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https://www.readbyqxmd.com/read/28735374/changes-in-global-transcriptional-profiling-of-women-following-obesity-surgery-bypass
#1
Marcela Augusta de Souza Pinhel, Natalia Yumi Noronha, Carolina Ferreira Nicoletti, Bruno Affonso Parente de Oliveira, Cristiana Cortes-Oliveira, Vitor Caressato Pinhanelli, Wilson Salgado Junior, Ana Julia Machry, Wilson Araújo da Silva Junior, Dorotéia Rossi Silva Souza, Júlio Sérgio Marchini, Carla Barbosa Nonino
BACKGROUND: Differential gene expression in peripheral blood mononuclear cells (PBMCs) after Roux-en-Y gastric bypass (RYGB) is poorly characterized. Markers of these processes may provide a deeper understanding of the mechanisms that underlie these events. The main goal of this study was to identify changes in PBMC gene expression in women with obesity before and 6 months after RYGB-induced weight loss. METHODS: The ribonucleic acid (RNA) of PBMCs from 13 obese women was analyzed before and 6 months after RYGB; the RNA of PBMCs from nine healthy women served as control...
July 22, 2017: Obesity Surgery
https://www.readbyqxmd.com/read/28734930/bidirectional-allosteric-interactions-between-cannabinoid-receptor-1-cb1-and-dopamine-receptor-2-long-d2l-heterotetramers
#2
Amina M Bagher, Robert B Laprairie, J Thomas Toguri, Melanie E M Kelly, Eileen M Denovan-Wright
Type 1 cannabinoid (CB1) and dopamine 2 long form (D2L) receptors can physically interact to form heteromers that display unique pharmacology in vitro compared to homomeric complexes. Co-expression of CB1 and D2L and co-application of CB1 and D2 agonists increases cAMP levels while administration of either agonist alone decreases cAMP levels. To understand the observed co-agonist response, our first goal of the current study was to define the stoichiometry of CB1/D2L/Gα protein complexes. Using bioluminescence resonance energy transfer 2 (BRET(2)), we confirmed that, CB1 homodimers, D2L homodimers, and CB1/D2L heteromers are formed...
July 19, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28734745/why-are-some-people-who-have-received-overdose-education-and-naloxone-reticent-to-call-emergency-medical-services-in-the-event-of-overdose
#3
Stephen Koester, Shane R Mueller, Lisa Raville, Sig Langegger, Ingrid A Binswanger
BACKGROUND: Overdose Education and Naloxone Distribution (OEND) training for persons who inject drugs (PWID) underlines the importance of summoning emergency medical services (EMS). To encourage PWID to do so, Colorado enacted a Good Samaritan law providing limited immunity from prosecution for possession of a controlled substance and/or drug paraphernalia to the overdose victim and the witnesses who in good faith provide emergency assistance. This paper examines the law's influence by describing OEND trained PWIDs' experience reversing overdoses and their decision about calling for EMS support...
July 19, 2017: International Journal on Drug Policy
https://www.readbyqxmd.com/read/28733814/neuroprotective-effect-of-ipriflavone-against-scopolamine-induced-memory-impairment-in-rats
#4
Hani S Hafez, Doaa A Ghareeb, Samar R Saleh, Mariam M Abady, Maha A El Demellawy, Hend Hussien, Nihad Abdel-Monem
BACKGROUND: Alzheimer's disease is an age-related neurodegenerative disorder characterized clinically by a progressive loss of memory and cognitive functions resulting in severe dementia. Ipriflavone (IPRI) is a non-hormonal, semi-synthetic isoflavone, clinically used in some countries for the treatment and prevention of postmenopausal osteoporosis. Moreover, ipriflavone is a non-peptidomimetic small molecule AChE inhibitor with an improved bioavailability after systemic administration, due to its efficient blood-brain barrier permeability in comparison with peptidomimetic inhibitors...
July 22, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28733084/reciprocal-regulation-of-%C3%AE-2-adrenoceptor-activated-camp-response-element-binding-protein-signalling-by-arrestin2-and-arrestin3
#5
Alexander Pearce, Lucy Sanders, Paul J Brighton, Shashi Rana, Justin C Konje, Jonathon M Willets
Activation of Gs coupled receptors (e.g. β2-adrenoreceptor (β2AR)) expressed within the uterine muscle layer (myometrium), promotes intracellular cAMP generation, inducing muscle relaxation through short-term inhibition of contractile proteins, and longer-term modulation of cellular phenotype to promote quiescence. In the myometrium cAMP-driven modulation of cell phenotype is facilitated by CREB activity, however despite the importance of CREB signalling in the promotion of myometrial quiescence during pregnancy, little is currently known regarding the molecular mechanisms involved...
