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Tony Hunter

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https://www.readbyqxmd.com/read/27909058/secreted-glioblastoma-nanovesicles-contain-intracellular-signaling-proteins-and-active-ras-incorporated-in-a-farnesylation-dependent-manner
#1
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/27899157/disorders-of-sex-development-insights-from-targeted-gene-sequencing-of-a-large-international-patient-cohort
#2
Stefanie Eggers, Simon Sadedin, Jocelyn A van den Bergen, Gorjana Robevska, Thomas Ohnesorg, Jacqueline Hewitt, Luke Lambeth, Aurore Bouty, Ingrid M Knarston, Tiong Yang Tan, Fergus Cameron, George Werther, John Hutson, Michele O'Connell, Sonia R Grover, Yves Heloury, Margaret Zacharin, Philip Bergman, Chris Kimber, Justin Brown, Nathalie Webb, Matthew F Hunter, Shubha Srinivasan, Angela Titmuss, Charles F Verge, David Mowat, Grahame Smith, Janine Smith, Lisa Ewans, Carolyn Shalhoub, Patricia Crock, Chris Cowell, Gary M Leong, Makato Ono, Antony R Lafferty, Tony Huynh, Uma Visser, Catherine S Choong, Fiona McKenzie, Nicholas Pachter, Elizabeth M Thompson, Jennifer Couper, Anne Baxendale, Jozef Gecz, Benjamin J Wheeler, Craig Jefferies, Karen MacKenzie, Paul Hofman, Philippa Carter, Richard I King, Csilla Krausz, Conny M A van Ravenswaaij-Arts, Leendert Looijenga, Sten Drop, Stefan Riedl, Martine Cools, Angelika Dawson, Achmad Zulfa Juniarto, Vaman Khadilkar, Anuradha Khadilkar, Vijayalakshmi Bhatia, Vũ Chí Dũng, Irum Atta, Jamal Raza, Nguyen Thi Diem Chi, Tran Kiem Hao, Vincent Harley, Peter Koopman, Garry Warne, Sultana Faradz, Alicia Oshlack, Katie L Ayers, Andrew H Sinclair
BACKGROUND: Disorders of sex development (DSD) are congenital conditions in which chromosomal, gonadal, or phenotypic sex is atypical. Clinical management of DSD is often difficult and currently only 13% of patients receive an accurate clinical genetic diagnosis. To address this we have developed a massively parallel sequencing targeted DSD gene panel which allows us to sequence all 64 known diagnostic DSD genes and candidate genes simultaneously. RESULTS: We analyzed DNA from the largest reported international cohort of patients with DSD (278 patients with 46,XY DSD and 48 with 46,XX DSD)...
November 29, 2016: Genome Biology
https://www.readbyqxmd.com/read/27798325/dynact-angiography-for-the-diagnosis-of-bilateral-bow-hunter-s-syndrome
#3
Tony Lu, Ponraj Chinnadurai, Javier E Anaya-Ayala, Orlando M Diaz
We herein present a rare case of bilateral positional vertebrobasilar insufficiency secondary to mechanical obstruction of the V2 segment of the vertebral artery in a 71-year-old patient presenting with vertigo, occipital headache, tremors and respiratory irregularities. Two-dimensional digital subtraction angiography is the traditional diagnostic imaging standard but does not capture any peri-vascular bony or soft tissue abnormalities that are important to understand the three-dimensional pathophysiology. Intra-procedural cone-beam computed tomography (CT) is an increasingly used diagnostic adjunct, available in most modern angiographic suites that allows for the three-dimensional visualization of the vasculature as well as CT-like soft tissue visualization of its surrounding anatomy...
