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https://www.readbyqxmd.com/read/28531801/ace-2-ang1-7-mas-cascade-mediates-ace-inhibitor-captopril-protective-effects-in-estrogen-deficient-osteoporotic-rats
#1
Hatem M Abuohashish, Mohammed M Ahmed, Dina Sabry, Mahmoud M Khattab, Salim S Al-Rejaie
The local role of the renin angiotensin system (RAS) was documented recently beside its conventional systemic functions. Studies showed that the effector angiotensin II (AngII) alters bone health, while inhibition of the angiotensin converting enzyme (ACE-1) preserved these effects. The newly identified Ang1-7 exerts numerous beneficial effects opposing the AngII. Thus, the current study examines the role of Ang1-7 in mediating the osteo-preservative effects of ACEI (captopril) through the G-protein coupled Mas receptor using an ovariectomized (OVX) rat model of osteoporosis...
May 19, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28531371/wing-1-of-protein-hop2-is-as-important-as-helix-3-in-dna-binding-by-md-simulation
#2
Hem Moktan, Donghua H Zhou
The repair of programmed DNA double-strand breaks through recombination is required for proper association and disjunction of the meiotic homologous chromosomes. Meiosis specific protein HOP2 plays essential roles in recombination by promoting recombinase activities. The N-terminal domain of HOP2 interacts with DNA through helix 3 (H3) and wing 1 (W1). Mutations in wing 1 (Y65A/K67A/Q68A) slightly weakened the binding but mutations in helices 2 and 3 (Q30A/K44A/K49A) nearly abolished the binding. To better understand such differential effects at atomic level, molecular dynamics simulations were employed...
May 20, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/28530703/trpv4-plays-a-role-in-breast-cancer-cell-migration-via-ca-2-dependent-activation-of-akt-and-downregulation-of-e-cadherin-cell-cortex-protein
#3
W H Lee, L Y Choong, T H Jin, N N Mon, S Chong, C S Liew, T Putti, S Y Lu, C Harteneck, Y P Lim
TRPV4 belongs to the 'Transient Receptor Potential' (TRP) superfamily. It has been identified to profoundly affect a variety of physiological processes, including nociception, heat sensation and inflammation. Unlike other TRP superfamily channels, its role in cancers are unknown until recently when we reported TRPV4 to be required for cancer cell softness that may promote breast cancer cell extravasation and metastasis. Here, we elucidated the molecular mechanisms mediated by TRPV4 in the metastatic breast cancer cells...
May 22, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28530170/k-modulates-genetic-competence-and-the-stress-regulon-of-streptococcus-mutans
#4
Gursonika Binepal, Iwona B Wenderska, Paula Crowley, Richard N Besingi, Dilani B Senadheera, L Jeannine Brady, Dennis G Cvitkovitch
Potassium (K+) is the most abundant cation in dental plaque fluid. Previously, we reported the link between K+ transport via Trk2 in Streptococcus mutans and its two critical virulence attributes: acid tolerance and surface adhesion. Herein, we build further on the intimate link between K+ levels and S. mutans biology. High (>25 mM) versus low (≤5 mM) K+ concentrations in the growth medium affected conformational epitopes of cell surface-localized adhesin P1. At low K+, the expression of stress response elements gcrR and codY, cell-adhesion-associated genes such as spaP and metabolism-associated genes such as bglP was induced at stationary phase (P<0...
May 22, 2017: Microbiology
https://www.readbyqxmd.com/read/28529362/study-of-sexual-functioning-and-disorder-in-women-before-and-after-tubal-sterilization-tubectomy
#5
Shweta Patil Kunkeri, T S Sathyanarayana Rao, Chittaranjan Andrade
INTRODUCTION: Sexual relationship is a basis for mental health and continuity of the healthy generation. There are very few studies on the female sexual functioning, especially in India. Sterilization being the most common contraceptive method, sexual functioning in women undergoing this surgical intervention has not been adequately explored. Available studies have found conflicting results; some have reported that sterilization has positive effects on sexual functioning since anxiety of getting pregnant is abolished...
