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https://www.readbyqxmd.com/read/27911343/pink1-parkin-and-mitochondrial-quality-control-what-can-we-learn-about-parkinson-s-disease-pathobiology
#1
Dominika Truban, Xu Hou, Thomas R Caulfield, Fabienne C Fiesel, Wolfdieter Springer
The first clinical description of Parkinson's disease (PD) will embrace its two century anniversary in 2017. For the past 30 years, mitochondrial dysfunction has been hypothesized to play a central role in the pathobiology of this devastating neurodegenerative disease. The identifications of mutations in genes encoding PINK1 (PTEN-induced kinase 1) and Parkin (E3 ubiquitin ligase) in familial PD and their functional association with mitochondrial quality control provided further support to this hypothesis. Recent research focused mainly on their key involvement in the clearance of damaged mitochondria, a process known as mitophagy...
November 30, 2016: Journal of Parkinson's Disease
https://www.readbyqxmd.com/read/27911148/effects-of-chronic-estrogen-administration-in-the-ventromedial-nucleus-of-the-hypothalamus-vmh-on-fat-and-bone-metabolism-in-ovariectomized-rats
#2
Z Zhang, J Liu, A G Veldhuis-Vlug, Y Su, E Foppen, B C J van der Eerden, M Koedam, N Bravenboer, A Kalsbeek, A Boelen, E Fliers, P H Bisschop
Estrogen deficiency after ovariectomy (OVX) results in increased adiposity and bone loss, which can be prevented by systemic 17-β estradiol (E2) replacement. Studies in transgenic mice suggested that in addition to direct actions of estrogen in peripheral tissues, also estrogen signaling in the hypothalamus regulates fat distribution and bone metabolism. We hypothesized that the protective effect of systemic E2 on fat and bone metabolism in the OVX model is partly mediated through the ventromedial nucleus of the hypothalamus (VMH)...
December 2016: Endocrinology
https://www.readbyqxmd.com/read/27910913/loss-of-egfr-asap1-signaling-in-metastatic-and-unresectable-hepatoblastoma
#3
Sarangarajan Ranganathan, Mylarappa Ningappa, Chethan Ashokkumar, Brandon W Higgs, Jun Min, Qing Sun, Lori Schmitt, Shankar Subramaniam, Hakon Hakonarson, Rakesh Sindhi
Hepatoblastoma (HBL), the most common childhood liver cancer is cured with surgical resection after chemotherapy or with liver transplantation if local invasion and multifocality preclude resection. However, variable survival rates of 60-80% and debilitating chemotherapy sequelae argue for more informed treatment selection, which is not possible by grading the Wnt-β-catenin over activity present in most HBL tumors. A hypothesis-generating whole transcriptome analysis shows that HBL tumors removed at transplantation are enriched most for cancer signaling pathways which depend predominantly on epidermal growth factor (EGF) signaling, and to a lesser extent, on aberrant Wnt-β-catenin signaling...
December 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27909006/a-neural-mechanism-for-surprise-related-interruptions-of-visuospatial-working-memory
#4
Jan R Wessel
Surprising perceptual events recruit a fronto-basal ganglia mechanism for inhibition, which suppresses motor activity following surprise. A recent study found that this inhibitory mechanism also disrupts the maintenance of verbal working memory (WM) after surprising tones. However, it is unclear whether this same mechanism also relates to surprise-related interruptions of non-verbal WM. We tested this hypothesis using a change-detection task, in which surprising tones impaired visuospatial WM. Participants also performed a stop-signal task (SST)...
November 30, 2016: Cerebral Cortex
https://www.readbyqxmd.com/read/27908665/diffuse-resistance-courtship-in-the-scorpion-rhopalurus-rochai-scorpiones-buthidae
#5
Shayanne Chantall-Rocha, Hilton F Japyassú
Male-female courtship signals are frequently subject to arms races, with patterns of behaviour evolving reciprocally to manipulate the reproductive output. Female resistance should be particularly effective when asymmetrical offspring care occurs under low and unpredictable resource distribution, because this would increase maternal costs. Our hypothesis is that under these conditions females will evolve diffuse mating strategies to avoid predictable exploitation by male optimal counter tactics. Mating in scorpions is a complex process, and female resistance occurs through specific behaviours...
