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https://www.readbyqxmd.com/read/28648560/switch-like-behavior-enables-wnt11-concentration-specific-response-during-dorso-ventral-axis-formation-in-xenopus-laevis
#1
Jan Eric Sträng, Rainer Schuler, Michael Kühl, Hans A Kestler
Wnt signaling plays a role in diverse processes such as cell proliferation, differentiation, migration or cell polarity. Dysfunction of Wnt signaling is associated with human diseases and aging. Wnts can activate several interacting intracellular signaling pathways, in particular the so called canonical and non-canonical pathways. The canonical Wnt response leads to a stabilization of cytoplasmic β-catenin whereas non-canonical Wnt signaling can result in the activation of calcium-calmodulin dependent kinase II (CamKII)...
June 23, 2017: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/28642476/prevention-of-long-term-memory-loss-after-retrieval-by-an-endogenous-camkii-inhibitor
#2
Fabio Antonio Vigil, Keiko Mizuno, Walter Lucchesi, Victoria Valls-Comamala, Karl Peter Giese
CaMK2N1 and CaMK2N2 are endogenous inhibitors of calcium/calmodulin-dependent protein kinase II (CaMKII), a key synaptic signaling molecule for learning and memory. Here, we investigated the learning and memory function of CaMK2N1 by knocking-down its expression in dorsal hippocampus of mice. We found that reduced CaMK2N1 expression does not affect contextual fear long-term memory (LTM) formation. However, we show that it impairs maintenance of established LTM, but only if retrieval occurs. CaMK2N1 knockdown prevents a decrease of threonine-286 (T286) autophosphorylation of αCaMKII and increases GluA1 levels in hippocampal synapses after retrieval of contextual fear LTM...
June 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28642137/overexpression-cdc42-attenuates-isoflurane-induced-neurotoxicity-in-developmental-brain-of-rats
#3
Xi Fang, Shiyong Li, Qiang Han, Yilin Zhao, Jie Gao, Jing Yan, Ailin Luo
Nowadays many children receive operations with general anesthesia. Isoflurane is a commonly-used general anesthetic. Numbers of studies demonstrated that isoflurane induced neurotoxicity and neurobehavioral deficiency in young rats, however, the underlying mechanism remained unknown. Cell division cycle 42 (cdc42) played an important role in regulating synaptic vesicle trafficking and actin dynamics in neuron, which closely linked to synaptic plasticity and dendritic spine formation. Meanwhile, cdc42 also involved in many neurodegenerative diseases...
June 19, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28640450/network-supervision-of-adult-experience-and-learning-dependent-sensory-cortical-plasticity
#4
David T Blake
The brain is capable of remodeling throughout life. The sensory cortices provide a useful preparation for studying neuroplasticity both during development and thereafter. In adulthood, sensory cortices change in the cortical area activated by behaviorally relevant stimuli, by the strength of response within that activated area, and by the temporal profiles of those responses. Evidence supports forms of unsupervised, reinforcement, and fully supervised network learning rules. Studies on experience-dependent plasticity have mostly not controlled for learning, and they find support for unsupervised learning mechanisms...
June 18, 2017: Comprehensive Physiology
https://www.readbyqxmd.com/read/28638088/chemokine-receptor-cxcr4-regulates-camkii-creb-pathway-in-spinal-neurons-that-underlies-cancer-induced-bone-pain
#5
Xue-Ming Hu, Hui Zhang, Heng Xu, Hai-Long Zhang, Li-Ping Chen, Wen-Qiang Cui, Wei Yang, Wen Shen
We previously demonstrated that the chemokine receptor CXCR4 plays an important role in cancer-induced bone pain by activating spinal neurons and glial cells. However, the specific neuronal mechanism of CXCR4 signaling is not clear. We further report that CXCR4 contributes to the activation of the neuronal CaMKII/CREB pathway in cancer-induced bone pain. We used a tumor cell implantation (TCI) model and observed that CXCR4, p-CaMKII and p-CREB were persistently up-regulated in spinal neurons. CXCR4 also co-expressed with p-CaMKII and p-CREB, and mediated p-CaMKII and p-CREB expression after TCI...
