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https://www.readbyqxmd.com/read/27911261/targeted-deletion-of-akap7-in-dentate-granule-cells-impairs-spatial-discrimination
#1
Brian W Jones, Jennifer Deem, Thomas J Younts, Michael Weisenhaus, Christina A Sanford, Margaret C Slack, Jenesa Chin, Daniela Nachmanson, Alex McKennon, Pablo E Castillo, G Stanley McKnight
Protein Kinase A (PKA) mediates synaptic plasticity and is widely implicated in learning and memory. The hippocampal dentate gyrus (DG) is thought to be responsible for processing and encoding distinct contextual associations in response to highly similar inputs. The mossy fiber (MF) axons of the dentate granule cells convey strong excitatory drive to CA3 pyramidal neurons and express presynaptic, PKA-dependent forms of plasticity. Here, we demonstrate an essential role for the PKA anchoring protein, AKAP7, in mouse MF axons and terminals...
December 2, 2016: ELife
https://www.readbyqxmd.com/read/27909971/gastrodin-attenuates-pentylenetetrazole-induced-seizures-by-modulating-the-mitogen-activated-protein-kinase-associated-inflammatory-responses-in-mice
#2
Liming Chen, Xinan Liu, Hua Wang, Min Qu
Gastrodin, the major component isolated from the rhizome of the Chinese traditional medicinal herb Gastrodia elata ("Tianma"), has a long history in the treatment of epilepsy and other neurological disorders. However, the molecular mechanisms are not clear. Here, we found that gastrodin ameliorated pentylenetetrazole (PTZ)-induced epileptic seizures with improvement of the electroencephalographic pattern in mice. Further studies demonstrated that gastrodin decreased the levels of the pro-inflammatory cytokines interleukin-1β and tumor necrosis factor-α while increasing interleukin-10, an anti-inflammatory cytokine in the brain...
December 1, 2016: Neuroscience Bulletin
https://www.readbyqxmd.com/read/27909378/perspectives-of-canadian-final-year-physiotherapy-students-on-cardiorespiratory-physiotherapy-as-a-career-choice
#3
Tania Janaudis-Ferreira, Tamara Araujo, Julia Marie Romano, Pat G Camp, Mark Hall, Sunita Mathur, Dina Brooks
Purpose: To investigate the opinions of final-year Canadian physiotherapy students of cardiorespiratory physiotherapy (CRP) and the factors influencing their decision about whether to pursue a career in CRP. Methods: A cross-sectional online survey was completed by final-year Master of Science of Physical Therapy students from three of the largest English-speaking physiotherapy schools in Canada. Results: A total of 120 students responded to the survey (overall response rate was 44%). Fifteen students (12.5%) responded that they were extremely or quite interested in specializing in CRP...
2016: Physiotherapy Canada. Physiothérapie Canada
https://www.readbyqxmd.com/read/27909373/exercise-telemonitoring-and-telerehabilitation-compared-with-traditional-cardiac-and-pulmonary-rehabilitation-a-systematic-review-and-meta-analysis
#4
Christen Chan, Cristiane Yamabayashi, Nafeez Syed, Ashley Kirkham, Pat G Camp
Background: Despite exercise capacity and quality-of-life benefits, pulmonary rehabilitation (PR) and cardiac rehabilitation (CR) programmes are not easily accessed because of several barriers. A solution may be telerehabilitation (TR), in which patients exercise in their communities while they are monitored via teletechnology. However, the benefits of TR for the purposes of PR and CR have not been systematically reviewed. Objective: To determine whether the benefits of the exercise component of PR and CR using TR are comparable to usual-care (UC) programmes...
2016: Physiotherapy Canada. Physiothérapie Canada
https://www.readbyqxmd.com/read/27908836/gq-and-gs-signaling-acting-in-synergy-to-control-glp-1-secretion
#5
Maria Hauge, Jeppe Pio Ekberg, Maja Storm Engelstoft, Pascal Timshel, Andreas N Madsen, Thue W Schwartz
GPR40 is generally known to signal through Gq. However, in transfected cells, certain synthetic agonists can make the receptor signal also through Gs and cAMP (Hauge et al., 2015). Here we find that, in colonic crypt cultures, the GLP-1 secretion induced by such Gq + Gs GPR40 agonists is indeed inhibited by blockers of both Gq and Gs and is eliminated by combining these. This in contrast to Gq-only GPR40 agonists which only are affected by the Gq inhibitor. Importantly, Gq-only GPR40 agonists in combination with low doses of selective synthetic agonists for Gs coupled receptors, e...
