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https://www.readbyqxmd.com/read/28900144/structural-and-functional-insights-into-the-periplasmic-detector-domain-of-the-gacs-histidine-kinase-controlling-biofilm-formation-in-pseudomonas-aeruginosa
#1
Ahmad Ali-Ahmad, Firas Fadel, Corinne Sebban-Kreuzer, Moly Ba, Gauthier Dangla Pélissier, Olivier Bornet, Françoise Guerlesquin, Yves Bourne, Christophe Bordi, Florence Vincent
Pseudomonas aeruginosa is an opportunistic pathogenic bacterium responsible for both acute and chronic infections and has developed resistance mechanisms due to its ability to promote biofilm formation and evade host adaptive immune responses. Here, we investigate the functional role of the periplasmic detector domain (GacSPD) from the membrane-bound GacS histidine kinase, which is one of the key players for biofilm formation and coordination of bacterial lifestyles. A gacS mutant devoid of the periplasmic detector domain is severely defective in biofilm formation...
September 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28891712/molecular-and-clinical-features-of-second-generation-anaplastic-lymphoma-kinase-inhibitors-ceritinib
#2
Tommaso De Pas, Laura Pala, Chiara Catania, Fabio Conforti
The discovery of ALK rearrangement in non-small-cell lung cancer (NSCLC) triggered rapid clinical development of a family of specific drugs targeting this alteration, called ALK inhibitors. Despite high rate of responses, the vast majority of patients treated with first-generation ALK inhibitor crizotinib will ultimately develop disease progression. The second-generation ALK inhibitor, ceritinib, is an oral, small-molecule that inhibits the ALK kinase activity with a potency 20-fold greater than crizotinib, being able to tackle some of the principal mechanisms of resistance to crizotinib...
September 11, 2017: Future Oncology
https://www.readbyqxmd.com/read/28882814/opsin-3-and-4-mediate-light-induced-pulmonary-vasorelaxation-that-is-potentiated-by-g-protein-receptor-kinase-2-inhibition
#3
Sebastian Barreto Ortiz, Daijiro Hori, Yohei Nomura, Xin Yun, Haiyang Jiang, Hwanmee Yong, James Chen, Sam Paek, Deepesh Pandey, Gautam Sikka, Anil Bhatta, Andrew Gillard, Jochen Steppan, Jae Hyung Kim, Hideo Adachi, Viachaslau Barodka, Lewis Romer, Steven S An, Larissa A Shimoda, Lakshmi Santhanam, Dan E Berkowitz
We recently demonstrated that blue light induces vasorelaxation in the systemic mouse circulation, a phenomenon mediated by the non-visual G protein-coupled receptor (GPCR) melanopsin (opsin 4; Opn4). Here we tested the hypothesis that non-visual opsins mediate photorelaxation in the pulmonary circulation. We discovered Opsin 3 (Opn3), Opn4, and G-protein coupled receptor kinase 2 (GRK2) in rat pulmonary arteries (PAs) and in pulmonary arterial smooth muscle cells (PASMCs), where the opsins interact directly with GRK2 as demonstrated with a proximity ligation assay...
September 7, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28815778/mapk8-regulates-chicken-male-germ-cell-differentiation-through-jnk-signaling-pathway
#4
Yingjie Wang, Yulin Bi, Qisheng Zuo, Wenhui Zhang, Dong Li, Na-Na He, Shaoze Cheng, Ya-Ni Zhang, Bichun Li
The study aims to analyze the key signaling pathways in regulating the process of embryonic stem cells (ESCs) differentiation into spermatogonial stem cells (SSCs). We explored the specific regulating mechanisms of C-Jun amino-terminal kinase (JNK) signaling in this process. Interference/overexpression of MAPK8 allows the JNK signaling pathway to be blocked/activated. In Retinoic acid (RA) induced in vitro differentiation assays, the expression of germ cell marker genes, cvh, c-kit, integrin α6 and integrin β1, was observed to upregulate while activating JNK signaling significantly...
August 16, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28679058/pharmacological-inhibition-of-mtor-kinase-reverses-right-ventricle-remodeling-and-improves-right-ventricle-structure-and-function-in-rats
#5
Andressa Pena, Ahasanul Kobir, Dmitry Goncharov, Akiko Goda, Tatiana V Kudryashova, Arnab Ray, Rebecca Vanderpool, Jeffrey Baust, Baojun Chang, Ana L Mora, John Gorcsan Iii, Elena A Goncharova
Pulmonary arterial hypertension (PAH) is characterized by pulmonary vascular remodeling, increased pulmonary artery pressure (PAP), right heart afterload and death. Mechanistic target of rapamycin (mTOR) promotes smooth muscle cell proliferation, survival and pulmonary vascular remodeling via two functionally distinct complexes, mTORC1 (supports cell growth) and mTORC2 (promotes cell survival), and dual mTORC1/mTORC2 inhibition selectively induces PAH PAVSMC apoptosis and reverses pulmonary vascular remodeling...
