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Michael O'Brien

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https://www.readbyqxmd.com/read/28530713/bach2-immunodeficiency-illustrates-an-association-between-super-enhancers-and-haploinsufficiency
#1
Behdad Afzali, Juha Grönholm, Jana Vandrovcova, Charlotte O'Brien, Hong-Wei Sun, Ine Vanderleyden, Fred P Davis, Ahmad Khoder, Yu Zhang, Ahmed N Hegazy, Alejandro V Villarino, Ira W Palmer, Joshua Kaufman, Norman R Watts, Majid Kazemian, Olena Kamenyeva, Julia Keith, Anwar Sayed, Dalia Kasperaviciute, Michael Mueller, Jason D Hughes, Ivan J Fuss, Mohammed F Sadiyah, Kim Montgomery-Recht, Joshua McElwee, Nicholas P Restifo, Warren Strober, Michelle A Linterman, Paul T Wingfield, Holm H Uhlig, Rahul Roychoudhuri, Timothy J Aitman, Peter Kelleher, Michael J Lenardo, John J O'Shea, Nichola Cooper, Arian D J Laurence
The transcriptional programs that guide lymphocyte differentiation depend on the precise expression and timing of transcription factors (TFs). The TF BACH2 is essential for T and B lymphocytes and is associated with an archetypal super-enhancer (SE). Single-nucleotide variants in the BACH2 locus are associated with several autoimmune diseases, but BACH2 mutations that cause Mendelian monogenic primary immunodeficiency have not previously been identified. Here we describe a syndrome of BACH2-related immunodeficiency and autoimmunity (BRIDA) that results from BACH2 haploinsufficiency...
May 22, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28530549/a-genetic-basis-for-molecular-asymmetry-at-vertebrate-electrical-synapses
#2
Adam C Miller, Alex C Whitebirch, Arish N Shah, Kurt C Marsden, Michael Granato, John O'Brien, Cecilia B Moens
Neural network function is based upon the patterns and types of connections made between neurons. Neuronal synapses are adhesions specialized for communication and they come in two types, chemical and electrical. Communication at chemical synapses occurs via neurotransmitter release whereas electrical synapses utilize gap junctions for direct ionic and metabolic coupling. Electrical synapses are often viewed as symmetrical structures, with the same components making both sides of the gap junction. By contrast, we show that a broad set of electrical synapses in zebrafish, Danio rerio, require two gap-junction-forming Connexins for formation and function...
May 22, 2017: ELife
https://www.readbyqxmd.com/read/28499981/mitochondrial-dysfunction-in-ocular-disease-focus-on-glaucoma
#3
Khalid Kamel, Michael Farrell, Colm O'Brien
Mitochondrial dysfunction commonly presents with ocular findings as a part of a systemic disorder. These ophthalmic manifestations can be the first sign of a mitochondrial abnormality, which highlights the key role of a comprehensive ophthalmic assessment. On the other hand, a number of visually disabling genetic and acquired eye diseases with no curative treatment show abnormal mitochondrial function. Recent advances in mitochondrial research have improved our understanding of previously unexplained ocular disorders utilising better diagnostic approaches...
May 9, 2017: Mitochondrion
https://www.readbyqxmd.com/read/28493849/effects-of-pressure-variation-and-atrial-fibrillation-on-cardiomems-%C3%A2-hf-measured-pulmonary-artery-diastolic-pressure-comparison-of-device-averaged-and-visually-inspected-waveforms
#4
Aaron M Wolfson, Omid Yousefian, Lindsay Short, Daniel O'Brien, Guy Talmor, Jessica Qiu, Andrew Yoon, Michael Fong, Leslie Saxon, Rahul Doshi, Luanda Grazette, David M Shavelle
OBJECTIVE: Heart failure (HF) management guided by implantable hemodynamic monitoring reduces hospitalization rates. Hemodynamic data from the CardioMEMS(™) HF system includes device-averaged pulmonary artery pressures (PAP) and heart rate. Agreement of device-averaged values compared to the standard method of visual inspection of pressure waveforms at end-expiration is unknown. We evaluated the agreement between device-averaged and visually inspected end-expiratory PAP. APPROACH: Twenty-one patients implanted with the CardioMEMS(™) HF system were evaluated...