November 28, 2016: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/27908835/modulation-of-signaling-through-gpcr-camp-pka-pathways-by-pde4-depends-on-stimulus-intensity-possible-implications-for-the-pathogenesis-of-acrodysostosis-without-hormone-resistance
#6
Emmanuelle Motte, Catherine Le Stunff, Claire Briet, Nicolas Dumaz, Caroline Silve
In acrodysostosis without hormone resistance, a disease caused by phosphodiesterase (PDE)-4D mutations, increased PDE activity leads to bone developmental defects but with normal renal responses to PTH. To identify potential mechanisms for these disparate responses, we compared the effect of PDE activity on hormone signaling through the GPCR-Gsα-cAMP-PKA pathway in cells from two lineages, HEK-293 cells stably overexpressing PTH1R (HEKpthr) and human dermal fibroblasts, including studies evaluating cAMP levels using an Epac-based BRET-sensor for cAMP (CAMYEL)...
November 28, 2016: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/27908723/oxidation-inhibits-pth-receptor-signaling-and-trafficking
#7
Juan A Ardura, Verónica Alonso, Pedro Esbrit, Peter A Friedman
Reactive Oxygen Species (ROS) increase during aging, potentially affecting many tissues including brain, heart, and bone. ROS alter signaling pathways and constitute potential therapeutic targets to limit oxidative damaging effects in aging-associated diseases. Parathyroid hormone receptors (PTHR) are widely expressed and PTH is the only anabolic therapy for osteoporosis. The effects of oxidative stress on PTHR signaling and trafficking have not been elucidated. Here, we used Fluorescence Resonance Energy Transfer (FRET)-based cAMP, ERK, and calcium fluorescent biosensors to analyze the effects of ROS on PTHR signaling and trafficking by live-cell imaging...
November 28, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27908638/using-the-acmge-milestones-as-a-handover-tool-from-medical-school-to-surgery-residency
#8
Lauren M Wancata, Helen Morgan, Gurjit Sandhu, Sally Santen, David T Hughes
OBJECTIVE: To map current medical school assessments for graduating students to the Accreditation Council for Graduate Medical Education (ACGME) milestones in general surgery, and to pass forward individual performance metrics on level 1 milestones to receiving residency programs. DESIGN: The study included 20 senior medical students who were accepted into surgery internship positions. Data from medical school performance assessments from the third-year surgery clerkship, fourth-year surgery rotations, fourth-year surgery boot camp, Clinical Competency Assessment Examination, and United States Medical Licensing Examination (USMLE) Step 1 and 2 examinations were used to map each student's competency assessments to the General Surgery Milestones based on a scoring system created and validated by independent assessors...
November 28, 2016: Journal of Surgical Education
https://www.readbyqxmd.com/read/27908619/correlation-of-dna-repair-gene-polymorphisms-with-clinical-outcome-in-patients-with-locally-advanced-non-small-cell-lung-cancer-receiving-induction-chemotherapy-followed-by-surgery
#9
Mariacarmela Santarpia, Jose Luis Ramirez, Itziar de Aguirre, Pilar Garrido, Maria Pérez Cano, Cristina Queralt, Jose Luis Gonzalez-Larriba, Amelia Insa, Mariano Provencio, Dolores Isla, Carlos Camps, Remei Blanco, Teresa Moran, Rafael Rosell
OBJECTIVE: The aim of this study was to evaluate whether xeroderma pigmentosum group D (XPD) and ribonucleotide reductase subunit M1 (RRM1) polymorphisms influenced clinical outcome in patients with stage IIIA-B non-small-cell lung cancer (NSCLC) treated with neoadjuvant gemcitabine/cisplatin/docetaxel followed by surgery. MATERIALS AND METHODS: A total of 109 patients with stage IIIA and IIIB NSCLC were prospectively genotyped to examine a potential association between XPD 312 (aspartic acid [Asp]/asparagine [Asn]), XPD 751 (lysine [Lys]/glutamine [Gln]), and RRM1 (-37 C/A) polymorphisms with response and survival...
November 9, 2016: Clinical Lung Cancer
https://www.readbyqxmd.com/read/27908592/activation-of-gpr30-stimulates-gtp-binding-of-g%C3%AE-i1-protein-to-sustain-activation-of-erk1-2-in-inhibition-of-prostate-cancer-cell-growth-and-modulates-metastatic-properties
#10
Lau Kin-Mang, Ma Fanny Man-Ting, Xia Jenny Tian, Chan Queeny Kwan Yi, Ng Chi-Fai, To Ka-Fai
Previously, we reported that GPR30 activation by the receptor-specific, non-estrogenic ligand G-1 inhibited in vitro and in vivo growth of prostate cancer (PCa) cells via sustained Erk1/2 activation. Mechanism underlying the sustained Erk1/2 activation for PCa cell growth inhibition remains unclear. Here we report that G-1, through GPR30, activated Gαi1 proteins to sustain Erk1/2 activation but failed to activate adenylyl cyclase (AC) for cAMP production in PCa cells. The chemical-induced activation of AC-cAMP-PKA signaling attenuated Erk1/2 activity and blocked the cell growth inhibitory effects of G-1...
