels of drinking and income. METHODS: Tobit analysis is employed to estimate own- and cross-price elasticities of alcohol demand among 11 subcategories of beverage based on beverage type and on- or off-premise supply, using cross-sectional data from the Australian arm of the International Alcohol Control Survey 2013...
June 1, 2016: Drug and Alcohol Dependence
Sarika Srivastava, Ryan McMillan, Jeffery Willis, Helen Clark, Vrushali Chavan, Chen Liang, Haiyan Zhang, Matthew Hulver, Konark Mukherjee
The phenotypic spectrum among girls with heterozygous mutations in the X-linked intellectual disability (XLID) gene CASK (calcium/calmodulin-dependent serine protein kinase) includes postnatal microcephaly, ponto-cerebellar hypoplasia, seizures, optic nerve hypoplasia, growth retardation and hypotonia. Although CASK knockout mice were previously reported to exhibit perinatal lethality and a 3-fold increased apoptotic rate in the brain, CASK deletion was not found to affect neuronal physiology and their electrical properties...
2016: Acta Neuropathologica Communications
Leslie E W LaConte, Vrushali Chavan, Chen Liang, Jeffery Willis, Eva-Maria Schönhense, Susanne Schoch, Konark Mukherjee
CASK, a MAGUK family protein, is an essential protein present in the presynaptic compartment. CASK's cellular role is unknown, but it interacts with multiple proteins important for synapse formation and function, including neurexin, liprin-α, and Mint1. CASK phosphorylates neurexin in a divalent ion-sensitive manner, although the functional relevance of this activity is unclear. Here we find that liprin-α and Mint1 compete for direct binding to CASK, but neurexin1β eliminates this competition, and all four proteins form a complex...
September 2016: Cellular and Molecular Life Sciences: CMLS
Patrick Rump, Omid Jazayeri, Krista K van Dijk-Bos, Lennart F Johansson, Anthonie J van Essen, Johanna B G M Verheij, Hermine E Veenstra-Knol, Egbert J W Redeker, Marcel M A M Mannens, Morris A Swertz, Behrooz Z Alizadeh, Conny M A van Ravenswaaij-Arts, Richard J Sinke, Birgit Sikkema-Raddatz
BACKGROUND: Clinical and genetic heterogeneity in monogenetic disorders represents a major diagnostic challenge. Although the presence of particular clinical features may aid in identifying a specific cause in some cases, the majority of patients remain undiagnosed. Here, we investigated the utility of whole-exome sequencing as a diagnostic approach for establishing a molecular diagnosis in a highly heterogeneous group of patients with varied intellectual disability and microcephaly. METHODS: Whole-exome sequencing was performed in 38 patients, including three sib-pairs, in addition to or in parallel with genetic analyses that were performed during the diagnostic work-up of the study participants...
2016: BMC Medical Genomics
Hsiao-Tang Hu, Pu-Yun Shih, Yu-Tzu Shih, Yi-Ping Hsueh
Dendritic spines are the location of excitatory synapses in the mammalian nervous system and are neuron-specific subcellular structures essential for neural circuitry and function. Dendritic spine morphology is determined by the F-actin cytoskeleton. F-actin remodeling must coordinate with different stages of dendritic spinogenesis, starting from dendritic filopodia formation to the filopodia-spines transition and dendritic spine maturation and maintenance. Hundreds of genes, including F-actin cytoskeleton regulators, membrane proteins, adaptor proteins, and signaling molecules, are known to be involved in regulating synapse formation...
2016: Neural Plasticity
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