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https://www.readbyqxmd.com/read/28431243/cryo-em-structure-of-the-open-human-ether-%C3%A3-go-go-related-k-channel-herg
#1
Weiwei Wang, Roderick MacKinnon
The human ether-à-go-go-related potassium channel (hERG, Kv11.1) is a voltage-dependent channel known for its role in repolarizing the cardiac action potential. hERG alteration by mutation or pharmacological inhibition produces Long QT syndrome and the lethal cardiac arrhythmia torsade de pointes. We have determined the molecular structure of hERG to 3.8 Å using cryo-electron microscopy. In this structure, the voltage sensors adopt a depolarized conformation, and the pore is open. The central cavity has an atypically small central volume surrounded by four deep hydrophobic pockets, which may explain hERG's unusual sensitivity to many drugs...
April 20, 2017: Cell
https://www.readbyqxmd.com/read/28429885/intravenous-self-administration-of-benzydamine-a-non-steroidal-anti-inflammatory-drug-with-a-central-cannabinoidergic-mechanism-of-action
#2
Riccardo Avvisati, Maria Meringolo, Emiliana Stendardo, Elisa Malavasi, Silvia Marinelli, Aldo Badiani
Benzydamine (BZY) is a non-steroidal anti-inflammatory drug used for the topical treatment of inflammations of the oral and vaginal mucosae. Virtually nothing is known about the central pharmacological actions of BZY. Yet there are reports of voluntary systemic overdosage of BZY in drug addicts, resulting in a euphoric, hallucinatory state. In the present study, we investigated the reinforcing properties of BZY in a rat self-administration paradigm. We found that BZY has a powerful reinforcing effect and that this effect is greatly facilitated in animals that already had substance experience, having previously self-administered heroin and cocaine, indicating cross sensitization between BZY and other common drugs of abuse...
April 21, 2017: Addiction Biology
https://www.readbyqxmd.com/read/28429878/a-systematic-review-of-ultrasound-imaging-as-a-tool-for-evaluating-haemophilic-arthropathy-in-children-and-adults
#3
REVIEW
C C Ligocki, A Abadeh, K C Wang, T Adams-Webber, V S Blanchette, A S Doria
The purpose of this study was to semi-quantitatively assess the evidence on the value of ultrasound (US) for assessment of haemophilic arthropathy (HA) in children and adults based on the following questions: (1) Does early diagnosis of pathological findings, using available US techniques, impact the functional status of the joint? (2) Do current available US techniques have the ability to accurately detect pathological changes in target joints in haemophilic patients? (3) Does treatment (prophylaxis) improve US evidence of haemophilic arthropathy in children and adults? (4) Is there any association between various US scoring systems and other clinical/radiological constructs? Of the 6880 citations identified searching databases such as MEDLINE, Embase, CENTRAL and Web of Science, 20 articles investigating either the diagnostic accuracy of US and/or US scanning protocols and scoring systems for assessment of HA met the inclusion criteria for the study...
April 21, 2017: Haemophilia: the Official Journal of the World Federation of Hemophilia
https://www.readbyqxmd.com/read/28429383/altered-eigenvector-centrality-is-related-to-local-resting-state-network-functional-connectivity-in-patients-with-longstanding-type-1-diabetes-mellitus
#4
Eelco van Duinkerken, Menno M Schoonheim, Richard G IJzerman, Annette C Moll, Jesus Landeira-Fernandez, Martin Klein, Michaela Diamant, Frank J Snoek, Frederik Barkhof, Alle-Meije Wink
INTRODUCTION: Longstanding type 1 diabetes (T1DM) is associated with microangiopathy and poorer cognition. In the brain, T1DM is related to increased functional resting-state network (RSN) connectivity in patients without, which was decreased in patients with clinically evident microangiopathy. Subcortical structure seems affected in both patient groups. How these localized alterations affect the hierarchy of the functional network in T1DM is unknown. Eigenvector centrality mapping (ECM) and degree centrality are graph theoretical methods that allow determining the relative importance (ECM) and connectedness (degree centrality) of regions within the whole-brain network hierarchy...
April 21, 2017: Human Brain Mapping
https://www.readbyqxmd.com/read/28429110/inhibition-of-the-crf1-receptor-influences-the-activity-of-antidepressant-drugs-in-the-forced-swim-test-in-rats
#5
Andrzej Wróbel, Anna Serefko, Aleksandra Szopa, Karol Rojek, Ewa Poleszak, Krystyna Skalicka-Woźniak, Jarosław Dudka
Hyperactivity of the hypothalamic-pituitary-adrenal axis (HPA) and impairment of the central corticotropin-releasing factor (CRF) system are factors in the pathogenesis of depression. Though several antagonists of the CRF1 receptor were effective in the recognized behavioral tests for antidepressant activity, there is still little information on the potential interactions between CRF1 receptor inhibitors and conventional antidepressant therapy. The aim of our study was to assess the influence of SN003, a CRF1 receptor blocker, on the activity of imipramine and fluoxetine in the forced swim test (FST) in rats which presented some signs of depression...