November 28, 2016: Experimental Cell Research
https://www.readbyqxmd.com/read/27907934/restriction-of-postoperative-joint-loading-in-a-murine-model-of-anterior-cruciate-ligament-reconstruction-botulinum-toxin-paralysis-and-external-fixation
#11
Amir Lebaschi, Xiang-Hua Deng, Nathan W Coleman, Christopher L Camp, Jianchun Zong, Andrew Carbone, Camila B Carballo, Guang-Ting Cong, Zoe M Album, Scott A Rodeo
Control of knee motion in small animal models is necessary to study the effect of mechanical load on the healing process. This can be especially challenging in mice, which are being increasingly used for various orthopedic reconstruction models. We explored the feasibility of botulinum toxin (Botox; Allergan, Dublin, Ireland) paralysis and a newly designed external fixator to restrict motion of the knee in mice undergoing anterior cruciate ligament (ACL) reconstruction. Nineteen C57BL/6 mice were allocated to two groups: (1) Botox group (n = 9) and (2) external fixator group (n = 10)...
December 1, 2016: Journal of Knee Surgery
https://www.readbyqxmd.com/read/27907846/modelling-life-satisfaction-and-adjustment-to-trauma-in-children-exposed-to-ongoing-military-violence-an-exploratory-study-in-palestine
#12
Guido Veronese, Alessandro Pepe, Alaa Jaradah, Feda Al Muranak, Husam Hamdouna
Exposure to war and ongoing political violence increases mental health risks among children, especially in terms of posttraumatic stress disorder (PTSD), and depressive or somatic symptoms. However, an exclusive focus on negative functioning can lead to underestimating the coping abilities and natural potential for adjusting to trauma of war-affected children at different developmental phases. Using structural equation modelling, we tested the extent to which data gathered in a predominantly nonclinical sample of Palestinian children (N=1276) living in refugee camps supported a conceptual model in which the relationship between subjective wellbeing and the effects of trauma is mainly top-down in direction...
November 28, 2016: Child Abuse & Neglect
https://www.readbyqxmd.com/read/27907116/rnai-mediated-functional-analysis-of-bursicon-genes-related-to-adult-cuticle-formation-and-tanning-in-the-honeybee-apis-mellifera
#13
Claudinéia Pereira Costa, Moysés Elias-Neto, Tiago Falcon, Rodrigo Pires Dallacqua, Juliana Ramos Martins, Marcia Maria Gentile Bitondi
Bursicon is a heterodimeric neurohormone that acts through a G protein-coupled receptor named rickets (rk), thus inducing an increase in cAMP and the activation of tyrosine hydroxylase, the rate-limiting enzyme in the cuticular tanning pathway. In insects, the role of bursicon in the post-ecdysial tanning of the adult cuticle and wing expansion is well characterized. Here we investigated the roles of the genes encoding the bursicon subunits during the adult cuticle development in the honeybee, Apis mellifera...
2016: PloS One
https://www.readbyqxmd.com/read/27907106/brain-transcriptional-profiles-of-male-alternative-reproductive-tactics-and-females-in-bluegill-sunfish
#14
Charlyn G Partridge, Matthew D MacManes, Rosemary Knapp, Bryan D Neff
Bluegill sunfish (Lepomis macrochirus) are one of the classic systems for studying male alternative reproductive tactics (ARTs) in teleost fishes. In this species, there are two distinct life histories: parental and cuckolder, encompassing three reproductive tactics, parental, satellite, and sneaker. The parental life history is fixed, whereas individuals who enter the cuckolder life history transition from sneaker to satellite tactic as they grow. For this study, we used RNAseq to characterize the brain transcriptome of the three male tactics and females during spawning to identify gene ontology (GO) categories and potential candidate genes associated with each tactic...
