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Ian zachary

William R Critchley, Caroline Pellet-Many, Benjamin Ringham-Terry, Michael A Harrison, Ian C Zachary, Sreenivasan Ponnambalam
Receptor tyrosine kinases (RTKs) are membrane-based sensors that enable rapid communication between cells and their environment. Evidence is now emerging that interdependent regulatory mechanisms, such as membrane trafficking, ubiquitination, proteolysis and gene expression, have substantial effects on RTK signal transduction and cellular responses. Different RTKs exhibit both basal and ligand-stimulated ubiquitination, linked to trafficking through different intracellular compartments including the secretory pathway, plasma membrane, endosomes and lysosomes...
March 15, 2018: Cells
Philip P Vu, Zachary T Irwin, Autumn J Bullard, Shoshana W Ambani, Ian C Sando, Melanie G Urbanchek, Paul S Cederna, Cynthia A Chestek
Loss of the upper limb imposes a devastating interruption to everyday life. Full restoration of natural arm control requires the ability to simultaneously control multiple degrees of freedom of the prosthetic arm and maintain that control over an extended period of time. Current clinically available myoelectric prostheses do not provide simultaneous control or consistency for transradial amputees. To address this issue, we have implemented a standard Kalman filter for continuous hand control using intramuscular electromyography (EMG) from both regenerative peripheral nerve interfaces (RPNI) and an intact muscle within non-human primates...
February 2018: IEEE Transactions on Neural Systems and Rehabilitation Engineering
Ajaya K Biswal, Melani A Atmodjo, Mi Li, Holly L Baxter, Chang Geun Yoo, Yunqiao Pu, Yi-Ching Lee, Mitra Mazarei, Ian M Black, Ji-Yi Zhang, Hema Ramanna, Adam L Bray, Zachary R King, Peter R LaFayette, Sivakumar Pattathil, Bryon S Donohoe, Sushree S Mohanty, David Ryno, Kelsey Yee, Olivia A Thompson, Miguel Rodriguez, Alexandru Dumitrache, Jace Natzke, Kim Winkeler, Cassandra Collins, Xiaohan Yang, Li Tan, Robert W Sykes, Erica L Gjersing, Angela Ziebell, Geoffrey B Turner, Stephen R Decker, Michael G Hahn, Brian H Davison, Michael K Udvardi, Jonathan R Mielenz, Mark F Davis, Richard S Nelson, Wayne A Parrott, Arthur J Ragauskas, C Neal Stewart, Debra Mohnen
Cell walls in crops and trees have been engineered for production of biofuels and commodity chemicals, but engineered varieties often fail multi-year field trials and are not commercialized. We engineered reduced expression of a pectin biosynthesis gene (Galacturonosyltransferase 4, GAUT4) in switchgrass and poplar, and find that this improves biomass yields and sugar release from biomass processing. Both traits were maintained in a 3-year field trial of GAUT4-knockdown switchgrass, with up to sevenfold increased saccharification and ethanol production and sixfold increased biomass yield compared with control plants...
March 2018: Nature Biotechnology
Filipa Mota, Constantina Fotinou, Rohini Rhana, A W Edith Chan, Tamas Yelland, Mohamed T Arooz, Andrew P O'Leary, Jennie Hutton, Paul Frankel, Ian Zachary, David Selwood, Snezana Djordjevic
Neuropilin-1 (NRP1) is a transmembrane co-receptor involved in binding interactions with variety of ligands and receptors, including receptor tyrosine kinases. Expression of NRP1 in several cancers correlates with cancer stages and poor prognosis. Thus, NRP1 has been considered a therapeutic target and is the focus of multiple drug discovery initiatives. Vascular endothelial growth factor (VEGF) binds to the b1 domain of NRP1 through interactions between the C-terminal arginine of VEGF and residues in the NRP1 binding site including Tyr297, Tyr353, Asp320, Ser346, and Thr349...