April 20, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/28428739/high-salt-intake-augments-excitability-of-pvn-neurons-in-rats-role-of-the-endoplasmic-reticulum-ca-2-store
#6
Robert A Larson, Andrew D Chapp, Le Gui, Michael J Huber, Zixi Jack Cheng, Zhiying Shan, Qing-Hui Chen
High salt (HS) intake sensitizes central autonomic circuitry leading to sympathoexcitation. However, its underlying mechanisms are not fully understood. We hypothesized that inhibition of PVN endoplasmic reticulum (ER) Ca(2+) store function would augment PVN neuronal excitability and sympathetic nerve activity (SNA). We further hypothesized that a 2% (NaCl) HS diet for 5 weeks would reduce ER Ca(2+) store function and increase excitability of PVN neurons with axon projections to the rostral ventrolateral medulla (PVN-RVLM) identified by retrograde label...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28427400/monitoring-mandibular-movements-to-detect-cheyne-stokes-breathing
#7
Jean-Benoît Martinot, Jean-Christian Borel, Nhat-Nam Le-Dong, Hervé Jean-Pierre Guénard, Valerie Cuthbert, Philip E Silkoff, David Gozal, Jean-Louis Pepin
BACKGROUND: The patterns of mandibular movements (MM) during sleep can be used to identify increased respiratory effort periodic large-amplitude MM (LPM), and cortical arousals associated with "sharp" large-amplitude MM (SPM). We hypothesized that Cheyne Stokes breathing (CSB) may be identified by periodic abnormal MM patterns. The present study aims to evaluate prospectively the concordance between CSB detected by periodic MM and polysomnography (PSG) as gold-standard. The present study aims to evaluate prospectively the concordance between CSB detected by periodic MM and polysomnography (PSG) as gold-standard...
April 20, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28427368/complications-of-miliary-tuberculosis-low-mortality-and-predictive-biomarkers-from-a-uk-cohort
#8
Jonathan Underwood, Fiona Cresswell, Alex P Salam, Alex J Keeley, Charles Cleland, Laurence John, Robert N Davidson
BACKGROUND: Untreated, miliary tuberculosis (TB) has a mortality approaching 100%. As it is uncommon there is little specific data to guide its management. We report detailed data from a UK cohort of patients with miliary tuberculosis and the associations and predictive ability of admission blood tests with clinical outcomes. METHODS: Routinely collected demographic, clinical, blood, imaging, histopathological and microbiological data were assessed for all patients with miliary TB identified from the London TB register from 2008 to 2012 from Northwest London Hospitals NHS Trust...
April 20, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28426945/testosterone-levels-in-healthy-men-correlate-negatively-with-serotonin-4-receptor-binding
#9
Erik Perfalk, Sofi da Cunha-Bang, Klaus K Holst, Sune Keller, Claus Svarer, Gitte M Knudsen, Vibe G Frokjaer
The serotonergic system integrates sex steroid information and plays a central role in mood and stress regulation, cognition, appetite and sleep. This interplay may be critical for likelihood of developing depressive episodes, at least in a subgroup of sensitive individuals. The serotonin 4 receptor (5-HT4R) indexes central serotonergic tonus, which may be related to endogenous sex-steroid levels in the mentally healthy state even though this remains elusive. Here we evaluate if peripheral levels of estradiol and testosterone are associated with 5-HT4R binding as imaged by [(11)C]SB207145 positron emission tomography in a group of 41 healthy men...
March 22, 2017: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/28426228/ultrafast-dynamics-of-a-triazene-excited-state-pathways-and-the-impact-of-binding-to-the-minor-groove-of-dna-and-further-biomolecular-systems
#10
Lena Grimmelsmann, Alireza Marefat Khah, Christian Spies, Christof Hättig, Patrick Nuernberger
Many synthetic DNA minor groove binders exhibit a strong increase in fluorescence when bound to DNA. The pharmaceutical-relevant berenil (diminazene aceturate) is an exception with an extremely low fluorescence quantum yield (on the order of 10(-4)). We investigate the ultrafast excited-state dynamics of this triazene by femtosecond time-resolved fluorescence experiments in water, ethylene glycol, and buffer and bound to the enzyme β-trypsin, the minor groove of AT-rich DNA, and G-quadruplex DNA. Ab initio calculations provide additional mechanistic insight...
