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Ras protein

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https://www.readbyqxmd.com/read/27914563/differential-effects-of-testosterone-and-estradiol-on-clitoral-function-an-experimental-study-in-rats
#1
Paolo Comeglio, Ilaria Cellai, Sandra Filippi, Chiara Corno, Francesca Corcetto, Annamaria Morelli, Elena Maneschi, Elisa Maseroli, Edoardo Mannucci, Massimiliano Fambrini, Mario Maggi, Linda Vignozzi
INTRODUCTION: Female sexual response is a complex phenomenon in which psychological, neurologic, and vascular mechanisms and hormonal factors interact. During the arousal phase, they cooperate to increase genital blood flow, thus inducing engorgement of the clitoris and lubrication of the vagina. Regulation of vascular and non-vascular smooth muscle tone is the crucial event in the erectile process. Preclinical studies have suggested that nitric oxide (NO) is the main vasodilator neurotransmitter modulating, through the second messenger cyclic guanosine monophosphate (cGMP), clitoral flow vessels...
December 2016: Journal of Sexual Medicine
https://www.readbyqxmd.com/read/27913671/l-rrk-de-triomphe-a-solution-for-lrrk2-gtpase-activity
#2
REVIEW
Jonathon Nixon-Abell, Daniel C Berwick, Kirsten Harvey
Leucine-rich repeat kinase 2 (LRRK2) is a central protein in the pathogenesis of Parkinson's disease (PD), yet its normal function has proved stubbornly hard to elucidate. Even though it remains unclear how pathogenic mutations affect LRRK2 to cause PD, recent findings provide increasing cause for optimism. We summarise here the developing consensus over the effect of pathogenic mutations in the Ras of complex proteins and C-terminal of Roc domains on LRRK2 GTPase activity. This body of work has been greatly reinforced by our own study of the protective R1398H variant contained within the LRRK2 GTPase domain...
December 15, 2016: Biochemical Society Transactions
https://www.readbyqxmd.com/read/27913669/the-unconventional-g-protein-cycle-of-lrrk2-and-roco-proteins
#3
REVIEW
Susanne Terheyden, Laura M Nederveen-Schippers, Arjan Kortholt
Mutations in the human leucine-rich repeat kinase 2 (LRRK2) are the most frequent cause of hereditary Parkinson's disease (PD). LRRK2 belongs to the Roco family of proteins, which are characterized by the presence of a Ras of complex proteins domain (Roc), a C-terminal of Roc domain (COR) and a kinase domain. Despite intensive research, much remains unknown about activity and the effect of PD-associated mutations. Recent biochemical and structural studies suggest that LRRK2 and Roco proteins are noncanonical G-proteins that do not depend on guanine nucleotide exchange factors or GTPase-activating proteins for activation...
December 15, 2016: Biochemical Society Transactions
https://www.readbyqxmd.com/read/27911940/isoform-specific-effects-of-wild-type-ras-genes-on-carcinogen-induced-lung-tumorigenesis-in-mice
#4
Jamie D Weyandt, John M Carney, Elizabeth N Pavlisko, MengMeng Xu, Christopher M Counter
The gene KRAS is commonly mutated in lung cancer to encode a constitutively active and oncogenic protein that is well established to initiate and maintain lung tumorigenesis. However, the remaining wild-type KRAS protein, or the other family members HRAS and NRAS, can still be activated in the presence of oncogenic KRAS. Moreover, loss of any one of these three genes has been shown to increase the sensitivity of mice to the carcinogen urethane, which induces Kras mutation-positive early lung lesions. To determine the contribution of progressively disrupting Hras and Nras genes on urethane lung tumorigenesis, mice with different combinations of wild-type and null alleles of Hras and Nras were exposed with urethane and tumor burden was assessed...
2016: PloS One
https://www.readbyqxmd.com/read/27911910/molecular-markers-of-radiation-induced-attenuation-in-intrahepatic-plasmodium-falciparum-parasites
#5
Miranda S Oakley, Nitin Verma, Hong Zheng, Vivek Anantharaman, Kazuyo Takeda, Yamei Gao, Timothy G Myers, Phuong Thao Pham, Babita Mahajan, Nirbhay Kumar, Davison Sangweme, Abhai K Tripathi, Godfree Mlambo, L Aravind, Sanjai Kumar
Experimental immunization with radiation attenuated sporozoites (RAS) and genetically attenuated sporozoites has proved to be a promising approach for malaria vaccine development. However, parasite biomarkers of growth attenuation and enhanced immune protection in response to radiation remain poorly understood. Here, we report on the effect of an attenuating dose of γ-irradiation (15 krad) on the Plasmodium falciparum sporozoite (PfSPZ) ultrastructure by electron microscopy, growth rate of liver stage P. falciparum in liver cell cultures, and genome-wide transcriptional profile of liver stage parasites by microarray...
