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Inhibitory receptor

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https://www.readbyqxmd.com/read/27922130/the-nmda-receptor-glun2c-subunit-controls-cortical-excitatory-inhibitory-balance-neuronal-oscillations-and-cognitive-function
#1
Subhash C Gupta, Aparna Ravikrishnan, Jinxu Liu, Zhihao Mao, Ratnamala Pavuluri, Brandon G Hillman, Pauravi J Gandhi, Dustin J Stairs, Ming Li, Rajesh R Ugale, Daniel T Monaghan, Shashank M Dravid
Despite strong evidence for NMDA receptor (NMDAR) hypofunction as an underlying factor for cognitive disorders, the precise roles of various NMDAR subtypes remains unknown. The GluN2C-containing NMDARs exhibit unique biophysical properties and expression pattern, and lower expression of GluN2C subunit has been reported in postmortem brains from schizophrenia patients. We found that loss of GluN2C subunit leads to a shift in cortical excitatory-inhibitory balance towards greater inhibition. Specifically, pyramidal neurons in the medial prefrontal cortex (mPFC) of GluN2C knockout mice have reduced mEPSC frequency and dendritic spine density and a contrasting higher frequency of mIPSCs...
December 6, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27922047/new-arylated-benzo-h-quinolines-induce-anti-cancer-activity-by-oxidative-stress-mediated-dna-damage
#2
Dharmendra K Yadav, Reeta Rai, Naresh Kumar, Surjeet Singh, Sanjeev Misra, Praveen Sharma, Priyanka Shaw, Horacio Pérez-Sánchez, Ricardo L Mancera, Eun Ha Choi, Mi-Hyun Kim, Ramendra Pratap
The anti-cancer activity of the benzo[h]quinolines was evaluated on cultured human skin cancer (G361), lung cancer (H460), breast cancer (MCF7) and colon cancer (HCT116) cell lines. The inhibitory effect of these compounds on the cell growth was determined by the MTT assay. The compounds 3e, 3f, 3h and 3j showed potential cytotoxicity against these human cancer cell lines. Effect of active compounds on DNA oxidation and expression of apoptosis related gene was studied. We also developed a quantitative method to measure the activity of cyclin-dependent kinases-2 (CDK2) by western blotting in the presence of active compound...
December 6, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27922009/pet-imaging-guided-chemogenetic-silencing-reveals-a-critical-role-of-primate-rostromedial-caudate-in-reward-evaluation
#3
Yuji Nagai, Erika Kikuchi, Walter Lerchner, Ken-Ichi Inoue, Bin Ji, Mark A G Eldridge, Hiroyuki Kaneko, Yasuyuki Kimura, Arata Oh-Nishi, Yukiko Hori, Yoko Kato, Toshiyuki Hirabayashi, Atsushi Fujimoto, Katsushi Kumata, Ming-Rong Zhang, Ichio Aoki, Tetsuya Suhara, Makoto Higuchi, Masahiko Takada, Barry J Richmond, Takafumi Minamimoto
The rostromedial caudate (rmCD) of primates is thought to contribute to reward value processing, but a causal relationship has not been established. Here we use an inhibitory DREADD (Designer Receptor Exclusively Activated by Designer Drug) to repeatedly and non-invasively inactivate rmCD of macaque monkeys. We inject an adeno-associated viral vector expressing the inhibitory DREADD, hM4Di, into the rmCD bilaterally. To visualize DREADD expression in vivo, we develop a non-invasive imaging method using positron emission tomography (PET)...
