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https://www.readbyqxmd.com/read/29351460/macrophage-dependent-impairment-of-%C3%AE-2-adrenergic-autoreceptor-function-in-sympathetic-neurons-from-doca-salt-but-not-high-fat-diet-induced-hypertensive-rats
#1
Ryan Kwun-Yee Mui, Roxanne Fernandes, Hannah Garver, Nico van Rooijen, James J Galligan
DOCA-salt and obesity-related hypertension are associated with inflammation and sympathetic nervous system hyperactivity. Prejunctional α2-adrenergic receptors (α2ARs) provide negative feedback to norepinephrine release from sympathetic nerves through inhibition of N-type Ca2+ channels. Increased neuronal norepinephrine release in DOCA-salt and obesity-related hypertension occurs through impaired α2AR signaling, however, the mechanisms involved are unclear. Mesenteric arteries are resistance arteries that receive sympathetic innervation from the superior mesenteric and celiac ganglia (SMCG)...
January 5, 2018: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/29351444/activated-human-t-lymphocytes-inhibit-tgf%C3%AE-induced-fibroblast-to-myofibroblast-differentiation-via-prostaglandins-d2-and-e2
#2
Shannon H Lacy, Amali P Epa, Stephen J Pollock, Collynn F Woeller, Thomas H Thatcher, Richard P Phipps, Patricia J Sime
In pulmonary fibrosis (PF), fibroblasts and myofibroblasts proliferate and deposit excessive extracellular matrix in the interstitium, impairing normal lung function. As most forms of PF have a poor prognosis and limited treatment options, PF represents an urgent unmet need for novel, effective therapeutics. While the role of immune cells in lung fibrosis is unclear, recent studies suggest that T lymphocyte (T cell) activation may be impaired in PF patients. Further, we have previously shown that activated T cells can produce prostaglandins with anti-scarring potential...
December 20, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29351410/hypoxia-selectively-upregulates-cation-channels-and-increases-cytosolic-ca2-in-pulmonary-but-not-coronary-arterial-smooth-muscle-cells
#3
Xi He, Shanshan Song, Ramon J Ayon, Angela Balisterieri, Stephen M Black, Ayako Makino, W Gil Wier, Wei-Jin Zang, Jason X-J Yuan
Ca2+ signaling, particularly the mechanism via store-operated Ca2+ entry (SOCE) and receptor-operated Ca2+ entry (ROCE), plays a critical role in the development of acute hypoxia-induced pulmonary vasoconstriction and chronic hypoxia-induced pulmonary hypertension. This study aimed to test the hypothesis that chronic hypoxia differentially regulates the expression of proteins that mediate SOCE and ROCE (STIM, Orai, and TRPC6) in pulmonary (PASMC) and coronary (CASMC) artery smooth muscle cells. The resting cytosolic [Ca2+] ([Ca2+]cyt) and the stored [Ca2+] in the sarcoplasmic reticulum (SR) were not different in CASMC and PASMC...
January 3, 2018: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/29351018/the-behavior-and-reproductive-physiology-of-a-solitary-progressive-provisioning-vespid-wasp-evidence-for-a-solitary-cycle-origin-of-reproductive-castes
#4
Hans C Kelstrup, Klaus Hartfelder, Tiago Falcon Lopes, Theresa C Wossler
The emergence of queens and workers from solitary antecedents mark a major evolutionary transition in the history of life. The solitary progressive provisioning wasp Synagris cornuta, a member of the subfamily Eumeninae (basal to eusocial vespid wasps), alternates between behavioral states characterized as queenlike and worker-like. Akin to a queen in eusocial wasps, a S. cornuta female initiates construction of a cell into which she oviposits and then, similar to a worker, cares for the brood as it develops...
February 2018: American Naturalist
https://www.readbyqxmd.com/read/29350876/mechanism-of-mer-receptor-tyrosine-kinase-inhibition-of-glomerular-endothelial-cell-inflammation
#5
Yuxuan Zhen, Fred D Finkelman, Wen-Hai Shao
Endotoxin induces a variety of proinflammatory mediators and plays a crucial role in kidney inflammation. The receptor tyrosine kinase, Mer, diminishes renal inflammation by attenuating inflammatory responses. We previously reported that Mer is predominantly expressed on glomerular endothelial cells (GECs) and that Mer deficiency is associated with increased renal inflammation when mice are challenged with nephrotoxic serum. We consequently hypothesized that Mer signaling down-regulates LPS-driven inflammatory responses in GECs...