2016: PloS One
https://www.readbyqxmd.com/read/27911734/the-spatiotemporal-regulation-of-ras-signalling
#6
REVIEW
Ana Herrero, David Matallanas, Walter Kolch
Nearly 30% of human tumours harbour mutations in RAS family members. Post-translational modifications and the localisation of RAS within subcellular compartments affect RAS interactions with regulator, effector and scaffolding proteins. New insights into the control of spatiotemporal RAS signalling reveal that activation kinetics and subcellular compartmentalisation are tightly coupled to the generation of specific biological outcomes. Computational modelling can help utilising these insights for the identification of new targets and design of new therapeutic approaches...
October 15, 2016: Biochemical Society Transactions
https://www.readbyqxmd.com/read/27909410/mechanosensitive-molecular-networks-involved-in-transducing-resistance-exercise-signals-into-muscle-protein-accretion
#7
REVIEW
Emil Rindom, Kristian Vissing
Loss of skeletal muscle myofibrillar protein with disease and/or inactivity can severely deteriorate muscle strength and function. Strategies to counteract wasting of muscle myofibrillar protein are therefore desirable and invite for considerations on the potential superiority of specific modes of resistance exercise and/or the adequacy of low load resistance exercise regimens as well as underlying mechanisms. In this regard, delineation of the potentially mechanosensitive molecular mechanisms underlying muscle protein synthesis (MPS), may contribute to an understanding on how differentiated resistance exercise can transduce a mechanical signal into stimulation of muscle accretion...
2016: Frontiers in Physiology
https://www.readbyqxmd.com/read/27909058/secreted-glioblastoma-nanovesicles-contain-intracellular-signaling-proteins-and-active-ras-incorporated-in-a-farnesylation-dependent-manner
#8
Natalie Luhtala, Aaron Aslanian, John R Yates, Tony Hunter
Glioblastomas (GBMs) are malignant brain tumors with a median survival of less than 18 months. Redundancy of signaling pathways represented within GBMs contributes to their therapeutic resistance. Exosomes are extracellular nanovesicles released from cells and present in human biofluids that represent a possible biomarker of tumor signaling state that could aid in personalized treatment. Herein, we demonstrate that mouse GBM cell-derived extracellular nanovesicles resembling exosomes from an H-RasV12 myr-Akt mouse model for GBM are enriched for intracellular signaling cascade proteins (GO: 0007242) and Ras protein signal transduction (GO: 0007265), and contain active Ras...
December 1, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27904769/disruption-of-actin-filaments-and-suppression-of-pancreatic-cancer-cell-viability-and-migration-following-treatment-with-polyisoprenylated-cysteinyl-amides
#9
Augustine T Nkembo, Olufisayo Salako, Rosemary A Poku, Felix Amissah, Elizabeth Ntantie, Hernan Flores-Rozas, Nazarius S Lamango
Pancreatic cancer is characterized by K-Ras mutations in over 90% of the cases. The mutations make the tumors aggressive and resistant to current therapies resulting in very poor prognoses. Valiant efforts to drug mutant K-Ras and related proteins for the treatment of cancers with Ras mutations have been elusive. The need thus persists for therapies to target and suppress the hyperactive K-Ras mutant proteins to normal levels of activity. Polyisoprenylated cysteinyl amide inhibitors (PCAIs) of polyisoprenylated methylated protein methyl esterase (PMPMEase) were designed to disrupt polyisoprenylated protein metabolism and/or functions...
2016: American Journal of Cancer Research
https://www.readbyqxmd.com/read/27904154/circadian-rhythm-of-blood-pressure-and-the-renin-angiotensin-system-in-the-kidney
#10
REVIEW
Naro Ohashi, Shinsuke Isobe, Sayaka Ishigaki, Hideo Yasuda
Activation of the intrarenal renin-angiotensin system (RAS) has a critical role in the pathophysiology of the circadian rhythm of blood pressure (BP) and renal injury, independent of circulating RAS. Although it is clear that the circulating RAS has a circadian rhythm, reports of a circadian rhythm in tissue-specific RAS are limited. Clinical studies evaluating intrarenal RAS activity by urinary angiotensinogen (AGT) levels have indicated that urinary AGT levels were equally low during both the daytime and nighttime in individuals without chronic kidney disease (CKD) and that urinary AGT levels were higher during the daytime than at nighttime in patients with CKD...
