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https://www.readbyqxmd.com/read/28449103/novel-degenerative-and-developmental-defects-in-a-zebrafish-model-of-mucolipidosis-type-iv
#1
Huiqing Li, Wuhong Pei, Sivia Vergarajauregui, Patricia M Zerfas, Nina Raben, Shawn M Burgess, Rosa Puertollano
Mucolipidosis type IV (MLIV) is a lysosomal storage disease characterized by neurologic and ophthalmologic abnormalities. There is currently no effective treatment. MLIV is caused by mutations in MCOLN1, a lysosomal cation channel from the transient receptor potential (TRP) family. In this study we used genome editing to knockout the two mcoln1 genes present in Dario rerio (zebrafish). Our model successfully reproduced the retinal and neuromuscular defects observed in MLIV patients, indicating that this model is suitable for studying the disease pathogenesis...
April 25, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28448702/ketamine-for-depression-1-clinical-summary-of-issues-related-to-efficacy-adverse-effects-and-mechanism-of-action
#2
Chittaranjan Andrade
Ketamine is an anesthetic drug that is also used for off-label indications such as the mediation of analgesia and sedation in various settings. It is additionally recognized as an agent with antidepressant potential. For depression, it is most commonly administered as a slow intravenous infusion in subanesthetic doses (usually 0.5 mg/kg). As an antidepressant, is strikingly different from conventional antidepressant drugs in that it brings about rapid and marked attenuation of depressive symptoms even in patients with refractory depression...
April 2017: Journal of Clinical Psychiatry
https://www.readbyqxmd.com/read/28448473/transcriptomic-analysis-of-calcium-remodeling-in-colorectal-cancer
#3
Enrique Pérez-Riesgo, Lucía G Gutiérrez, Daniel Ubierna, Alberto Acedo, Mary P Moyer, Lucía Núñez, Carlos Villalobos
Colorectal cancer (CRC) cells undergo the remodeling of intracellular Ca(2+) homeostasis, which contributes to cancer hallmarks such as enhanced proliferation, invasion and survival. Ca(2+) remodeling includes critical changes in store-operated Ca(2+) entry (SOCE) and Ca(2+) store content. Some changes have been investigated at the molecular level. However, since nearly 100 genes are involved in intracellular Ca(2+) transport, a comprehensive view of Ca(2+) remodeling in CRC is lacking. We have used Next Generation Sequencing (NGS) to investigate differences in expression of 77 selected gene transcripts involved in intracellular Ca(2+) transport in CRC...
April 27, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28446875/cannabinoid-modulation-of-memory-consolidation-in-rats-beyond-the-role-of-cannabinoid-receptor-subtype-1
#4
Patrizia Ratano, Maura Palmery, Viviana Trezza, Patrizia Campolongo
The effects induced by exogenous manipulation of endocannabinoid neurotransmission on emotion and memory are often contradictory. Among the different factors involved, of particular interest is the binding affinity of endocannabinoids, and their analogs, for other receptor families beyond cannabinoid receptors, such as the peroxisome proliferator-activated receptors (PPARs), and the transient receptor potential cation channel subfamily V member 1 (TRPV1). The aim of this study was to investigate which receptor subtype mediates cannabinoid effects on memory consolidation for emotionally arousing experiences...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28444767/the-dual-orexin-receptor-antagonist-dora-22-lowers-histamine-levels-in-the-lateral-hypothalamus-and-prefrontal-cortex-without-lowering-hippocampal-acetylcholine
#5
Lihang Leon Yao, Andres Ramirez, Anthony J Roecker, Steven Fox, Jason Uslaner, Sean M Smith, Robert Hodgson, Paul J Coleman, John J Renger, Christopher J Winrow, Anthony L Gotter
Chronic insomnia is defined as a persistent difficulty with sleep initiation maintenance or non-restorative sleep. The therapeutic standard of care for this condition is treatment with gamma-aminobutyric acid (GABA)A receptor modulators, which promote sleep but are associated with a panoply of side effects, including cognitive and memory impairment. Dual orexin receptor antagonists (DORAs) have recently emerged as an alternative therapeutic approach that acts via a distinct and more selective wake-attenuating mechanism with the potential to be associated with milder side effects...