January 19, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29350260/modulation-rate-transfer-functions-from-four-species-of-stranded-odontocete-stenella-longirostris-feresa-attenuata-globicephala-melas-and-mesoplodon-densirostris
#6
Adam B Smith, Aude F Pacini, Paul E Nachtigall
Odontocete marine mammals explore the environment by rapidly producing echolocation signals and receiving the corresponding echoes, which likewise return at very rapid rates. Thus, it is important that the auditory system has a high temporal resolution to effectively process and extract relevant information from click echoes. This study used auditory evoked potential methods to investigate auditory temporal resolution of individuals from four different odontocete species, including a spinner dolphin (Stenella longirostris), pygmy killer whale (Feresa attenuata), long-finned pilot whale (Globicephala melas), and Blainville's beaked whale (Mesoplodon densirostris)...
January 19, 2018: Journal of Comparative Physiology. A, Neuroethology, Sensory, Neural, and Behavioral Physiology
https://www.readbyqxmd.com/read/29350251/pyramidal-cell-selective-glun1-knockout-causes-impairments-in-salience-attribution-and-related-eeg-activity
#7
Alexandra D Forrest, Jakyung Bang, Robert E Featherstone, Jonathan H Bloom, Matthew S Luminais, Rebecca V Zhang, Christopher R Gajewski, Mary F McMullen, Yuling Liang, Steven J Siegel
Schizophrenia is a disabling psychiatric disease characterized by symptoms including hallucinations, delusions, social withdrawal, loss of pleasure, and inappropriate affect. Although schizophrenia is marked by dysfunction in dopaminergic and glutamatergic signaling, it is not presently clear how these dysfunctions give rise to symptoms. The aberrant salience hypothesis of schizophrenia argues that abnormal attribution of motivational salience to stimuli is one of the main contributors to both positive and negative symptoms of schizophrenia...
January 19, 2018: Experimental Brain Research. Experimentelle Hirnforschung. Expérimentation Cérébrale
https://www.readbyqxmd.com/read/29350067/soluble-neuregulin1-is-strongly-up-regulated-in-the-rat-model-of-charcot-marie-tooth-1a-disease
#8
Benedetta Elena Fornasari, Giulia Ronchi, Davide Pascal, Davide Visigalli, Giovanna Capodivento, Lucilla Nobbio, Isabelle Perroteau, Angelo Schenone, Stefano Geuna, Giovanna Gambarotta
Neuregulin1 (NRG1) is a growth factor playing a pivotal role in peripheral nerve development through the activation of the transmembrane co-receptors ErbB2-ErbB3. Soluble NRG1 isoforms, mainly secreted by Schwann cells, are strongly and transiently up-regulated after acute peripheral nerve injury, thus suggesting that they play a crucial role also in the response to nerve damage. Here we show that in the rat experimental model of the peripheral demyelinating neuropathy Charcot-Marie-Tooth 1A (CMT1A) the expression of the different NRG1 isoforms (soluble, type α and β, type a and b) is strongly up-regulated, as well as the expression of NRG1 co-receptors ErbB2-ErbB3, thus showing that CMT1A nerves have a gene expression pattern highly reminiscent of injured nerves...
January 1, 2018: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/29346407/relaxin-reverses-inflammatory-and-immune-signals-in-aged-hearts
#9
Brian Martin, Beth Ann Gabris-Weber, Rajiv Reddy, Guillermo Romero, Ansuman Chattopadhyay, Guy Salama
BACKGROUND: 'Healthy' aging drives structural and functional changes in the heart including maladaptive electrical remodeling, fibrosis and inflammation, which lower the threshold for cardiovascular diseases such as heart failure (HF) and atrial fibrillation (AF). Despite mixed results in recent clinical trials, Relaxin-therapy for 2-days could reduce mortality by 37% at 180-days post-treatment, in patients with acute decompensated HF. Relaxin's short life-span (hours) but long-lasting protective actions led us to test the hypothesis that relaxin acts at a genomic level to reverse maladaptive remodeling in aging and HF...
2018: PloS One
https://www.readbyqxmd.com/read/29345930/%C3%AE-amino-%C3%AE-carboxymuconate-%C3%AE%C2%B5-semialdehyde-decarboxylase-acmsd-inhibitors-as-novel-modulators-of-de-novo-nicotinamide-adenine-dinucleotide-nad-biosynthesis
#10
Roberto Pellicciari, Paride Liscio, Nicola Giacchè, Francesca De Franco, Andrea Carotti, Janet Robertson, Lucia Cialabrini, Elena Katsyuba, Nadia Raffaelli, Johan Auwerx
NAD+ has a central function in linking cellular metabolism to major cell signaling and gene regulation pathways. Defects in NAD+ homeostasis underpin a wide range of diseases, including cancer, metabolic disorders, and aging. Whilst the beneficial effects of NAD+ boosting are well established in mitochondrial fitness, metabolism, and lifespan, to date, no therapeutic enhancers of de novo NAD+ biosynthesis have been reported. Herein we report the discovery of 3-[[[5-cyano-1,6-dihydro-6-oxo-4-(2-thienyl)-2-pyrimidinyl]thio]methyl]phenylacetic acid (TES-1025, 22) the first potent and selective inhibitor of human ACMSD (IC50 = 0...
