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https://www.readbyqxmd.com/read/28817800/tia1-mutations-in-amyotrophic-lateral-sclerosis-and-frontotemporal-dementia-promote-phase-separation-and-alter-stress-granule-dynamics
#1
Ian R Mackenzie, Alexandra M Nicholson, Mohona Sarkar, James Messing, Maria D Purice, Cyril Pottier, Kavya Annu, Matt Baker, Ralph B Perkerson, Aishe Kurti, Billie J Matchett, Tanja Mittag, Jamshid Temirov, Ging-Yuek R Hsiung, Charles Krieger, Melissa E Murray, Masato Kato, John D Fryer, Leonard Petrucelli, Lorne Zinman, Sandra Weintraub, Marsel Mesulam, Julia Keith, Sasha A Zivkovic, Veronica Hirsch-Reinshagen, Raymond P Roos, Stephan Züchner, Neill R Graff-Radford, Ronald C Petersen, Richard J Caselli, Zbigniew K Wszolek, Elizabeth Finger, Carol Lippa, David Lacomis, Heather Stewart, Dennis W Dickson, Hong Joo Kim, Ekaterina Rogaeva, Eileen Bigio, Kevin B Boylan, J Paul Taylor, Rosa Rademakers
Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are age-related neurodegenerative disorders with shared genetic etiologies and overlapping clinical and pathological features. Here we studied a novel ALS/FTD family and identified the P362L mutation in the low-complexity domain (LCD) of T cell-restricted intracellular antigen-1 (TIA1). Subsequent genetic association analyses showed an increased burden of TIA1 LCD mutations in ALS patients compared to controls (p = 8.7 × 10(-6)). Postmortem neuropathology of five TIA1 mutations carriers showed a consistent pathological signature with numerous round, hyaline, TAR DNA-binding protein 43 (TDP-43)-positive inclusions...
August 16, 2017: Neuron
https://www.readbyqxmd.com/read/28817688/the-extremely-divergent-maternally-and-paternally-transmitted-mitochondrial-genomes-are-co-expressed-in-somatic-tissues-of-two-freshwater-mussel-species-with-doubly-uniparental-inheritance-of-mtdna
#2
Sophie Breton, Karim Bouvet, Gabrielle Auclair, Stéphanie Ghazal, Bernard E Sietman, Nathan Johnson, Stefano Bettinazzi, Donald T Stewart, Davide Guerra
Freshwater mussel species with doubly uniparental inheritance (DUI) of mtDNA are unique because they are naturally heteroplasmic for two extremely divergent mtDNAs with ~50% amino acid differences for protein-coding genes. The paternally-transmitted mtDNA (or M mtDNA) clearly functions in sperm in these species, but it is still unknown whether it is transcribed when present in male or female soma. In the present study, we used PCR and RT-PCR to detect the presence and expression of the M mtDNA in male and female somatic and gonadal tissues of the freshwater mussel species Venustaconcha ellipsiformis and Utterbackia peninsularis (Unionidae)...
2017: PloS One
https://www.readbyqxmd.com/read/28817473/scaffolding-interprofessional-education-unfolding-case-studies-virtual-world-simulations-and-patient-centered-care
#3
Sharon Strang Zook, Linda J Hulton, Carol C Dudding, Anne L Stewart, Amy C Graham
Fragmentation of health care negatively impacts quality; one of the contributing factors may be ineffective collaboration among health care professionals. This article describes the implementation of an interprofessional education curriculum for graduate students enrolled in nursing, psychology, and speech-language pathology programs. Over 3 semesters, students engaged in interprofessional collaboration modules, unfolding case studies, virtual simulation, and shared case planning experiences. The curriculum's impact on students' attitudes and values toward interprofessional collaborative practice was measured...
August 16, 2017: Nurse Educator
https://www.readbyqxmd.com/read/28817458/noninvasive-derivation-of-fractional-flow-reserve-from-coronary-computed-tomographic-angiography-a-review
#4
Stewart M Benton, Christian Tesche, Carlo N De Cecco, Taylor M Duguay, U Joseph Schoepf, Richard R Bayer
Coronary computed tomographic angiography (CCTA) has evolved as a rapid and highly sensitive method for the exclusion of obstructive coronary artery disease. Unfortunately, as it pertains to moderate and severe lesions, the ability to discriminate between those that are hemodynamically significant and those that are nonobstructive is lacking. Consequently, this deficiency can result in a significant number of unnecessary referrals for invasive angiography that yields nonobstructive results. Fractional flow reserve (FFR), which assesses the hemodynamic significance of a specific lesion, when performed during invasive angiography, results in improved patient outcomes compared with visual stenosis assessment alone...
