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https://www.readbyqxmd.com/read/27740621/tetraspanin-cd9-stabilizes-gp130-by-preventing-its-ubiquitin-dependent-lysosomal-degradation-to-promote-stat3-activation-in-glioma-stem-cells
#1
Yu Shi, Wenchao Zhou, Lin Cheng, Cong Chen, Zhi Huang, Xiaoguang Fang, Qiulian Wu, Zhicheng He, Senlin Xu, Justin D Lathia, Yifang Ping, Jeremy N Rich, Xiu-Wu Bian, Shideng Bao
Glioblastoma (GBM) is the most malignant and lethal brain tumor harboring glioma stem cells (GSCs) that promote tumor propagation and therapeutic resistance. GSCs preferentially express several critical cell surface molecules that regulate the pro-survival signaling for maintaining the stem cell-like phenotype. Tetraspanin CD9 has recently been reported as a GSC biomarker that is relevant to the GSC maintenance. However, the underlying molecular mechanisms of CD9 in maintaining GSC property remain elusive. Herein, we report that CD9 stabilizes the IL-6 receptor glycoprotein 130 (gp130) by preventing its ubiquitin-dependent lysosomal degradation to facilitate the STAT3 activation in GSCs...
October 14, 2016: Cell Death and Differentiation
https://www.readbyqxmd.com/read/27709295/topically-applied-manganese-porphyrins-bmx-001-and-bmx-010-display-a-significant-anti-inflammatory-response-in-a-mouse-model-of-allergic-dermatitis
#2
Kelsey Stover, Tomoki Fukuyama, Ashlyn T Young, Michael A Daniele, Rebecca Oberley, James D Crapo, Wolfgang Bäumer
In this study, we topically administered two antioxidant compounds, the manganese-porphyrin-derivatives BMX-001 and BMX-010, in a mouse model of allergic dermatitis and compared the efficacy for reduction of itch and inflammation. In vitro effects of BMX-001 and BMX-010 on keratinocytes, bone marrow derived dendritic cells (BMDCs) and T-cells were initially analysed. For assessment of scratching behaviour, BMX-001 and BMX-010 (0.01 and 0.1 %) were topically applied 16 h and/or 1 h before compound 48/80 or toluene-2,4,-diisocyanate (TDI) challenge in a TDI induced mouse dermatitis model...
October 5, 2016: Archives of Dermatological Research
https://www.readbyqxmd.com/read/27601470/phosphorylation-impacts-n-end-rule-degradation-of-the-proteolytically-activated-form-of-bmx-kinase
#3
Mohamed A Eldeeb, Richard P Fahlman
Cellular signaling leading to the initiation of apoptosis typically results in the activation of caspases, which in turn leads to the proteolytic generation of protein fragments with new or altered cellular functions. Increasing numbers of reports are demonstrating that the activity of many of these proteolytically activated protein fragments can be attenuated by their selective degradation by the N-end rule pathway. Here we report the first evidence that selective degradation of a caspase product by the N-end rule pathway can be modulated by phosphorylation...
October 21, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27544886/bicycling-crash-characteristics-an-in-depth-crash-investigation-study
#4
Ben Beck, Mark Stevenson, Stuart Newstead, Peter Cameron, Rodney Judson, Elton R Edwards, Andrew Bucknill, Marilyn Johnson, Belinda Gabbe
The aim of this study was to describe the crash characteristics and patient outcomes of a sample of patients admitted to hospital following bicycle crashes. Injured cyclists were recruited from the two major trauma services for the state of Victoria, Australia. Enrolled cyclists completed a structured interview, and injury details and patient outcomes were extracted from the Victorian State Trauma Registry (VSTR) and the Victorian Orthopaedic Trauma Outcomes Registry (VOTOR). 186 cyclists consented to participate in the study...
November 2016: Accident; Analysis and Prevention
https://www.readbyqxmd.com/read/27485288/effect-of-gear-ratio-on-peak-power-and-time-to-peak-power-in-bmx-cyclists
#5
Lee P Rylands, Simon J Roberts, Howard T Hurst
The aim of this study was to ascertain if gear ratio selection would have an effect on peak power and time to peak power production in elite Bicycle Motocross (BMX) cyclists. Eight male elite BMX riders volunteered for the study. Each rider performed three, 10-s maximal sprints on an Olympic standard indoor BMX track. The riders' bicycles were fitted with a portable SRM power meter. Each rider performed the three sprints using gear ratios of 41/16, 43/16 and 45/16 tooth. The results from the 41/16 and 45/16 gear ratios were compared to the current standard 43/16 gear ratio...
