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https://www.readbyqxmd.com/read/29145487/defining-external-factors-that-determine-neuronal-survival-apoptosis-and-necrosis-during-excitotoxic-injury-using-a-high-content-screening-imaging-platform
#1
Ujval Anilkumar, Petronela Weisova, Jasmin Schmid, Tytus Bernas, Heinrich J Huber, Heiko Düssmann, Niamh M C Connolly, Jochen H M Prehn
Cell death induced by excessive glutamate receptor overactivation, excitotoxicity, has been implicated in several acute and chronic neurological disorders. While numerous studies have demonstrated the contribution of biochemically and genetically activated cell death pathways in excitotoxic injury, the factors mediating passive, excitotoxic necrosis are less thoroughly investigated. To address this question, we developed a high content screening (HCS) based assay to collect high volumes of quantitative cellular imaging data and elucidated the effects of intrinsic and external factors on excitotoxic necrosis and apoptosis...
2017: PloS One
https://www.readbyqxmd.com/read/29145451/stromal-interaction-molecule-1-haploinsufficiency-causes-maladaptive-response-to-pressure-overload
#2
Takayoshi Ohba, Hiroyuki Watanabe, Manabu Murakami, Kenji Iino, Takeshi Adachi, Yoshihiro Baba, Tomohiro Kurosaki, Kyoichi Ono, Hiroshi Ito
Stromal interaction molecule 1 (STIM1), an endo/sarcoplasmic reticulum Ca2+ sensor, has been shown to control a Ca2+-dependent signal that promotes cardiac hypertrophy. However, whether STIM1 has adaptive role that helps to protect against cardiac overload stress remains unknown. We hypothesized that STIM1 deficiency causes a maladaptive response to pressure overload stress. We investigated STIM1 heterozygous KO (STIM1+/-) mice hearts, in which STIM1 protein levels decreased to 27% of wild-type (WT) with no compensatory increase in STIM2...
2017: PloS One
https://www.readbyqxmd.com/read/29145393/estimating-the-probabilities-of-rare-arrhythmic-events-in-multiscale-computational-models-of-cardiac-cells-and-tissue
#3
Mark A Walker, Viatcheslav Gurev, John J Rice, Joseph L Greenstein, Raimond L Winslow
Ectopic heartbeats can trigger reentrant arrhythmias, leading to ventricular fibrillation and sudden cardiac death. Such events have been attributed to perturbed Ca2+ handling in cardiac myocytes leading to spontaneous Ca2+ release and delayed afterdepolarizations (DADs). However, the ways in which perturbation of specific molecular mechanisms alters the probability of ectopic beats is not understood. We present a multiscale model of cardiac tissue incorporating a biophysically detailed three-dimensional model of the ventricular myocyte...
November 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/29144736/inference-of-calmodulin-s-ca2-dependent-free-energy-landscapes-via-gaussian-mixture-model-validation
#4
Annie M Westerlund, Tyler J Harpole, Christian Blau, Lucie Delemotte
A free energy landscape estimation-method based on the well-known Gaussian mixture model (GMM) is used for comparing the efficiency of thermally enhanced sampling methods with respect to regular molecular dynamics. The simulations are carried out on two binding states of calmodulin and the free energy estimation method is compared to other estimators using a toy model. We show that GMM with cross-validation provides a robust estimate that is not subject to overfitting. The continuous nature of Gaussians provides better estimates on sparse data than canonical histogramming...
November 16, 2017: Journal of Chemical Theory and Computation
https://www.readbyqxmd.com/read/29141899/atypical-g-protein-%C3%AE-5-promotes-cardiac-oxidative-stress-apoptosis-and-fibrotic-remodeling-in-response-to-multiple-cancer-chemotherapeutics
#5
Biswanath Maity, Sreemoyee Chakraborti, Arnab Pramanick, Sudipta Saha, Somnath Singha Roy, Arnab Ray Chaudhuri, Madhusudan Das, Sujoy Ghosh, Adele Stewart
The clinical use of multiple classes of cancer chemotherapeutics is limited by irreversible, dose-dependent, and sometimes life-threatening cardiotoxicity. We report here that, though distinct in their mechanisms of action, doxorubicin, paclitaxel, and 5-FU all induce rapid and robust upregulation of atypical G protein Gβ5 in the myocardium, correlating with oxidative stress, myocyte apoptosis, and the accumulation of pro-inflammatory and pro-fibrotic cytokines. In ventricular cardiac myocytes (VCM), Gβ5 deficiency provided substantial protection against the cytotoxic actions of chemotherapeutics, including reductions in oxidative stress and simultaneous attenuation of ROS-dependent activation of the ATM and CaMKII pro-apoptotic signaling cascades...