June 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28636948/pten%C3%AE-modulates-camkii-signaling-and-controls-contextual-fear-memory-and-spatial-learning
#6
Pan Wang, Fan Mei, Jiapan Hu, Minglu Zhu, Hailong Qi, Xi Chen, Ruiqi Li, Michael A McNutt, Yuxin Yin
PTEN (phosphatase and tensin homology deleted on chromosome 10) has multiple functions, and recent studies have shown that the PTEN family has isoforms. The roles of these PTEN family members in biologic activities warrant specific evaluation. Here, we show that PTENα maintains CaMKII in a state that is competent to induce long-term potentiation (LTP) with resultant regulation of contextual fear memory and spatial learning. PTENα binds to CaMKII with its distinctive N terminus and resets CaMKII to an activatable state by dephosphorylating it at sites T305/306...
June 20, 2017: Cell Reports
https://www.readbyqxmd.com/read/28634643/acute-high-caffeine-exposure-increases-autophagic-flux-and-reduces-protein-synthesis-in-c2c12-skeletal-myotubes
#7
M A Hughes, R M Downs, G W Webb, C L Crocker, S T Kinsey, Bradley L Baumgarner
Caffeine is a highly catabolic dietary stimulant. High caffeine concentrations (1-10 mM) have previously been shown to inhibit protein synthesis and increase protein degradation in various mammalian cell lines. The purpose of this study was to examine the effect of short-term caffeine exposure on cell signaling pathways that regulate protein metabolism in mammalian skeletal muscle cells. Fully differentiated C2C12 skeletal myotubes either received vehicle (DMSO) or 5 mM caffeine for 6 h. Our analysis revealed that caffeine promoted a 40% increase in autolysosome formation and a 25% increase in autophagic flux...
June 20, 2017: Journal of Muscle Research and Cell Motility
https://www.readbyqxmd.com/read/28614711/dapk1-mediates-ltd-by-making-camkii-glun2b-binding-ltp-specific
#8
Dayton J Goodell, Vincent Zaegel, Steven J Coultrap, Johannes W Hell, K Ulrich Bayer
The death-associated protein kinase 1 (DAPK1) is a potent mediator of neuronal cell death. Here, we find that DAPK1 also functions in synaptic plasticity by regulating the Ca(2+)/calmodulin (CaM)-dependent protein kinase II (CaMKII). CaMKII and T286 autophosphorylation are required for both long-term potentiation (LTP) and depression (LTD), two opposing forms of synaptic plasticity underlying learning, memory, and cognition. T286-autophosphorylation induces CaMKII binding to the NMDA receptor (NMDAR) subunit GluN2B, which mediates CaMKII synaptic accumulation during LTP...
June 13, 2017: Cell Reports
https://www.readbyqxmd.com/read/28612156/reduction-of-sr-ca-2-leak-and-arrhythmogenic-cellular-correlates-by-smp-114-a-novel-camkii-inhibitor-with-oral-bioavailability
#9
Stefan Neef, Christian Mann, Anne Zwenger, Nataliya Dybkova, Lars S Maier
Sarcoplasmic reticulum (SR) Ca(2+) leak induced by Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) is centrally involved in atrial and ventricular arrhythmogenesis as well as heart failure remodeling. Consequently, treating SR Ca(2+) leak has been proposed as a novel therapeutic paradigm, but compounds for use in humans are lacking. SMP-114 ("Rimacalib") is a novel, orally available CaMKII inhibitor developed for human use that has already entered clinical phase II trials to treat rheumatoid arthritis...
July 2017: Basic Research in Cardiology
https://www.readbyqxmd.com/read/28612155/the-role-of-spatial-organization-of-ca-2-release-sites-in-the-generation-of-arrhythmogenic-diastolic-ca-2-release-in-myocytes-from-failing-hearts
#10
Andriy E Belevych, Hsiang-Ting Ho, Ingrid M Bonilla, Radmila Terentyeva, Karsten E Schober, Dmitry Terentyev, Cynthia A Carnes, Sándor Györke
In heart failure (HF), dysregulated cardiac ryanodine receptors (RyR2) contribute to the generation of diastolic Ca(2+) waves (DCWs), thereby predisposing adrenergically stressed failing hearts to life-threatening arrhythmias. However, the specific cellular, subcellular, and molecular defects that account for cardiac arrhythmia in HF remain to be elucidated. Patch-clamp techniques and confocal Ca(2+) imaging were applied to study spatially defined Ca(2+) handling in ventricular myocytes isolated from normal (control) and failing canine hearts...
