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https://www.readbyqxmd.com/read/28647913/how-adaptation-makes-low-firing-rates-robust
#1
Arthur S Sherman, Joon Ha
Low frequency firing is modeled by Type 1 neurons with a SNIC, but, because of the vertical slope of the square-root-like f-I curve, low f only occurs over a narrow range of I. When an adaptive current is added, however, the f-I curve is linearized, and low f occurs robustly over a large I range. Ermentrout (Neural Comput. 10(7):1721-1729, 1998) showed that this feature of adaptation paradoxically arises from the SNIC that is responsible for the vertical slope. We show, using a simplified Hindmarsh-Rose neuron with negative feedback acting directly on the adaptation current, that whereas a SNIC contributes to linearization, in practice linearization over a large interval may require strong adaptation strength...
December 2017: Journal of Mathematical Neuroscience
https://www.readbyqxmd.com/read/28646789/data-mining-for-detecting-signals-of-adverse-drug-reactions-of-fluoxetine-using-the-korea-adverse-event-reporting-system-kaers-database
#2
Seonji Kim, Kyounghoon Park, Mi-Sook Kim, Bo Ram Yang, Hyun Jin Choi, Byung-Joo Park
Selective serotonin reuptake inhibitors (SSRIs) have become one of the most broadly used medications in psychiatry. Fluoxetine is the first representative antidepressant SSRI drug approved by the Food and Drug Administration (FDA) in 1987. Safety information on fluoxetine use alone was less reported than its combined use with other drugs. There were no published papers on adverse drug reactions (ADRs) of fluoxetine analyzing spontaneous adverse events reports. We detected signals of the adverse drug reactions of fluoxetine by data mining using the Korea Adverse Events Reporting System (KAERS) database...
June 13, 2017: Psychiatry Research
https://www.readbyqxmd.com/read/28646516/tofacitinib-restores-the-inhibition-of-reverse-cholesterol-transport-induced-by-inflammation-understanding-the-lipid-paradox-associated-with-rheumatoid-arthritis
#3
S Pérez-Baos, J I Barrasa, P Gratal, A Larrañaga-Vera, I Prieto-Potin, G Herrero-Beaumont, R Largo
BACKGROUND AND PURPOSE: Patients with active rheumatoid arthritis (RA) have increased cardiovascular mortality, paradoxically associated with reduced circulating lipid levels. The Janus kinase (Jak) inhibitor tofacitinib ameliorates systemic and joint inflammation in RA with a concomitant increase in serum lipids. We analyzed the effect of tofacitinib on the lipid profile of hyperlipidemic rabbits with chronic arthritis (CA) and on the regulation of reverse cholesterol transport (RCT) during chronic inflammation...
June 23, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28645859/discovery-of-a-novel-pan-raf-inhibitor-with-potent-anti-tumor-activity-in-preclinical-models-of-braf-v600e-mutant-cancer
#4
Sung Pyo Hong, Soon Kil Ahn
AIMS: BRAF mutations, especially BRAF V600E, are a frequent occurrence in malignant melanomas. The BRAF inhibitors are used as the care standard for BRAF-mutant metastatic melanomas. However, melanomas rapidly develop resistance to BRAF inhibitors after a median response duration of 6months, and the subsequent rapid development of cutaneous toxicity is enhanced by the paradoxical activation of CRAF. In this study, we discovered a potent and selective pan-RAF inhibitor: INU-152. The goal of this study was to investigate whether the inhibition of pan-RAF with INU-152 completely disrupts the MAPK pathway in cancer cells bearing BRAF or RAS mutations...
June 20, 2017: Life Sciences
https://www.readbyqxmd.com/read/28645226/the-fragile-spell-of-desire-a-functional-perspective-on-changes-in-sexual-desire-across-relationship-development
#5
Gurit E Birnbaum
The sexual behavioral system evolved to motivate reproductive acts by arousing sexual desire. Building on the idea that this system has also been "exploited" by evolutionary processes to promote enduring bonds between romantic partners, the present article introduces an integrative model that delineates the functional significance of sexual desire in relationship formation and maintenance. This model explains why individuals' sexual reaction to their partner is context-dependent, clarifying how changes in the nature of interdependence over the course of relationships alter the ways in which specific predictors of sexual desire tend to promote (or inhibit) desire and thereby affect relationship depth and stability...