January 2017: Indian Journal of Psychiatry
https://www.readbyqxmd.com/read/28528905/a-pheromone-antagonist-regulates-optimal-mating-time-in-the-moth-helicoverpa-armigera
#6
Hetan Chang, Yang Liu, Dong Ai, Xingchuan Jiang, Shuanglin Dong, Guirong Wang
Many insect species use multi-component sex pheromones to discriminate among potential mating partners [1-5]. In moths, pheromone blends tend to be dominated by one or two major components, but behavioral responses are frequently optimized by the inclusion of less abundant minor components [6]. An increasing number of studies have shown that female insects use these chemicals to convey their mating availability to males, who can assess the maturity of females and thus decide when to mate [7, 8]. However, little is known about the biological mechanisms that enable males to assess female reproductive status...
May 17, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28528776/structural-basis-of-tpr-mediated-oligomerization-and-activation-of-oncogenic-fusion-kinases
#7
Kuntal Pal, Abhishek Bandyopadhyay, X Edward Zhou, Qingping Xu, David P Marciano, Joseph S Brunzelle, Smitha Yerrum, Patrick R Griffin, George Vande Woude, Karsten Melcher, H Eric Xu
The nuclear pore complex subunit TPR is found in at least five different oncogenic fusion kinases, including TPR-MET, yet how TPR fusions promote activation of kinases and their oncogenic activities remains poorly understood. Here we report the crystal structure of TPR(2-142), the MET fusion partner of oncogenic TPR-MET. TPR(2-142) contains a continuous 124-residue α helix that forms an antiparallel tetramer from two leucine zipper-containing parallel coiled coils. Remarkably, single mutations cause strikingly different conformations of the coiled coil, indicating its highly dynamic nature...
May 18, 2017: Structure
https://www.readbyqxmd.com/read/28527875/magnolol-attenuates-the-inflammation-and-apoptosis-through-the-activation-of-sirt1-in-experimental-stroke-rats
#8
Dong-Quan Kou, Yan-Ling Jiang, Jia-Hua Qin, Yin-Hui Huang
BACKGROUND: Silent information regulator 1 (SIRT1), a histone deacetylase, plays a protective role in ischemic brain injury. Previous studies have shown that magnolol has a beneficial effect on ischemic stroke; however, the role of SIRT1 in the protective effect of magnolol against cerebral ischemia has not been investigated. METHODS: We used a middle cerebral artery occlusion model of stroke in rats. Before stroke induction, the rats received intraperitoneal injections of magnolol with or without the SIRT1 inhibitor, EX527...
January 10, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/28527717/inhibition-of-the-lateral-habenular-camk%C3%A2-abolishes-naloxone-precipitated-conditioned-place-aversion-in-morphine-dependent-mice
#9
Jing Wang, Min Li, Ping Wang, Yunhong Zha, Zhi He, Zicheng Li
Addictive substances mediate positive and negative states promoting compulsive drug use. However, substrates for aversive effects of drugs are not fully understood. We found that inactivation of the lateral habenula (LHb) by microinjection of tetrodotoxin (TTX) abolished naloxone-precipitated conditioned place aversion (CPA) in morphine-dependent mice. We also found that lateral habenular administration of KN-62, a specific inhibitor for calcium/calmodulin dependent protein kinase II (CaMKII), abolished naloxone-precipitated CPA in morphine-dependent mice...
May 17, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28527616/catalase-increases-ethanol-oxidation-through-the-purine-catabolism-in-rat-liver
#10
Daniel Villalobos-García, Rolando Hernández-Muñoz
Hepatic ethanoloxidationincreases according to its concentration and is raised to near-saturation levels of alcohol dehydrogenase (ADH); therefore, re-oxidation of NADH becomes rate limiting in ethanol metabolism by the liver. Adenosine is able to increase liver ethanol oxidation in both in vivo and in vitro conditions; the enhancement being related with the capacity of the nucleoside to accelerate the transport of cytoplasmic reducing equivalents to mitochondria, by modifying the subcellular distribution of the malate-aspartate shuttle components...
May 17, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28527237/the-n-terminus-of-the-prion-protein-is-a-toxic-effector-regulated-by-the-c-terminus
#11
Bei Wu, Alex McDonald, Markham Kathleen, Celeste B Rich, Kyle P Mchugh, Jörg Tatzelt, Colby David, Glenn L Millhauser, David Harris
PrP(C), the cellular isoform of the prion protein, serves to transduce the neurotoxic effects of PrP(Sc), the infectious isoform, but how this occurs is mysterious. Here, using a combination of electrophysiological, cellular, and biophysical techniques, we show that the flexible, N-terminal domain of PrP(C) functions as a powerful toxicity-transducing effector whose activity is tightly regulated in cis by the globular C-terminal domain. Ligands binding to the N-terminal domain abolish the spontaneous ionic currents associated with neurotoxic mutants of PrP, and the isolated N-terminal domain induces currents when expressed in the absence of the C-terminal domain...
