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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...
September 12, 2016: Life Sciences
(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
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
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...
August 24, 2016: Nature
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
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 if additional adaptive resistance mechanisms may co-exist, 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...
July 15, 2016: Molecular Cancer Research: MCR
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
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
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
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
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
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
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
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
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
Haichun Li, Minghui Wang, Xiaoyi Xu
Protein phosphorylation catalyzed by kinases plays essential roles in various intracellular processes. With an increasing number of phosphorylation sites verified experimentally by high-throughput technologies and assigned as substrates of specific kinases, prediction of potential kinase-substrate relations (KSRs) attracts increasing attention. Although a large number of computational methods have been designed, most of them only focus on local protein sequence information. A few KSR prediction approaches integrate protein-protein interaction and protein sequence information into existing machine learning algorithms at the cost of high feature dimensions or reduced sensitivity...
December 2015: Journal of Bioinformatics and Computational Biology
Yizhi Yin, Sean Donlevy, Sarit Smolikove
Meiosis is a tightly regulated process requiring coordination of diverse events. A conserved ERK/MAPK-signaling cascade plays an essential role in the regulation of meiotic progression. The Thousand And One kinase (TAO) kinase is a MAPK kinase kinase, the meiotic role of which is unknown. We have analyzed the meiotic functions of KIN-18, the homolog of mammalian TAO kinases, in Caenorhabditis elegans. We found that KIN-18 is essential for normal meiotic progression; mutants exhibit accelerated meiotic recombination as detected both by analysis of recombination intermediates and by crossover outcome...
January 2016: Genetics
Feng Liu, Chunhong Cai, Xin Wu, Yanxia Cheng, Tao Lin, Guanghui Wei, Dawei He
To compare KnockOut serum replacement (KSR) and fetal bovine serum (FBS) for the development of germ cells. Testicular tissues from Sprague-Dawley rats were cultured for 4 weeks in culture media supplemented with FBS or KSR. Tissue area was measured at the beginning and end of the culturing period. Testicular histology, development of the germ cells, and the diameter of seminiferous tubules were analyzed by hematoxylin and eosin staining. After 4 weeks in culture, apoptosis and expression of the stage-specific spermatogenesis marker genes Kit, Sycp3, and Crisp1 were assayed...
January 15, 2016: Theriogenology
G Thiruvenkadam, Sharath Asokan, J Baby John, P R Geetha Priya, J Prathiba
AIMS: The aim of this study was to assess oral health-related quality of life (OHRQoL) using short form (SF) of child oral health impact profile (COHIP) in children aged 11-15 years who sought orthodontic treatment. A comparison was done between these children and age-matched peers who never had or sought orthodontic treatment. METHODOLOGY: This cross-sectional study included 227 children aged 11-15 years. A total of 110 participants had sought orthodontic treatment at KSR Institute of Dental Science and Research (orthodontic group) and 117 participants from a nearby school who had never undergone or sought orthodontic treatment (comparison group)...
July 2015: Contemporary Clinical Dentistry
Hedwig M Blommestein, Nigel Armstrong, Steve Ryder, Sohan Deshpande, Gill Worthy, Caro Noake, Rob Riemsma, Jos Kleijnen, Johan L Severens, Maiwenn J Al
The National Institute for Health and Care Excellence (NICE) invited the manufacturer of lenalidomide (Celgene) to submit evidence of the clinical and cost effectiveness of the drug for treating adults with myelodysplastic syndromes (MDS) associated with deletion 5q cytogenetic abnormality, as part of the Institute's single technology appraisal (STA) process. Kleijnen Systematic Reviews Ltd (KSR), in collaboration with Erasmus University Rotterdam, was commissioned to act as the Evidence Review Group (ERG)...
January 2016: PharmacoEconomics
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