August 2, 2016: European Journal of Sport Science
https://www.readbyqxmd.com/read/27477519/effect-of-cadence-selection-on-peak-power-and-time-of-power-production-in-elite-bmx-riders-a-laboratory-based-study
#6
Lee P Rylands, Simon J Roberts, Howard T Hurst, Ian Bentley
The aims of this study were to analyse the optimal cadence for peak power production and time to peak power in bicycle motocross (BMX) riders. Six male elite BMX riders volunteered for the study. Each rider completed 3 maximal sprints at a cadence of 80, 100, 120 and 140 revs · min(-1) on a laboratory Schoberer Rad Messtechnik (SRM) cycle ergometer in isokinetic mode. The riders' mean values for peak power and time of power production in all 3 tests were recorded. The BMX riders produced peak power (1105 ± 139 W) at 100 revs · min(-1) with lower peak power produced at 80 revs · min(-1) (1060 ± 69 W, (F(2,15) = 3...
August 1, 2016: Journal of Sports Sciences
https://www.readbyqxmd.com/read/27378077/adolescents-ratings-of-features-of-parks-that-encourage-park-visitation-and-physical-activity
#7
Jenny Veitch, Jo Salmon, Kate Parker, Shaun Bangay, Benedicte Deforche, Anna Timperio
BACKGROUND: The neighbourhood environment such as the availability of parks are a key, but under-researched, influence on adolescents' physical activity. In addition to overall physical activity levels, park-based physical activity and park visitation is low in this age group. Thus, it is critical to identify park features that may encourage or discourage adolescents from visiting parks. This study used a novel methodology to identify key physical characteristics of parks that are perceived to be important for park visitation and park-based physical activity among adolescents...
2016: International Journal of Behavioral Nutrition and Physical Activity
https://www.readbyqxmd.com/read/27270311/direct-contact-with-perivascular-tumor-cells-enhances-integrin-%C3%AE-v%C3%AE-3-signaling-and-migration-of-endothelial-cells
#8
Monica E Burgett, Justin D Lathia, Patrick Roth, Amy S Nowacki, Deni S Galileo, Elena Pugacheva, Ping Huang, Amit Vasanji, Meizhang Li, Tatiana Byzova, Tom Mikkelsen, Shideng Bao, Jeremy N Rich, Michael Weller, Candece L Gladson
The secretion of soluble pro-angiogenic factors by tumor cells and stromal cells in the perivascular niche promotes the aggressive angiogenesis that is typical of glioblastoma (GBM). Here, we show that angiogenesis also can be promoted by a direct interaction between brain tumor cells, including tumor cells with cancer stem-like properties (CSCs), and endothelial cells (ECs). As shown in vitro, this direct interaction is mediated by binding of integrin αvβ3 expressed on ECs to the RGD-peptide in L1CAM expressed on CSCs...
July 12, 2016: Oncotarget
https://www.readbyqxmd.com/read/27255222/efficient-microscale-basic-reverse-phase-peptide-fractionation-for-global-and-targeted-proteomics
#9
Hyoung-Joo Lee, Hye-Jung Kim, Daniel C Liebler
Analysis of small biological samples would benefit from an efficient microscale fractionation strategy that minimizes sample handling, transfer steps, and accompanying losses. Here we describe a microscale basic reverse phase liquid chromatographic (bRPLC) fractionation method that offers high reproducibility and efficiency for peptide mixtures from small (5-20 μg) samples. We applied our platform to detect differentially expressed proteins from lung tumor cell lines that are sensitive (11-18) and resistant (11-18R) to the tyrosine kinase inhibitor erlotinib...
July 1, 2016: Journal of Proteome Research
https://www.readbyqxmd.com/read/27253834/the-effect-of-pumping-and-non-pumping-techniques-on-velocity-production-and-muscle-activity-during-field-based-bmx-cycling
#10
Lee P Rylands, Howard T Hurst, Simon J Roberts, Robert Graydon
The aim of the current study was to determine if a technique called 'pumping' had a significant effect on velocity production in BMX cycling. Ten National standard male BMX riders fitted with sEMG sensors completed a timed lap of an indoor BMX track using the technique of pumping, and a lap without pumping. The lap times were recorded for both trials and their surface sEMG recorded to ascertain any variation in muscle activation of the biceps brachii, triceps brachii, vastus lateralis and medial gastrocnemius...
May 28, 2016: Journal of Strength and Conditioning Research
https://www.readbyqxmd.com/read/27220256/a-novel-redox-active-metalloporphyrin-reduces-reactive-oxygen-species-and-inflammatory-markers-but-does-not-improve-marginal-mass-engraftment-in-a-murine-donation-after-circulatory-death-islet-transplantation-model
#11
Antonio Bruni, Andrew R Pepper, Boris Gala-Lopez, Rena Pawlick, Nasser Abualhassan, James D Crapo, Jon D Piganelli, A M James Shapiro
Islet transplantation is a highly effective treatment for stabilizing glycemic control for select patients with type-1 diabetes. Despite improvements to clinical transplantation, single-donor transplant success has been hard to achieve routinely, necessitating increasing demands on viable organ availability. Donation after circulatory death (DCD) may be an alternative option to increase organ availability however, these organs tend to be more compromised. The use of metalloporphyrin anti-inflammatory and antioxidant (MnP) compounds previously demonstrated improved in vivo islet function in preclinical islet transplantation...