May 11, 2017: Physiological Measurement
https://www.readbyqxmd.com/read/28487411/a-microrna-129-5p-rbfox-crosstalk-coordinates-homeostatic-downscaling-of-excitatory-synapses
#5
Marek Rajman, Franziska Metge, Roberto Fiore, Sharof Khudayberdiev, Ayla Aksoy-Aksel, Silvia Bicker, Cristina Ruedell Reschke, Rana Raoof, Gary P Brennan, Norman Delanty, Michael A Farrell, Donncha F O'Brien, Sebastian Bauer, Braxton Norwood, Morten T Veno, Marcus Krüger, Thomas Braun, Jørgen Kjems, Felix Rosenow, David C Henshall, Christoph Dieterich, Gerhard Schratt
Synaptic downscaling is a homeostatic mechanism that allows neurons to reduce firing rates during chronically elevated network activity. Although synaptic downscaling is important in neural circuit development and epilepsy, the underlying mechanisms are poorly described. We performed small RNA profiling in picrotoxin (PTX)-treated hippocampal neurons, a model of synaptic downscaling. Thereby, we identified eight microRNAs (miRNAs) that were increased in response to PTX, including miR-129-5p, whose inhibition blocked synaptic downscaling in vitro and reduced epileptic seizure severity in vivo Using transcriptome, proteome, and bioinformatic analysis, we identified the calcium pump Atp2b4 and doublecortin (Dcx) as miR-129-5p targets...
May 9, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28482114/innovations-in-gene-and-growth-factor-delivery-systems-for-diabetic-wound-healing
#6
REVIEW
Ashang Luwang Laiva, Fergal J O'Brien, Michael B Keogh
The rise in lower extremity amputations (LEAs) due to non-healing of foot ulcers in diabetic patients calls for rapid improvement in effective treatment regimens. Administration of growth factors (GFs) are thought to offer an off-the-shelf treatment however, the dose- and time-dependent efficacy of the GFs together with the hostile environment of diabetic wound beds impose a major hindrance in the selection of an ideal route for GFs delivery. As an alternative, the delivery of therapeutic genes using viral and non-viral vectors, capable of transiently expressing the genes until the recovery of the wounded tissue offers promise...
May 8, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28473233/relapse-to-opioid-use-disorder-after-inpatient-treatment-protective-effect-of-injection-naltrexone
#7
Edward V Nunes, Michael Gordon, Peter D Friedmann, Marc J Fishman, Joshua D Lee, Donna T Chen, Mei Chen Hu, Tamara Y Boney, Donna Wilson, Charles P O'Brien
BACKGROUND: Opioid use disorder is often treated with short term hospitalization and medically supervised withdrawal from opioids followed by counseling alone without medication assisted treatment (MAT). More evidence is needed to confirm the expectation that the rate of relapse would be high after short term inpatient treatment and withdrawal from opioids without follow-up MAT. OBJECTIVE/METHODS: To examine relapse to opioid use disorder in a randomized, multi-site effectiveness trial of extended-release injection naltrexone (XR-NTX) vs community-based treatment as usual (TAU) without medication, as a function of the type of clinical service where treatment was initiated-short-term inpatient (N=59), long-term inpatient (N=48), or outpatient (N=201)...
