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https://www.readbyqxmd.com/read/28069069/arresting-kinase-suppressor-of-ras-in-an-inactive-state
#1
EDITORIAL
Syed Lal Badshah, Yahia Mabkhot
Ras protein signaling pathways are important in controlling the plight of different types of cancer. Here we discussed the paper entitled "Small molecule stabilization of the KSR inactive state antagonizes oncogenic Ras signalling" published in Nature journal on inactivating the kinase suppressor of Ras (KSR) protein using a small molecule as an inhibitor by Dhawan et al. A biphenyl ether analogue of a quinazoline binds in one of the binding pockets of KSR and results in stabilization of its inactive state...
January 9, 2017: Chinese Journal of Cancer
https://www.readbyqxmd.com/read/28003362/phosphorylation-of-rap1-by-camp-dependent-protein-kinase-pka-creates-a-binding-site-for-ksr-to-sustain-erk-activation-by-camp
#2
Maho Takahashi, Yanping Li, Tara J Dillon, Philip J S Stork
Cyclic adenosine monophosphate (cAMP) is an important mediator of hormonal stimulation of cell growth and differentiation through its activation of the extracellular signal-regulated kinase (ERK) cascade. Two small G proteins, Ras and Rap1 have been proposed to mediate this activation. Using Hek293 cells as a model system, we have recently shown that both Ras and Rap1 are required for cAMP signaling to ERKs. However, cAMP-dependent Ras signaling to ERKs is transient and rapidly terminated by PKA phosphorylation of the Raf isoforms C-Raf and B-Raf...
December 21, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27988128/pathway-based-genome-wide-association-analysis-of-milk-coagulation-properties-curd-firmness-cheese-yield-and-curd-nutrient-recovery-in-dairy-cattle
#3
C Dadousis, S Pegolo, G J M Rosa, D Gianola, G Bittante, A Cecchinato
It is becoming common to complement genome-wide association studies (GWAS) with gene-set enrichment analysis to deepen the understanding of the biological pathways affecting quantitative traits. Our objective was to conduct a gene ontology and pathway-based analysis to identify possible biological mechanisms involved in the regulation of bovine milk technological traits: coagulation properties, curd firmness modeling, individual cheese yield (CY), and milk nutrient recovery into the curd (REC) or whey loss traits...
December 14, 2016: Journal of Dairy Science
https://www.readbyqxmd.com/read/27934825/molecular-analysis-of-rv0679c-and-rv0180c-genes-of-mycobacterium-tuberculosis-from-clinical-isolates-of-pulmonary-tuberculosis
#4
L Rupa, A Srikantam, S S Lakshmana Rao, U Devi, Ksr Sivasai
CONTEXT: Two novel proteins/genes Rv0679c and Rv0180c of Mycobacterium tuberculosis (MTB) H37Rv were classified as a hypothetical membrane and transmembrane proteins which might have a role in the invasion. Molecular analysis of these genes in human clinical isolates of pulmonary tuberculosis (PTB) patients was not well characterised. AIMS: To assess the molecular diversity of Rv0679c and Rv0180c genes of MTB from clinical isolates of PTB patients. SETTINGS AND DESIGN: DNA from 97 clinical isolates was extracted and subjected to amplification using selective primers by polymerase chain reaction (PCR)...
October 2016: Indian Journal of Medical Microbiology
https://www.readbyqxmd.com/read/27818241/poly-vinyl-acetate-and-ammonio-methacrylate-copolymer-as-unconventional-polymer-blends-increase-the-mechanical-robustness-of-hpmc-matrix-tablets
#5
R Ali, A Dashevsky, R Bodmeier
: The objective was to investigate poly vinyl acetate (Kollicoat(®) SR 30 D) and ammonio methacrylate copolymer (Eudragit(®) RL 30 D) blends as coatings to increase the mechanical robustness of hydroxypropyl methylcellulose (HPMC) matrix tablets. Poly vinyl acetate (Kollicoat(®) SR 30 D - KSR) was selected for its flexibility and ammonio methacrylate copolymer (Eudragit(®) RL 30 D - ERL) because of its high permeability. Films based on KSR:ERL blends were prepared by casting or spraying aqueous dispersions of these polymers and were characterized by water uptake, dry mass loss and mechanical properties...