November 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/29141547/cardioprotective-effects-of-serca2a-overexpression-against-ischemia-reperfusion-induced-injuries-in-rats
#6
Yan Jian, Li-Li Tian, Lin-Hui Wang, Xiao-Dong Zhao, Jing-Wei Chen, Koji Murao, Wei Zhu, Liang Dong, Guo-Qing Wang, Wan-Ping Sun, Guo-Xing Zhang
AIMS: The aim of the present study is to assess how genetically increased Sarcoplasmic reticulum Ca2+-ATPase (Serca2a) expression affects cardiac injury after ischemia/reperfusion (I/R) exposure and the related mechanisms involved. METHODS AND RESULTS: Rats were subjected to left anterior descending coronary artery (LAD) occlusion for 30 min followed by a 24-hour reperfusion. Cardiac function analysis revealed that cardiac function dramatically improved in Serca2a transgenic rats (Serca2aTG) rats compared to wild type (WT) rats...
November 10, 2017: Current Gene Therapy
https://www.readbyqxmd.com/read/29141003/trpa1-and-trpv1-are-required-for-lidocaine-evoked-calcium-influx-and-neuropeptide-release-but-not-cytotoxicity-in-mouse-sensory-neurons
#7
Mirjam Eberhardt, Thomas Stueber, Jeanne de la Roche, Christine Herzog, Andreas Leffler, Peter W Reeh, Katrin Kistner
BACKGROUND: Local anaesthetics (LA) reduce neuronal excitability by inhibiting voltage-gated Na+ channels. When applied at high concentrations in the direct vicinity of nerves, LAs can also induce relevant irritation and neurotoxicity via mechanisms involving an increase of intracellular Ca2+. In the present study we explored the role of the Ca2+-permeable ion channels TRPA1 and TRPV1 for lidocaine-induced Ca2+-influx, neuropeptide release and neurotoxicity in mouse sensory neurons. METHODS: Cultured dorsal root ganglion (DRG) neurons from wildtype and mutant mice lacking TRPV1, TRPA1 or both channels were explored by means of calcium imaging, whole-cell patch clamp recordings and trypan blue staining for cell death...
2017: PloS One
https://www.readbyqxmd.com/read/29140711/probing-the-surface-charge-on-the-basal-planes-of-kaolinite-particles-with-high-resolution-atomic-force-microscopy
#8
Naveen Kumar, Martin Peter Andersson, Dirk van den Ende, Frieder Mugele, Igor Siretanu
High resolution Atomic Force Microscopy is used to map the surface charge on the basal planes of kaolinite nanoparticles in an ambient solution of variable pH and NaCl or CaCl2 concentration. Using DLVO theory with charge regulation we determine from the measured force-distance curves the surface charge distribution on both the silica-like and the gibbsite-like basal plane of the kaolinite particles. We observe that both basal planes do carry charge that varies with pH and salt concentration. The silica facet was found to be negatively charged at pH 4 and above, whereas the gibbsite facet is positively charged at pH below 7, and negatively charged at pH above 7...
November 15, 2017: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/29138822/fucoidan-inhibits-ca2-responses-induced-by-a-wide-spectrum-of-agonists-for-g%C3%A2-protein%C3%A2-coupled-receptors
#9
Hong Wu, Shuibo Gao, Min Fu, Takashi Sakurai, Susumu Terakawa
Fucoidan, a sulfated polysaccharide extracted from brown seaweed, has been used in traditional Chinese herbal medicine to treat thyroid tumors for many years. Although a number of its cellular effects have been investigated, the role of fucoidan in molecular signaling, particularly in Ca2+ signaling, remains largely unknown. In the present study, the effects of fucoidan on Ca2+ responses in HeLa cells, human umbilical vein endothelial cells and astrocytes were investigated using a wide range of receptor agonists...
November 13, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29138698/soluble-epoxide-hydrolase-inhibitor-and-14-15-epoxyeicosatrienoic-acid-facilitated-long-term-potentiation-through-camp-and-camkii-in-the-hippocampus
#10
Han-Fang Wu, Yi-Ju Chen, Su-Zhen Wu, Chi-Wei Lee, I-Tuan Chen, Yi-Chao Lee, Chi-Chen Huang, Chung-Hsi Hsing, Chih-Wei Tang, Hui-Ching Lin
Epoxyeicosatrienoic acids (EETs) are derived from arachidonic acid and metabolized by soluble epoxide hydrolase (sEH). The role of EETs in synaptic function in the central nervous system is still largely unknown. We found that pharmacological inhibition of sEH to stabilize endogenous EETs and exogenous 14,15-EET significantly increased the field excitatory postsynaptic potential (fEPSP) response in the CA1 area of the hippocampus, while additionally enhancing high-frequency stimulation- (HFS-) induced long-term potentiation (LTP) and forskolin- (FSK-) induced LTP...