November 28, 2016: Behavioural Processes
https://www.readbyqxmd.com/read/27908068/perception-of-music-dynamics-in-concert-hall-acoustics
#6
Jukka Pätynen, Tapio Lokki
Dynamics is one of the principal means of expressivity in Western classical music. Still, preceding research on room acoustics has mostly neglected the contribution of music dynamics to the acoustic perception. This study investigates how the different concert hall acoustics influence the perception of varying music dynamics. An anechoic orchestra signal, containing a step in music dynamics, was rendered in the measured acoustics of six concert halls at three seats in each. Spatial sound was reproduced through a loudspeaker array...
November 2016: Journal of the Acoustical Society of America
https://www.readbyqxmd.com/read/27907088/silver-nanoparticle-directed-mast-cell-degranulation-is-mediated-through-calcium-and-pi3k-signaling-independent-of-the-high-affinity-ige-receptor
#7
Nasser B Alsaleh, Indushekhar Persaud, Jared M Brown
Engineered nanomaterial (ENM)-mediated toxicity often involves triggering immune responses. Mast cells can regulate both innate and adaptive immune responses and are key effectors in allergic diseases and inflammation. Silver nanoparticles (AgNPs) are one of the most prevalent nanomaterials used in consumer products due to their antimicrobial properties. We have previously shown that AgNPs induce mast cell degranulation that was dependent on nanoparticle physicochemical properties. Furthermore, we identified a role for scavenger receptor B1 (SR-B1) in AgNP-mediated mast cell degranulation...
2016: PloS One
https://www.readbyqxmd.com/read/27906555/ligand-biased-regulation-of-ptdins-3-4-5-p3-dependent-signal-transduction-in-gpcr-control-of-pituitary-hormone-release
#8
Joshua G Pemberton, John P Chang
Biased signaling describes the selective activation of signal transduction cascades by structurally-related ligands downstream of shared G protein-coupled receptors (GPCRs). Although class I phosphoinositide 3-kinases (PI3Ks) are important components of GPCR-controlled transduction networks, little is known regarding the potential for biased regulation of class I PI3K-dependent signaling. The full compliment of class I PI3K catalytic subunits (p110α, p110β, p110δ and p110γ) first appear in bony fishes and, despite being associated with distinct cellular functions, all class I PI3Ks produce the lipid second-messenger phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3)...
December 1, 2016: Endocrinology
https://www.readbyqxmd.com/read/27906090/muscle-specific-deletion-of-socs3-increases-the-early-inflammatory-response-but-does-not-affect-regeneration-after-myotoxic-injury
#9
Kristy Swiderski, Savant S Thakur, Timur Naim, Jennifer Trieu, Annabel Chee, David I Stapleton, René Koopman, Gordon S Lynch
BACKGROUND: Muscles of old animals are injured more easily and regenerate poorly, attributed in part to increased levels of circulating pro-inflammatory cytokines. The Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling cascade is a key mediator of inflammatory cytokine action, and signaling via this pathway is increased in muscles with aging. As a negative regulator of JAK/STAT signaling, a key mediator of myogenic proliferation and differentiation, altered expression of suppressor of cytokine signaling (SOCS3) is likely to have important consequences for muscle regeneration...
October 24, 2016: Skeletal Muscle
https://www.readbyqxmd.com/read/27906033/the-role-of-the-backbone-torsion-in-protein-folding
#10
EDITORIAL
Irina Sorokina, Arcady Mushegian
BACKGROUND: The set of forces and sequence of events that govern the transition from an unfolded polypeptide chain to a functional protein with correct spatial structure remain incompletely known, despite the importance of the problem and decades of theory development, computer simulations, and laboratory experiments. Information about the correctly folded state of most proteins is likely to be present in their sequences, and yet many proteins fail to attain native structure after overexpression in a non-native environment or upon experimental denaturation and refolding...