January 18, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29345372/truncation-of-neurokinin-1-receptor-negative-regulation-of-substance-p-signaling
#11
REVIEW
Sergei Spitsin, Vasiliki Pappa, Steven D Douglas
Substance P (SP) is a tachykinin peptide, which triggers intracellular signaling in the nervous and immune systems, as well as, other local and systemic events. The interaction between SP and its receptor, neurokinin-1 receptor (NK1R), results in major downstream cellular actions, which include changes in calcium fluxes, ERK, and p21-activated kinase phosphorylation and NFκB activation. Two naturally occurring variants of the NK1R, the full-length, 407 aa receptor (NK1R-F) and the truncated, 311 aa isoform (NK1R-T), mediate the actions of SP...
January 10, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29345254/the-mtor-inhibitor-azd8055-overcomes-tamoxifen-resistance-in-breast-cancer-cells-by-down-regulating-hspb8
#12
Jia-Jie Shi, Si-Meng Chen, Chen-Liang Guo, Yi-Xue Li, Jian Ding, Ling-Hua Meng
Tamoxifen, an important endocrine therapeutic agent, is widely used for the treatment of estrogen receptor positive (ER+) breast cancer. However, de novo or acquired resistance prevents patients from benefitting from endocrine approaches and necessitates alternative treatments. In this study, we report that small heat protein beta-8 (HSPB8) may serve as an important molecule in tamoxifen resistance. HSPB8 expression is enhanced in MCF-7 cells resistant to tamoxifen (MCF-7/R) compared to parent cells. Moreover, high expression of HSPB8 associates with poor prognosis in ER+ breast cancer patients but not in patients without classification...
January 18, 2018: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/29344721/post-mortem-mr-angiography-quantitative-investigation-and-intravascular-retention-of-perfusates-in-ex-situ-porcine-hearts
#13
Bridgette Webb, Thomas Widek, Sylvia Scheicher, Thorsten Schwark, Rudolf Stollberger
As the implementation of minimally invasive imaging techniques in both forensic and pathological practice increases, research in this area focuses on addressing recognised diagnostic weaknesses of current approaches. Assessment of sudden cardiac death (SCD) can be considered one such area in which post-mortem imaging still shows diagnostic weaknesses. We hypothesise that magnetic resonance imaging (MRI) with an angiographic adjunct may improve the visualisation and interpretation of cardiac pathologies in a post-mortem setting...
January 18, 2018: International Journal of Legal Medicine
https://www.readbyqxmd.com/read/29343636/non-cell-autonomous-control-of-precerebellar-neuron-migration-by-slit-and-robo-proteins
#14
Chloé Dominici, Quentin Rappeneau, Pavol Zelina, Stéphane Fouquet, Alain Chédotal
During development, precerebellar neurons migrate tangentially from the dorsal hindbrain to the floor plate. Their axons cross it but their cell bodies stop their ventral migration upon reaching the midline. It has previously been shown that Slit chemorepellents and their receptors, Robo1 and Robo2, might control the migration of precerebellar neurons in a repulsive manner. Here, we have used a conditional knockout strategy in mice to test this hypothesis. We show that the targeted inactivation of the expression of Robo1 and Robo2 receptors in precerebellar neurons does not perturb their migration and that they still stop at the midline...
January 17, 2018: Development
https://www.readbyqxmd.com/read/29341465/p2y12-deficiency-in-mouse-impairs-noradrenergic-system-in-brain-and-alters-anxiety-like-neurobehavior-and-memory
#15
Fang Zheng, Qiang Zhou, Yin Cao, Hailian Shi, Hui Wu, Beibei Zhang, Fei Huang, Xiaojun Wu
Purinergic receptor P2Y12 (P2Y12 ), a G protein-coupled (GPCR) purinergic receptor, is widely distributed in nervous system and involved in the progression of neurological diseases such as multiple sclerosis and neuropathic pain. The central noradrenergic system actively participates in a number of neurophysiological processes. Nevertheless, whether there is any direct relevance between P2Y12 and noradrenergic signal transduction remains unknown. In the present study, we tested the hypothesis that lack of P2Y12 impaired noradrenergic signal transduction in mouse brain...