October 26, 2016: Interventional Neuroradiology
https://www.readbyqxmd.com/read/27754503/acoustofluidic-coating-of-particles-and-cells
#4
Bugra Ayan, Adem Ozcelik, Hunter Bachman, Shi-Yang Tang, Yuliang Xie, Mengxi Wu, Peng Li, Tony Jun Huang
On-chip microparticle and cell coating technologies enable a myriad of applications in chemistry, engineering, and medicine. Current microfluidic coating technologies often rely on magnetic labeling and concurrent deflection of particles across laminar streams of chemicals. Herein, we introduce an acoustofluidic approach for microparticle and cell coating by implementing tilted-angle standing surface acoustic waves (taSSAWs) into microchannels with multiple inlets. The primary acoustic radiation force generated by the taSSAW field was exploited in order to migrate the particles across the microchannel through multiple laminar streams, which contained the buffer and coating chemicals...
October 18, 2016: Lab on a Chip
https://www.readbyqxmd.com/read/27562445/idelalisib-in-waldenstr%C3%A3-m-macroglobulinemia-high-incidence-of-hepatotoxicity
#5
Jorge J Castillo, Joshua N Gustine, Kirsten Meid, Toni Dubeau, Guang Yang, Lian Xu, Zachary R Hunter, Steven P Treon
No abstract text is available yet for this article.
August 26, 2016: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/27554103/consent-and-widespread-access-to-personal-health-information-for-the-delivery-of-care-a-large-scale-telephone-survey-of-consumers-attitudes-using-vignettes-in-new-zealand
#6
Dick Whiddett, Inga Hunter, Barry McDonald, Tony Norris, John Waldon
OBJECTIVES: In light of recent health policy, to examine factors which influence the public's willingness to consent to share their health information in a national electronic health record (EHR). DESIGN: Data were collected in a national telephone survey in 2008. Respondents were presented with vignettes that described situations in which their health information was shared and asked if they would consent to such sharing. The subset, consisting of the 18 vignettes that covered proving care, was reanalysed in depth using new statistical methods in 2016...
2016: BMJ Open
https://www.readbyqxmd.com/read/27542194/histidine-phosphorylation-relieves-copper-inhibition-in-the-mammalian-potassium-channel-kca3-1
#7
Shekhar Srivastava, Saswati Panda, Zhai Li, Stephen R Fuhs, Tony Hunter, Dennis J Thiele, Stevan R Hubbard, Edward Y Skolnik
KCa2.1, KCa2.2, KCa2.3 and KCa3.1 constitute a family of mammalian small- to intermediate-conductance potassium channels that are activated by calcium-calmodulin. KCa3.1 is unique among these four channels in that activation requires, in addition to calcium, phosphorylation of a single histidine residue (His358) in the cytoplasmic region, by nucleoside diphosphate kinase-B (NDPK-B). The mechanism by which KCa3.1 is activated by histidine phosphorylation is unknown. Histidine phosphorylation is well characterized in prokaryotes but poorly understood in eukaryotes...
2016: ELife
https://www.readbyqxmd.com/read/27468978/renal-disease-related-to-waldenstr%C3%A3-m-macroglobulinaemia-incidence-pathology-and-clinical-outcomes
#8
Josephine M Vos, Joshua Gustine, Helmut G Rennke, Zachary Hunter, Robert J Manning, Toni E Dubeau, Kirsten Meid, Monique C Minnema, Marie-Jose Kersten, Steven P Treon, Jorge J Castillo
The incidence and prognostic impact of nephropathy related to Waldenström macroglobulinaemia (WM) is currently unknown. We performed a retrospective study to assess biopsy-confirmed WM-related nephropathy in a cohort of 1391 WM patients seen at a single academic institution. A total of 44 cases were identified, the estimated cumulative incidence was 5·1% at 15 years. There was a wide variation in kidney pathology, some directly related to the WM: amyloidosis (n = 11, 25%), monoclonal-IgM deposition disease/cryoglobulinaemia (n = 10, 23%), lymphoplasmacytic lymphoma infiltration (n = 8, 18%), light-chain deposition disease (n = 4, 9%) and light-chain cast nephropathy (n = 4, 9%), and some probably related to the WM: thrombotic microangiopathy (TMA) (n = 3, 7%), minimal change disease (n = 2, 5%), membranous nephropathy (n = 1, 2%) and crystal-storing tubulopathy (n = 1, 2%)...