May 20, 2017: ELife
https://www.readbyqxmd.com/read/28526910/expression-and-regulation-of-type-2a-protein-phosphatases-and-alpha4-signalling-in-cardiac-health-and-hypertrophy
#12
Olga Eleftheriadou, Andrii Boguslavskyi, Michael R Longman, Jonathan Cowan, Asvi Francois, Richard J Heads, Brian E Wadzinski, Ali Ryan, Michael J Shattock, Andrew K Snabaitis
Cardiac physiology and hypertrophy are regulated by the phosphorylation status of many proteins, which is partly controlled by a poorly defined type 2A protein phosphatase-alpha4 intracellular signalling axis. Quantitative PCR analysis revealed that mRNA levels of the type 2A catalytic subunits were differentially expressed in H9c2 cardiomyocytes (PP2ACβ > PP2ACα > PP4C > PP6C), NRVM (PP2ACβ > PP2ACα = PP4C = PP6C), and adult rat ventricular myocytes (PP2ACα > PP2ACβ > PP6C > PP4C)...
July 2017: Basic Research in Cardiology
https://www.readbyqxmd.com/read/28526886/fk866-attenuates-acute-hepatic-failure-through-c-jun-n-terminal-kinase-jnk-dependent-autophagy
#13
Enshuang Guo, Renlong Li, Jiankun Yang, Jun Zhang, Anyi Li, Yan Yang, Shenpei Liu, Anding Liu, Xiaojing Jiang
FK866 exhibits a protective effect on D-galactosamine (GaIN)/lipopolysaccharide (LPS) and concanavalin A (ConA)-induced acute liver failure (ALF), but the mechanism by which FK866 affords this benefit has not yet been elucidated. Autophagy has a protective effect on acute liver injury. However, the contribution of autophagy to FK866-conferred hepatoprotection is still unclear. This study aimed to investigate whether FK866 could attenuate GaIN/LPS and ConA-induced ALF through c-jun-N-terminal kinase (JNK)-dependent autophagy...
May 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28526714/constans-imparts-dna-sequence-specificity-to-the-histone-fold-nf-yb-nf-yc-dimer
#14
Nerina Gnesutta, Roderick W Kumimoto, Swadhin Swain, Matteo Chiara, Chamindika Siriwardana, David Stephen Horner, Ben F Holt, Roberto Mantovani
NF-Y is a heterotrimeric transcription factor that binds CCAAT elements. The NF-Y trimer is composed of a Histone Fold Domain (HFD) dimer (NF-YB/NF-YC) and NF-YA, which confers DNA sequence-specificity. NF-YA shares a conserved domain with the CCT (CONSTANS, CONSTANS-LIKE, TOC1) proteins. We show that CONSTANS (CO/BBX1), a master flowering regulator, forms a trimer with Arabidopsis NF-YB2/NF-YC3 to efficiently bind the CORE element of the FT promoter. We term this complex NF-CO. Using saturation mutagenesis EMSAs and RNA-Seq profiling of co, nf-yb, and nf-yc mutants, we identify CCACA elements as the core NF-CO binding site...
May 19, 2017: Plant Cell
https://www.readbyqxmd.com/read/28526701/netrin-1-preserves-blood-brain-barrier-integrity-through-deleted-in-colorectal-cancer-focal-adhesion-kinase-rhoa-signaling-pathway-following-subarachnoid-hemorrhage-in-rats
#15
Zongyi Xie, Budbazar Enkhjargal, Cesar Reis, Lei Huang, Weifeng Wan, Jiping Tang, Yuan Cheng, John H Zhang
BACKGROUND: Netrin-1 (NTN-1) has been established to be a novel intrinsic regulator of blood-brain barrier (BBB) maintenance. This study was carried out to investigate the potential roles of exogenous NTN-1 in preserving BBB integrity after experimental subarachnoid hemorrhage (SAH) as well as the underlying mechanisms of its protective effects. METHODS AND RESULTS: A total of 309 male Sprague-Dawley rats were subjected to an endovascular perforation model of SAH...