April 23, 2017: Journal of Substance Abuse Treatment
https://www.readbyqxmd.com/read/28467455/year-round-spatiotemporal-distribution-of-harbour-porpoises-within-and-around-the-maryland-wind-energy-area
#8
Jessica E Wingfield, Michael O'Brien, Vyacheslav Lyubchich, Jason J Roberts, Patrick N Halpin, Aaron N Rice, Helen Bailey
Offshore windfarms provide renewable energy, but activities during the construction phase can affect marine mammals. To understand how the construction of an offshore windfarm in the Maryland Wind Energy Area (WEA) off Maryland, USA, might impact harbour porpoises (Phocoena phocoena), it is essential to determine their poorly understood year-round distribution. Although habitat-based models can help predict the occurrence of species in areas with limited or no sampling, they require validation to determine the accuracy of the predictions...
2017: PloS One
https://www.readbyqxmd.com/read/28451770/multi-modality-imaging-of-the-leaking-ureter-why-does-detection-of-traumatic-and-iatrogenic-ureteral-injuries-remain-a-challenge
#9
Abdullah Alabousi, Michael N Patlas, Christine O Menias, David Dreizin, Sanjeev Bhalla, Man Hon, Andres O'Brien, Douglas S Katz
Ureteral injuries are uncommon in trauma patients, accounting for fewer than 1% of all injuries to the urinary tract. These uncommon, yet problematic, injuries can often be overlooked in the standard search pattern on abdominal and pelvic multi-detector CT (MDCT) images, as radiologists focus on more immediate life-threatening injuries. However, early diagnosis and management are vital to reduce potential morbidity. If there is a high clinical index of suspicion for ureteral injuries with penetrating or blunt trauma, or if there is suspected iatrogenic ureteral injury, delayed-phase/urographic-phase MDCT images are essential for confirming the diagnosis...
April 27, 2017: Emergency Radiology
https://www.readbyqxmd.com/read/28447475/olaratumab-for-advanced-soft-tissue-sarcoma
#10
Alexander Tobias, Michael P O'brien, Mark Agulnik
Olaratumab is a humanized IgG1 monoclonal antibody that blocks the platelet-derived growth factor receptor alpha (PDGFRα). Its antagonistic behavior inhibits the receptor's tyrosine kinase activity, thereby, turning off the downstream signaling cascades responsible for soft tissue sarcoma tumorigenesis. In October 2016, olaratumab received Food and Drug Administration (FDA) approval for its use in combination with doxorubicin for treatment of advanced soft tissue sarcoma. Areas covered: This drug profile takes a comprehensive look at the clinical studies leading to FDA approval of olaratumab as well as its safety and efficacy as a front-line treatment option for sarcoma patients...
May 5, 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28439021/differences-between-measured-and-reported-volatile-organic-compound-emissions-from-oil-sands-facilities-in-alberta-canada
#11
Shao-Meng Li, Amy Leithead, Samar G Moussa, John Liggio, Michael D Moran, Daniel Wang, Katherine Hayden, Andrea Darlington, Mark Gordon, Ralf Staebler, Paul A Makar, Craig A Stroud, Robert McLaren, Peter S K Liu, Jason O'Brien, Richard L Mittermeier, Junhua Zhang, George Marson, Stewart G Cober, Mengistu Wolde, Jeremy J B Wentzell
Large-scale oil production from oil sands deposits in Alberta, Canada has raised concerns about environmental impacts, such as the magnitude of air pollution emissions. This paper reports compound emission rates (E) for 69-89 nonbiogenic volatile organic compounds (VOCs) for each of four surface mining facilities, determined with a top-down approach using aircraft measurements in the summer of 2013. The aggregate emission rate (aE) of the nonbiogenic VOCs ranged from 50 ± 14 to 70 ± 22 t/d depending on the facility...
May 9, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28436674/general-dialdehyde-click-chemistry-for-amine-bioconjugation
#12
Sina Elahipanah, Paul J O'Brien, Dmitry Rogozhnikov, Muhammad N Yousaf
The development of methods for conjugating a range of molecules to primary amine functional groups has revolutionized the fields of chemistry, biology, and material science. The primary amine is a key functional group and one of the most important nucleophiles and bases used in all of synthetic chemistry. Therefore, tremendous interest in the synthesis of molecules containing primary amines and strategies to devise chemical reactions to react with primary amines has been at the core of chemical research. In particular, primary amines are a ubiquitous functional group found in biological systems as free amino acids, as key side chain lysines in proteins, and in signaling molecules and metabolites and are also present in many natural product classes...