December 1, 2016: Biology Direct
https://www.readbyqxmd.com/read/27904994/rapamycin-protects-sepsis-induced-cognitive-impairment-in-mouse-hippocampus-by-enhancing-autophagy
#11
Wenyu Liu, Jia'nan Guo, Jie Mu, Linyu Tian, Dong Zhou
The purpose of this study is to test the hypothesis that the mammalian target of rapamycin (mTOR) signaling pathway might mediate neuroprotection in a mouse model of septic encephalopathy and also to identify the role of autophagy. Mice were subjected to cecal ligation and puncture (CLP) or a sham operation, and all 50 mice were randomly assigned to five groups: sham, CLP+ saline, CLP+ rapamycin (1, 5, 10 mg/kg) groups. Two weeks after the operation, Morris water maze was conducted for behavioral test; Nissl staining was used for observing glia infiltration; immunohistochemical staining and biochemical measures in hippocampi were performed to detect mTOR targets and autophagy indicators...
December 1, 2016: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/27904901/effect-of-ticagrelor-on-endothelial-calcium-signalling-and-barrier-function
#12
Dursun Gündüz, Christian Tanislav, Klaus-Dieter Schlüter, Rainer Schulz, Christian Hamm, Muhammad Aslam
The P2Y12 receptor is a Gi-coupled receptor whose activation inhibits adenylyl cyclase and thereby reduces the concentration of intracellular cAMP. Here the hypothesis was tested whether AR-C 66096 or ticagrelor, two direct-acting and reversibly binding P2Y12 receptor antagonists, protect endothelial cell (EC) barrier function by raising intracellular cAMP in ECs. The study was carried out on primary human umbilical vein ECs (HUVECs) and human pulmonary microvascular ECs (hPMECs). AR-C66096 (10 µM) induced a 50 % increase in cAMP in ECs whereas ticagrelor (2-10 µM) had no effect...
December 1, 2016: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/27904493/beta-2-adrenergic-receptor-activation-enhances-neurogenesis-in-alzheimer-s-disease-mice
#13
Gao-Shang Chai, Yang-Yang Wang, Amina Yasheng, Peng Zhao
Impaired hippocampal neurogenesis is one of the early pathological features of Alzheimer's disease. Enhancing adult hippocampal neurogenesis has been pursued as a potential therapeutic strategy for Alzheimer's disease. Recent studies have demonstrated that environmental novelty activates β2-adrenergic signaling and prevents the memory impairment induced by amyloid-β oligomers. Here, we hypothesized that β2-adrenoceptor activation would enhance neurogenesis and ameliorate memory deficits in Alzheimer's disease...
October 2016: Neural Regeneration Research
https://www.readbyqxmd.com/read/27903921/a-two-pool-model-to-describe-the-ivim-cerebral-perfusion
#14
Gabrielle Fournet, Jing-Rebecca Li, Alex M Cerjanic, Bradley P Sutton, Luisa Ciobanu, Denis Le Bihan
IntraVoxel Incoherent Motion (IVIM) is a magnetic resonance imaging (MRI) technique capable of measuring perfusion-related parameters. In this manuscript, we show that the mono-exponential model commonly used to process IVIM data might be challenged, especially at short diffusion times. Eleven rat datasets were acquired at 7T using a diffusion-weighted pulsed gradient spin echo sequence with b-values ranging from 7 to 2500 s/mm(2) at three diffusion times. The IVIM signals, obtained by removing the diffusion component from the raw MR signal, were fitted to the standard mono-exponential model, a bi-exponential model and the Kennan model...
November 30, 2016: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/27903597/impact-of-organic-cation-transporters-oct-slc22a-on-differential-diagnosis-of-intrahepatic-lesions
#15
Michele Visentin, Belle V van Rosmalen, Christian Hiller, Matthanja Bieze, Lia Hofstetter, Joanne Verheij, Gerd A Kullak-Ublick, Hermann Koepsell, Saffire Sks Phoa, Ikumi Tamai, Roelof J Bennink, Thomas M van Gulik, Bruno Stieger
Positron emission tomography (PET) using the cationic compound [(18)F]fluoromethylcholine (FCH) enhances the sensitivity for non-invasive classification of hepatic tumours due to peculiar patterns of accumulation. The underlying transporters are not known. We aim to identify the carriers mediating uptake of FCH in liver and to correlate their expression pattern with PET intrahepatic signal distribution to clarify the role of membrane transporters in FCH accumulation. FCH transport was characterized in cells overexpressing organic cation transporters (OCTs)...