December 6, 2016: Nature Communications
https://www.readbyqxmd.com/read/27920219/the-proprotein-convertases-in-hypercholesterolemia-and-cardiovascular-diseases-emphasis-on-proprotein-convertase-subtilisin-kexin-9
#4
REVIEW
Nabil G Seidah, Marianne Abifadel, Stefan Prost, Catherine Boileau, Annik Prat
The secretory proprotein convertase (PC) family comprises nine members, as follows: PC1/3, PC2, furin, PC4, PC5/6, paired basic amino acid cleaving enzyme 4, PC7, subtilisin kexin isozyme 1/site 1 protease (SKI-1/S1P), and PC subtilisin/kexin type 9 (PCSK9). The first seven PCs cleave their substrates at single/paired basic residues and exhibit specific and often essential functions during development and/or in adulthood. The essential SKI-1/S1P cleaves membrane-bound transcription factors at nonbasic residues...
January 2017: Pharmacological Reviews
https://www.readbyqxmd.com/read/27920123/selective-enhancement-of-insulin-sensitivity-in-the-endothelium-in-vivo-reveals-a-novel-proatherosclerotic-signalling-loop
#5
Hema Viswambharan, Nadira Y Yuldasheva, Anshuman Sengupta, Helen Imrie, Matthew C Gage, Natalie J Haywood, Andrew M Walker, Anna Skromna, Natalia Makova, Stacey L Galloway, Pooja Shah, Piruthivi Sukumar, Karen E Porter, Peter J Grant, Ajay M Shah, Celio X Santos, Jing Li, David J Beech, Stephen Wheatcroft, Richard M Cubbon, Mark T Kearney
RATIONALE: In the endothelium, insulin stimulates endothelial nitric oxide synthase (eNOS) to generate the anti-atherosclerotic signalling radical NO. Insulin resistant type 2 diabetes is associated with reduced NO availability and accelerated atherosclerosis. The effect of enhancing endothelial insulin sensitivity on NO availability is unclear. OBJECTIVE: To answer this question we generated a mouse with endothelial cell (EC)-specific over-expression of the human insulin receptor (hIRECO) using the Tie2 promoter-enhancer...
December 5, 2016: Circulation Research
https://www.readbyqxmd.com/read/27920091/interferon-gamma-limits-diabetogenic-cd8-t-cell-effector-responses-in-type-1-diabetes
#6
John P Driver, Jeremy J Racine, Cheng Ye, Deanna J Lamont, Brittney N Newby, Caroline G McPhee-Leeth, Harold D Chapman, Todd M Brusko, Yi-Guang Chen, Clayton E Mathews, David V Serreze
Type 1 diabetes development in the NOD mouse model is widely reported to be dependent on high-level production by autoreactive CD4(+) and CD8(+) T-cells of IFNγ, generally considered a pro-inflammatory cytokine. However, IFNγ can also participate in tolerance induction pathways, indicating it is not solely pro-inflammatory. This study addresses how IFNγ can suppress activation of diabetogenic CD8(+) T-cells. CD8(+) T-cells transgenically expressing the diabetogenic AI4 T-cell receptor (TCR) adoptively transferred disease to otherwise unmanipulated NOD...
December 5, 2016: Diabetes
https://www.readbyqxmd.com/read/27920040/regulation-of-tgf-%C3%AE-family-signaling-by-inhibitory-smads
#7
Keiji Miyazawa, Kohei Miyazono
Inhibitory Smads (I-Smads) have conserved carboxy-terminal MH2 domains but highly divergent amino-terminal regions when compared with receptor-regulated Smads (R-Smads) and common-partner Smads (co-Smads). Smad6 preferentially inhibits Smad signaling initiated by the bone morphogenetic protein (BMP) type I receptors ALK-3 and ALK-6, whereas Smad7 inhibits both transforming growth factor β (TGF-β)- and BMP-induced Smad signaling. I-Smads also regulate some non-Smad signaling pathways. Here, we discuss the vertebrate I-Smads, their roles as inhibitors of Smad activation and regulators of receptor stability, as scaffolds for non-Smad signaling, and their possible roles in the nucleus...