December 1, 2016: Hypertension Research: Official Journal of the Japanese Society of Hypertension
https://www.readbyqxmd.com/read/27903913/functional-rnas-combined-assembly-and-packaging-in-vlps
#11
Po-Yu Fang, Lizzette M Gómez Ramos, Stefany Y Holguin, Chiaolong Hsiao, Jessica C Bowman, Hung-Wei Yang, Loren Dean Williams
We describe here a one pot RNA production, packaging and delivery system based on bacteriophage Qβ. We demonstrate a method for production of a novel RNAi scaffold, packaged within Qβ virus-like particles (VLPs). The RNAi scaffold is a general utility chimera that contains a functional RNA duplex with paired silencing and carrier sequences stabilized by a miR-30 stem-loop. The Qβ hairpin on the 5' end confers affinity for the Qβ coat protein (CP). Silencing sequences can include mature miRNAs and siRNAs, and can target essentially any desired mRNA...
November 29, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27903653/the-phosphatidylinositol-3-4-5-trisphosphate-pi-3-4-5-p3-binder-rasa3-regulates-phosphoinositide-3-kinase-pi-3-kinase-dependent-integrin-%C3%AE-iib%C3%AE-3-outside-in-signaling
#12
Anthony M Battram, Tom N Durrant, Ejaife O Agbani, Kate J Heesom, David S Paul, Raymond Piatt, Alastair W Poole, Peter J Cullen, Wolfgang Bergmeier, Samantha F Moore, Ingeborg Hers
The class I phosphoinositide 3-kinase (PI 3-kinase) family of lipid kinases plays an important role in integrin αIIbβ3 function, thereby supporting thrombus growth and consolidation. Here, we identify the Ras/Rap1GAP Rasa3 (GAP1IP4BP) as a major phosphatidylinositol-3,4,5-trisphosphate (PI(3,4,5)P3)-binding protein in human platelets and a key regulator of integrin αIIbβ3 outside-in signaling. We demonstrate that cytosolic Rasa3 translocates to the plasma membrane in a PI 3kinase-dependent manner upon activation of human platelets...
November 30, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27902699/modeling-cellular-noise-underlying-heterogeneous-cell-responses-in-the-epidermal-growth-factor-signaling-pathway
#13
Kazunari Iwamoto, Yuki Shindo, Koichi Takahashi
Cellular heterogeneity, which plays an essential role in biological phenomena, such as drug resistance and migration, is considered to arise from intrinsic (i.e., reaction kinetics) and extrinsic (i.e., protein variability) noise in the cell. However, the mechanistic effects of these types of noise to determine the heterogeneity of signal responses have not been elucidated. Here, we report that the output of epidermal growth factor (EGF) signaling activity is modulated by cellular noise, particularly by extrinsic noise of particular signaling components in the pathway...
November 2016: PLoS Computational Biology
https://www.readbyqxmd.com/read/27902448/rasgrp1-promotes-amphetamine-induced-motor-behavior-through-a-rhes-interaction-network-rhesactome-in-the-striatum
#14
Neelam Shahani, Supriya Swarnkar, Vincenzo Giovinazzo, Jenny Morgenweck, Laura M Bohn, Catherina Scharager-Tapia, Bruce Pascal, Pablo Martinez-Acedo, Kshitij Khare, Srinivasa Subramaniam
The striatum of the brain coordinates motor function. Dopamine-related drugs may be therapeutic to patients with striatal neurodegeneration, such as Huntington's disease (HD) and Parkinson's disease (PD), but these drugs have unwanted side effects. In addition to stimulating the release of norepinephrine, amphetamines, which are used for narcolepsy and attention-deficit/hyperactivity disorder (ADHD), trigger dopamine release in the striatum. The guanosine triphosphatase Ras homolog enriched in the striatum (Rhes) inhibits dopaminergic signaling in the striatum, is implicated in HD and L-dopa-induced dyskinesia, and has a role in striatal motor control...
November 15, 2016: Science Signaling
https://www.readbyqxmd.com/read/27902336/characterization-of-the-banana-streak-virus-capsid-protein-and-mapping-of-the-immunodominant-continuous-b-cell-epitopes-to-the-surface-exposed-n-terminus
#15
Jenny Vo, Paul Campbell, Nur N Mahfuzc, Ras Ramli, Daniel Pagendam, Ross Barnard, Andrew Geering
This study identified the structural proteins of two badnavirus species, Banana streak MY virus (BSMYV) and Banana streak OL virus (BSOLV), and mapped the distribution of continuous B-cell epitopes. Two different CP isoforms of about 44 and 40 kDa (CP1 and CP2) and the virion-associated protein (VAP) were consistently associated with purified virions. For both viral species, the N-terminus of CP2 was successfully sequenced by Edman degradation but that of CP1 was chemically blocked. De novo peptide sequencing of tryptic digests suggested that CP1 and CP2 derive from the same region of the P3 polyprotein but differ in the length of either the N- or C-terminus...