2017: Neural Plasticity
https://www.readbyqxmd.com/read/29135233/time-dependent-determination-of-unbiased-selectivity-coefficients-of-ion-selective-electrodes-for-multivalent-ions
#11
Elena Zdrachek, Eric Bakker
A new method for the determination of unbiased low selectivity coefficients for two of the most prevalent cases of multivalent ions (zi = 2, zj = 1 and zi = 1, zj = 2) was theoretically and experimentally substantiated. The method is based on eliminating the primary ion concentration near the membrane by extrapolating the linearized time-dependencies of selectivity coefficients determined by the separate solutions method (KijPot(SSM))) as a function of t^-1/3 or t^-1/6, depending on the charge combination of the two ions, to infinite time...
November 14, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/29135229/effects-of-nh4-k-and-mg2-and-ca2-on-the-cesium-adsorption-desorption-in-binding-sites-of-vermiculitized-biotite
#12
Xiangbiao Yin, Xinpeng Wang, Hao Wu, Hideharu Takahashi, Yusuke Inaba, Toshihiko Ohnuki, Kenji Takeshita
The reversibility of cesium adsorption in contaminated soil is largely dependent on its interaction with micaceous minerals, which may be greatly influenced by various cations. Herein, we systematically investigated the effects of NH4+, K+, Mg2+, and Ca2+ on the adsorption/desorption of Cs+ into different binding sites of vermiculitized biotite (VB). Original VB was initially saturated by NH4+, K+, or Mg2+; we then evaluated the adsorption of Cs+ on three treated VBs, and the desorption by extraction with NH4+, K+, Mg2+, or Ca2+ was further evaluated...
November 14, 2017: Environmental Science & Technology
https://www.readbyqxmd.com/read/29134803/a-fluorescent-binary-ensemble-based-on-pyrene-derivative-and-sds-assemblies-as-a-chemical-tongue-for-discriminating-metal-ions-and-brand-water
#13
Lijun Zhang, Xinyan Huang, Yuan Cao, Yunhong Xin, Liping Ding
Enormous effort has been put to the detection and recognition of various heavy metal ions due to their involvement in serious environmental pollution and many major diseases. The present work developed a single fluorescent sensor ensemble that can distinguish and identify a variety of heavy metal ions. A pyrene-based fluorophore (PB) containing a metal ion receptor group was specially designed and synthesized. Anionic surfactant SDS assemblies can effectively adjust its fluorescence behavior. The selected binary ensemble based on PB/SDS assemblies can exhibit multiple emission bands and provide wavelength-based cross-reactive responses to a series of metal ions to realize pattern recognition ability...
November 14, 2017: ACS Sensors
https://www.readbyqxmd.com/read/29133594/competitive-kinase-enrichment-proteomics-reveals-that-abemaciclib-inhibits-gsk3%C3%AE-and-activates-wnt-signaling
#14
Emily M Cousins, Dennis Goldfarb, Feng Yan, Jose Roques, David B Darr, Gary L Johnson, Michael B Major
The cellular and organismal phenotypic response to a small-molecule kinase inhibitor is defined collectively by the inhibitor's targets and their functions. The selectivity of small-molecule kinase inhibitors is commonly determined in vitro, using purified kinases and substrates. Recently, competitive chemical proteomics has emerged as a complementary, unbiased, cell-based methodology to define the target landscape of kinase inhibitors. Here, we evaluated and optimized a competitive multiplexed inhibitor bead mass spectrometry (MIB/MS) platform using cell lysates, live cells, and treated mice...
November 13, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29133590/genotoxic-damage-activates-the-ampk-%C3%AE-1-isoform-in-the-nucleus-via-ca2-camkk2-signaling-to-enhance-tumor-cell-survival
#15
Diana Vara Ciruelos, Madhumita Dandapani, Alexander Gray, Ejaife O Egbani, A Mark Evans, D Grahame Hardie
Many genotoxic cancer treatments activate AMP-activated protein kinase (AMPK), but the mechanisms of AMPK activation in response to DNA damage, and its downstream consequences, have been unclear. In this study, etoposide activates the α1 but not the α2 isoform of AMPK, primarily within the nucleus. AMPK activation is independent of ataxia-telangiectasia mutated (ATM), a DNA damage-activated kinase, and the principal upstream kinase for AMPK, LKB1, but correlates with increased nuclear Ca2+ and requires the Ca2+/calmodulin-dependent kinase, CaMKK2...
