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Brian smith

Keqiang Xie, Lesley A Colgan, Maria T Dao, Brian S Muntean, Laurie P Sutton, Cesare Orlandi, Sanford L Boye, Shannon E Boye, Chien-Cheng Shih, Yuqing Li, Baoji Xu, Roy G Smith, Ryohei Yasuda, Kirill A Martemyanov
It is well recognized that G-protein-coupled receptors (GPCRs) can activate Ras-regulated kinase pathways to produce lasting changes in neuronal function. Mechanisms by which GPCRs transduce these signals and their relevance to brain disorders are not well understood. Here, we identify a major Ras regulator, neurofibromin 1 (NF1), as a direct effector of GPCR signaling via Gβγ subunits in the striatum. We find that binding of Gβγ to NF1 inhibits its ability to inactivate Ras. Deletion of NF1 in striatal neurons prevents the opioid-receptor-induced activation of Ras and eliminates its coupling to Akt-mTOR-signaling pathway...
October 18, 2016: Current Biology: CB
Richard L Pyle, Raymond Boland, Holly Bolick, Brian W Bowen, Christina J Bradley, Corinne Kane, Randall K Kosaki, Ross Langston, Ken Longenecker, Anthony Montgomery, Frank A Parrish, Brian N Popp, John Rooney, Celia M Smith, Daniel Wagner, Heather L Spalding
Although the existence of coral-reef habitats at depths to 165 m in tropical regions has been known for decades, the richness, diversity, and ecological importance of mesophotic coral ecosystems (MCEs) has only recently become widely acknowledged. During an interdisciplinary effort spanning more than two decades, we characterized the most expansive MCEs ever recorded, with vast macroalgal communities and areas of 100% coral cover between depths of 50-90 m extending for tens of km(2) in the Hawaiian Archipelago...
2016: PeerJ
Jennifer L Smith, Corey L Anderson, Don E Burgess, Claude S Elayi, Craig T January, Brian P Delisle
The molecular mechanisms underlying congenital long QT syndrome (LQTS) are now beginning to be understood. New insights into the etiology and therapeutic strategies are emerging from heterologous expression studies of LQTS-linked mutant proteins, as well as inducible pluripotent stem cell derived cardiomyocytes (iPSC-CMs) from LQTS patients. This review focuses on the major molecular mechanism that underlies LQTS type 2 (LQT2). LQT2 is caused by loss of function (LOF) mutations in KCNH2 (also known as the human Ether-à-go-go-Related Gene or hERG)...
October 2016: Journal of Arrhythmia
András Kotschy, Zoltán Szlavik, James Murray, James Davidson, Ana Leticia Maragno, Gaëtane Le Toumelin-Braizat, Maïa Chanrion, Gemma L Kelly, Jia-Nan Gong, Donia M Moujalled, Alain Bruno, Márton Csekei, Attila Paczal, Zoltán B Szabo, Szabolcs Sipos, Gábor Radics, Agnes Proszenyak, Balázs Balint, Levente Ondi, Gábor Blasko, Alan Robertson, Allan Surgenor, Pawel Dokurno, Ijen Chen, Natalia Matassova, Julia Smith, Christopher Pedder, Christopher Graham, Aurélie Studeny, Gaëlle Lysiak-Auvity, Anne-Marie Girard, Fabienne Gravé, David Segal, Chris D Riffkin, Giovanna Pomilio, Laura C A Galbraith, Brandon J Aubrey, Margs S Brennan, Marco J Herold, Catherine Chang, Ghislaine Guasconi, Nicolas Cauquil, Fabien Melchiore, Nolwen Guigal-Stephan, Brian Lockhart, Frédéric Colland, John A Hickman, Andrew W Roberts, David C S Huang, Andrew H Wei, Andreas Strasser, Guillaume Lessene, Olivier Geneste
Avoidance of apoptosis is critical for the development and sustained growth of tumours. The pro-survival protein myeloid cell leukemia 1 (MCL1) is overexpressed in many cancers, but the development of small molecules targeting this protein that are amenable for clinical testing has been challenging. Here we describe S63845, a small molecule that specifically binds with high affinity to the BH3-binding groove of MCL1. Our mechanistic studies demonstrate that S63845 potently kills MCL1-dependent cancer cells, including multiple myeloma, leukaemia and lymphoma cells, by activating the BAX/BAK-dependent mitochondrial apoptotic pathway...