November 2016: British Journal of Haematology
https://www.readbyqxmd.com/read/27453048/identification-of-pgam5-as-a-mammalian-protein-histidine-phosphatase-that-plays-a-central-role-to-negatively-regulate-cd4-t-cells
#9
Saswati Panda, Shekhar Srivastava, Zhai Li, Martin Vaeth, Stephen R Fuhs, Tony Hunter, Edward Y Skolnik
Whereas phosphorylation of serine, threonine, and tyrosine is exceedingly well characterized, the role of histidine phosphorylation in mammalian signaling is largely unexplored. Here we show that phosphoglycerate mutase family 5 (PGAM5) functions as a phosphohistidine phosphatase that specifically associates with and dephosphorylates the catalytic histidine on nucleoside diphosphate kinase B (NDPK-B). By dephosphorylating NDPK-B, PGAM5 negatively regulates CD4(+) T cells by inhibiting NDPK-B-mediated histidine phosphorylation and activation of the K(+) channel KCa3...
August 4, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27415417/histological-transformation-to-diffuse-large-b-cell-lymphoma-in-patients-with-waldenstr%C3%A3-m-macroglobulinemia
#10
Jorge J Castillo, Joshua Gustine, Kirsten Meid, Toni Dubeau, Zachary R Hunter, Steven P Treon
Histological transformation to diffuse large B-cell lymphoma (DLBCL) rarely occurs in patients with Waldenström Macroglobulinemia (WM). We identified 20 patients out of a cohort of 1,466 WM patients who experienced histologic transformation. The 5, 10, and 15-year cumulative incidence rates were 1, 2.4, and 3.8%, respectively. Approximately half of the patients were naive to nucleoside analogues, and a quarter were previously untreated for WM at the time of transformation. More than 80% of patients presented with extranodal involvement, 65% with high IPI scores...
October 2016: American Journal of Hematology
https://www.readbyqxmd.com/read/27414747/synthesis-and-biological-activity-of-a-new-class-of-insecticides-the-n-5-aryl-1-3-4-thiadiazol-2-yl-amides
#11
Joseph D Eckelbarger, Marshall H Parker, Maurice C H Yap, Ann M Buysse, Jonathan M Babcock, Ricky Hunter, Yelena Adelfinskaya, Jack G Samaritoni, Negar Garizi, Tony K Trullinger
BACKGROUND: Optimization studies on a high throughput screening (HTS) hit led to the discovery of a series of N-(6-arylpyridazin-3-yl)amides with insecticidal activity. It was hypothesized that the isosteric replacement of the pyridazine ring with a 1,3,4-thiadiazole ring could lead to more potent biological activity and/or broader sap-feeding pest spectrum. The resulting N-(5-aryl-1,3,4-thiadiazol-2-yl)amides were explored as a new class of insecticides. RESULTS: Several methods for 2-amino-1,3,4-thiadiazole synthesis were used for the preparation of key synthetic intermediates...
July 14, 2016: Pest Management Science
https://www.readbyqxmd.com/read/27398816/rural-people-who-inject-drugs-a-cross-sectional-survey-addressing-the-dimensions-of-access-to-secondary-needle-and-syringe-program-outlets
#12
Karin Fisher, Tony Smith, Karen Nairn, Donna Anderson
OBJECTIVE: To better understand issues related to access to injecting equipment for people who inject drugs (PWID) in a rural area of New South Wales (NSW), Australia. DESIGN: Cross-sectional face-to-face survey using convenience and snowball sampling. SETTING: Six regional and rural population centres in Northern NSW, within the Hunter New England Local Health District. PARTICIPANTS: The sample included 190 PWID who had accessed a needle and syringe program outlet within 4 weeks of the survey...