February 12, 2018: FEBS Journal
Ian W H Jarvis, Zachary Enlo-Scott, Eszter Nagy, Ian S Mudway, Teresa D Tetley, Volker M Arlt, David H Phillips
Human exposure to airborne particulate matter (PM) is associated with adverse cardiopulmonary health effects, including lung cancer. Ambient PM represents a heterogeneous mixture of chemical classes including transition metals, polycyclic aromatic hydrocarbons (PAHs) and their derivatives such as nitro-PAHs, many of which are classified as putative carcinogens. As the primary site of human exposure to PM is the lungs, we investigated the response of two alveolar epithelial cell lines, the tumour-derived A549 and newly described TT1 cells, to fine and coarse PM collected from background and roadside locations...
January 25, 2018: Environmental and Molecular Mutagenesis
Zachary C Ryan, Theodore A Craig, Xuewei Wang, Philippe Delmotte, Jeffrey L Salisbury, Ian R Lanza, Gary C Sieck, Rajiv Kumar
Cancer cachexia is associated with muscle weakness and atrophy. We investigated whether 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3), which has previously been shown to increase skeletal myoblast oxygen consumption rate, could reverse the deleterious effects of tumor cell conditioned medium on myoblast function. Conditioned medium from Lewis lung carcinoma (LLC1) cells inhibits oxygen consumption, increases mitochondrial fragmentation, inhibits pyruvate dehydrogenase activity, and enhances proteasomal activity in human skeletal muscle myoblasts...
January 20, 2018: Biochemical and Biophysical Research Communications
Zachary Ian Grunewald, Nathan C Winn, Michelle L Gastecki, Makenzie L Woodford, James R Ball, Sarah A Hansen, Harold S Sacks, Victoria J Vieira-Potter, Jaume Padilla
Brown adipose tissue (BAT) is considered protective against obesity and related cardiometabolic dysfunction. Indeed, activation of BAT improves glucose homeostasis and attenuates cardiovascular disease development. However, whether a reduction in BAT mass perturbs metabolic function and increases risk for cardiovascular disease remains largely unknown. To address this question, C57BL/6J male mice underwent sham or surgical bilateral excision of interscapular BAT (iBATx) and were fed a normal chow or Western diet (WD) for 18 weeks, creating four groups (n=10/group)...
December 20, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
Bharathi Vennapusa, Brian Baker, Marcin Kowanetz, Jennifer Boone, Ina Menzl, Jean-Marie Bruey, Gregg Fine, Sanjeev Mariathasan, Ian McCaffery, Simonetta Mocci, Sandra Rost, Dustin Smith, Eslie Dennis, Szu-Yu Tang, Bita Damadzadeh, Espen Walker, Priti S Hegde, J Andrew Williams, Hartmut Koeppen, Zachary Boyd
Cancer immunotherapies, such as atezolizumab, are proving to be a valuable therapeutic strategy across indications, including non-small cell lung cancer (NSCLC) and urothelial cancer (UC). Here, we describe a diagnostic assay that measures programmed-death ligand 1 (PD-L1) expression, via immunohistochemistry, to identify patients who will derive the most benefit from treatment with atezolizumab, a humanized monoclonal anti-PD-L1 antibody. We describe the performance of the VENTANA PD-L1 (SP142) Assay in terms of specificity, sensitivity, and the ability to stain both tumor cells (TC) and tumor-infiltrating immune cells (IC), in NSCLC and UC tissues...
January 16, 2018: Applied Immunohistochemistry & Molecular Morphology: AIMM
Altayyeb Yousef, Zachary MacDonald, Trevor Simard, Juan J Russo, Joshua Feder, Michael V Froeschl, Alexander Dick, Christopher Glover, Ian G Burwash, Azeem Latib, Josep Rodés-Cabau, Marino Labinaz, Benjamin Hibbert
BACKGROUND: Transcatheter aortic valve implantation (TAVI) has become the standard of care for management of high-risk patients with aortic stenosis. Limited data is available regarding the performance of TAVI in patients with native aortic valve regurgitation (NAVR).Methods and Results:We performed a systematic review from 2002 to 2016. The primary outcome was device success as per VARC-2 criteria. Secondary endpoints included procedural complications, and 30-day and 1-year mortality rates...