April 26, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28443064/loss-of-vagal-sensitivity-to-cholecystokinin-in-rats-born-with-intrauterine-growth-retardation-and-consequence-on-food-intake
#6
Marième Ndjim, Camille Poinsignon, Patricia Parnet, Gwenola Le Dréan
Perinatal malnutrition is associated with low birth weight and an increased risk of developing metabolic syndrome in adulthood. Modification of food intake (FI) regulation was observed in adult rats born with intrauterine growth retardation induced by maternal dietary protein restriction during gestation and maintained restricted until weaning. Gastrointestinal peptides and particularly cholecystokinin (CCK) play a major role in short-term regulation of FI by relaying digestive signals to the hindbrain via the vagal afferent nerve (VAN)...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28442922/inhibition-of-pcsk9-protects-against-radiation-induced-damage-of-prostate-cancer-cells
#7
Si-Shun Gan, Jian-Qing Ye, Lei Wang, Fa-Jun Qu, Chuan-Min Chu, Yi-Jun Tian, Wei Yang, Xin-Gang Cui
BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a protein expressed primarily in the liver, formerly known to maintain plasma lipid homeostasis by regulating low-density lipoprotein receptor levels, and its exact role in the radioresistance of prostate cancer (PCa) remains unclear. We aim to investigate the function of PCSK9 in the radioresistance of PCa cells. METHODS: PCSK9 small interfering RNA (siRNA) was introduced into the PCa cells by transient transfection...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28442546/modeled-structural-basis-for-the-recognition-of-%C3%AE-2-3-sialyllactose-by-soluble-klotho
#8
Jon D Wright, Sung-Wan An, Jian Xie, Joonho Yoon, Nicole Nischan, Jennifer J Kohler, Noelynn Oliver, Carmay Lim, Chou-Long Huang
Soluble Klotho (sKlotho) is the shed ectodomain of antiaging membrane Klotho that contains 2 extracellular domains KL1 and KL2, each of which shares sequence homology to glycosyl hydrolases. sKlotho elicits pleiotropic cellular responses with a poorly understood mechanism of actions. Notably, in injury settings, sKlotho confers cardiac and renal protection by down-regulating calcium-permeable transient receptor potential canonical type isoform 6 (TRPC6) channels in cardiomyocytes and glomerular podocytes. Inhibition of PI3K-dependent exocytosis of TRPC6 is thought to be the underlying mechanism, and recent studies showed that sKlotho interacts with α2-3-sialyllactose-containing gangliosides enriched in lipid rafts to inhibit raft-dependent PI3K signaling...
April 25, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28441725/sweet-taste-receptor-activation-in-the-gut-is-of-limited-importance-for-glucose-stimulated-glp-1-and-gip-secretion
#9
Monika Y Saltiel, Rune E Kuhre, Charlotte B Christiansen, Rasmus Eliasen, Kilian W Conde-Frieboes, Mette M Rosenkilde, Jens J Holst
Glucose stimulates the secretion of the incretin hormones: glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP). It is debated whether the sweet taste receptor (STR) triggers this secretion. We investigated the role of STR activation for glucose-stimulated incretin secretion from an isolated perfused rat small intestine and whether selective STR activation by artificial sweeteners stimulates secretion. Intra-luminal administration of the STR agonists, acesulfame K (3.85% w/v), but not sucralose (1...
April 22, 2017: Nutrients
https://www.readbyqxmd.com/read/28438981/acute-inflammation-reveals-gabaa-receptor-mediated-nociception-in-mouse-dorsal-root-ganglion-neurons-via-pge2-receptor-4-signaling
#10
In Jeong Jang, Alexander J Davies, Nozomi Akimoto, Seung Keun Back, Pa Reum Lee, Heung Sik Na, Hidemasa Furue, Sung Jun Jung, Yong Ho Kim, Seog Bae Oh
Gamma-aminobutyric acid (GABA) depolarizes dorsal root ganglia (DRG) primary afferent neurons through activation of Cl(-) permeable GABAA receptors but the physiologic role of GABAA receptors in the peripheral terminals of DRG neurons remains unclear. In this study, we investigated the role of peripheral GABAA receptors in nociception using a mouse model of acute inflammation. In vivo, peripheral administration of the selective GABAA receptor agonist muscimol evoked spontaneous licking behavior, as well as spinal wide dynamic range (WDR) neuron firing, after pre-conditioning with formalin but had no effect in saline-treated mice...