July 5, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28674068/structural-and-functional-analysis-of-the-escherichia-coli-acid-sensing-histidine-kinase-evgs
#6
Hrishiraj Sen, Nikhil Aggarwal, Chibueze Ishionwu, Nosheen Hussain, Chandni Parmar, Mohammed Jamshad, Vassiliy N Bavro, Peter A Lund
The EvgS/EvgA two-component system of Escherichia coli is activated in response to low pH and alkali metals and regulates many genes, including those for the glutamate-dependent acid resistance system and a number of efflux pumps. EvgS, the sensor kinase, is one of five unconventional histidine kinases (HKs) in E. coli and has a large periplasmic domain and a cytoplasmic PAS domain in addition to phospho-acceptor, HK and dimerization, internal receiver, and phosphotransfer domains. Mutations that constitutively activate the protein at pH 7 map to the PAS domain...
September 15, 2017: Journal of Bacteriology
https://www.readbyqxmd.com/read/28656209/hydrogen-sulfide-reduced-renal-tissue-fibrosis-by-regulating-autophagy-in-diabetic-rats
#7
Lin Li, Ting Xiao, Fang Li, Yan Li, Ou Zeng, Maojun Liu, Biao Liang, Zining Li, Chun Chu, Jun Yang
The present study aimed to explore the effect of hydrogen sulfide (H2S) on renal tissue fibrosis and its mechanism in diabetic rats. Rats were randomly divided into four groups (n=13/group): Control group; induced diabetes mellitus group (STZ); induced diabetes mellitus treated with H2S group (STZ + H2S); normal rats treated with H2S group (H2S). The diabetic model was induced by intraperitoneal (i.p.) injections of 40 mg/kg body weight streptozotocin (STZ); the control group was treated with saline every day (i...
August 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28607819/mtor-activation-is-increased-in-pilocytic-astrocytomas-from-older-adults-compared-with-children
#8
Mahlon D Johnson, Mary O'Connell, Kevin Walter, Howard Silberstein
BACKGROUND: Recent studies suggest that the behavior and biology of WHO grade I pilocytic astrocytomas (PAs) in adults is different than that associated with grade I PAs in children. METHODS: We evaluated Ki-67 labeling, BRAF abnormalities, isocitrate dehydrogenase R132 immunoreactivity phosphorylation (activation) of p44/42 mitogen activated protein kinase (MAPK), and mammalian target of rapamycin (mTOR) in formalin-fixed tissue from 21 adult (18 years or older, mean age 37 years) and 10 children (mean age 9...
2017: Surgical Neurology International
https://www.readbyqxmd.com/read/28597334/jak-stat-signaling-regulation-of-chicken-embryonic-stem-cell-differentiation-into-male-germ-cells
#9
Yu Zhang, Lei Zhang, Qisheng Zuo, Yinjie Wang, Yani Zhang, Qi Xu, Bichun Li, Guohong Chen
The Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling is crucial in chicken germ stem cell differentiation, but its role in the regulation of germ cell differentiation is unknown. To address this, cucurbitacin I or interleukin 6 was used to inhibit or activate JAK-STAT signaling during embryonic stem cells (ESCs) differentiation. The expression of downstream JAK-STAT signaling molecules was assessed by Western blotting and quantitative real-time polymerase chain reaction (qRT-PCR)...
June 8, 2017: In Vitro Cellular & Developmental Biology. Animal
https://www.readbyqxmd.com/read/28585197/human-protein-kinases-and-obesity
#10
REVIEW
Atilla Engin
The action of protein kinases and protein phosphatases is essential for multiple physiological responses. Each protein kinase displays its own unique substrate specificity, and a regulatory mechanism that may be modulated by association with other proteins. Protein kinases are classified by the target amino acid in their substrates. Some protein kinases can phosphorylate both serine/threonine, as well as tyrosine residues. This group of kinases has been known as dual specificity kinases. Unlike the dual specificity kinases, a heterogeneous group of protein phosphatases are known as dual-specificity phosphatases...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28580356/fungal-histidine-phosphotransferase-plays-a-crucial-role-in-photomorphogenesis-and-pathogenesis-in-magnaporthe-oryzae
#11
Varsha C Mohanan, Pinal M Chandarana, Bharat B Chattoo, Rajesh N Patkar, Johannes Manjrekar
Two-component signal transduction (TCST) pathways play crucial roles in many cellular functions such as stress responses, biofilm formation, and sporulation. The histidine phosphotransferase (HPt), which is an intermediate phosphotransfer protein in a two-component system, transfers a phosphate group to a phosphorylatable aspartate residue in the target protein(s), and up-regulates stress-activated MAP kinase cascades. Most fungal genomes carry a single copy of the gene coding for HPt, which are potential antifungal targets...