July 18, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28732330/legacy-persistent-organic-pollutants-including-pbdes-in-the-trophic-web-of-the-ross-sea-antarctica
#6
Simonetta Corsolini, Nicoletta Ademollo, Tania Martellini, Demetrio Randazzo, Marino Vacchi, Alessandra Cincinelli
The ecological features of the Ross Sea trophic web are peculiar and different from other polar food webs, with respect to the use of habitat and species interactions; due to its ecosystem integrity, it is the world's largest Marine Protected Area, established in 2016. Polar organisms are reported to bioaccumulate lipophilic contaminant, viz persistent organic pollutants (POPs). Legacy POPs and flame retardants (polybrominated diphenyl ethers, PBDEs) were studied in key species of the Ross Sea (Euphausia superba, Pleuragramma antarctica) and their predators (Dissostichus mawsoni, Pygoscelis adeliae, Aptenodytes forsteri, Catharacta maccormicki, Leptonychotes weddellii)...
July 12, 2017: Chemosphere
https://www.readbyqxmd.com/read/28732166/mel-n16-a-series-of-novel-endomorphin-analogs-with-good-analgesic-activity-and-a-favorable-side-effect-profile
#7
Xin Liu, Long Zhao, Yuan Wang, Jingjing Zhou, Dan Wang, Yixin Zhang, Xianghui Zhang, Zhaojuan Wang, Dongxu Yang, Lingyun Mou, Rui Wang
Opioid peptides are neuromodulators that bind to opioid receptors and reduce pain sensitivity. Endomorphins are one of the most active endogenous opioid peptides, and they have good affinity and selectivity toward the μ opioid receptor. However, their clinical usage is hindered by their inability to cross the blood-brain barrier, and their poor in vivo activity after peripheral injection. In order to overcome these defects, we have designed and synthesized a series of novel endomorphin analogs with multiple site modifications...
July 21, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28732013/the-kp1_4563-gene-is-regulated-by-the-camp-receptor-protein-and-controls-type-3-fimbrial-function-in-klebsiella-pneumoniae-ntuh-k2044
#8
Mei Luo, Shiya Yang, Xuan Li, Pin Liu, Jian Xue, Xipeng Zhou, Kewen Su, Xuan Xu, Ying Qing, Jingfu Qiu, Yingli Li
Klebsiella pneumoniae (K. pneumoniae) is an opportunistic pathogen that can adhere to host cells or extracellular matrix via type 1 and type 3 fimbriae. KP1_4563 is a gene encoding a hypothetical protein in K. pneumoniae NTUH-K2044. KP1_4563 is located between the type 1 and type 3 fimbrial gene clusters and is likely associated with fimbrial function given its putative conserved domains of unknown function (DUF1471). Cyclic AMP receptor protein (CRP) regulates virulence-related gene expression and is a crucial transcriptional regulator in many bacteria...
2017: PloS One
https://www.readbyqxmd.com/read/28731589/effects-of-nitric-oxide-on-large-conductance-ca-2-activated-k-currents-in-human-cardiac-fibroblasts-through-pka-and-pkg-related-pathways
#9
Hyemi Bae, Inja Lim
The human cardiac fibroblast (HCF) is the most abundant cell type in the myocardium, and HCFs play critical roles in maintaining normal cardiac function. However, unlike cardiomyocytes, the electrophysiology of HCFs is not well established. In the cardiovascular system, Ca(2+) -activated K(+) (KCa) channels have distinct physiological and pathological functions, and nitric oxide (NO) play key roles. In this study, we investigated the potential effects of NO on KCa channels in HCFs. We recorded strong oscillating, well-maintained outward K(+) currents without marked inactivation throughout the test pulse period and detected outward rectification in the I-V curve; these are all characteristics that are typical of KCa currents...
July 21, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28731505/calcium-calmodulin-dependent-kinase-2-camkii-mediates-epac-induced-spontaneous-transient-outward-currents-stocs-in-rat-vascular-smooth-muscle
#10
Edward S A Humphries, Tomoko Kamishima, John M Quayle, Caroline Dart
Activation of the major cAMP effector, exchange protein directly activated by cAMP (Epac), induces vascular smooth muscle relaxation by increasing the activity of ryanodine (RyR)-sensitive release channels on the peripheral sarcoplasmic reticulum. Resultant Ca(2+) sparks activate plasma membrane Ca(2+) -activated K(+) (BKCa ) channels, evoking spontaneous transient outward currents (STOCs) that hyperpolarize the cell and reduce voltage-dependent Ca(2+) entry. In this study we investigate the mechanism by which Epac increases STOC activity...