April 20, 2017: Journal of Physical Chemistry Letters
https://www.readbyqxmd.com/read/28424988/overcoming-chemotherapy-drug-resistance-by-targeting-inhibitors-of-apoptosis-proteins-iaps
#11
REVIEW
Rama Rathore, Jennifer E McCallum, Elizabeth Varghese, Ana-Maria Florea, Dietrich Büsselberg
Inhibitors of apoptosis (IAPs) are a family of proteins that play a significant role in the control of programmed cell death (PCD). PCD is essential to maintain healthy cell turnover within tissue but also to fight disease or infection. Uninhibited, IAPs can suppress apoptosis and promote cell cycle progression. Therefore, it is unsurprising that cancer cells demonstrate significantly elevated expression levels of IAPs, resulting in improved cell survival, enhanced tumor growth and subsequent metastasis. Therapies to target IAPs in cancer has garnered substantial scientific interest and as resistance to anti-cancer agents becomes more prevalent, targeting IAPs has become an increasingly attractive strategy to re-sensitize cancer cells to chemotherapies, antibody based-therapies and TRAIL therapy...
April 19, 2017: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/28424823/-coma-in-the-emergency-room
#12
M Braun, C J Ploner, T Lindner, M Möckel, W U Schmidt
Coma of unknown origin (CUO) is a frequent unspecific emergency symptom associated with a high mortality. A fast diagnostic work-up is essential given the wide spectrum of underlying diagnoses that are made up of approximately 50% primary central nervous system (CNS) pathologies and approximately 50% extracerebral, almost exclusively internal medical causes. Despite the high mortality associated with this symptom, there are currently no generally accepted management guidelines for adult patients presenting with CUO...
April 19, 2017: Der Nervenarzt
https://www.readbyqxmd.com/read/28424788/fully-automated-robust-system-to-detect-retinal-edema-central-serous-chorioretinopathy-and-age-related-macular-degeneration-from-optical-coherence-tomography-images
#13
Samina Khalid, M Usman Akram, Taimur Hassan, Ammara Nasim, Amina Jameel
Maculopathy is the excessive damage to macula that leads to blindness. It mostly occurs due to retinal edema (RE), central serous chorioretinopathy (CSCR), or age related macular degeneration (ARMD). Optical coherence tomography (OCT) imaging is the latest eye testing technique that can detect these syndromes in early stages. Many researchers have used OCT images to detect retinal abnormalities. However, to the best of our knowledge, no research that presents a fully automated system to detect all of these macular syndromes is reported...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28424512/human-umbilical-cord-plasma-proteins-revitalize-hippocampal-function-in-aged-mice
#14
Joseph M Castellano, Kira I Mosher, Rachelle J Abbey, Alisha A McBride, Michelle L James, Daniela Berdnik, Jadon C Shen, Bende Zou, Xinmin S Xie, Martha Tingle, Izumi V Hinkson, Martin S Angst, Tony Wyss-Coray
Ageing drives changes in neuronal and cognitive function, the decline of which is a major feature of many neurological disorders. The hippocampus, a brain region subserving roles of spatial and episodic memory and learning, is sensitive to the detrimental effects of ageing at morphological and molecular levels. With advancing age, synapses in various hippocampal subfields exhibit impaired long-term potentiation, an electrophysiological correlate of learning and memory. At the molecular level, immediate early genes are among the synaptic plasticity genes that are both induced by long-term potentiation and downregulated in the aged brain...
April 19, 2017: Nature
https://www.readbyqxmd.com/read/28424165/suppression-of-b-cell-development-genes-is-key-to-glucocorticoid-efficacy-in-treatment-of-acute-lymphoblastic-leukemia
#15
Karina Kruth, Mimi Fang, Dawne N Shelton, Ossama Abu-Halawa, Ryan Mahling, Hongxing Yang, Jonathan S Weissman, Mignon L Loh, Markus Müschen, Sarah K Tasian, Michael C Bassik, Martin Kampmann, Miles A Pufall
Glucocorticoids (GCs), including dexamethasone (dex), are a central component of combination chemotherapy for childhood B-cell precursor acute lymphoblastic leukemia (B-ALL). GCs work by activating the glucocorticoid receptor (GR), a ligand-induced transcription factor, which in turn regulates genes that induce leukemic cell death. Which GR-regulated genes are required for GC cytotoxicity, which pathways affect their regulation, and how resistance arises are not well understood. Here we systematically integrate the transcriptional response of B-ALL to GCs with a next-generation shRNA screen to identify GC-regulated "effector" genes that contribute to cell death as well as genes that affect the sensitivity of B-ALL cells to dex...