February 23, 2018: Circulation Journal: Official Journal of the Japanese Circulation Society
Maria Zachari, Ian G Ganley
Autophagy is a vital lysosomal degradation pathway that serves as a quality control mechanism. It rids the cell of damaged, toxic or excess cellular components, which if left to persist could be detrimental to the cell. It also serves as a recycling pathway to maintain protein synthesis under starvation conditions. A key initial event in autophagy is formation of the autophagosome, a unique double-membrane organelle that engulfs the cytosolic cargo destined for degradation. This step is mediated by the serine/threonine protein kinase ULK1 (unc-51-like kinase 1), which functions in a complex with at least three protein partners: FIP200 (focal adhesion kinase family interacting protein of 200 kDa), ATG (autophagy-related protein) 13 (ATG13), and ATG101...
December 12, 2017: Essays in Biochemistry
Jaymin Jhaveri, Yuan Liu, Mudit Chowdhary, Zachary S Buchwald, Theresa W Gillespie, Jeffrey J Olson, Alfredo D Voloschin, Bree R Eaton, Hui-Kuo G Shu, Ian R Crocker, Walter J Curran, Kirtesh R Patel
BACKGROUND: The addition of chemotherapy to adjuvant radiotherapy (chemotherapy and radiation therapy [CRT]) improves overall survival (OS) for patients with high-risk grade 2 gliomas; however, the impact of chemotherapy alone (CA) is unknown. This study compares the OS of patients with high-risk grade 2 gliomas treated with CA versus CRT. METHODS: Patients with high-risk grade 2 gliomas (subtotal resection or age ≥ 40 years) with oligodendrogliomas, astrocytomas, or mixed tumors were identified with the National Cancer Data Base...
March 15, 2018: Cancer
Zachary A Marcum, Christopher W Forsberg, Kathryn P Moore, Ian H de Boer, Nicholas L Smith, Edward J Boyko, James S Floyd
BACKGROUND: For patients with type 2 diabetes and chronic kidney disease (CKD), high-quality evidence about the relative benefits and harms of oral glucose-lowering drugs is limited. OBJECTIVE: To evaluate whether mortality risk differs after the initiation of monotherapy with either metformin or a sulfonylurea in Veterans with type 2 diabetes and CKD. DESIGN: Observational, national cohort study in the Veterans Health Administration (VHA)...
February 2018: Journal of General Internal Medicine
Elise Landais, Ben Murrell, Bryan Briney, Sasha Murrell, Kimmo Rantalainen, Zachary T Berndsen, Alejandra Ramos, Lalinda Wickramasinghe, Melissa Laird Smith, Kemal Eren, Natalia de Val, Mengyu Wu, Audrey Cappelletti, Jeffrey Umotoy, Yolanda Lie, Terri Wrin, Paul Algate, Po-Ying Chan-Hui, Etienne Karita, Andrew B Ward, Ian A Wilson, Dennis R Burton, Davey Smith, Sergei L Kosakovsky Pond, Pascal Poignard
Understanding how broadly neutralizing antibodies (bnAbs) to HIV envelope (Env) develop during natural infection can help guide the rational design of an HIV vaccine. Here, we described a bnAb lineage targeting the Env V2 apex and the Ab-Env co-evolution that led to development of neutralization breadth. The lineage Abs bore an anionic heavy chain complementarity-determining region 3 (CDRH3) of 25 amino acids, among the shortest known for this class of Abs, and achieved breadth with only 10% nucleotide somatic hypermutation and no insertions or deletions...
November 21, 2017: Immunity
T Dylan Olver, Zachary Ian Grunewald, Thomas J Jurrissen, Rebecca Ek MacPherson, Paul J LeBlanc, Teagan R Schnurbusch, Alana M Czajkowski, Maurice Harold Laughlin, R Scott Rector, Shawn B Bender, Eric M Walters, Craig A Emter, Jaume Padilla
BACKGROUND: Impaired microvascular insulin signaling may develop prior to overt indices of microvascular endothelial dysfunction and represent an early pathological feature of adolescent obesity. Using a translational porcine model of juvenile obesity, we tested the hypotheses that in the early stages of obesity development, impaired insulin signaling manifests in skeletal muscle (triceps), brain (prefrontal cortex) and corresponding vasculatures, and that depressed insulin-induced vasodilation is reversible with acute inhibition of protein kinase C beta (PKCβ)...