July 11, 2016: Australian Journal of Rural Health
https://www.readbyqxmd.com/read/27332209/operationalizing-the-tanic-and-nica-l3-l4-tools-to-improve-informatics-competencies
#13
Carolyn Sipes, Dee McGonigle, Kathy Hunter, Toni Hebda, Taryn Hill, Jean Lamblin
Two tools were developed for nurses to self-assess different levels of informatics competencies. The TANIC is used for all nurses to self-assess; the NICA-L3/L4 is a tool for the informatics nurse specialist (INS) to self-assess skill levels. There are 167 informatics items in the TANIC and 178 advanced informatics items in the NICA-L3/L4. These tools were piloted; the results presented here. Based on the evaluation, the tools have been integrated into informatics courses at the BSN and MSN programs at Chamberlain College of Nursing, and presented in two AACN webinars and other national conferences...
2016: Studies in Health Technology and Informatics
https://www.readbyqxmd.com/read/27332159/competency-skills-assessment-successes-and-areas-for-improvement-identified-during-collaboration-between-informaticists-and-a-national-organization
#14
Carolyn Sipes, Kathy Hunter, Dee McGonigle, Toni Hebda, Taryn Hill, Jean Lamblin
The Association of periOperative Registered Nurses (AORN) approached the Nursing Informatics Research Team (NIRT) with a request to collaborate and conduct a competency assessment for their organization. An online tool was developed to determine current technology in perioperative settings. This presentation shares the process used to conduct research that led to a method for assessing perioperative nurses' competencies skills in their practice as well as identified gaps in curricula that faculty could address...
2016: Studies in Health Technology and Informatics
https://www.readbyqxmd.com/read/27301862/transcriptome-sequencing-reveals-a-profile-that-corresponds-to-genomic-variants-in-waldenstr%C3%A3-m-macroglobulinemia
#15
Zachary R Hunter, Lian Xu, Guang Yang, Nicholas Tsakmaklis, Josephine M Vos, Xia Liu, Jie Chen, Robert J Manning, Jiaji G Chen, Philip Brodsky, Christopher J Patterson, Joshua Gustine, Toni Dubeau, Jorge J Castillo, Kenneth C Anderson, Nikhil M Munshi, Steven P Treon
Whole-genome sequencing has identified highly prevalent somatic mutations including MYD88, CXCR4, and ARID1A in Waldenström macroglobulinemia (WM). The impact of these and other somatic mutations on transcriptional regulation in WM remains to be clarified. We performed next-generation transcriptional profiling in 57 WM patients and compared findings to healthy donor B cells. Compared with healthy donors, WM patient samples showed greatly enhanced expression of the VDJ recombination genes DNTT, RAG1, and RAG2, but not AICDA Genes related to CXCR4 signaling were also upregulated and included CXCR4, CXCL12, and VCAM1 regardless of CXCR4 mutation status, indicating a potential role for CXCR4 signaling in all WM patients...
August 11, 2016: Blood
https://www.readbyqxmd.com/read/27282387/metabolic-reprogramming-during-neuronal-differentiation-from-aerobic-glycolysis-to-neuronal-oxidative-phosphorylation
#16
Xinde Zheng, Leah Boyer, Mingji Jin, Jerome Mertens, Yongsung Kim, Li Ma, Li Ma, Michael Hamm, Fred H Gage, Tony Hunter
How metabolism is reprogrammed during neuronal differentiation is unknown. We found that the loss of hexokinase (HK2) and lactate dehydrogenase (LDHA) expression, together with a switch in pyruvate kinase gene splicing from PKM2 to PKM1, marks the transition from aerobic glycolysis in neural progenitor cells (NPC) to neuronal oxidative phosphorylation. The protein levels of c-MYC and N-MYC, transcriptional activators of the HK2 and LDHA genes, decrease dramatically. Constitutive expression of HK2 and LDHA during differentiation leads to neuronal cell death, indicating that the shut-off aerobic glycolysis is essential for neuronal survival...
2016: ELife
https://www.readbyqxmd.com/read/27123371/the-c-elegans-ortholog-of-usp7-controls-daf-16-stability-in-insulin-igf-1-like-signaling
#17
Thomas Heimbucher, Tony Hunter
FOXO family transcription factors are downstream effectors of Insulin/IGF-1 signaling (IIS) and are regulated by posttranslational modification and coregulators, including components of the ubiquitin-proteasome system (UPS). Cofactors promoting DAF-16/FOXO protein stability and function in IIS have not been described yet. In a recent study, we have identified the deubiquitylating enzyme MATH-33, the ortholog of mammalian USP7/HAUSP, as an essential DAF-16 coregulator. We found that MATH-33 actively stabilizes DAF-16 protein levels when IIS is downregulated...