2017: Frontiers in Chemistry
https://www.readbyqxmd.com/read/28552597/vasodilation-effect-of-volatile-oil-from-allium-macrostemon-bunge-are-mediated-by-pka-no-pathway-and-its-constituent-dimethyl-disulfide-in-isolated-rat-pulmonary-arterials
#12
Chenghua Han, Jing Qi, Sainan Gao, Chunxiang Li, Ying Ma, Jing Wang, Yuhua Bai, Xiaodong Zheng
The present study aimed to investigate the vasodilation effects of Allium macrostemon Bunge (AMB) on isolated rat pulmonary arterials (PAs) and to assess the underling mechanisms. The volatile oil was extracted by steam distillation from the bulbs of AMB. Then the volatile oil from AMB was studied on isolated rat PA, removal of endothelium, or pretreatment with nitro oxide (NO) synthase (NOS) inhibitor NG-nitro-L-arginine methyl ester (L-NAME), or with protein kinase A (PKA) inhibitor PKI but not cyclooxygenase inhibitor indomethacin significantly blocked the AMB induced relaxation on PE-contracted PA rings...
July 2017: Fitoterapia
https://www.readbyqxmd.com/read/28549152/mdsnrk1-1-interacts-with-mdjaz18-to-regulate-sucrose-induced-anthocyanin-and-proanthocyanidin-accumulation-in-apple
#13
Xiao-Juan Liu, Xiu-Hong An, Xin Liu, Da-Gang Hu, Xiao-Fei Wang, Chun-Xiang You, Yu-Jin Hao
Sugars induce anthocyanin biosynthesis in plants. As a conserved energy sensor, SnRK1 (SNF1-related kinase 1) is involved in sucrose-induced anthocyanin accumulation. However, the exact molecular mechanism by which SnRK1 regulates the biosynthesis of anthocyanins and proanthocyanidins (PAs) in response to sucrose in plants is not clear. In this study, it was found that MdSnRK1.1 interacted with MdJAZ18 protein which acts as a repressor in the jasmonate (JA) signaling pathway. MdSnRK1.1 then phosphorylated MdJAZ18 to facilitate its 26S proteasome-mediated degradation, which released MdbHLH3 thereby activating the expression of the regulatory and structural genes, thus finally promoting the biosynthesis of anthocyanins and PAs...
May 17, 2017: Journal of Experimental Botany
https://www.readbyqxmd.com/read/28542433/beneficial-effect-of-combined-treatment-with-octreotide-and-pasireotide-in-pck-rats-an-orthologous-model-of-human-autosomal-recessive-polycystic-kidney-disease
#14
Masanori Kugita, Kazuhiro Nishii, Tamio Yamaguchi, Atsushi Suzuki, Yukio Yuzawa, Shigeo Horie, Eiji Higashihara, Shizuko Nagao
Increased intracellular cyclic AMP (cAMP) in renal tubular epithelia accelerates the progression of polycystic kidney disease (PKD). Thus, decreasing cAMP levels by an adenylyl cyclase inhibitory G protein activator is considered to be an effective approach in ameliorating PKD. In fact, pasireotide (PAS) was effective in reducing disease progression in animal models of PKD. However, hyperglycemia caused by the administration of PAS is an adverse effect in its clinical use. Whereas, co-administration of octreotide (OCT) with PAS did not increase serum glucose in normal rats...
2017: PloS One
https://www.readbyqxmd.com/read/28507245/conformational-changes-of-an-interdomain-linker-mediate-mechanical-signal-transmission-in-sensor-kinase-bvgs
#15
Elodie Lesne, Elian Dupré, Camille Locht, Rudy Antoine, Françoise Jacob-Dubuisson
The whooping cough agent, Bordetella pertussis, controls the expression of its large virulence regulon in a coordinated manner through the two-component system BvgAS. BvgS is a dimeric, multidomain sensor kinase. Each monomer comprises, in succession, tandem periplasmic Venus flytrap (VFT) domains, a transmembrane segment, a cytoplasmic Per-Arnt-Sim (PAS) domain, a kinase module, and additional phosphorelay domains. BvgS shifts between kinase and phosphatase modes of activity in response to chemical modulators that modify the clamshell motions of the VFT domains...