July 3, 2016: Islets
https://www.readbyqxmd.com/read/27197306/inhibition-of-pi3k-bmx-cell-survival-pathway-sensitizes-to-bh3-mimetics-in-sclc
#12
Danielle S Potter, Melanie Galvin, Stewart Brown, Alice Lallo, Cassandra L Hodgkinson, Fiona Blackhall, Christopher J Morrow, Caroline Dive
Most small cell lung cancer (SCLC) patients are initially responsive to cytotoxic chemotherapy, but almost all undergo fatal relapse with progressive disease, highlighting an urgent need for improved therapies and better patient outcomes in this disease. The proapoptotic BH3 mimetic ABT-737 that targets BCL-2 family proteins demonstrated good single-agent efficacy in preclinical SCLC models. However, so far clinical trials of the BH3 mimetic Navitoclax have been disappointing. We previously demonstrated that inhibition of a PI3K/BMX cell survival signaling pathway sensitized colorectal cancer cells to ABT-737...
June 2016: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/27158663/kinomic-alterations-in-atypical-meningioma
#13
Joshua C Anderson, Robert B Taylor, John B Fiveash, Rik de Wijn, G Yancey Gillespie, Christopher D Willey
BACKGROUND: We sought to profile Atypical Meningioma in a high-throughput manner to better understand the altered signaling within these tumors and specifically the kinases altered in recurrent atypical meningioma. Kinomic Profiles could be used to identify prognostic biomarkers for responders/non-responders to classify future patients that are unlikely to benefit from current therapies. Directly these results could be used to identify drug-actionable kinase targets as well. METHODS: Peptide-substrate microarray kinase activity analysis was conducted with a PamStation(®)12 analyzing the tyrosine kinome in each tumor kinetically against ~144 target peptides...
July 2015: Medical Research Archives
https://www.readbyqxmd.com/read/27146149/activation-of-endothelial-%C3%AE-catenin-signaling-induces-heart-failure
#14
Akito Nakagawa, Atsuhiko T Naito, Tomokazu Sumida, Seitaro Nomura, Masato Shibamoto, Tomoaki Higo, Katsuki Okada, Taku Sakai, Akihito Hashimoto, Yuki Kuramoto, Toru Oka, Jong-Kook Lee, Mutsuo Harada, Kazutaka Ueda, Ichiro Shiojima, Florian P Limbourg, Ralf H Adams, Tetsuo Noda, Yasushi Sakata, Hiroshi Akazawa, Issei Komuro
Activation of β-catenin-dependent canonical Wnt signaling in endothelial cells plays a key role in angiogenesis during development and ischemic diseases, however, other roles of Wnt/β-catenin signaling in endothelial cells remain poorly understood. Here, we report that sustained activation of β-catenin signaling in endothelial cells causes cardiac dysfunction through suppressing neuregulin-ErbB pathway in the heart. Conditional gain-of-function mutation of β-catenin, which activates Wnt/β-catenin signaling in Bmx-positive arterial endothelial cells (Bmx/CA mice) led to progressive cardiac dysfunction and 100% mortality at 40 weeks after tamoxifen treatment...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27101199/epha3-regulates-the-multidrug-resistance-of-small-cell-lung-cancer-via-the-pi3k-bmx-stat3-signaling-pathway
#15
Juan Peng, Qiongyao Wang, Huanxin Liu, Minting Ye, Xiaoxia Wu, Linlang Guo
Multidrug resistance (MDR) is a major obstacle to the treatment of small cell lung cancer (SCLC). EPHA3 has been revealed to be the most frequently mutated Eph receptor gene in lung cancer with abnormal expression. Growing evidence indicates that the signaling proteins of EPHA3 downstream, including PI3K, BMX and STAT3, play crucial roles in tumorigenesis and cancer progression. To explore the possible role of EPHA3 in MDR, we assessed the influence of EPHA3 on chemoresistance, cell cycle, apoptosis, and tumor growth, as well as the relationship between EPHA3 and the expression of PI3K, BMX, and STAT3 in SCLC...