October 19, 2016: Nature
Kelsey S Kalous, Sarah L Wynia-Smith, Michael D Olp, Brian C Smith
The sirtuin family of proteins catalyze the NAD+-dependent deacylation of acyl-lysine residues. Humans encode seven sirtuins (Sirt1-7) and recent studies have suggested that post-translational modification of Sirt1 by cysteine S-nitrosation correlates with increased acetylation of Sirt1 deacetylase substrates. However, the mechanism of Sirt1 inhibition by S-nitrosation was unknown. Here, we show that Sirt1 is transnitrosated and inhibited by the physiologically-relevant nitrosothiol S-nitrosoglutathione (GSNO)...
October 18, 2016: Journal of Biological Chemistry
Jesus Gonzalez Bosquet, Andreea M Newtson, Rebecca K Chung, Kristina W Thiel, Timothy Ginader, Michael J Goodheart, Kimberly K Leslie, Brian J Smith
BACKGROUND: Nearly one-third of serous ovarian cancer (OVCA) patients will not respond to initial treatment with surgery and chemotherapy and die within one year of diagnosis. If patients who are unlikely to respond to current standard therapy can be identified up front, enhanced tumor analyses and treatment regimens could potentially be offered. Using the Cancer Genome Atlas (TCGA) serous OVCA database, we previously identified a robust molecular signature of 422-genes associated with chemo-response...
October 19, 2016: Molecular Cancer
Srikanth Ravisankar, Devon Kuehn, Reese H Clark, Rachel G Greenberg, P Brian Smith, Christoph P Hornik
BACKGROUND: Systemic hypertension is increasingly recognised in premature infants. There is limited evidence regarding treatment, and most published treatment recommendations are based solely on expert opinions. METHODS: We identified all infants born ⩽32 weeks of gestation and ⩽1500 g birth weight discharged from one of 348 neonatal ICUs managed by the Pediatrix Medical Group between 1997 and 2013. We defined antihypertensive drugs as vasodilators, angiotensin-converting enzyme inhibitors, β receptor blockers, calcium channel blockers, and central α2 receptor agonists...
October 17, 2016: Cardiology in the Young
P Brian Smith, Daniel K Benjamin, Ann M Reed
No abstract text is available yet for this article.
October 11, 2016: Journal of Pediatrics
Joseph Em van Agteren, Kristin V Carson, Leong Ung Tiong, Brian J Smith
BACKGROUND: Lung volume reduction surgery (LVRS) performed to treat patients with severe diffuse emphysema was reintroduced in the nineties. Lung volume reduction surgery aims to resect damaged emphysematous lung tissue, thereby increasing elastic properties of the lung. This treatment is hypothesised to improve long-term daily functioning and quality of life, although it may be costly and may be associated with risks of morbidity and mortality. Ten years have passed since the last version of this review was prepared, prompting us to perform an update...
October 14, 2016: Cochrane Database of Systematic Reviews
Luke E Grzeskowiak, Brian Smith, Anil Roy, Gustaaf A Dekker, Vicki L Clifton
There exists a paucity of data for socially disadvantaged populations describing patterns and predictors of asthma control status and exacerbations during pregnancy, and their relationship to adverse perinatal outcomes. Asthmatic women (n=189) were followed prospectively during pregnancy, with visits at 12, 20, 28 and 36 weeks gestation. Data on loss of control, recurrent uncontrolled asthma and moderate/severe exacerbations were collected at each visit and their relationship to perinatal outcomes examined following stratification for fetal sex...