November 15, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
Mudit Chowdhary, Derick Okwan-Duodu, Jeffrey M Switchenko, Robert H Press, Jaymin Jhaveri, Zachary S Buchwald, Jim Zhong, Bhavana V Chapman, Ranjit S Bindra, Joseph N Contessa, Henry S Park, James B Yu, Roy H Decker, Jeffrey J Olson, Nelson M Oyesiku, Ross A Abrams, Hui-Kuo G Shu, Walter J Curran, Ian R Crocker, Kirtesh R Patel
Preclinical evidence suggests angiotensin blockade therapy (ABT) decreases late radiation toxicities. This study aims to investigate the association between ABT and symptomatic radiation necrosis (SRN) following stereotactic radiosurgery (SRS). Resected brain metastases (rBM) and arteriovenous malformation (AVM) patients treated with SRS from 2002 to 2015 were identified. Patients in the ABT cohort were on therapy during SRS and at 1-month follow up. Kaplan Meier method and cumulative incidence model were used to analyze overall survival (OS) and intracranial outcomes...
November 9, 2017: Journal of Neuro-oncology
Mark W Bruner, Ian D Boardley, Alex J Benson, Kathleen S Wilson, Zachary Root, Jennifer Turnnidge, Jordan Sutcliffe, Jean Côté
The social identities formed through membership on extracurricular activity groups may contribute to the frequency with which youth engage in prosocial and antisocial behavior. However, researchers have yet to disentangle the individual- and group-level processes social identification effects operate through; sex and perceived norms may also moderate such effects. Thus, we investigated the hierarchical and conditional relations between three dimensions of social identity (i.e., ingroup ties, cognitive centrality, ingroup affect) and prosocial and antisocial behavior in youth ice hockey players (N = 376; 33% female)...
October 23, 2017: Journal of Youth and Adolescence
Ellen L Goode, Matthew S Block, Kimberly R Kalli, Robert A Vierkant, Wenqian Chen, Zachary C Fogarty, Aleksandra Gentry-Maharaj, Aleksandra Toloczko, Alexander Hein, Aliecia L Bouligny, Allan Jensen, Ana Osorio, Andreas D Hartkopf, Andy Ryan, Anita Chudecka-Glaz, Anthony M Magliocco, Arndt Hartmann, Audrey Y Jung, Bo Gao, Brenda Y Hernandez, Brooke L Fridley, Bryan M McCauley, Catherine J Kennedy, Chen Wang, Chloe Karpinskyj, Christiani B de Sousa, Daniel G Tiezzi, David L Wachter, Esther Herpel, Florin Andrei Taran, Francesmary Modugno, Gregg Nelson, Jan Lubinski, Janusz Menkiszak, Jennifer Alsop, Jenny Lester, Jesús García-Donas, Jill Nation, Jillian Hung, José Palacios, Joseph H Rothstein, Joseph L Kelley, Jurandyr M de Andrade, Luis Robles-Díaz, Maria P Intermaggio, Martin Widschwendter, Matthias W Beckmann, Matthias Ruebner, Mercedes Jimenez-Linan, Naveena Singh, Oleg Oszurek, Paul R Harnett, Peter F Rambau, Peter Sinn, Philipp Wagner, Prafull Ghatage, Raghwa Sharma, Robert P Edwards, Roberta B Ness, Sandra Orsulic, Sara Y Brucker, Sharon E Johnatty, Teri A Longacre, Ursula Eilber, Valerie McGuire, Weiva Sieh, Yanina Natanzon, Zheng Li, Alice S Whittemore, Anna deFazio, Annette Staebler, Beth Y Karlan, Blake Gilks, David D Bowtell, Estrid Høgdall, Francisco J Candido Dos Reis, Helen Steed, Ian G Campbell, Jacek Gronwald, Javier Benítez, Jennifer M Koziak, Jenny Chang-Claude, Kirsten B Moysich, Linda E Kelemen, Linda S Cook, Marc T Goodman, María José García, Peter A Fasching, Stefan Kommoss, Suha Deen, Susanne K Kjaer, Usha Menon, James D Brenton, Paul D P Pharoah, Georgia Chenevix-Trench, David G Huntsman, Stacey J Winham, Martin Köbel, Susan J Ramus
Importance: Cytotoxic CD8+ tumor-infiltrating lymphocytes (TILs) participate in immune control of epithelial ovarian cancer; however, little is known about prognostic patterns of CD8+ TILs by histotype and in relation to other clinical factors. Objective: To define the prognostic role of CD8+ TILs in epithelial ovarian cancer. Design, Setting, and Participants: This was a multicenter observational, prospective survival cohort study of the Ovarian Tumor Tissue Analysis Consortium...