2016: PloS One
https://www.readbyqxmd.com/read/27906551/ald1613-a-novel-long-acting-monoclonal-antibody-to-control-acth-driven-pharmacology
#15
Andrew L Feldhaus, Katie Anderson, Benjamin Dutzar, Ethan Ojala, Patricia Dianne McNeill, Pei Fan, Jenny Mulligan, Sam Marzolf, Charlie Karasek, Michelle Scalley-Kim, Erica Stewart, Jens Billgren, Vanessa Rubin, Kathleen Schneider, David Jurchen, Kathy Snow, Shaun Barnett, Barbara Bengtsson, Brian Baker, John A Latham, Dan Allison, Leon F Garcia-Martinez
ACTH is the primary regulator of adrenal glucocorticoid production. Elevated levels of ACTH play a critical role in disease progression in several indications including congenital adrenal hyperplasia and Cushing's disease. We have generated a specific, high affinity, neutralizing monoclonal antibody (ALD1613) to ACTH. In vitro, ALD1613 neutralizes ACTH-induced signaling via all five melanocortin receptors and inhibited ACTH-induced cAMP accumulation in a mouse adrenal cell line (Y1). ALD1613 administration to wild-type rats significantly reduced plasma corticosterone levels in a dose dependent manner...
December 1, 2016: Endocrinology
https://www.readbyqxmd.com/read/27906173/sensitivity-of-gbm-cells-to-camp-agonist-mediated-apoptosis-correlates-with-cd44-expression-and-agonist-resistance-with-mapk-signaling
#16
Paul M Daniel, Gulay Filiz, Theo Mantamadiotis
In some cell types, activation of the second messenger cAMP leads to increased expression of proapoptotic Bim and subsequent cell death. We demonstrate that suppression of the cAMP pathway is a common event across many cancers and that pharmacological activation of cAMP in glioblastoma (GBM) cells leads to enhanced BIM expression and apoptosis in specific GBM cell types. We identified the MAPK signaling axis as the determinant of cAMP agonist sensitivity in GBM cells, with high MAPK activity corresponding to cAMP resistance and low activity corresponding to sensitization to cAMP-induced apoptosis...
December 1, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27905271/the-effects-of-climate-factors-on-scabies-a-14-year-population-based-study-in-taiwan
#17
Jui-Ming Liu, Hsiao-Wei Wang, Fung-Wei Chang, Yueh-Ping Liu, Feng-Hsiang Chiu, Yi-Chun Lin, Kuan-Chen Cheng, Ren-Jun Hsu
Scabies is a common infectious disease and can cause severe outbreaks if not controlled quickly. Besides personal contact history, environmental factors are also important. This study analyzed the effects of environmental climate factors on the incidence of scabies in Taiwan. We conducted a 14-year nationwide population-based study: a total of 14,883 patients with scabies infestation were enrolled. Monthly climate data were collected from Taiwan's Central Weather Bureau, including data on temperature, relative humidity, total rainfall, total rain days, and total sunshine hours...
2016: Parasite: Journal de la Société Française de Parasitologie
https://www.readbyqxmd.com/read/27904901/effect-of-ticagrelor-on-endothelial-calcium-signalling-and-barrier-function
#18
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/27903987/mapping-heterogeneity-in-patient-derived-melanoma-cultures-by-single-cell-rna-seq
#19
Tobias Gerber, Edith Willscher, Henry Loeffler-Wirth, Lydia Hopp, Dirk Schadendorf, Manfred Schartl, Ulf Anderegg, Gray Camp, Barbara Treutlein, Hans Binder, Manfred Kunz
Recent technological advances in single-cell genomics make it possible to analyze cellular heterogeneity of tumor samples. Here, we applied single-cell RNA-seq to measure the transcriptomes of 307 single cells cultured from three biopsies of three different patients with a BRAF/NRAS wild type, BRAF mutant/NRAS wild type and BRAF wild type/NRAS mutant melanoma metastasis, respectively. Analysis based on self-organizing maps identified sub-populations defined by multiple gene expression modules involved in proliferation, oxidative phosphorylation, pigmentation and cellular stroma...
November 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27902776/inhibition-of-candida-albicans-biofilm-formation-by-the-synthetic-lactoferricin-derived-peptide-hlf1-11
#20
Paola Morici, Roberta Fais, Cosmeri Rizzato, Arianna Tavanti, Antonella Lupetti
The aim of this study was to evaluate the in vitro activity of the synthetic peptide hLF1-11 against biofilm produced by clinical isolates of Candida albicans with different fluconazole susceptibility. The antibiofilm activity of the peptide hLF1-11 was assessed in terms of reduction of biofilm cellular density, metabolic activity and sessile cell viability. The extent of morphogenesis in hLF1-11 treated and untreated biofilms was also investigated microscopically. Transcription levels of genes related to cell adhesion, hyphal development and extracellular matrix production were analysed by qRT-PCR in hLF1-11 treated and untreated biofilms...
2016: PloS One
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