January 2016: ERJ Open Research
Bryan J Liming, John Carter, Alan Cheng, Daniel Choo, John Curotta, Daniela Carvalho, John A Germiller, Stephen Hone, Margaret A Kenna, Natalie Loundon, Diego Preciado, Anne Schilder, Brian J Reilly, Stephane Roman, Julie Strychowsky, Jean-Michel Triglia, Nancy Young, Richard J H Smith
OBJECTIVE: To provide recommendations for the workup of hearing loss in the pediatric patient. METHODS: Expert opinion by the members of the International Pediatric Otolaryngology Group. RESULTS: Consensus recommendations include initial screening and diagnosis as well as the workup of sensorineural, conductive and mixed hearing loss in children. The consensus statement discusses the role of genetic testing and imaging and provides algorithms to guide the workup of children with hearing loss...
November 2016: International Journal of Pediatric Otorhinolaryngology
Kristine E Day, Nicholas J Smith, Brian D Kulbersh
OBJECTIVE: Diagnosis and treatment of type 1 laryngeal clefts remains a challenge. The purpose of this study is to determine if early surgical intervention in type I laryngeal clefts improves outcomes. METHODS: A retrospective case series was conducted at an academic tertiary care children's hospital. 18 children undergoing early (≤3 months from diagnosis) surgical intervention for type I laryngeal cleft repair between August of 2012 and December 2014. Data was compiled through a manual chart review...
November 2016: International Journal of Pediatric Otorhinolaryngology
Darrell Sawmiller, Ahsan Habib, Song Li, Donna Darlington, Huayan Hou, Jun Tian, R Douglas Shytle, Adam Smith, Brian Giunta, Takashi Mori, Jun Tan
Naturally-occurring bioactive flavonoids such as diosmin significantly reduces amyloid beta (Aβ) associated pathology in Alzheimer's disease (AD) mouse models. In the present study, oral administration of diosmin reduced cerebral Aβ oligomer levels, tau-hyperphosphorylation and cognitive impairment in the 3xTg-AD mouse model through glycogen synthase kinase-3 (GSK-3) and transient receptor potential canonical 6-related mechanisms. Diosmetin, one major bioactive metabolite of diosmin, increased inhibitory GSK-3β phosphorylation, while selectively reducing γ-secretase activity, Aβ generation, tau hyperphosphorylation and pro-inflammatory activation of microglia in vitro, without altering Notch processing...
October 15, 2016: Journal of Neuroimmunology
Sarah L Wynia-Smith, Brian C Smith
Nitric oxide (NO) is a gaseous signaling molecule impacting many biological pathways. NO is produced in mammals by three nitric oxide synthase (NOS) isoforms: neuronal (nNOS), endothelial (eNOS), and inducible (iNOS). nNOS and eNOS produce low concentrations of NO for paracrine signaling; NO produced and released from one cell diffuses to a neighboring cell where it binds and activates soluble guanylyl cyclase (sGC). iNOS produces high concentrations of NO using NO toxicity to amplify the innate immune response...
October 5, 2016: Nitric Oxide: Biology and Chemistry
Sachin V Surve, Brian C Jensen, Meredith Heestand, Muriel Mazet, Terry K Smith, Frédéric Bringaud, Marilyn Parsons, Achim Schnaufer
In the slender bloodstream form, Trypanosoma brucei mitochondria are repressed for many functions. Multiple components of mitochondrial complex I, NADH:ubiquinone oxidoreductase, are expressed in this stage, but electron transfer through complex I is not essential. Here we investigate the role of the parasite's second NADH:ubiquinone oxidoreductase, NDH2, which is composed of a single subunit that also localizes to the mitochondrion. While inducible knockdown of NDH2 had a modest growth effect in bloodstream forms, NDH2 null mutants, as well as inducible knockdowns in a complex I deficient background, showed a greater reduction in growth...