August 16, 2017: Journal of Thoracic Imaging
https://www.readbyqxmd.com/read/28816800/acute-sickle-cell-orbitopathy-masquerading-as-orbital-cellulitis
#5
Christopher M Stewart, Zuzana Sipkova, Goran D Hildebrand, Jonathan H Norris
Sickle cell orbitopathy is a rare manifestation of a sickle cell crisis and can closely mimic orbital cellulitis, both clinically and radiologically. We present a case where a child presented with what was thought to be orbital cellulitis and was treated accordingly. Subtle radiologic features of sickle cell orbitopathy were initially overlooked, resulting in an incorrect diagnosis and a treatment delay for the patient. Correctly treated most cases resolve with no adverse affects, highlighting how important it is to consider acute sickle cell orbitopathy in the differential diagnosis of acute periorbital swelling in children with sickle disease...
August 14, 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/28815126/a-simple-text-mining-approach-for-ranking-pairwise-associations-in-biomedical-applications
#6
Finn Kuusisto, John Steill, Zhaobin Kuang, James Thomson, David Page, Ron Stewart
We present a simple text mining method that is easy to implement, requires minimal data collection and preparation, and is easy to use for proposing ranked associations between a list of target terms and a key phrase. We call this method KinderMiner, and apply it to two biomedical applications. The first application is to identify relevant transcription factors for cell reprogramming, and the second is to identify potential drugs for investigation in drug repositioning. We compare the results from our algorithm to existing data and state-of-the-art algorithms, demonstrating compelling results for both application areas...
2017: AMIA Summits on Translational Science Proceedings
https://www.readbyqxmd.com/read/28815043/the-mek-inhibitor-selumetinib-complements-ctla-4-blockade-by-reprogramming-the-tumor-immune-microenvironment
#7
Edmund Poon, Stefanie Mullins, Amanda Watkins, Geoffrey S Williams, Jens-Oliver Koopmann, Gianfranco Di Genova, Marie Cumberbatch, Margaret Veldman-Jones, Shaun E Grosskurth, Vasu Sah, Alwin Schuller, Corrine Reimer, Simon J Dovedi, Paul D Smith, Ross Stewart, Robert W Wilkinson
BACKGROUND: T-cell checkpoint blockade and MEK inhibitor combinations are under clinical investigation. Despite progress elucidating the immuno-modulatory effects of MEK inhibitors as standalone therapies, the impact of MEK inhibition on the activity of T-cell checkpoint inhibitors remains incompletely understood. Here we sought to characterize the combined effects of MEK inhibition and anti-CTLA-4 mAb (anti-CTLA-4) therapy, examining effects on both T-cells and tumor microenvironment (TME)...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28814777/the-microbial-ecosystem-distinguishes-chronically-diseased-tissue-from-adjacent-tissue-in-the-sigmoid-colon-of-chronic-recurrent-diverticulitis-patients
#8
Kathleen M Schieffer, Kate Sabey, Justin R Wright, David R Toole, Rebecca Drucker, Vasily Tokarev, Leonard R Harris, Sue Deiling, Melanie A Eshelman, John P Hegarty, Gregory S Yochum, Walter A Koltun, Regina Lamendella, David B Stewart
Diverticular disease is commonly associated with the older population in the United States. As individual's age, diverticulae, or herniation of the mucosa through the colonic wall, develop. In 10-25% of individuals, the diverticulae become inflamed, resulting in diverticulitis. The gut ecosystem relies on the interaction of bacteria and fungi to maintain homeostasis. Although bacterial dysbiosis has been implicated in the pathogenesis of diverticulitis, associations between the microbial ecosystem and diverticulitis remain largely unstudied...
August 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28814306/blood-acid-base-status-in-impala-aepyceros-melampus-immobilised-and-maintained-under-total-intravenous-anaesthesia-using-two-different-drug-protocols
#9
Gareth E Zeiler, Leith C R Meyer
BACKGROUND: In mammals, homeostasis and survival are dependent on effective trans-membrane movement of ions and enzyme function, which are labile to extreme acid-base changes, but operate efficiently within a narrow regulated pH range. Research in patients demonstrating a pH shifts outside the narrow regulated range decreased the cardiac output and systemic vascular resistance and altered the oxygen binding to haemoglobin. These cardiopulmonary observations may be applicable to the risks associated with anaesthesia and performance of wildlife ungulates on game farms...
August 16, 2017: BMC Veterinary Research
https://www.readbyqxmd.com/read/28813437/a-systematic-review-of-the-relationship-between-internet-use-self-harm-and-suicidal-behaviour-in-young-people-the-good-the-bad-and-the-unknown
#10
Amanda Marchant, Keith Hawton, Ann Stewart, Paul Montgomery, Vinod Singaravelu, Keith Lloyd, Nicola Purdy, Kate Daine, Ann John
BACKGROUND: Research exploring internet use and self-harm is rapidly expanding amidst concerns regarding influences of on-line activities on self-harm and suicide, especially in young people. We aimed to systematically review evidence regarding the potential influence of the internet on self-harm/suicidal behaviour in young people. METHODS: We conducted a systematic review based on an electronic search for articles published between 01/01/2011 and 26/01/2015 across databases including Medline, Cochrane and PsychInfo...