May 19, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28526517/regulation-of-rhoa-rock-and-sustained-arterial-contraction-by-low-cytosolic-ca-2-levels-during-prolonged-depolarization-of-arterial-smooth-muscle
#16
Cristina Porras-González, Antonio Ordóñez, Antonio Castellano, Juan Ureña
The role of L-type Ca(2+) channels (LTCCs) and RhoA/Rho kinase (ROCK) on depolarization-induced sustained arterial contraction lasting several minutes is already known. However, in vivo, vascular smooth muscle cells can be depolarized for longer periods, inducing substantial inactivation of LTCCs and markedly reducing Ca(2+) influx into the myocytes. We have examined, in femoral arterial rings, the role of LTCCs and RhoA/ROCK during long-lasting depolarization. Our results reveal a new vasoreactive response after 20-30min of depolarization in 2...
May 16, 2017: Vascular Pharmacology
https://www.readbyqxmd.com/read/28526263/n-stearoyl-l-tyrosine-inhibits-the-cell-senescence-and-apoptosis-induced-by-h2o2-in-hek293-tau-cells-via-the-cb2-receptor
#17
Yue Hu, Kai-Yi Zhou, Ze-Jian Wang, Yang Lu, Ming Yin
Although considerable energy and money have been spent trying to inhibit Aβ production and its related metabolic enzyme activities, there are still no drug treatments available to cure even slow for Alzheimer's disease. Therefore, tau protein has been focused recently as the new target for the treatment of Alzheimer's disease. The transfected human embryonic kidney 293 (HEK 293) cells with or without Tau 411 plasmid were used to evaluate the effect of tau protein on cell viability. H2O2 was added to simulate microenvironment of oxidative stress (OS) during aging...
May 16, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28525896/activation-of-cannabinoid-receptor-type-ii-by-am1241-protects-adipose-derived-mesenchymal-stem-cells-from-oxidative-damage-and-enhances-their-therapeutic-efficacy-in-myocardial-infarction-mice-via-stat3-activation
#18
Dong Han, Xiang Li, Wen-Si Fan, Jiang-Wei Chen, Tian-Tian Gou, Tao Su, Miao-Miao Fan, Meng-Qi Xu, Ya-Bin Wang, Sai Ma, Ya Qiu, Feng Cao
The poor survival of cells in ischemic sites diminishes the therapeutic efficacy of stem cell therapy. Previously we and others have reported that Cannabinoid receptor type II (CB2) is protective during heart ischemic injury for its anti-oxidative activity. However, whether CB2 activation could improve the survival and therapeutic efficacy of stem cells in ischemic myocardium and the underlying mechanisms remain elusive. Here, we showed evidence that CB2 agonist AM1241 treatment could improve the functional survival of adipose-derived mesenchymal stem cells (AD-MSCs) in vitro as well as in vivo...
May 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28525794/stat6-silencing-induces-hepatocellular-carcinoma-derived-cell-apoptosis-and-growth-inhibition-by-decreasing-the-rankl-expression
#19
Tian Qing, Zhang Yamin, Wang Guijie, Jin Yan, Shen Zhongyang
Signal transducer and activator of transcription-6 (STAT6) is highly expressed in various human cancers and considered a regulator of multiple biological processes in cancers, including cell apoptosis. Evidence has indicated that STAT6 predicts a worse prognosis in hepatocellular carcinoma (HCC) patients. The objective of this study was to investigate the effects and mechanism of STAT6 in human HCC cells. We found that STAT6 silencing significantly inhibited HepG2 and Hep3B cell survival and proliferation. We observed that depletion of STAT6 increased HepG2 and Hep3B cell apoptosis by using a histone DNA ELISA detection kit...
May 16, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28525741/in%C3%A2-vivo-ubiquitin-linkage-type-analysis-reveals-that-the-cdc48-rad23-dsk2-axis-contributes-to-k48-linked-chain-specificity-of-the-proteasome
#20
Hikaru Tsuchiya, Fumiaki Ohtake, Naoko Arai, Ai Kaiho, Sayaka Yasuda, Keiji Tanaka, Yasushi Saeki
Ubiquitin-binding domain (UBD) proteins regulate numerous cellular processes, but their specificities toward ubiquitin chain types in cells remain obscure. Here, we perform a quantitative proteomic analysis of ubiquitin linkage-type selectivity of 14 UBD proteins and the proteasome in yeast. We find that K48-linked chains are directed to proteasomal degradation through selectivity of the Cdc48 cofactor Npl4. Mutating Cdc48 results in decreased selectivity, and lacking Rad23/Dsk2 abolishes interactions between ubiquitylated substrates and the proteasome...
May 18, 2017: Molecular Cell
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