April 2017: Physiological Reports
https://www.readbyqxmd.com/read/28437833/transient-receptor-potential-trp-channels-and-exercise-associated-muscle-cramping-eamc-a-tale-of-multiple-complexities
#11
EDITORIAL
M P Schwellnus, M D Hoffman
No abstract text is available yet for this article.
April 24, 2017: Muscle & Nerve
https://www.readbyqxmd.com/read/28436534/a-novel-trpa1-variant-is-associated-with-carbamazepine-responsive-cramp-fasciculation-syndrome
#12
M J Nirenberg, R Chaouni, T M Biller, R M Gilbert, C Paisán-Ruiz
Cramp-fasciculation syndrome (CFS) is a rare muscle hyperexcitability syndrome that presents with muscle cramps, fasciculations, and stiffness, as well as pain, fatigue, anxiety, hyperreflexia, and paresthesias. Although familial cases have been reported, a genetic etiology has not yet been identified. We performed whole-exome sequencing followed by validation and cosegregation analyses on a father-son pair with CFS. Both subjects manifested other hypersensitivity-hyperexcitability symptoms, including asthma, gastroesophageal reflux, migraine, restless legs syndrome, tremor, cold hyperalgesia, and cardiac conduction defects...
April 24, 2017: Clinical Genetics
https://www.readbyqxmd.com/read/28436098/lecrk-v-an-l-type-lectin-receptor-kinase-in-haynaldia-villosa-plays-positive-role-in-resistance-to-wheat-powdery-mildew
#13
Zongkuan Wang, Jiangyue Cheng, Anqi Fan, Jia Zhao, Zhongyu Yu, Yingbo Li, Heng Zhang, Jin Xiao, Faheem Mohammad, Haiyan Wang, Aizhong Cao, Liping Xing, Xiue Wang
Plant sense potential microbial pathogen by using pattern recognition receptors (PRRs) to recognize pathogen associated molecular patterns (PAMPs). The Lectin receptor like kinase genes (LecRKs) are involved in various cellular processes mediated by signal transduction pathways. In the present study, an L-type lectin receptor kinase gene LecRK-V was cloned from Haynaldia villosa, a diploid wheat relative which is highly resistant to powdery mildew. The expression of LecRK-V was rapidly up-regulated by Bgt inoculation and chitin treatment...
April 24, 2017: Plant Biotechnology Journal
https://www.readbyqxmd.com/read/28434588/the-endocannabinoid-system-as-a-target-for-novel-anxiolytic-drugs
#14
REVIEW
Sachin Patel, Mathew N Hill, Joseph F Cheer, Carsten T Wotjak, Andrew Holmes
The endocannabinoid (eCB) system has attracted attention for its role in various behavioral and brain functions, and as a therapeutic target in neuropsychiatric disease states, including anxiety disorders and other conditions resulting from dysfunctional responses to stress. In this mini-review, we highlight components of the eCB system that offer potential 'druggable' targets for new anxiolytic medications, emphasizing some of the less well-discussed options. We discuss how selectively amplifying eCBs recruitment by interfering with eCB-degradation, via fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), has been linked to reductions in anxiety-like behaviors in rodents and variation in human anxiety symptoms...
May 2017: Neuroscience and Biobehavioral Reviews
https://www.readbyqxmd.com/read/28433656/impaired-endothelium-derived-hyperpolarization-type-relaxation-in-superior-mesenteric-arteries-isolated-from-female-otsuka-long-evans-tokushima-fatty-rats
#15
Takayuki Matsumoto, Shota Kobayashi, Makoto Ando, Shun Watanabe, Maika Iguchi, Kumiko Taguchi, Tsuneo Kobayashi
Endothelium-derived hyperpolarization (EDH) is an important signaling mechanism of endothelium-dependent vasorelaxation, and little attention has been paid to the EDH-type responses in female metabolic syndrome such as that observed with type-2 diabetes. We previously reported that EDH-type relaxation was impaired in superior mesenteric arteries from male Otsuka Long-Evans Tokushima Fatty (OLETF) rat, a model of type-2 diabetes, however, the response was unclear in female OLETF rat. Thus, the aim of this study was to examine if EDH-type relaxation was altered in superior mesenteric arteries isolated from female OLETF rats compared to age-matched, control female Long-Evans Tokushima Otsuka (LETO) rats at age 50-59 weeks...