July 21, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28731148/molecular-genetics-and-targeted-therapy-of-wnt-related-human-diseases-review
#11
Masuko Katoh, Masaru Katoh
Canonical WNT signaling through Frizzled and LRP5/6 receptors is transduced to the WNT/β-catenin and WNT/stabilization of proteins (STOP) signaling cascades to regulate cell fate and proliferation, whereas non-canonical WNT signaling through Frizzled or ROR receptors is transduced to the WNT/planar cell polarity (PCP), WNT/G protein-coupled receptor (GPCR) and WNT/receptor tyrosine kinase (RTK) signaling cascades to regulate cytoskeletal dynamics and directional cell movement. WNT/β-catenin signaling cascade crosstalks with RTK/SRK and GPCR-cAMP-PKA signaling cascades to regulate β-catenin phosphorylation and β-catenin-dependent transcription...
July 19, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28730491/development-of-selected-reaction-monitoring-methods-to-systematically-quantify-kinase-abundance-and-phosphorylation-stoichiometry-in-human-samples
#12
Kirsten Beck, Nathan Camp, Michael Bereman, James Bollinger, Jarrett Egertson, Michael MacCoss, Alejandro Wolf-Yadlin
Protein phosphorylation, one of the most common types of post-translational modifications, is the central regulatory mechanism of cellular signaling networks. In human cells, thousands of proteins are continuously and dynamically phosphorylated and dephosphorylated at specific sites and times in response to external and internal stimuli. Reversible phosphorylation is facilitated by the action of two protein superfamilies: kinases and phosphatases. Kinases play an essential role in almost every relevant physiological process in human cells and their deregulation is linked to pathologies ranging from cancer to autoimmune diseases...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28730281/pk-pd-studies-on-non-selective-pde-inhibitors-in-rats-using-camp-as-a-marker-of-pharmacological-response
#13
Artur Świerczek, Elżbieta Wyska, Sebastian Baś, Marta Woyciechowska, Jacek Mlynarski
In recent years, phosphodiesterase (PDE) inhibitors have been frequently tested for the treatment of experimental inflammatory and immune disorders. It is suggested that anti-inflammatory properties of PDE inhibitors are related to their ability to increase cAMP levels. The aim of this study was to verify the hypothesis that cAMP may be a useful marker of pharmacological response following administration of non-selective PDE inhibitors (pentoxifylline and (±)-lisofylline) to endotoxemic rats. Male Wistar rats were administered LPS (1 mg kg(-1), i...
July 20, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/28730102/anti-scarring-effects-of-butaprost-on-human-subconjunctival-tenon-s-fibroblasts
#14
Jong Hoon Shin, Je Hyun Seo, Jae Ho Jung, Tae Woo Kim
AIM: To investigate the toxicity of the E-prostanoid 2 (EP2) receptor agonist, butaprost against human subconjunctival (Tenon's capsule) fibroblasts, and to determine the underlying mechanism. METHODS: We isolated Tenon's fibroblasts from the subconjunctival area of healthy subjects and evaluated the types of EP receptors expressed using quantitative real-time reverse transcription polymerase chain reaction (RT-PCR). The toxicity of butaprost against the fibroblasts was evaluated using methyl thiazolyl tetrazolium and lactic dehydrogenase assays...
2017: International Journal of Ophthalmology
https://www.readbyqxmd.com/read/28729922/meningococcal-disease-outbreak-related-to-the-world-scout-jamboree-in-japan-2015
#15
Mizue Kanai, Hajime Kamiya, Alison Smith-Palmer, Hideyuki Takahashi, Yushi Hachisu, Munehisa Fukusumi, Takehito Saitoh, Makoto Ohnishi, Tomimasa Sunagawa, Tamano Matsui, Kazunori Oishi
PROBLEM: Six invasive meningococcal disease cases occurred among Scottish and Swedish nationals associated with the World Scout Jamboree (WSJ), an international mass gathering, held in Japan. The index case developed symptoms while returning home. The strains from all six cases were identical and seldom seen in Japan. CONTEXT: Over 33 000 participants from 155 countries attended WSJ. At the Jamboree site, participants of the North of Scotland's and Sweden's units camped within the same subcamp and kept the same schedule of events...