September 15, 2017: Journal of Bacteriology
https://www.readbyqxmd.com/read/28449380/the-pas-domains-of-the-major-sporulation-kinase-in-bacillus-subtilis-play-a-role-in-tetramer-formation-that-is-essential-for-the%C3%A2-autokinase-activity
#16
Brittany Kiehler, Lindsey Haggett, Masaya Fujita
Sporulation in Bacillus subtilis is induced upon starvation. In a widely accepted model, an N-terminal "sensor" domain of the major sporulation kinase KinA recognizes a hypothetical starvation signal(s) and autophosphorylates a histidine residue to activate the master regulator Spo0A via a multicomponent phosphorelay. However, to date no confirmed signal has been found. Here, we demonstrated that PAS-A, the most N-terminal of the three PAS domains (PAS-ABC), is dispensable for the activity, contrary to a previous report...
August 2017: MicrobiologyOpen
https://www.readbyqxmd.com/read/28428249/crystal-structure-and-redox-properties-of-a-novel-cyanobacterial-heme-protein-with-a-his-cys-heme-axial-ligation-and-a-per-arnt-sim-pas-like-domain
#17
Taiki Motomura, Michihiro Suga, Rainer Hienerwadel, Akiko Nakagawa, Thanh-Lan Lai, Wolfgang Nitschke, Takahiro Kuma, Miwa Sugiura, Alain Boussac, Jian-Ren Shen
Photosystem II catalyzes light-induced water oxidation leading to the generation of dioxygen indispensable for sustaining aerobic life on Earth. The Photosystem II reaction center is composed of D1 and D2 proteins encoded by psbA and psbD genes, respectively. In cyanobacteria, different psbA genes are present in the genome. The thermophilic cyanobacterium Thermosynechococcus elongatus contains three psbA genes: psbA1, psbA2, and psbA3, and a new c-type heme protein, Tll0287, was found to be expressed in a strain expressing the psbA2 gene only, but the structure and function of Tll0287 are unknown...
June 9, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28427013/the-accelerated-path-of-ceritinib-translating-pre-clinical-development-into-clinical-efficacy
#18
REVIEW
Tony S K Mok, Lucio Crino, Enriqueta Felip, Ravi Salgia, Tommaso De Pas, Daniel S W Tan, Laura Q M Chow
The discovery of anaplastic lymphoma kinase (ALK)-rearranged non-small-cell lung cancer (NSCLC) in 2007 led to the development and subsequent approval of the ALK inhibitor crizotinib in 2011. However, despite its clinical efficacy, resistance to crizotinib invariably develops. There is now a next generation of ALK inhibitors, including two that have been approved-ceritinib and alectinib-and others that are in development-brigatinib, lorlatinib and X-396. Ceritinib and the other next-generation ALK inhibitors are more potent than crizotinib and can overcome tumor cell resistance mechanisms...
April 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28343064/a-barley-homolog-of-yeast-atg6-is-involved-in-multiple-abiotic-stress-responses-and-stress-resistance-regulation
#19
Xiaowei Zeng, Zhanghui Zeng, Cuicui Liu, Weiyi Yuan, Ning Hou, Hongwu Bian, Muyuan Zhu, Ning Han
Autophagy is a highly conserved degradation pathway among eukaryote cells, which can recycle damaged or unwanted cell materials upon encountering stress conditions. As a key component of the Class III PI3K kinase complex, ATG6/Beclin-1 is essential for autophagosome formation. In this study, we isolated a putative HvATG6 gene in barley genome. The protein encoded by HvATG6 shares high sequence identity to ATG6 orthologs in rice and wheat, and has a typical autophagy-specific domain containing segments of repeated β-sheet-α-helix...
June 2017: Plant Physiology and Biochemistry: PPB
https://www.readbyqxmd.com/read/28342113/crizotinib-for-untreated-anaplastic-lymphoma-kinase-positive-non-small-cell-lung-cancer-an-evidence-review-group-perspective-of-a-nice-single-technology-appraisal
#20
REVIEW
Philip Morgan, Nerys Woolacott, Mousumi Biswas, Teumzghi Mebrahtu, Melissa Harden, Robert Hodgson
As part of the National Institute for Health and Care Excellence (NICE) single technology appraisal process, the manufacturer of crizotinib submitted evidence on the clinical and cost effectiveness of crizotinib in untreated anaplastic lymphoma kinase-positive (ALK-positive) non-small-cell lung cancer (NSCLC). Crizotinib has previously been assessed by NICE for patients with previously treated ALK-positive NSCLC (TA 296). It was not approved in this previous appraisal, but had been made available through the cancer drugs fund...
March 24, 2017: PharmacoEconomics
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