December 5, 2016: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/27919002/inhibitory-effect-of-fentanyl-citrate-on-the-release-of-endothlin-1-induced-by-bradykinin-in-melanoma-cells
#8
Tsugunobu Andoh, Akira Shinohara, Yasushi Kuraishi
BACKGROUND: Our previous study showed that the μ-opioid receptor agonist fentanyl citrate inhibits endothelin-1-and bradykinin-mediated pain responses in mice orthotopically inoculated with melanoma cells. We also demonstrated that bradykinin induces endothelin-1 secretion in melanoma cells. However, the analgesic mechanisms of fentanyl citrate remain unclear. Thus, the present study was conducted to determine whether fentanyl citrate affects bradykinin-induced endothelin-1 secretion in B16-BL6 melanoma cells...
October 6, 2016: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/27918555/gene-expression-profiling-of-anti-ctla4-treated-metastatic-melanoma-in-patients-with-treatment-induced-autoimmunity
#9
Scott C Bresler, Le Min, Scott J Rodig, Andrew C Walls, Shuyun Xu, Songmei Geng, F Stephen Hodi, George F Murphy, Christine G Lian
Ipilimumab (IPI) is a monoclonal antibody that targets the inhibitory CTLA4 receptor of T cells, enhancing T-cell-driven antitumor responses. IPI therapy in metastatic melanoma results in significant improvement in disease-free and overall survival, although after initial responses disease progression generally ensues. Identification of specific responses in tissue where melanoma tumor cells are subjected to IPI-driven immune attack may reveal mechanisms of treatment efficacy or resistance, permitting refinement of targeted therapeutic approaches...
December 5, 2016: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/27916733/sirt1-regulates-lipopolysaccharide-induced-cd40-expression-in-renal-medullary-collecting-duct-cells-by-suppressing-the-tlr4-nf-%C3%AE%C2%BAb-signaling-pathway
#10
Qin-Qin Lin, Yuan-Wen Geng, Zhong-Wei Jiang, Zhen-Jun Tian
AIMS: Recent evidence indicates that sirtuin1 (SIRT1), a NAD(+)-dependent deacetylase, exerts a protective effect against inflammatory kidney injury by suppressing pro-inflammatory cytokines production. The co-stimulatory molecule, CD40, is expressed in a variety of inflammatory diseases in the kidney. Here, we aimed to investigate the potential effect of SIRT1 on CD40 expression induced by lipopolysaccharide (LPS) and to disclose the underlying mechanisms in renal inner medullary collecting duct (IMCD) cells...
December 1, 2016: Life Sciences
https://www.readbyqxmd.com/read/27916688/effects-of-repeated-treatment-with-a-delta-opioid-receptor-agonist-knt-127-on-hyperemotionality-in-olfactory-bulbectomized-rats
#11
Leo Gotoh, Akiyoshi Saitoh, Misa Yamada, Hideaki Fujii, Hiroshi Nagase, Mitsuhiko Yamada
We previously demonstrated that a single treatment of a non-peptidic delta opioid receptor agonist, KNT-127, has an antidepressant-like effect in rodents in the forced swim test. Here we evaluated the effect of repeated administration of the potential antidepressant KNT-127 in an olfactory-bulbectomized (OBX) rat model. Male Wistar rats (8-12 weeks old) underwent olfactory bulbectomy. From 14days after surgery each was weighed and administered either KNT-127 (3mgkg(-1)/day), the selective serotonin reuptake inhibitor (SSRI) fluoxetine (10mgkg(-1)/day), or vehicle, daily for 14 days...
December 1, 2016: Behavioural Brain Research
https://www.readbyqxmd.com/read/27916574/temperature-affects-sexual-maturation-through-the-control-of-kisspeptin-kisspeptin-receptor-gnrh-and-gth-subunit-gene-expression-in-the-grass-puffer-during-the-spawning-season
#12
Md Shahjahan, Takashi Kitahashi, Hironori Ando
Water temperature is an environmental factor of primary importance that influences reproductive function in fish. To understand the molecular and physiological mechanisms underlying the regulation of reproduction by temperature, we examined changes in expression of genes encoding kisspeptin (kiss2), kisspeptin receptor (kiss2r) and three gonadotropin-releasing hormones (gnrh1, gnrh2 and gnrh3) in the brain and genes encoding gonadotropin (GTH) subunits (gpa, fshb and lhb) in the pituitary of grass puffer exposed to a low temperature (14°C), normal temperature (21°C) and high temperature (28°C) for 7 days...