June 1, 2017: Personality and Social Psychology Review
https://www.readbyqxmd.com/read/28644880/o-glcnacylation-mediates-the-control-of-cytosolic-phosphoenolpyruvate-carboxykinase-activity-via-pgc1%C3%AE
#6
Pedro Latorre, Luis Varona, Carmen Burgos, José A Carrodeguas, Pascual López-Buesa
PGC1α is a coactivator of many transcription factors and cytosolic phosphoenolpyruvate carboxykinase (PCK1) is a key enzyme for gluconeogenesis. PGC1α interacts with the transcription factor PPARγ to stimulate PCK1 expression and thus de novo glucose synthesis. These proteins are not only important for central energy metabolism but also for supplying intermediates for other metabolic pathways, including lipidogenesis and protein synthesis and might therefore be important factors in the ethiopathogenesis of metabolic disorders like diabetes but also in other pathologies like cancer...
2017: PloS One
https://www.readbyqxmd.com/read/28644617/dynamic-covalent-chemistry-of-carbon-dioxide-opportunities-to-address-environmental-issues
#7
Jean Septavaux, Geoffroy Germain, Julien Leclaire
Extraction and purification of basic chemicals from complex mixtures has been a persistent issue throughout the development of the chemical sciences. The chemical industry and academic research have grown over the centuries by following a deconstruction-reconstruction approach, reminiscent of the metabolism process. Chemists have designed and optimized extraction, purification, and transformation processes of molecules from natural deposits (fossil fuels, biomass, ores), in order to reassemble them into complex adducts...
June 23, 2017: Accounts of Chemical Research
https://www.readbyqxmd.com/read/28644074/reinforcing-marginality-maternal-health-interventions-in-rural-nicaragua
#8
Birgit Kvernflaten
To achieve Millennium Development Goal 5 on maternal health, many countries have focused on marginalized women who lack access to care. Promoting facility-based deliveries to ensure skilled birth attendance and emergency obstetric care has become a main measure for preventing maternal deaths, so women who opt for home births are often considered 'marginal' and in need of targeted intervention. Drawing upon ethnographic data from Nicaragua, this paper critically examines the concept of marginality in the context of official efforts to increase institutional delivery amongst the rural poor, and discusses lack of access to health services among women living in peripheral areas as a process of marginalization...
June 23, 2017: Anthropology & Medicine
https://www.readbyqxmd.com/read/28642299/dysfunctional-neutrophil-effector-organelle-mobilisation-and-microbicidal-protein-release-in-alcohol-related-cirrhosis
#9
Thomas Henry Tranah, Godhev K Manakkat Vijay, Jennifer M Ryan, Robin Daniel Abeles, Paul Kevin Middleton, Debbie Lindsay Shawcross
BACKGROUND AND AIMS: Patients with alcohol-related cirrhosis (ALD) are prone to infection. Circulating neutrophils in ALD are dysfunctional and predict development of sepsis, organ dysfunction and survival. Neutrophil granules are important effector organelles containing a toxic array of microbicidal proteins, whose controlled release is required to kill micro-organisms whilst minimising inflammation and damage to host tissue. We investigated the role of these granular responses in contributing to immune disarray in ALD...
June 22, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28641942/the-top1-paradox-friend-and-foe-of-the-eukaryotic-genome
#10
REVIEW
Nayun Kim, Sue Jinks-Robertson
Topoisomerases manage the torsional stress associated with the separation of DNA strands during transcription and DNA replication. Eukaryotic Topoisomerase I (Top1) is a Type IB enzyme that nicks and rejoins only one strand of duplex DNA, and it is especially important during transcription. By resolving transcription-associated torsional stress, Top1 reduces the accumulation of genome-destabilizing R-loops and non-B DNA structures. The DNA nicking activity of Top1, however, can also initiate genome instability in the form of illegitimate recombination, homologous recombination and mutagenesis...