April 19, 2017: Blood
https://www.readbyqxmd.com/read/28423675/mir-219-5p-targets-camkii%C3%AE-to-attenuate-morphine-tolerance-in-rats
#16
Jian Wang, Wei Xu, Jiali Shao, Zhenghua He, Zhuofeng Ding, Jiangju Huang, Qulian Guo, Wangyuan Zou
Morphine tolerance is a clinical challenge in pain management. Emerging evidence suggests that microRNA (miRNA) plays a regulatory role in the development of morphine tolerance. miR-219-5p (miR-219) targets calmodulin-dependent protein kinase II γ (CaMKIIγ) to activate central pain sensitization via N-methyl-D-aspartate (NMDA) receptor. Therefore, we hypothesized that miR-219-5p attenuates morphine tolerance by targeting CaMKIIγ. We found that the expression of miR-219-5p was decreased significantly after chronic morphine treatment...
March 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423406/the-rise-of-radiomics-and-implications-for-oncologic-management
#17
Vivek Verma, Charles B Simone, Sunil Krishnan, Steven H Lin, Jinzhong Yang, Stephen M Hahn
Clinical medicine, particularly oncology, is progressing toward personalized care. Whereas the terms genomics, proteomics, transcriptomics, and metabolomics have dominated personalized medicine for the past couple decades, the concept of radiomics was first described in 2012. This nascent concept has major implications for personalized cancer care and involves extracting hundreds of standardized and quantifiable imaging characteristics from diagnostic computed tomography/magnetic resonance imaging images. The central hypothesis of radiomics is that these libraries of quantitative individual voxel-based variables are more sensitively associated with various clinical endpoints compared with the more qualitative radiologic, histopathologic, and clinical data more commonly utilized today...
July 1, 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28422829/impact-of-pain-on-cognitive-functions-in-primary-sj%C3%A3-gren-syndrome-with-small-fiber-neuropathy-10-cases-and-a-literature-review
#18
Sandrine Indart, Jacques Hugon, Pierre Jean Guillausseau, Alice Gilbert, Julien Dumurgier, Claire Paquet, Damien Sène
Primary Sjögren syndrome (pSS) is a chronic systemic autoimmune disease characterized by xerophthalmia, xerostomia, and potential peripheral or central neurological involvement. In pSS, the prevalence of cognitive disorders is generally sparse across literature and the impact of pain on cognitive profile is unclear. The aim of this study was to determine the relation between pain, cognitive complaint, and impairment in a very homogenous population of 10 pSS patients with painful small fiber neuropathy (PSFN) and spontaneous cognitive complaint...
April 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28422746/integrating-nanohybrid-membranes-of-reduced-graphene-oxide-chitosan-silica-sol-gel-with-fiber-optic-spr-for-caffeine-detection
#19
Ravi Kant, Rana Tabassum, Banshi D Gupta
Caffeine is the most popular psychoactive drug consumed in the world for improving alertness and enhancing wakefulness. However, caffeine consumption beyond limits can result in lot of physiological complications in human beings. In this work, we report a novel detection scheme for caffeine integrating nanohybrid membranes of reduced graphene oxide (rGO) in chitosan modified silica sol gel (rGO: chitosan: silica sol gel) with fiber optic surface plasmon resonance. The chemically synthesized nanohybrid membrane forming the sensing route has been dip coated over silver coated unclad central portion of an optical fiber...
May 12, 2017: Nanotechnology
https://www.readbyqxmd.com/read/28422478/reduction-of-ammineruthenium-iii-by-sulfide-enables-in-vivo-electrochemical-monitoring-of-free-endogenous-hydrogen-sulfide
#20
Shujun Wang, Xiaomeng Liu, Meining Zhang
The discovery of endogenous sulfide in mammalian brain opens up a door to understanding of the physiological function of hydrogen sulfide (H2S). The transformation of different forms of sulfide (i.e., S2-, HS-, H2S, bound sulfane sulfur, et al.) in various physiological conditions hurdles the direct detection of hydrogen sulfide in vivo. Here, we find that ammineruthenium (III) (Ru(NH3)63+) can catalyze the electrochemical oxidation of free sulfide including HS- and H2S in a neutral solution (pH 7.4). This property is used to constitute an electrochemical mechanism for selective detection of hydrogen sulfide...
April 19, 2017: Analytical Chemistry
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