November 13, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29133370/a-mucin-like-protein-of-planthopper-is-required-for-feeding-and-induces-immunity-response-in-plants
#16
Xinxin Shangguan, Jing Zhang, Bingfang Liu, Yan Zhao, Huiying Wang, Zhizheng Wang, Jianping Guo, Weiwei Rao, Shengli Jing, Wei Guan, Yinhua Ma, Yan Wu, Liang Hu, Rongzhi Chen, Bo Du, Lili Zhu, Dazhao Yu, Guangcun He
The brown planthopper, Nilaparvata lugens (Stål), is a pest that threatens rice production worldwide. While feeding on rice plants, planthoppers secrete saliva, which plays crucial roles in nutrient ingestion and modulating plant defense responses, although the specific functions of salivary proteins remain largely unknown. We identified a N. lugens-secreted mucin-like protein (NlMLP) by transcriptome and proteome analyses and characterized its function, both in brown planthopper and in plants. NlMLP is highly expressed in salivary glands and is secreted into rice during feeding...
November 13, 2017: Plant Physiology
https://www.readbyqxmd.com/read/29132211/aggregation-behavior-of-dissolved-black-carbon-implications-for-vertical-mass-flux-and-fractionation-in-aquatic-systems
#17
Fanchao Xu, Chenhui Wei, Qingqing Zeng, Xuening Li, Pedro J J Alvarez, Qilin Li, Xiaolei Qu, Dongqiang Zhu
The fluvial export of dissolved black carbon (DBC) is a major land-ocean flux in the global black carbon cycle, affecting the size of refractory carbon pool in the oceans. The aggregation behavior of DBC is a significant determinant of its transport and vertical mass flux. In this study, the aggregation kinetics and interaction energy of DBC leached from biochar were investigated. DBC was mainly stabilized by hydration force and underwent structural compacting in divalent cation solutions. Na+ and Mg2+ had limited impact on the colloidal stability of DBC due to the strong hydration of these cations...
November 13, 2017: Environmental Science & Technology
https://www.readbyqxmd.com/read/29131945/enantioselectivity-of-2-2-3-5-6-pentachlorobiphenyl-pcb-95-atropisomers-toward-ryanodine-receptors-ryrs-and-their-influences-on-hippocampal-neuronal-networks
#18
Wei Feng, Jing Zheng, Gaelle Robin, Yao Dong, Makoto Ichikawa, Yoshihisa Inoue, Tadashi Mori, Takeshi Nakano, Isaac N Pessah
Nineteen ortho-substituted PCBs are chiral and found enantioselectively enriched in ecosystems. Their differential actions on biological targets are not understood. PCB 95 (2,2',3,5',6-pentachlorobiphenyl), a chiral PCB of current environmental relevance, is among the most potent towards modifying ryanodine receptors (RyR) function and Ca2+ signaling. PCB 95 atropisomers are separated and assigned aR- and aS-PCB 95 using 3 chiral-columns HPLC and circular dichroism spectroscopy. Studies of RyR1-enriched microsomes show aR-PCB 95 with >4X greater potency (EC50=0...
November 13, 2017: Environmental Science & Technology
https://www.readbyqxmd.com/read/29131026/trpml1-participates-in-the-progression-of-alzheimer-s-disease-by-regulating-the-ppar%C3%AE-ampk-mtor-signalling-pathway
#19
Lu Zhang, Yu Fang, Xuan Cheng, Yajun Lian, Hongliang Xu, Zhaoshu Zeng, Hongcan Zhu
BACKGROUND: TRPML1 is reported to be involved in the pathogenesis of Alzheimer's disease (AD) by regulating autophagy; however, the underlying mechanism is not completely clear. METHODS: We developed an APP/PS1 transgenic animal model that presents with AD. TRPML1 was also overexpressed in these mice. Protein expression levels were determined by Western blot. Morris water maze (MWM) and recognition tasks were performed to characterize cognitive ability. TUNEL assays were analysed for the detection of neuronal apoptosis...
October 31, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29131013/a-new-baltic-population-specific-human-genetic-marker-in-the-pmca4-gene
#20
Janis Stavusis, Inna Inashkina, Baiba Lace, Dita Pelnena, Svetlana Limborska, Andrey Khrunin, Vaidutis Kucinskas, Astrida Krumina, Linda Piekuse, Branko Zorn, Violeta Fodina, Margus Punab, Juris Erenpreiss
OBJECTIVES: The PMCA gene family consists of 4 genes and at least 21 splice variants; among these, the Ca2+ ATPase 4 (PMCA4) gene encodes a plasma membrane protein abundantly expressed in several tissues, including the kidney, heart, and sperm. Knockout of PMCA4 causes infertility due to immotile sperm in mouse models. We therefore investigated variants in this gene for potential association with infertility in groups of Estonian (n = 191) and Latvian (n = 92) men with reduced sperm motility...
November 2, 2017: Human Heredity
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