April 24, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28431288/longitudinal-whole-brain-atrophy-and-ventricular-enlargement-in-nondemented-parkinson-s-disease
#13
Elijah Mak, Li Su, Guy B Williams, Michael J Firbank, Rachael A Lawson, Alison J Yarnall, Gordon W Duncan, Brit Mollenhauer, Adrian M Owen, Tien K Khoo, David J Brooks, James B Rowe, Roger A Barker, David J Burn, John T O'Brien
We investigated whole-brain atrophy and ventricular enlargement over 18 months in nondemented Parkinson's disease (PD) and examined their associations with clinical measures and baseline CSF markers. PD subjects (n = 100) were classified at baseline into those with mild cognitive impairment (MCI; PD-MCI, n = 36) and no cognitive impairment (PD-NC, n = 64). Percentage of whole-brain volume change (PBVC) and ventricular expansion over 18 months were assessed with FSL-SIENA and ventricular enlargement (VIENA) respectively...
March 16, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28427892/contour-adaptation-reduces-the-spreading-of-edge-induced-colors
#14
Andrew J Coia, Michael A Crognale
Brief exposure to flickering achromatic outlines of an area causes a reduction in the brightness contrast of the surface inside the area. This contour adaptation to achromatic contours does not reduce surface contrast when the surface is chromatic (the saturation or colorimetric purity of the surface is maintained). In addition to reducing the brightness of physical luminance contrast, contour adaptation also reduces (or even reverses) the illusory brightness contrast seen in the Craik-O'Brien-Cornsweet illusion, in which two physically identical grey areas appear different brightness because of a sharp luminance edge separating them...
April 17, 2017: Vision Research
https://www.readbyqxmd.com/read/28426856/adjunctive-oral-voriconazole-treatment-of-fusarium-keratitis-a-secondary-analysis-from-the-mycotic-ulcer-treatment-trial-ii
#15
N Venkatesh Prajna, Tiruvengada Krishnan, Revathi Rajaraman, Sushila Patel, Ranjeet Shah, Muthiah Srinivasan, Lumbini Devi, Manoranjan Das, Kathryn J Ray, Kieran S O'Brien, Catherine E Oldenburg, Stephen D McLeod, Michael E Zegans, Nisha R Acharya, Thomas M Lietman, Jennifer Rose-Nussbaumer
Importance: Fusarium keratitis is common and often results in poor outcomes. No new treatments since natamycin have become available. Objective: To explore the role of adjuvant oral voriconazole on clinical outcomes in Fusarium keratitis. Design, Setting, and Participants: In this prespecified subgroup analysis of a multicenter, double-masked, placebo-controlled randomized clinical trial, 240 patients from the Aravind Eye Care System in India, the Lumbini Eye Hospital and Bharatpur Eye Hospital in Nepal, and the University of California, San Francisco, who had culture-positive fungal ulcer and baseline visual acuity of 20/400 or worse were randomized to receive oral voriconazole vs placebo...
April 20, 2017: JAMA Ophthalmology
https://www.readbyqxmd.com/read/28419856/adenoma-prevalence-in-blacks-and-whites-having-equal-adherence-to-screening-colonoscopy-the-national-colonoscopy-study
#16
Robin B Mendelsohn, Sidney Winawer, Anjani Jammula, Glenn Mills, Paul Jordan, Michael J O'Brien, Georgia M Close, Michael Dorfman, Timothy R Church, Margaret T Mandelson, John Allen, Andrew Feld, Noah D Kauff, Georgia A Morgan, Julie M R Kumar, Victoria Serrano, Sharon Bayuga-Miller, Sara E Fischer, Deborah Kuk, Ann G Zauber
No abstract text is available yet for this article.