April 19, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28433438/analgesic-effects-of-transcutaneous-ultrasound-nerve-stimulation-in-a-rat-model-of-oxaliplatin-induced-mechanical-hyperalgesia-and-cold-allodynia
#16
Yueh-Ling Hsieh, Han-Yu Chen, Ching-Hsiang Yang, Chen-Chia Yang
This study investigated the effects and underlying mechanisms of therapeutic ultrasound (TUS) in a rat model of oxaliplatin-induced peripheral neuropathy. Animals received a total of eight injections with oxaliplatin (4 mg/kg), administered at 3-d intervals. TUS intervention (1 MHz, 0.5 W/cm(2)) started on the fifth oxaliplatin administration and continued for 10 consecutive d. Sensory behavioral examinations, protein levels of transient receptor potential channels (TRPM8 and TRPV1) in dorsal root ganglia (DRG) and substance P (SP) in spinal dorsal horn were examined...
April 19, 2017: Ultrasound in Medicine & Biology
https://www.readbyqxmd.com/read/28432761/protein-s-sulfhydration-by-hydrogen-sulfide-in-cardiovascular-system
#17
REVIEW
Guoliang Meng, Shuang Zhao, Liping Xie, Yi Han, Yong Ji
Hydrogen sulfide (H2 S), independent on any specific transporters, plays a number of biological effects on cardiovascular systems. However, the detailed mechanism of H2 S is not yet clear until now. Recently, a novel post-translational modification induced by H2 S, named S-sulfhydration, has been proposed. S-sulfhydration is a chemical modification on specific cysteine residues of target proteins by H2 S. There are several methods for S-sulfhydration detection, such as modified biotin switch assay, maleimide assay with fluorescent thiol modifying regents, tag-switch method and mass spectrometry...
April 22, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28432033/lipids-as-central-modulators-of-sensory-trp-channels
#18
REVIEW
Maria Grazia Ciardo, Antonio Ferrer-Montiel
The transient receptor potential (TRP) ion channel family is involved in a diversity of physiological processes including sensory and homeostatic functions, as well as muscle contraction and vasomotor control. Their dysfunction contributes to the etiology of several diseases, being validated as therapeutic targets. These ion channels may be activated by physical or chemical stimuli and their function is highly influenced by signaling molecules activated by extracellular signals. Notably, as integral membrane proteins, lipid molecules also modulate their membrane location and function either by direct interaction with the channel structure or by modulating the physico-chemical properties of the cellular membrane...
April 18, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28430879/role-of-phosphatase-and-tensin-homolog-pten-in-hypoxic-pulmonary-vasoconstriction
#19
Adrienn Krauszman, Tak Mak, Katalin Szaszi, Wolfgang M Kuebler
AIMS: Hypoxic pulmonary vasoconstriction (HPV) redistributes blood flow from poorly ventilated to better aerated areas in the lung, thereby optimizing ventilation-perfusion ratio (V/Q). Pulmonary artery smooth muscle cell (PASMC) contraction in response to hypoxia is triggered by Ca2+ influx via transient receptor potential canonical 6 (TRPC6) cation channels that have translocated to caveolae in the plasma membrane. Since phosphatase and tensin homolog (PTEN) was suggested to regulate TRPC6 in endothelial cells, we aimed to define its role in the hypoxic response of PASMCs and as a putative mediator of HPV...
April 18, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28430359/sulfur-containing-gaseous-signal-molecules-ion-channels-and-cardiovascular-diseases
#20
REVIEW
Wen Yu, Hongfang Jin, Chaoshu Tang, Junbao Du, Zhiren Zhang
Sulfur-containing gaseous signal molecules including hydrogen sulfide (H2 S) and sulfur dioxide (SO2 ) were previously recognized as toxic gases. However, extensive studies have revealed that they can be generated in the cardiovascular system via a sulfur-containing amino acid metabolic pathway, playing an important part in cardiovascular physiology and pathophysiology. Ion channels are pore-forming membrane proteins present in the membrane of all biological cells; functions include establishing a resting membrane potential and controlling action potentials and other electrical signals by conducting ions across the cell membrane...
April 21, 2017: British Journal of Pharmacology
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