December 1, 2016: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/27914809/actein-enhances-trail-effects-on-suppressing-gastric-cancer-progression-by-activating-p53-caspase-3-signaling
#13
Zhi-Chao Yang, Ji Ma
Actein (ACT), isolated from the rthizomes of Cimicifuga foetida, is a triterpene glycoside, showing inhibitory role in breast cancer cells. However, the effects of ACT treatment on gastric cancer have little been known. Thus, the study is conducted to explore the in vitro and in vivo role of ACT in gastric cancer. And the interactions between ACT and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) were investigated in gastric cancer cells. A synergistic effect of ACT and TRAIL combination on apoptosis induction in gastric cancer cells was observed...
November 30, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27914001/subtilosin-prevents-biofilm-formation-by-inhibiting-bacterial-quorum-sensing
#14
Ammar Algburi, Saskia Zehm, Victoria Netrebov, Anzhelica B Bren, Vladimir Chistyakov, Michael L Chikindas
Subtilosin, the cyclic lantibiotic protein produced by Bacillus subtilis KATMIRA1933, targets the surface receptor and electrostatically binds to the bacterial cell membrane. In this study, subtilosin was purified using ammonium sulfate ((NH4)2SO4) precipitation and purified via column chromatography. Subtilosin's antibacterial minimum and sub-minimum inhibitory concentrations (MIC and sub-MIC) and anti-biofilm activity (biofilm prevention) were established. Subtilosin was evaluated as a quorum sensing (QS) inhibitor in Gram-positive bacteria using Fe(III) reduction assay...
December 2, 2016: Probiotics and Antimicrobial Proteins
https://www.readbyqxmd.com/read/27913590/control-of-spike-transfer-at-hippocampal-mossy-fiber-synapses-in-vivo-by-gabaa-and-gabab-receptor-mediated-inhibition
#15
Stefano Zucca, Marilena Griguoli, Meryl Malézieux, Noëlle Grosjean, Mario Carta, Christophe Mulle
: Despite extensive studies in hippocampal slices and incentive from computational theories, the synaptic mechanisms underlying information transfer at mossy fiber (mf) connections between the dentate gyrus (DG) and CA3 neurons in vivo are still elusive. Here we used an optogenetic approach in mice to selectively target and control the activity of DG granule cells (GCs) while performing whole cell and juxtacellular recordings of CA3 neurons in vivo In CA3 pyramidal cells (PCs), mf-CA3 synaptic responses consisted predominantly of an inhibitory postsynaptic potential (IPSP) at low stimulation frequency (0...
December 2, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27913469/can-we-make-a-better-match-or-mismatch-with-kir-genotyping
#16
Rohtesh S Mehta, Katayoun Rezvani
Natural killer (NK) cell function is regulated by a fine balance between numerous activating and inhibitory receptors, of which killer-cell immunoglobulin-like receptors (KIRs) are among the most polymorphic and comprehensively studied. KIRs allow NK cells to recognize downregulation or the absence of HLA class I molecules on target cells (known as missing-self), a phenomenon that is commonly observed in virally infected cells or cancer cells. Because KIR and HLA genes are located on different chromosomes, in an allogeneic environment such as after hematopoietic stem cell transplantation, donor NK cells that express an inhibitory KIR for an HLA class I molecule that is absent on recipient targets (KIR/KIR-ligand mismatch), can recognize and react to this missing self and mediate cytotoxicity...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913299/the-inhibitory-effect-of-beta-lapachone-on-rankl-induced-osteoclastogenesis
#17
Dong Ryun Gu, Joon No Lee, Gi-Su Oh, Hyung Jin Kim, Min Seuk Kim, Seoung Hoon Lee
β-lapachone (β-L) is a substrate of reduced nicotinamide adenine dinucleotide (NADH): quinone oxidoreductase 1 (NQO1). NQO1 reduces quinones to hydroquinones using NADH as an electron donor and consequently increases the intracellular NAD+/NADH ratio. The activation of NQO1 by β-L has beneficial effects on several metabolic syndromes, such as obesity, hypertension, and renal injury. However, the effect of β-L on bone metabolism remains unclear. Here, we show that β-L might be a potent inhibitor of receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis...