June 9, 2017: DNA Repair
https://www.readbyqxmd.com/read/28641316/a-cancer-geography-paradox-poorer-cancer-outcomes-with-longer-travelling-times-to-healthcare-facilities-despite-prompter-diagnosis-and-treatment-a-data-linkage-study
#11
Melanie Turner, Shona Fielding, Yuhan Ong, Chris Dibben, Zhiqianq Feng, David H Brewster, Corri Black, Amanda Lee, Peter Murchie
BACKGROUND: Rurality and distance from cancer treatment centres have been shown to negatively impact cancer outcomes, but the mechanisms remain obscure. METHODS: We analysed the impact of travel time to key healthcare facilities and mainland/island residency on the cancer diagnostic pathway (treatment within 62 days of referral, and within 31 days of diagnosis) and 1-year mortality using a data-linkage study with 12 339 patients. RESULTS: After controlling for important confounders, mainland patients with more than 60 min of travelling time to their cancer treatment centre ((OR 1...
June 22, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28638230/role-of-three-dimensional-endoanal-ultrasound-in-assessing-the-anal-sphincter-morphology-of-female-patients-with-chronic-proctalgia
#12
Ya-Hong Xue, Shu-Qing Ding, Yi-Jiang Ding, Li-Qun Pan
AIM: To assess the role of three-dimensional endoanal ultrasound (3D-EAUS) for morphological assessment of the anal sphincter of female patients with chronic proctalgia (CP). METHODS: In this unmatched case control study, 30 consecutive female patients with CP and 25 normal women (control group) were enrolled. 3D-EAUS was performed in all subjects. Thickness and length of internal anal sphincter (IAS), thickness of puborectalis muscle (PR), length of the external anal sphincter (EAS) plus PR, and puborectalis angle were measured and compared between the two groups...
June 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28638214/two-paradoxes-in-linear-regression-analysis
#13
Ge Feng, Jing Peng, Dongke Tu, Julia Z Zheng, Changyong Feng
Regression is one of the favorite tools in applied statistics. However, misuse and misinterpretation of results from regression analysis are common in biomedical research. In this paper we use statistical theory and simulation studies to clarify some paradoxes around this popular statistical method. In particular, we show that a widely used model selection procedure employed in many publications in top medical journals is wrong. Formal procedures based on solid statistical theory should be used in model selection...
December 25, 2016: Shanghai Archives of Psychiatry
https://www.readbyqxmd.com/read/28638133/the-agenetic-body-prosthetics-or-the-new-promethean-ideal
#14
Cristina Lindenmeyer
In our rapidly changing world, we are often encouraged to treat our bodies as objects of constant improvement by means of various facilities and innovations. As part of this "Promethean tendency," the present-day alliance between medicine and technology has opened up a new perspective on the ill and disabled body, by providing access to sophisticated prosthetics that are increasingly seen as ideal remedies. These devices allow patients to benefit from previously unimaginable treatments and inestimable scientific advances, yet they also create new forms of dependency that go beyond simply forming a habit...
September 2016: American Journal of Psychoanalysis
https://www.readbyqxmd.com/read/28637818/the-cerebellum-does-more-than-sensory-prediction-error-based-learning-in-sensorimotor-adaptation-tasks
#15
Peter A Butcher, Richard B Ivry, Sheng-Han Kuo, David Rydz, John W Krakauer, Jordan A Taylor
Individuals with damage to the cerebellum perform poorly in sensorimotor adaptation paradigms. This deficit has been attributed to impairment in sensory-prediction-error-based updating of an internal forward model, a form of implicit learning. These individuals can, however, successfully counter a perturbation when instructed with an explicit aiming strategy. This successful use of an instructed aiming strategy presents a paradox: In adaptation tasks, why don't individuals with cerebellar damage come up with an aiming solution on their own to compensate for their implicit learning deficit? To explore this question, we employed a variant of a visuomotor rotation task in which, prior to executing a movement on each trial, the participants verbally reported their intended aiming location...