April 21, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/27098749/nonclinical-safety-and-toxicokinetics-of-mntnbuoe-2-pyp5-bmx-001
#16
Shayne Cox Gad, Dexter W Sullivan, Ivan Spasojevic, Cesar V Mujer, Charles B Spainhour, James D Crapo
BMX-001, a manganese porphyrin that has anti-inflammatory, antioxidant, and antitumor properties, is being developed as a potential therapeutic for high-grade glioma (HGG) and head and neck (H&N) cancer. An IND has been opened for BMX-001 in the treatment of HGG (NCT02655601) and another is in preparation for H&N. The safety of BMX-001 has been evaluated in a battery of nonclinical Good Laboratory Practice (GLP)-compliant studies. Systemic toxicity has been evaluated using the intended cGMP product administered subcutaneously for periods of up to 5 weeks in both the mouse and the monkey and included toxicokinetic evaluations to characterize systemic exposure and tissue distribution and clearance of BMX-001...
July 2016: International Journal of Toxicology
https://www.readbyqxmd.com/read/27077273/the-impact-response-of-traditional-and-bmx-style-bicycle-helmets-at-different-impact-severities
#17
Alyssa L DeMarco, Dennis D Chimich, John C Gardiner, Gunter P Siegmund
Bicycle helmets reduce the frequency and severity of severe to fatal head and brain injuries in bicycle crashes. Our goal here was to measure the impact attenuation performance of common bicycle helmets over a range of impact speeds. We performed 127 drop tests using 13 different bicycle helmet models (6 traditional style helmets and 7 BMX-style helmets) at impact speeds ranging from 1 to 10m/s onto a flat anvil. Helmets were struck on their left front and/or right front areas, a common impact location that was at or just below the test line of most bicycle helmet standards...
July 2016: Accident; Analysis and Prevention
https://www.readbyqxmd.com/read/26972789/glucose-dependent-insulinotropic-polypeptide-ameliorates-mild-traumatic-brain-injury-induced-cognitive-and-sensorimotor-deficits-and-neuroinflammation-in-rats
#18
Yu-Wen Yu, Tsung-Hsun Hsieh, Kai-Yun Chen, John Chung-Che Wu, Barry J Hoffer, Nigel H Greig, Yazhou Li, Jing-Huei Lai, Cheng-Fu Chang, Jia-Wei Lin, Yu-Hsin Chen, Liang-Yo Yang, Yung-Hsiao Chiang
Mild traumatic brain injury (mTBI) is a major public health issue, representing 75-90% of all cases of TBI. In clinical settings, mTBI, which is defined as a Glascow Coma Scale (GCS) score of 13-15, can lead to various physical, cognitive, emotional, and psychological-related symptoms. To date, there are no pharmaceutical-based therapies to manage the development of the pathological deficits associated with mTBI. In this study, the neurotrophic and neuroprotective properties of glucose-dependent insulinotropic polypeptide (GIP), an incretin similar to glucagon-like peptide-1 (GLP-1), was investigated after its steady-state subcutaneous administration, focusing on behavior after mTBI in an in vivo animal model...
November 15, 2016: Journal of Neurotrauma
https://www.readbyqxmd.com/read/26944939/synergistic-activation-of-er%C3%AE-by-estrogen-and-prolactin-in-breast-cancer-cells-requires-tyrosyl-phosphorylation-of-pak1
#19
Peter Oladimeji, Rebekah Skerl, Courtney Rusch, Maria Diakonova
Serine/threonine kinase PAK1 is activated by estrogen and plays an important role in breast cancer. However, the integration of PAK1 into the estrogen response is not fully understood. In this study, we investigated the mechanisms underlying the hormone-induced activation of estrogen receptor (ERα, ESR1). We show that estrogen activated PAK1 through both the ERα and GPER1 membrane receptors. Estrogen-dependent activation of PAK1 required the phosphorylation of tyrosine residues by Etk/Bmx and protein kinase A (PKA) within an assembled signaling complex comprising pTyr-PAK1, Etk/Bmx, the heterotrimer G-protein subunits Gβ1, Gγ2, and/or Gγ5, PAK-associated guanine nucleotide exchange factor (βPIX, ARHGEF7), and PKA...
May 1, 2016: Cancer Research
https://www.readbyqxmd.com/read/26928551/protease-activated-receptors-pars-in%C3%A2-cancer-novel-biased-signaling-and-targets-for%C3%A2-therapy
#20
R Bar-Shavit, M Maoz, A Kancharla, M Jaber, D Agranovich, S Grisaru-Granovsky, B Uziely
Despite the fact that G protein-coupled receptors (GPCRs) mediate numerous physiological processes and represent targets for therapeutics for a vast array of diseases, their role in tumor biology is under appreciated. Protease-activated receptors (PARs) form a family which belongs to GPCR class A. PAR1&2 emerge with a central role in epithelial malignancies. Although the part of PAR1&2 in cancer is on the rise, their underlying signaling events are poorly understood. We review hereby past, present, and future cancer-associated PAR biology...
2016: Methods in Cell Biology
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