January 10, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/27633838/chemically-defined-serum-free-conditions-for-cartilage-regeneration-from-human-embryonic-stem-cells
#6
Dandan Yang, Shubin Chen, Changzhao Gao, Xiaobo Liu, Yulai Zhou, Pengfei Liu, Jinglei Cai
AIMS: The aim of this study was to improve a method that induce cartilage differentiation of human embryoid stem cells (hESCs) in vitro, and test the effect of in vivo environments on the further maturation of hESCs derived cells. MAIN METHODS: Embryoid bodies (EBs) formed from hESCs, with serum-free KSR-based medium and mesodermal specification related factors, CHIR, and Noggin for first 8days. Then cells were digested and cultured as micropellets in serum-free KSR-based chondrogenic medium that was supplemented with PDGF-BB, TGF β3, BMP4 in sequence for 24days...
November 1, 2016: Life Sciences
https://www.readbyqxmd.com/read/27591198/ksr-mutations-guide-development-of-ras-pathway-antagonists
#7
(no author information available yet)
The small molecule APS-2-79 stabilizes an inactive form of the MAPK scaffold KSR to repress RAS signaling.
October 2016: Cancer Discovery
https://www.readbyqxmd.com/read/27566699/abiraterone-acetate-for-the-treatment-of-chemotherapy-na%C3%A3-ve-metastatic-castration-resistant-prostate-cancer-an-evidence-review-group-perspective-of-an-nice-single-technology-appraisal
#8
Bram L T Ramaekers, Rob Riemsma, Florian Tomini, Thea van Asselt, Sohan Deshpande, Steven Duffy, Nigel Armstrong, Johan L Severens, Jos Kleijnen, Manuela A Joore
The National Institute for Health and Care Excellence (NICE) invited Janssen, the company manufacturing abiraterone acetate (AA; tradename Zytiga(®)), to submit evidence for the clinical and cost effectiveness of AA in combination with prednisone/prednisolone (AAP) compared with watchful waiting (i.e. best supportive care [BSC]) for chemotherapy-naïve patients with metastatic castration-resistant prostate cancer (mCRPC). Kleijnen Systematic Reviews Ltd (KSR), in collaboration with Maastricht University Medical Center, was commissioned as the Evidence Review Group (ERG)...
August 26, 2016: PharmacoEconomics
https://www.readbyqxmd.com/read/27556948/small-molecule-stabilization-of-the-ksr-inactive-state-antagonizes-oncogenic-ras-signalling
#9
Neil S Dhawan, Alex P Scopton, Arvin C Dar
Deregulation of the Ras-mitogen activated protein kinase (MAPK) pathway is an early event in many different cancers and a key driver of resistance to targeted therapies. Sustained signalling through this pathway is caused most often by mutations in K-Ras, which biochemically favours the stabilization of active RAF signalling complexes. Kinase suppressor of Ras (KSR) is a MAPK scaffold that is subject to allosteric regulation through dimerization with RAF. Direct targeting of KSR could have important therapeutic implications for cancer; however, testing this hypothesis has been difficult owing to a lack of small-molecule antagonists of KSR function...
September 1, 2016: Nature
https://www.readbyqxmd.com/read/27514953/presence-of-viable-mycobacterium-leprae-in-environmental-specimens-around-houses-of-leprosy-patients
#10
R P Turankar, M Lavania, M Singh, U Sengupta, Ksr Siva Sai, R S Jadhav
PURPOSE: Leprosy is a chronic systemic infectious disease caused by Mycobacterium leprae, one of the first organisms to be established as the cause for disease in humans. Because of high prevalence pockets of leprosy in the endemic regions, it is necessary to identify the possible sources of M. leprae in the environment and its mode of transmission. MATERIALS AND METHODS: Slit skin smears (SSSs) from lesions were collected in 70% ethanol from 50 leprosy cases staying in the leprosy resettlement village and hospital from a high endemic area...