July 2017: Basic Research in Cardiology
https://www.readbyqxmd.com/read/28608248/the-analgesic-effect-of-trans-resveratrol-is-regulated-by-calcium-channels-in-the-hippocampus-of-mice
#11
Weijie Wang, Yingcong Yu, Jing Li, Lin Wang, Zhi Li, Chong Zhang, Linlin Zhen, Lianshu Ding, Gang Wang, Xiaoyang Sun, Ying Xu
Resveratrol has been widely studied in terms of it's potential to slow the progression of many diseases. But little is known about the mechanism of action in neuropathic pain. Neuropathic pain is the main type of chronic pain associated with tissue injury. Calcium channels and calcium/caffeine-sensitive pools are associated with analgesic pathway involving neuropathic pain. Our previous study suggested that the antinociceptive effect of resveratrol was involved in Ca(2+)/calmodulin-dependent signaling in the spinal cord of mice...
June 12, 2017: Metabolic Brain Disease
https://www.readbyqxmd.com/read/28606867/testosterone-deficiency-prevents-left-ventricular-contractility-dysfunction-after-myocardial-infarction
#12
REVIEW
R F Ribeiro Júnior, K S Ronconi, I C G Jesus, P W M Almeida, L Forechi, D V Vassallo, S Guatimosim, I Stefanon, A A Fernandes
Testosterone may affect myocardial contractility since its deficiency decreases the contraction and relaxation of the heart. Meanwhile, testosterone replacement therapy has raised concerns because it may worsen cardiac dysfunction and remodeling after myocardial infarction (MI). In this study, we evaluate cardiac contractility 60 days after MI in rats with suppressed testosterone. Male Wistar rats underwent bilateral orchidectomy one week before the ligation of the anterior descending left coronary artery. The animals were divided into orchidectomized (OCT); MI; orchidectomized + MI (OCT + MI); orchidectomized + MI + testosterone (OCT + MI + T) and control (Sham) groups...
June 9, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28600997/genistein-alleviates-anxiety-like-behaviors-in-post-traumatic-stress-disorder-model-through-enhancing-serotonergic-transmission-in-the-amygdala
#13
Zhong-Min Wu, Gui-Lian Ni, Ai-Min Shao, Rong Cui
Post-traumatic stress disorder (PTSD) is a chronic psychiatric disorder, characterized by intense fear, and increased arousal and avoidance of traumatic events. The current available treatments for PTSD have limited therapeutic value. Genistein, a natural isoflavone, modulates a variety of cell functions. In this study, we tested anti-anxiety activity and underlying mechanisms of genistein in a PTSD rat model. The rats were trained to associate a tone with foot shock delivery on day 0, then fear conditioning was performed on day 7, 14 and 21...
June 2, 2017: Psychiatry Research
https://www.readbyqxmd.com/read/28593193/differential-expression-and-cell-type-specificity-of-perineuronal-nets-in-hippocampus-medial-entorhinal-cortex-and-visual-cortex-examined-in-the-rat-and-mouse
#14
Kristian Kinden Lensjø, Ane Charlotte Christensen, Simen Tennøe, Marianne Fyhn, Torkel Hafting
Perineuronal nets (PNNs) are specialized extracellular matrix (ECM) structures that condense around the soma and proximal dendrites of subpopulations of neurons. Emerging evidence suggests that they are involved in regulating brain plasticity. However, the expression of PNNs varies between and within brain areas. A lack of quantitative studies describing the distribution and cell-specificity of PNNs makes it difficult to reveal the functional roles of PNNs. In the current study, we examine the distribution of PNNs and the identity of PNN-enwrapped neurons in three brain areas with different cognitive functions: the dorsal hippocampus, medial entorhinal cortex (mEC) and primary visual cortex (V1)...
May 2017: ENeuro
https://www.readbyqxmd.com/read/28592272/betaine-promotes-cell-differentiation-of-human-osteoblasts-in-primary-culture
#15
Isabella Villa, Pamela Senesi, Anna Montesano, Anita Ferraretto, Fernanda Vacante, Alice Spinello, Michela Bottani, Simona Bolamperti, Alessandro Rubinacci, Livio Luzi, Ileana Terruzzi
BACKGROUND: Betaine (BET), a component of many foods, is an essential osmolyte and a source of methyl groups; it also shows an antioxidant activity. Moreover, BET stimulates muscle differentiation via insulin like growth factor I (IGF-I). The processes of myogenesis and osteogenesis involve common mechanisms with skeletal muscle cells and osteoblasts sharing the same precursor. Therefore, we have hypothesized that BET might be effective on osteoblast cell differentiation. METHODS: The effect of BET was tested in human osteoblasts (hObs) derived from trabecular bone samples obtained from waste material of orthopedic surgery...