November 30, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27912872/anti-allergic-potential-of-typhonium-blumei-inhibition-of-degranulation-via-suppression-of-pi3k-plc%C3%AE-2-phosphorylation-and-calcium-influx
#18
Michal Korinek, Kuan-Ming Chen, Yu-Han Jiang, Mohamed El-Shazly, Joel Stocker, Chon-Kit Chou, Tsong-Long Hwang, Yang-Chang Wu, Bing-Hung Chen, Fang-Rong Chang
BACKGROUND: Typhonium blumei Nicolson & Sivadasan (Araceae) is a traditional Chinese medicinal herb possessing detumescent, detoxifying, and anti-inflammatory activities. It is used in Taiwan as a folk medicine to treat cancer and inflammatory diseases. Typhonium blumei is usually not distinguished from Typhonium roxburghii Schott and they are commonly used interchangeably. PURPOSE: To evaluate and compare the anti-allergic and anti-inflammatory properties of T...
December 15, 2016: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/27912762/regulation-of-effector-function-of-cns-autoreactive-cd4-t-cells-through-inhibitory-receptors-and-il-7r%C3%AE
#19
Patrick K Nuro-Gyina, Elizabeth L Rieser, Marissa C Granitto, Wei Pei, Yue Liu, Priscilla W Lee, Saba Aqel, Jian Zhang, Amy E Lovett-Racke, Michael K Racke, Yuhong Yang
BACKGROUND: Multiple sclerosis (MS) is a chronic CNS autoimmune disease characterized by inflammation, demyelination, and neuronal degeneration, where myelin-specific CD4 T cells play critical roles in the formation of acute MS lesions and disease progression. The suppression of IL-7Rα expression and the upregulation of inhibitory receptors (PD-1, etc.) are essential parts of the cell-intrinsic immunosuppressive program regulating T effector functions to prevent autoimmunity. However, little is known on the factors regulating IL-7Rα/PD-1 balance in myelin-specific CD4 T effector/memory cells during the development of CNS autoimmunity...
December 3, 2016: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/27912061/tumor-interferon-signaling-regulates-a-multigenic-resistance-program-to-immune-checkpoint-blockade
#20
Joseph L Benci, Bihui Xu, Yu Qiu, Tony J Wu, Hannah Dada, Christina Twyman-Saint Victor, Lisa Cucolo, David S M Lee, Kristen E Pauken, Alexander C Huang, Tara C Gangadhar, Ravi K Amaravadi, Lynn M Schuchter, Michael D Feldman, Hemant Ishwaran, Robert H Vonderheide, Amit Maity, E John Wherry, Andy J Minn
Therapeutic blocking of the PD1 pathway results in significant tumor responses, but resistance is common. We demonstrate that prolonged interferon signaling orchestrates PDL1-dependent and PDL1-independent resistance to immune checkpoint blockade (ICB) and to combinations such as radiation plus anti-CTLA4. Persistent type II interferon signaling allows tumors to acquire STAT1-related epigenomic changes and augments expression of interferon-stimulated genes and ligands for multiple T cell inhibitory receptors...
December 1, 2016: Cell
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