July 2016: Indian Journal of Medical Microbiology
https://www.readbyqxmd.com/read/27422710/phosphoproteomics-reveals-mapk-inhibitors-enhance-met-and-egfr-driven-akt-signaling-in-kras-mutant-lung-cancer
#11
Jae-Young Kim, Eric A Welsh, Bin Fang, Yun Bai, Fumi Kinose, Steven A Eschrich, John M Koomen, Eric B Haura
: Pathway inhibition of the RAS-driven MAPK pathway using small-molecule kinase inhibitors has been a key focus for treating cancers driven by oncogenic RAS, yet significant clinical responses are lacking. Feedback reactivation of ERK driven by drug-induced RAF activity has been suggested as one of the major drug resistance mechanisms, especially in the context of oncogenic RAS. To determine whether additional adaptive resistance mechanisms may coexist, we characterized global phosphoproteomic changes after MEK inhibitor selumetinib (AZD6244) treatment in KRAS-mutant A427 and A549 lung adenocarcinoma cell lines employing mass spectrometry-based phosphoproteomics...
October 2016: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/27368419/stabilization-of-c-raf-ksr1-complex-by-diras3-reduces-availability-of-c-raf-for-dimerization-with-b-raf
#12
Angela Baljuls, Maciej Dobrzyński, Jens Rauch, Nora Rauch, Walter Kolch
RAF family kinases are central components of the Ras-RAF-MEK-ERK cascade. Dimerization is a key mechanism of RAF activation in response to physiological, pathological and pharmacological signals. It is mediated by a dimer interface region in the RAF kinase domain that is also conserved in KSR, a scaffolding protein that binds RAF, MEK and ERK. The regulation of RAF dimerization is incompletely understood. Especially little is known about the molecular mechanism involved in the selection of the dimerization partner...
October 2016: Cellular Signalling
https://www.readbyqxmd.com/read/27336693/unraveling-kinase-activation-dynamics-using-kinase-substrate-relationships-from-temporal-large-scale-phosphoproteomics-studies
#13
Westa Domanova, James Krycer, Rima Chaudhuri, Pengyi Yang, Fatemeh Vafaee, Daniel Fazakerley, Sean Humphrey, David James, Zdenka Kuncic
In response to stimuli, biological processes are tightly controlled by dynamic cellular signaling mechanisms. Reversible protein phosphorylation occurs on rapid time-scales (milliseconds to seconds), making it an ideal carrier of these signals. Advances in mass spectrometry-based proteomics have led to the identification of many tens of thousands of phosphorylation sites, yet for the majority of these the kinase is unknown and the underlying network topology of signaling networks therefore remains obscured...
2016: PloS One
https://www.readbyqxmd.com/read/27226552/protein-kinase-ck2%C3%AE-maintains-extracellular-signal-regulated-kinase-erk-activity-in-a-ck2%C3%AE-kinase-independent-manner-to-promote-resistance-to-inhibitors-of-raf-and-mek-but-not-erk-in-braf-mutant-melanoma
#14
Bingying Zhou, Daniel A Ritt, Deborah K Morrison, Channing J Der, Adrienne D Cox
The protein kinase casein kinase 2 (CK2) is a pleiotropic and constitutively active kinase that plays crucial roles in cellular proliferation and survival. Overexpression of CK2, particularly the α catalytic subunit (CK2α, CSNK2A1), has been implicated in a wide variety of cancers and is associated with poorer survival and resistance to both conventional and targeted anticancer therapies. Here, we found that CK2α protein is elevated in melanoma cell lines compared with normal human melanocytes. We then tested the involvement of CK2α in drug resistance to Food and Drug Administration-approved single agent targeted therapies for melanoma...
August 19, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27193385/serum-replacement-with-albumin-associated-lipids-prevents-excess-aggregation-and-enhances-growth-of-induced-pluripotent-stem-cells-in-suspension-culture
#15
Ikki Horiguchi, Yasuyuki Sakai
Suspension culture systems are currently under investigation for the mass production of pluripotent stem (PS) cells for tissue engineering; however, the control of cell aggregation in suspension culture remains challenging. Existing methods to control aggregation such as microwell culture are difficult to scale up. To address this issue, in this study a novel method that incorporates the addition of KnockOut Serum Replacement (KSR) to the PS cell culture medium was described. The method regulated cellular aggregation and significantly improved cell growth (a 2- to 10-fold increase) without any influence on pluripotency...