April 15, 2017: Clinical Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28417544/urine-biomarkers-of-acute-kidney-injury-in-noncritically-ill-hospitalized-children-treated-with-chemotherapy
#17
Maya Sterling, Zubaida Al-Ismaili, Kelly R McMahon, Melissa Piccioni, Michael Pizzi, Theresa Mottes, Larry C Lands, Sharon Abish, Adam J Fleming, Michael R Bennett, Ana Palijan, Prasad Devarajan, Stuart L Goldstein, Maureen M O'Brien, Michael Zappitelli
BACKGROUND: Cisplatin (Cis), carboplatin (Carb), and ifosfamide (Ifos) are common nephrotoxic chemotherapies. Biomarkers of tubular injury may allow for early acute kidney injury (AKI) diagnosis. PROCEDURE: We performed a two-center (Canada, United States) pilot study to prospectively measure serum creatinine (SCr), urine neutrophil gelatinase-associated lipocalin (NGAL), and interleukin-18 (IL-18) in children receiving Cis/Carb (27 episodes), Ifos (30 episodes), and in 15 hospitalized, nonchemotherapy patients...
April 18, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28408229/pharmacological-evaluation-of-a-novel-series-of-urea-thiourea-and-guanidine-derivatives-as-p2x7-receptor-antagonists
#18
Erick C N Wong, Tristan A Reekie, Eryn L Werry, James O'Brien-Brown, Sarah L Bowyer, Michael Kassiou
We report on P2X7 receptor antagonists based on a lead adamantly-cyanoguanidine-aryl moiety. We have investigated the importance of the central cyanoguanidine moiety by replacing it with urea, thiourea or guanidine moieties. We have also investigated the linker length between the central moiety and the aryl portion. All compounds were assessed for their inhibitory potency in a pore-formation dye uptake assay at the P2X7 receptor. None of the compounds resulted in an improved potency illustrating the importance of the cyanoguanidine moiety in this chemotype...
April 4, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28407997/the-diagnosis-of-urinary-tract-infection-in-young-children-duty-study-clinical-rule-economic-evaluation
#19
MULTICENTER STUDY
William Hollingworth, John Busby, Christopher C Butler, Kathryn O'Brien, Jonathan A C Sterne, Kerenza Hood, Paul Little, Michael Lawton, Kate Birnie, Emma Thomas-Jones, Kim Harman, Alastair D Hay
OBJECTIVE: To estimate the cost-effectiveness of a two-step clinical rule using symptoms, signs and dipstick testing to guide the diagnosis and antibiotic treatment of urinary tract infection (UTI) in acutely unwell young children presenting to primary care. METHODS: Decision analytic model synthesising data from a multicentre, prospective cohort study (DUTY) and the wider literature to estimate the short-term and lifetime costs and healthcare outcomes (symptomatic days, recurrent UTI, quality adjusted life years) of eight diagnostic strategies...
April 2017: Value in Health: the Journal of the International Society for Pharmacoeconomics and Outcomes Research
https://www.readbyqxmd.com/read/28405307/the-shift-from-plant-plant-facilitation-to-competition-under-severe-water-deficit-is-spatially-explicit
#20
Michael J O'Brien, Francisco I Pugnaire, Cristina Armas, Susana Rodríguez-Echeverría, Christian Schöb
The stress-gradient hypothesis predicts a higher frequency of facilitative interactions as resource limitation increases. Under severe resource limitation, it has been suggested that facilitation may revert to competition, and identifying the presence as well as determining the magnitude of this shift is important for predicting the effect of climate change on biodiversity and plant community dynamics. In this study, we perform a meta-analysis to compare temporal differences of species diversity and productivity under a nurse plant (Retama sphaerocarpa) with varying annual rainfall quantity to test the effect of water limitation on facilitation...
April 2017: Ecology and Evolution
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