October 12, 2017: JAMA Oncology
Tavvs M Alves, Zachary P Marston, Ian V MacRae, Robert L Koch
Pest-induced changes in plant reflectance are crucial for the development of pest management programs using remote sensing. However, it is unknown if plant reflectance data is also affected by foliar insecticides applied for pest management. Our study assessed the effects of foliar insecticides on leaf reflectance of soybean. A 2-yr field trial and a greenhouse trial were conducted using randomized complete block and completely randomized designs, respectively. Treatments consisted of an untreated check, a new systemic insecticide (sulfoxaflor), and two representatives of the most common insecticide classes used for soybean pest management in the north-central United States (i...
December 5, 2017: Journal of Economic Entomology
Sharadha Dayalan Naidu, Dina Dikovskaya, Egle Gaurilcikaite, Elena V Knatko, Zachary R Healy, Hema Mohan, Glenn Koh, Axel Laurell, Graeme Ball, David Olagnier, Laureano de la Vega, Ian G Ganley, Paul Talalay, Albena T Dinkova-Kostova
Autophagy plays a critical role in the maintenance of cellular homeostasis by degrading proteins, lipids and organelles. Autophagy is activated in response to stress, but its regulation in the context of other stress response pathways, such as those mediated by heat shock factor 1 (HSF1) and nuclear factor-erythroid 2 p45-related factor 2 (NRF2), is not well understood. We found that the Michael acceptor bis(2-hydoxybenzylidene)acetone (HBB2), a dual activator of NRF2 and HSF1, protects against the development of UV irradiation-mediated cutaneous squamous cell carcinoma in mice...
September 8, 2017: Scientific Reports
Cynthia X Ma, Vera Suman, Matthew P Goetz, Donald Northfelt, Mark E Burkard, Foluso Ademuyiwa, Michael Naughton, Julie Margenthaler, Rebecca Aft, Richard Gray, Amye Tevaarwerk, Lee Wilke, Tufia Haddad, Timothy Moynihan, Charles Loprinzi, Tina Hieken, Erica K Barnell, Zachary L Skidmore, Yan-Yang Feng, Kilannin Krysiak, Jeremy Hoog, Zhanfang Guo, Leslie Nehring, Kari B Wisinski, Elaine Mardis, Ian S Hagemann, Kiran Vij, Souzan Sanati, Hussam Al-Kateb, Obi L Griffith, Malachi Griffith, Laurence Doyle, Charles Erlichman, Matthew J Ellis
Purpose: Hyperactivation of AKT is common and associated with endocrine resistance in estrogen receptor-positive (ER(+)) breast cancer. The allosteric pan-AKT inhibitor MK-2206 induced apoptosis in PIK3CA-mutant ER(+) breast cancer under estrogen-deprived condition in preclinical studies. This neoadjuvant phase II trial was therefore conducted to test the hypothesis that adding MK-2206 to anastrozole induces pathologic complete response (pCR) in PIK3CA mutant ER(+) breast cancer.Experimental Design: Potential eligible patients with clinical stage II/III ER(+)/HER2(-) breast cancer were preregistered and received anastrozole (goserelin if premenopausal) for 28 days in cycle 0 pending tumor PIK3CA sequencing...
September 5, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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