July 8, 2016: Biotechnology Progress
https://www.readbyqxmd.com/read/27179860/the-nonlinear-effect-of-somatic-cell-count-on-milk-composition-coagulation-properties-curd-firmness-modeling-cheese-yield-and-curd-nutrient-recovery
#16
T Bobbo, C Cipolat-Gotet, G Bittante, A Cecchinato
The aim of this study was to investigate the relationships between somatic cell count (SCC) in milk and several milk technological traits at the individual cow level. In particular, we determined the effects of very low to very high SCC on traits related to (1) milk yield and composition; (2) coagulation properties, including the traditional milk coagulation properties (MCP) and the new curd firming model parameters; and (3) cheese yield and recovery of milk nutrients in the curd (or loss in the whey). Milk samples from 1,271 Brown Swiss cows from 85 herds were used...
July 2016: Journal of Dairy Science
https://www.readbyqxmd.com/read/27151576/specification-of-embryonic-stem-cell-derived-tissues-into-eye-fields-by-wnt-signaling-using-rostral-diencephalic-tissue-inducing-culture
#17
Eriko Sakakura, Mototsugu Eiraku, Nozomu Takata
The eyes are subdivided from the rostral diencephalon in early development. How the neuroectoderm regulates this subdivision, however, is largely unknown. Taking advantage of embryonic stem cell (ESC) culture using a Rax reporter line to monitor rostral diencephalon formation, we found that ESC-derived tissues at day 7 grown in Glasgow Minimum Expression Media (GMEM) containing knockout serum replacement (KSR) exhibited higher levels of expression of axin2, a Wnt target gene, than those grown in chemically defined medium (CDM)...
August 2016: Mechanisms of Development
https://www.readbyqxmd.com/read/27050091/remission-for-loss-of-odontogenic-potential-in-a-new-micromilieu-in-vitro
#18
Yunfei Zheng, Jinglei Cai, Andrew Paul Hutchins, Lingfei Jia, Pengfei Liu, Dandan Yang, Shubin Chen, Lihong Ge, Duanqing Pei, Shicheng Wei
During embryonic organogenesis, the odontogenic potential resides in dental mesenchyme from the bud stage until birth. Mouse dental mesenchymal cells (mDMCs) isolated from the inductive dental mesenchyme of developing molars are frequently used in the context of tooth development and regeneration. We wondered if and how the odontogenic potential could be retained when mDMCs were cultured in vitro. In the present study, we undertook to test the odontogenic potential of cultured mDMCs and attempted to maintain the potential during culturing...
2016: PloS One
https://www.readbyqxmd.com/read/26957902/asian-radiology-forum-2015-for-building-an-asian-friendship-a-step-toward-the-vigorous-intersociety-collaboration-in-asia
#19
Ho Sung Kim, Jung-Ah Choi, Jongmin Lee
According to the reports presented at the Asian Radiology Forum 2015, organized by the Korean Society of Radiology (KSR) during the Korean Congress of Radiology (KCR) in September 2015 in Seoul, there is an increasing need to promote international exchange and collaboration amongst radiology societies in Asian countries. The Asian Radiology Forum was first held by KSR and the national delegates of Asian radiological partner societies, who attended this meeting with the aim of discussing selected subjects of global relevance in radiology...
March 2016: Korean Journal of Radiology: Official Journal of the Korean Radiological Society
https://www.readbyqxmd.com/read/26646319/synthesis-and-thermal-stability-of-perovskite-alkali-metal-strontium-borohydrides
#20
Kasper T Møller, Morten B Ley, Pascal Schouwink, Radovan Černý, Torben R Jensen
Three new perovskite-type bimetallic alkali metal strontium borohydride compounds, α-MSr(BH4)3 (M = K, Rb, Cs), have been synthesized and investigated by in situ synchrotron radiation powder X-ray diffraction, thermal analysis combined with mass spectrometry and Sievert's measurements. The bimetallic borohydrides were synthesized via an addition reaction between Sr(BH4)2 and MBH4 (M = K, Rb, Cs) by mechanochemical treatment. The Sr(BH4)2-NaBH4 system, which was treated in a similar manner, did not undergo reaction...
January 14, 2016: Dalton Transactions: An International Journal of Inorganic Chemistry
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