November 30, 2016: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/27903123/drug-priming-enhances-radiosensitivity-of-adamantinomatous-craniopharyngioma-via-downregulation-of-survivin
#16
Christina Stache, Christiane Bils, Rudolf Fahlbusch, Jörg Flitsch, Michael Buchfelder, Harald Stefanits, Thomas Czech, Udo Gaipl, Benjamin Frey, Rolf Buslei, Annett Hölsken
OBJECTIVE In this study, the authors investigated the underlying mechanisms responsible for high tumor recurrence rates of adamantinomatous craniopharyngioma (ACP) after radiotherapy and developed new targeted treatment protocols to minimize recurrence. ACPs are characterized by the activation of the receptor tyrosine kinase epidermal growth factor receptor (EGFR), known to mediate radioresistance in various tumor entities. The impact of tyrosine kinase inhibitors (TKIs) gefitinib or CUDC-101 on radiation-induced cell death and associated regulation of survivin gene expression was evaluated...
December 2016: Neurosurgical Focus
https://www.readbyqxmd.com/read/27903008/brightness-in-human-rod-vision-depends-on-slow-neural-adaptation-to-quantum-statistics-of-light
#17
Michael E Rudd, Fred Rieke
In human rod-mediated vision, threshold for small, brief flashes rises in proportion to the square root of adapting luminance at all but the lowest and highest adapting intensities. A classical signal detection theory from Rose (1942, 1948) and de Vries (1943) attributed this rise to the perceptual masking of weak flashes by Poisson fluctuations in photon absorptions from the adapting field. However, previous work by Brown and Rudd (1998) demonstrated that the square-root law also holds for suprathreshold brightness judgments, a finding that supports an alternative explanation of the square-root sensitivity changes as a consequence of physiological adaptation (i...
November 1, 2016: Journal of Vision
https://www.readbyqxmd.com/read/27899518/variable-mr-and-pathologic-patterns-of-hemorrhage-after-iodinated-contrast-infusion-in-mca-occlusion-reperfusion-model
#18
Humberto Morales, Aigang Lu, Yuko Kurosawa, Joseph F Clark, Thomas Tomsick
OBJECTIVE: To examine the hypothesis that IA reperfusion with iso-osmolar iodixanol, low-osmolar iopamidol, or saline causes different effects on MR signal changes and pathologic cut-brain section related to hemorrhagic transformation (HT) or iodinated radiographic contrast media (IRCM) deposition. METHODS: Infarct was induced in 30 rats by middle cerebral artery suture occlusion. Reperfusion was performed after 5 hours with iso-osmolar iodixanol (n=9), low-osmolar iopamidol (n=12) or saline (n=9)...
November 29, 2016: Journal of Neurointerventional Surgery
https://www.readbyqxmd.com/read/27899483/integrin-linked-kinase-is-necessary-for-the-development-of-diet-induced-hepatic-insulin-resistance
#19
Ashley S Williams, Elijah Trefts, Louise Lantier, Carrie Grueter, Deanna P Bracy, Freyja D James, Ambra Pozzi, Roy Zent, David H Wasserman
The liver extracellular matrix (ECM) expands with high fat (HF) feeding. This finding led us to address whether receptors for the ECM, integrins, are key to the development of diet-induced hepatic insulin resistance. Integrin-linked kinase (ILK) is a downstream integrin signaling molecule involved in multiple hepatic processes including those related to differentiation, wound healing and metabolism. We tested the hypothesis that deletion of ILK in mice on a HF diet would disrupt the ECM-Integrin signaling axis thereby preventing the transformation into the insulin resistant liver...
November 29, 2016: Diabetes
https://www.readbyqxmd.com/read/27898753/-oncogen-dependent-regulation-of-the-migration-and-proliferation-of-human-tumor-cells
#20
Tamás M Garay
The high mortality of solid tumors can be attributed to their invasive and metastatic potential that is based on their migration and proliferation. Importantly, growth factor receptor (GF) signaling pathways regulating proliferation and migration are often affected by oncogenic mutations and are important targets for antitumor therapy. We found positive correlation between migration and proliferation in melanoma and lung cancer cells using videomicroscopy, not supporting the "go or grow" hypothesis. Furthermore, the invasion into collagen I matrices from brain tumor spheroids was not impaired upon the inhibition of proliferation...
November 29, 2016: Magyar Onkologia
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