April 2017: Western Pacific Surveillance and Response Journal: WPSAR
https://www.readbyqxmd.com/read/28729859/transcriptomic-insight-in-the-control-of-legume-root-secondary-infection-by-the-sinorhizobium-meliloti-transcriptional-regulator-clr
#16
Lan Zou, Amandine Gastebois, Céline Mathieu-Demazière, Fernando Sorroche, Catherine Masson-Boivin, Jacques Batut, Anne-Marie Garnerone
The cAMP-dependent transcriptional regulator Clr of Sinorhizobium meliloti regulates the overall number of infection events on Medicago roots by a so-far unknown mechanism requiring smc02178, a Clr-target gene of unknown function. In order to shed light on the mode of action of Clr on infection and potentially reveal additional biological functions for Clr, we inventoried genomic Clr target genes by transcriptome profiling. We have found that Clr positively controls the synthesis of cAMP-dependent succinoglycan as well as the expression of genes involved in the synthesis of a so-far unknown polysaccharide compound...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28729592/refugees-addressing-the-burden-of-oral-disease-through-prevention
#17
K Zaheer, S Sheikh, O U Khalid, Z Rizvi
In February 2017 a cohort of dental students travelled to Athens, Greece where they assisted in providing dental care to refugees and conducted oral hygiene workshops in Skaramagas Refugee camp. With respect to patient presentation, caries was found to be extremely prevalent due to patient diet, accessibility to care and oral hygiene practices. Due to the extensive nature of the work, time constraints and resource availability focus was directed on reducing disease burden through prevention. This article explores the challenges of delivering preventative treatment as well as its advantage over conventional therapeutic care in the context of a humanitarian crisis...
July 21, 2017: British Dental Journal
https://www.readbyqxmd.com/read/28729453/pi3k-and-calcium-signaling-in-cardiovascular-disease
#18
REVIEW
Alessandra Ghigo, Muriel Laffargue, Mingchuan Li, Emilio Hirsch
Receptor signaling relays on intracellular events amplified by secondary and tertiary messenger molecules. In cardiomyocytes and smooth muscle cells, cyclic AMP (cAMP) and subsequent calcium (Ca(2+)) fluxes are the best characterized receptor-regulated signaling events. However, most of receptors able to modify contractility and other intracellular responses signal through a variety of other messengers, and whether these signaling events are interconnected has long remained unclear. For example, the PI3K (phosphoinositide 3-kinase) pathway connected to the production of the lipid second messenger PIP3/PtdIns(3,4,5)P3 (phosphatidylinositol (3,4,5)-trisphosphate) is potentially involved in metabolic regulation, activation of hypertrophy, and survival pathways...
July 21, 2017: Circulation Research
https://www.readbyqxmd.com/read/28729436/regulation-of-adrenal-and-ovarian-steroidogenesis-by-mir-132
#19
Zhigang Hu, Wen-Jun Shen, Fredric B Kraemer, Salman Azhar
miR-132 is hormonally regulated in steroidogenic cells of the adrenal gland, ovary and testis. Here, we examined the potential role of miR-132 in the control of steroidogenesis. Transfection of Y1 adrenal cells with miR-132 increased mRNAs of 3β-HSD and 20α-HSD enzymes, which catalyze the sequential conversion of pregnenolone to progesterone to biologically inactive 20α-OHP. Overexpression of miR-132 reduced MeCP2 and StAR protein expression, basal progestin (progesterone and 20α-OHP) production, but enhanced their production in response to cAMP stimulation...
July 20, 2017: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/28729421/the-small-g-protein-ras2-is-involved-in-the-metabolic-compensation-of-the-circadian-clock-in-the-circadian-model-neurospora-crassa
#20
Norbert Gyöngyösi, Anita Szöke, Krisztina Ella, Krisztina Káldi
Accumulating evidence from both experimental and clinical investigations indicate a tight interaction between metabolism and circadian timekeeping; however, knowledge of the underlying mechanism is still incomplete. Metabolic compensation allows circadian oscillators to run with a constant speed at different substrate levels and therefore is a substantial criterion of a robust rhythm in a changing environment. Because previous data have suggested a central role of RAS2-mediated signaling in the adaptation of yeast to different nutritional environments, we examined the involvement of RAS2 in the metabolic regulation of the clock in the circadian model organism Neurospora crassa...
July 20, 2017: Journal of Biological Chemistry
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