October 4, 2016: Molecular and Biochemical Parasitology
Na Li, Lakshman Subrahmanyan, Emily Smith, Xiaoqing Yu, Samir Zaidi, Murim Choi, Shrikant Mane, Carol Nelson-Williams, Mohaddeseh Behjati, Mohammad Kazemi, Mohammad Hashemi, Mohsen Fathzadeh, Anand Narayanan, Likun Tian, Farhad Montazeri, Mitra Mani, Michael L Begleiter, Brian G Coon, Henry T Lynch, Eric N Olson, Hongyu Zhao, Jürgen Ruland, Richard P Lifton, Arya Mani
No abstract text is available yet for this article.
October 6, 2016: American Journal of Human Genetics
Dawn K Smith, Emily Maier, Joshua Betts, Simone Gray, Brian Kolodziejski, Karen W Hoover
Community-based organizations (CBOs) are critical to delivery of effective HIV prevention because of their reach to key populations. This online survey of a national sample of CBOs assessed their awareness of, interest in, and resources needed to provide nonoccupational postexposure prophylaxis (nPEP), preexposure prophylaxis (PrEP), and HIV treatment as prevention (TasP). One hundred seventy-five CBOs participated: 87 clinical and 88 nonclinical CBOs. For nPEP, PrEP, and TasP, program managers reported that awareness was high (94%, 90%, 85%), meeting current client need was low (20%, 13%, 18%), and the likelihood of increasing their current provision with additional resources was somewhat high (62%, 64%, 62%)...
October 2016: AIDS Education and Prevention: Official Publication of the International Society for AIDS Education
Mir Amaan Ali, Kate T Carroll, Robert C Rennert, Thomas Hamelin, Leon Chang, Brian P Lemkuil, Mayur Sharma, Jill S Barnholtz-Sloan, Charlotte Myers, Gene H Barnett, Kris Smith, Alireza M Mohammadi, Andrew E Sloan, Clark C Chen
OBJECTIVE Therapeutic options for brain metastases (BMs) that recur after stereotactic radiosurgery (SRS) remain limited. METHODS The authors provide the collective experience of 4 institutions where treatment of BMs that recurred after SRS was performed with stereotactic laser ablation (SLA). RESULTS Twenty-six BMs (in 23 patients) that recurred after SRS were treated with SLA (2 patients each underwent 2 SLAs for separate lesions, and a third underwent 2 serial SLAs for discrete BMs). Histological findings in the BMs treated included the following: breast (n = 6); lung (n = 6); melanoma (n = 5); colon (n = 2); ovarian (n = 1); bladder (n = 1); esophageal (n = 1); and sarcoma (n = 1)...
October 2016: Neurosurgical Focus
Stuart R Young, Bruce Gardiner, Arash Mehdizadeh, Jonas Rubenson, Brian Umberger, David W Smith
While it is known that musculotendon units adapt to their load environments, there is only a limited understanding of tendon adaptation in vivo. Here we develop a computational model of tendon remodeling based on the premise that mechanical damage and tenocyte-mediated tendon damage and repair processes modify the distribution of its collagen fiber lengths. We explain how these processes enable the tendon to geometrically adapt to its load conditions. Based on known biological processes, mechanical and strain-dependent proteolytic fiber damage are incorporated into our tendon model...
September 2016: PLoS Computational Biology
Thomas E Getzen, Albert A Okunade
Significant contributions have been made since the World Health Organization published Brian Abel-Smith's pioneering comparative study of national health expenditures more than 50 years ago. There have been major advances in theories, model specifications, methodological approaches, and data structures. This introductory essay provides a historical context for this line of work, highlights four newly published studies that move health economics research forward, and indicates several important areas of challenging but potentially fruitful research to strengthen future contributions to the literature and make empirical findings more useful for evaluating health policy decisions...
September 29, 2016: Health Economics
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