June 21, 2017: Journal of Neurophysiology
https://www.readbyqxmd.com/read/28637783/paradoxical-suppression-of-atherosclerosis-in-the-absence-of-microrna-146a
#16
Henry S Cheng, Rickvinder Besla, Angela Li, Zhiqi Chen, Eric A Shikatani, Maliheh Nazari-Jahantigh, Adel Hammoutène, My-Anh Nguyen, Michele Geoffrion, Lei Cai, Nadiya Khyzha, Tong Li, Sonya A MacParland, Mansoor Husain, Myron I Cybulsky, Chantal M Boulanger, Ryan E Temel, Andreas Schober, Katey J Rayner, Clinton Robbins, Jason E Fish
Rationale: Inflammation is a key contributor to atherosclerosis. MicroRNA-146a (miR-146a) has been identified as a critical brake on pro-inflammatory NF-κB signalling in several cell types, including endothelial cells and bone marrow-derived cells. Importantly, miR-146a expression is elevated in human atherosclerotic plaques, and polymorphisms in the miR-146a pre-cursor have been associated with risk of coronary artery disease. Objective: To define the role of endogenous miR-146a during atherogenesis. Methods and Results: Paradoxically, Low-density lipoprotein receptor (Ldlr)(-/-) mice deficient in miR-146a develop less atherosclerosis, despite having highly elevated levels of circulating pro-inflammatory cytokines...
June 21, 2017: Circulation Research
https://www.readbyqxmd.com/read/28637491/stable-centromere-positioning-in-diverse-sequence-contexts-of-complex-and-satellite-centromeres-of-maize-and-wild-relatives
#17
Jonathan I Gent, Na Wang, R Kelly Dawe
BACKGROUND: Paradoxically, centromeres are known both for their characteristic repeat sequences (satellite DNA) and for being epigenetically defined. Maize (Zea mays mays) is an attractive model for studying centromere positioning because many of its large (~2 Mb) centromeres are not dominated by satellite DNA. These centromeres, which we call complex centromeres, allow for both assembly into reference genomes and for mapping short reads from ChIP-seq with antibodies to centromeric histone H3 (cenH3)...
June 21, 2017: Genome Biology
https://www.readbyqxmd.com/read/28637383/inflammation-induced-osteogenesis-in-a-rabbit-tibia-model
#18
Michiel Croes, Willemijn Boot, Moyo C Kruyt, Harrie Weinans, Behdad Pouran, Yvonne van der Helm, Debby Gawlitta, Charles Vogely, Jacqueline Alblas, Wouter Dhert, F Cumhur Oner
Pathologic conditions associated with bone formation can serve as models to identify bone-promoting mediators. The inflammatory response to bacterial infections generally leads to osteolysis and impaired bone healing, but paradoxically, it can also have pro-osteogenic effects. As a potential model to investigate pro-osteogenic stimuli, this study characterizes the bone formation in an established rabbit tibia model of periprosthetic infection. Our hypothesis was that the infection with Staphylococcus aureus (S...
June 22, 2017: Tissue Engineering. Part C, Methods
https://www.readbyqxmd.com/read/28636912/channeling-of-camp-in-pde-pka-complexes-promotes-signal-adaptation
#19
Nikhil Kumar Tulsian, Srinath Krishnamurthy, Ganesh Srinivasan Anand
Spatiotemporal control of the cAMP signaling pathway is governed by both hormonal stimulation of cAMP generation by adenylyl cyclases (activation phase) and cAMP hydrolysis by phosphodiesterases (PDEs) (termination phase). The termination phase is initiated by PDEs actively targeting the protein kinase A (PKA) R-subunit through formation of a PDE-PKAR-cyclic adenosine monophosphate (cAMP) complex (the termination complex). Our results using PDE8 as a model PDE, reveal that PDEs mediate active hydrolysis of cAMP bound to its receptor RIα by enhancing the enzymatic activity...
June 20, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28634406/enhancing-kcc2-function-counteracts-morphine-induced-hyperalgesia
#20
Francesco Ferrini, Louis-Etienne Lorenzo, Antoine G Godin, Miorie Le Quang, Yves De Koninck
Morphine-induced hyperalgesia (MIH) is a severe adverse effect accompanying repeated morphine treatment, causing a paradoxical decrease in nociceptive threshold. Previous reports associated MIH with a decreased expression of the Cl(-) extruder KCC2 in the superficial dorsal horn (SDH) of the spinal cord, weakening spinal GABAA/glycine-mediated postsynaptic inhibition. Here, we tested whether the administration of small molecules enhancing KCC2, CLP257 and its pro-drug CLP290, may counteract MIH. MIH was typically expressed within 6-8 days of morphine treatment...
June 20, 2017: Scientific Reports
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