January 17, 2018: Genes, Brain, and Behavior
https://www.readbyqxmd.com/read/29339801/cardiac-glycoside-aglycones-inhibit-hiv-1-gene-expression-by-a-mechanism-requiring-mek1-2-erk1-2-signaling
#16
Raymond W Wong, Clifford A Lingwood, Mario A Ostrowski, Tyler Cabral, Alan Cochrane
The capacity of HIV-1 to develop resistance to current drugs calls for innovative strategies to control this infection. We aimed at developing novel inhibitors of HIV-1 replication by targeting viral RNA processing-a stage dependent on conserved host processes. We previously reported that digoxin is a potent inhibitor of this stage. Herein, we identify 12 other cardiac glycoside/aglycones or cardiotonic steroids (CSs) that impede HIV growth in HIV-infected T cells from clinical patients at IC50s (1.1-1.3 nM) that are 2-26 times below concentrations used in patients with heart conditions...
January 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29337984/anteroposterior-axis-patterning-by-early-canonical-wnt-signaling-during-hemichordate-development
#17
Sébastien Darras, Jens H Fritzenwanker, Kevin R Uhlinger, Ellyn Farrelly, Ariel M Pani, Imogen A Hurley, Rachael P Norris, Michelle Osovitz, Mark Terasaki, Mike Wu, Jochanan Aronowicz, Marc Kirschner, John C Gerhart, Christopher J Lowe
The Wnt family of secreted proteins has been proposed to play a conserved role in early specification of the bilaterian anteroposterior (A/P) axis. This hypothesis is based predominantly on data from vertebrate embryogenesis as well as planarian regeneration and homeostasis, indicating that canonical Wnt (cWnt) signaling endows cells with positional information along the A/P axis. Outside of these phyla, there is strong support for a conserved role of cWnt signaling in the repression of anterior fates, but little comparative support for a conserved role in promotion of posterior fates...
January 16, 2018: PLoS Biology
https://www.readbyqxmd.com/read/29337307/a-double-negative-inhibition-of-hepatic-gi-signaling-improves-glucose-homeostasis
#18
Allen M Spiegel
Hepatic glucose production (HGP) is a key determinant of glucose homeostasis. Glucagon binding to its cognate seven-transmembrane Gs-coupled receptor in hepatocytes stimulates cAMP production, resulting in increased HGP. In this issue of the JCI, Rossi and colleagues tested the hypothesis that activation of hepatic Gi-coupled receptors, which should inhibit cAMP production, would oppose the cAMP-inducing action of glucagon and thereby decrease HGP. Surprisingly, however, the opposite occurred: activation of Gi signaling increased HGP via a novel mechanism, while inhibition of Gi signaling reduced HGP...
January 16, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29337301/hepatic-gi-signaling-regulates-whole-body-glucose-homeostasis
#19
Mario Rossi, Lu Zhu, Sara M McMillin, Sai Prasad Pydi, Shanu Jain, Lei Wang, Yinghong Cui, Regina J Lee, Amanda H Cohen, Hideaki Kaneto, Morris J Birnbaum, Yanling Ma, Yaron Rotman, Jie Liu, Travis J Cyphert, Toren Finkel, Owen P McGuinness, Jürgen Wess
An increase in hepatic glucose production (HGP) is a key feature of type 2 diabetes. Excessive signaling through hepatic Gs-linked glucagon receptors critically contributes to pathologically elevated HGP. Here, we tested the hypothesis that this metabolic impairment can be counteracted by enhancing hepatic Gi signaling. Specifically, we used a chemogenetic approach to selectively activate Gi-type G proteins in mouse hepatocytes in vivo. Unexpectedly, activation of hepatic Gi signaling triggered a pronounced increase in HGP and severely impaired glucose homeostasis...
January 16, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29337054/deficiency-of-primary-cilia-in-kidney-epithelial-cells-induces-epithelial-to-mesenchymal-transition
#20
Sang Jun Han, Jin Ki Jung, Seung-Soon Im, Seong-Ryong Lee, Byeong-Churl Jang, Kwon Moo Park, Jee In Kim
Primary cilium is a microtubule-based non-motile organelle that plays critical roles in kidney pathophysiology. Our previous studies revealed that the lengths of primary cilia decreased upon renal ischemia/reperfusion injury and oxidative stress, and restored with recovery. Here, we tested the hypothesis that lack of primary cilium causes epithelial to mesenchymal transition (EMT) of kidney tubule cells. We investigated the alteration of length of primary cilia in TGF-β-induced EMT via visualization of primary cilia by fluorescence staining against acetylated α-tubulin...
January 11, 2018: Biochemical and Biophysical Research Communications
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