October 2015: Worm
https://www.readbyqxmd.com/read/27008180/alleviation-of-neuronal-energy-deficiency-by-mtor-inhibition-as-a-treatment-for-mitochondria-related-neurodegeneration
#18
Xinde Zheng, Leah Boyer, Mingji Jin, Yongsung Kim, Weiwei Fan, Cedric Bardy, Travis Berggren, Ronald M Evans, Fred H Gage, Tony Hunter
mTOR inhibition is beneficial in neurodegenerative disease models and its effects are often attributable to the modulation of autophagy and anti-apoptosis. Here, we report a neglected but important bioenergetic effect of mTOR inhibition in neurons. mTOR inhibition by rapamycin significantly preserves neuronal ATP levels, particularly when oxidative phosphorylation is impaired, such as in neurons treated with mitochondrial inhibitors, or in neurons derived from maternally inherited Leigh syndrome (MILS) patient iPS cells with ATP synthase deficiency...
2016: ELife
https://www.readbyqxmd.com/read/26998258/simulating-social-ecological-systems-the-island-digital-ecosystem-avatars-idea-consortium
#19
Neil Davies, Dawn Field, David Gavaghan, Sally J Holbrook, Serge Planes, Matthias Troyer, Michael Bonsall, Joachim Claudet, George Roderick, Russell J Schmitt, Linda Amaral Zettler, Véronique Berteaux, Hervé C Bossin, Charlotte Cabasse, Antoine Collin, John Deck, Tony Dell, Jennifer Dunne, Ruth Gates, Mike Harfoot, James L Hench, Marania Hopuare, Patrick Kirch, Georgios Kotoulas, Alex Kosenkov, Alex Kusenko, James J Leichter, Hunter Lenihan, Antonios Magoulas, Neo Martinez, Chris Meyer, Benoit Stoll, Billie Swalla, Daniel M Tartakovsky, Hinano Teavai Murphy, Slava Turyshev, Fernanda Valdvinos, Rich Williams, Spencer Wood
Systems biology promises to revolutionize medicine, yet human wellbeing is also inherently linked to healthy societies and environments (sustainability). The IDEA Consortium is a systems ecology open science initiative to conduct the basic scientific research needed to build use-oriented simulations (avatars) of entire social-ecological systems. Islands are the most scientifically tractable places for these studies and we begin with one of the best known: Moorea, French Polynesia. The Moorea IDEA will be a sustainability simulator modeling links and feedbacks between climate, environment, biodiversity, and human activities across a coupled marine-terrestrial landscape...
2016: GigaScience
https://www.readbyqxmd.com/read/26942675/mitochondria-translocated-pgk1-functions-as-a-protein-kinase-to-coordinate-glycolysis-and-the-tca-cycle-in-tumorigenesis
#20
Xinjian Li, Yuhui Jiang, Jill Meisenhelder, Weiwei Yang, David H Hawke, Yanhua Zheng, Yan Xia, Kenneth Aldape, Jie He, Tony Hunter, Liwei Wang, Zhimin Lu
It is unclear how the Warburg effect that exemplifies enhanced glycolysis in the cytosol is coordinated with suppressed mitochondrial pyruvate metabolism. We demonstrate here that hypoxia, EGFR activation, and expression of K-Ras G12V and B-Raf V600E induce mitochondrial translocation of phosphoglycerate kinase 1 (PGK1); this is mediated by ERK-dependent PGK1 S203 phosphorylation and subsequent PIN1-mediated cis-trans isomerization. Mitochondrial PGK1 acts as a protein kinase to phosphorylate pyruvate dehydrogenase kinase 1 (PDHK1) at T338, which activates PDHK1 to phosphorylate and inhibit the pyruvate dehydrogenase (PDH) complex...
March 3, 2016: Molecular Cell
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