June 7, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28591834/cholinergic-grb2-associated-binding-protein-1-regulates-cognitive-function
#16
Nan-Nan Lu, Chao Tan, Ning-He Sun, Ling-Xiao Shao, Xiu-Xiu Liu, Yin-Ping Gao, Rong-Rong Tao, Quan Jiang, Cheng-Kun Wang, Ji-Yun Huang, Kui Zhao, Guang-Fa Wang, Zhi-Rong Liu, Kohji Fukunaga, Ying-Mei Lu, Feng Han
Grb2-associated-binding protein 1 (Gab1) is a docking/scaffolding molecule known to play an important role in cell growth and survival. Here, we report that Gab1 is decreased in cholinergic neurons in Alzheimer's disease (AD) patients and in a mouse model of AD. In mice, selective ablation of Gab1 in cholinergic neurons in the medial septum impaired learning and memory and hippocampal long-term potentiation. Gab1 ablation also inhibited SK channels, leading to an increase in firing in septal cholinergic neurons...
June 7, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28589927/the-camkii-holoenzyme-structure-in-activation-competent-conformations
#17
Janette B Myers, Vincent Zaegel, Steven J Coultrap, Adam P Miller, K Ulrich Bayer, Steve L Reichow
The Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) assembles into large 12-meric holoenzymes, which is thought to enable regulatory processes required for synaptic plasticity underlying learning, memory and cognition. Here we used single particle electron microscopy (EM) to determine a pseudoatomic model of the CaMKIIα holoenzyme in an extended and activation-competent conformation. The holoenzyme is organized by a rigid central hub complex, while positioning of the kinase domains is highly flexible, revealing dynamic holoenzymes ranging from 15-35 nm in diameter...
June 7, 2017: Nature Communications
https://www.readbyqxmd.com/read/28587781/wnt5a-induces-catabolic-signaling-and-matrix-metalloproteinase-production-in-human-articular-chondrocytes
#18
G Huang, S Chubinskaya, W Liao, R F Loeser
OBJECTIVE: Aberrant Wnt signaling may contribute to osteoarthritis (OA) but the Wnt family members involved have not been fully identified. The purpose of this study was to investigate the role of Wnt5a as a potential mediator of cartilage destruction in OA. DESIGN: Immunohistochemistry to detect Wnt5a was performed using normal and OA human articular cartilage. Cultured normal human chondrocytes were treated with fibronectin fragments (FN-f) as a catabolic stimulus or recombinant Wnt5a protein with or without pretreatment using a panel of signaling inhibitors...
June 3, 2017: Osteoarthritis and Cartilage
https://www.readbyqxmd.com/read/28586109/fyn-kinase-mediates-cortical-actin-ring-depolymerization-required-for-mast-cell-migration-in-response-to-tgf-%C3%AE-in-mice
#19
Karla A Ramírez-Valadez, Genaro Vázquez-Victorio, Marina Macías-Silva, Claudia González-Espinosa
Transforming Growth Factor-β (TGF-β) is a potent mast cell (MC) chemoattractant able to modulate local inflammatory reactions. The molecular mechanism leading to TGF-β-directed MC migration is not fully described. Here we analyzed the role of the Src family protein kinase Fyn on the main TGF-β-induced cytoskeletal changes leading to MC migration. Utilizing bone marrow-derived mast cells (BMMCs) from WT and Fyn-deficient mice we found that BMMC migration to TGF-β was impaired in the absence of the kinase...
June 6, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28573491/p2x7-receptor-large-pore-signaling-in-avian-m%C3%A3-ller-glial-cells
#20
Robson X Faria, Hercules R Freitas, Ricardo A M Reis
ATP is a pleiotropic molecule that promotes extra- and intracellular signaling to regulate numerous functions. This nucleotide activates purine and pyrimidine receptors at the plasma membrane, categorized as ionotropic P2X or G-protein-coupled receptor (GPCR) P2Y receptors. P2X are ligand-gated ion channel receptors, expressed in both retinal neurons and Müller cells leading to neuron-glia communication, calcium waves and neurovascular coupling. However, how P2X pore is formed upon ATP activation and how signaling pathways regulates the complex is still a matter of controversy...
June 1, 2017: Journal of Bioenergetics and Biomembranes
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