October 24, 2016: Journal of General Virology
https://www.readbyqxmd.com/read/27900601/rna-seq-expression-analysis-of-enteric-neuron-cells-with-rotenone-treatment-and-prediction-of-regulated-pathways
#16
Qiang Guan, Xijin Wang, Yanyan Jiang, Lijuan Zhao, Zhiyu Nie, Lingjing Jin
The enteric nervous system (ENS) is involved in the initiation and development of the pathological process of Parkinson's disease (PD). The effect of rotenone on the ENS may trigger the progression of PD through the central nervous system (CNS). In this study, we used RNA-sequencing (RNA-seq) analysis to examine differential expression genes (DEGs) and pathways induced by in vitro treatment of rotenone in the enteric nervous cells isolated from rats. We identified 45 up-regulated and 30 down-regulated genes...
November 30, 2016: Neurochemical Research
https://www.readbyqxmd.com/read/27900042/antitumor-activity-of-7rh-a-discoidin-domain-receptor-1-inhibitor-alone-or-in-combination-with-dasatinib-exhibits-antitumor-effects-in-nasopharyngeal-carcinoma-cells
#17
Qiu-Ping Lu, Wen-Dan Chen, Jie-Ren Peng, Yao-Dong Xu, Qian Cai, Gong-Kan Feng, Ke Ding, Xiao-Feng Zhu, Zhong Guan
Dysregulation of the discoidin domain receptors (DDRs) has been implicated in the development of numerous types of tumors, including head and neck cancer, and nasopharyngeal, breast, ovarian and esophageal carcinomas. Furthermore, agents that inhibit DDR1 activity are hypothesized to be useful for the treatment of nasopharyngeal carcinoma (NPC). The aim of the present study was to evaluate the effect of the DDR1 inhibitory (3-(2-(pyrazolo(1,5-a)pyrimidin-6-yl)-ethynyl)benzamide compound, 7RH, in NPC cells both in vitro and in vivo, and its effect when used in combination with dasatinib, a SRC family kinase (SFK) inhibitor...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27899992/beside-p53-and-pten-identification-of-molecular-alterations-of-the-ras-mapk-and-pi3k-akt-signaling-pathways-in-high-grade-serous-ovarian-carcinomas-to-determine-potential-novel-therapeutic-targets
#18
Shuhui Chen, Elisa Cavazza, Catherine Barlier, Julia Salleron, Pierre Filhine-Tresarrieu, Céline Gavoilles, Jean-Louis Merlin, Alexandre Harlé
Despite great histological and molecular heterogeneity, the clinical management of high-grade ovarian carcinomas remains unspecialized. As a major subgroup, high-grade serous ovarian carcinomas (HGSOCs) require novel therapies. In addition to utilizing conventional histological prognostic markers and performing oncogenetic investigations, the molecular diagnostic method of next generation sequencing (NGS) was performed to identify 'druggable' targets that could provide access to innovative therapy. The present study was performed in 45 HGSOC patients (mean age, 59...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27899122/endocytosed-nanoparticles-hold-endosomes-and-stimulate-binucleated-cells-formation
#19
Lin Xia, Weihong Gu, Mingyi Zhang, Ya-Nan Chang, Kui Chen, Xue Bai, Lai Yu, Juan Li, Shan Li, Gengmei Xing
BACKGROUND: Nanotechnology developed rapidly in cellular diagnosis and treatment, the endocytic system was an important pathway for targeting cell. In the research of developing macrophages as drug carriers or important therapeutic targets, an interesting phenomenon, internalized nanoparticles induced to form binucleated macrophages, was found although the particles dose did not cause obvious cytotoxicity. RESULTS: Under 25 μg/ml, internalized 30 nm polystyrene beads(30 nm Ps nanoparticles) induced the formation of binucleated macrophages when they entered into endosomes via the endocytic pathway...
November 29, 2016: Particle and Fibre Toxicology
https://www.readbyqxmd.com/read/27896943/ang-1-7-protects-cardiomyocytes-against-hg-induced-injuries-through-inhibiting-ros-activated-leptin-p38-mapk-erk1-2-pathways-but-not-leptin-jnk-pathway-in-vitro
#20
Yiyan Lei, Qing Xu, Bo Zeng, Wei Zhang, Yulan Zhen, Yuansheng Zhai, Fei Cheng, Weiyi Mei, Dongdan Zheng, Jianqiang Feng, Jun Lan, Jingfu Chen
AIMS: Angiotensin-(1-7) [Ang-(1-7)], recognized as a new bioactive peptide in renin-angiotensin system (RAS), shows biological and pharmacological properties in diabetic cardiovascular diseases. Leptin induced-p38 MAPK pathway has been reported to contribute to the high glucose (HG)-induced injury. In this study, we demonstrated the mechanism that how Ang-(1-7) can protect from HG-stimulated injuries in H9c2 cells. METHODS: H9c2 cells were treated with 35 mM glucose (HG) for 24 h to establish a model of HG-induced damage...
November 29, 2016: Journal of Diabetes Investigation
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