2017: PloS One
https://www.readbyqxmd.com/read/28813354/new-directions-in-the-psychology-of-optimal-performance-in-sport-flow-and-clutch-states
#11
REVIEW
Christian Swann, Lee Crust, Stewart A Vella
Csikszentmihalyi's conceptualisation of flow is the primary framework for understanding the psychology of optimal experience and performance in sport. However, emerging evidence suggests a more dynamic, multi-state perspective. This review focuses primarily on recent studies highlighting a second, overlapping 'clutch' state which - in addition to flow - underlies optimal performance in sport. We also examine how the nature of goals ('open' or 'fixed') athletes pursue influence the experience of flow and clutch respectively...
August 2017: Current Opinion in Psychology
https://www.readbyqxmd.com/read/28813091/guillain-barr%C3%A3-syndrome-celebrating-a-century
#12
Marcos R G de Freitas, Cecília M Vidal, Marco Orsini
A hundred years ago, Guillain, Barré and Strohl described a syndrome with a predominant motor acute or subacute polyneuritis, albumin-cytologic dissociation in the cerebrospinal fluid, and a benign course. Before them, many other authors, such as Landry, Duménil, Osler, and Grainger Stewart had described similar cases although they had not performed lumbar punctures. In this work, we outline certain features of the beginning of this famous syndrome.
August 2017: Arquivos de Neuro-psiquiatria
https://www.readbyqxmd.com/read/28812630/our-path-to-better-science-in-less-time-using-open-data-science-tools
#13
Julia S Stewart Lowndes, Benjamin D Best, Courtney Scarborough, Jamie C Afflerbach, Melanie R Frazier, Casey C O'Hara, Ning Jiang, Benjamin S Halpern
Reproducibility has long been a tenet of science but has been challenging to achieve-we learned this the hard way when our old approaches proved inadequate to efficiently reproduce our own work. Here we describe how several free software tools have fundamentally upgraded our approach to collaborative research, making our entire workflow more transparent and streamlined. By describing specific tools and how we incrementally began using them for the Ocean Health Index project, we hope to encourage others in the scientific community to do the same-so we can all produce better science in less time...
May 23, 2017: Nature ecology & evolution
https://www.readbyqxmd.com/read/28812589/connecting-earth-observation-to-high-throughput-biodiversity-data
#14
Alex Bush, Rahel Sollmann, Andreas Wilting, Kristine Bohmann, Beth Cole, Heiko Balzter, Christopher Martius, András Zlinszky, Sébastien Calvignac-Spencer, Christina A Cobbold, Terence P Dawson, Brent C Emerson, Simon Ferrier, M Thomas P Gilbert, Martin Herold, Laurence Jones, Fabian H Leendertz, Louise Matthews, James D A Millington, John R Olson, Otso Ovaskainen, Dave Raffaelli, Richard Reeve, Mark-Oliver Rödel, Torrey W Rodgers, Stewart Snape, Ingrid Visseren-Hamakers, Alfried P Vogler, Piran C L White, Martin J Wooster, Douglas W Yu
Understandably, given the fast pace of biodiversity loss, there is much interest in using Earth observation technology to track biodiversity, ecosystem functions and ecosystem services. However, because most biodiversity is invisible to Earth observation, indicators based on Earth observation could be misleading and reduce the effectiveness of nature conservation and even unintentionally decrease conservation effort. We describe an approach that combines automated recording devices, high-throughput DNA sequencing and modern ecological modelling to extract much more of the information available in Earth observation data...
June 22, 2017: Nature ecology & evolution
https://www.readbyqxmd.com/read/28812017/valve-calcification-in-aortic-stenosis-etiology-and-diagnostic-imaging-techniques
#15
REVIEW
María Manuela Izquierdo-Gómez, Iván Hernández-Betancor, Javier García-Niebla, Belén Marí-López, Ignacio Laynez-Cerdeña, Juan Lacalzada-Almeida
Aortic stenosis is the most common valvulopathy in the Western world. Its prevalence has increased significantly in recent years due to population aging; hence, up to 8% of westerners above the age of 84 now have severe aortic stenosis (Lindroos et al., 1993). This causes increased morbidity and mortality and therein lies the importance of adequate diagnosis and stratification of the degree of severity which allows planning the best therapeutic option in each case. Long understood as a passive age-related degenerative process, it is now considered a rather more complex entity involving mechanisms and factors similar to those of atherosclerosis (Stewart et al...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28811952/divorce-and-severity-of-coronary-artery-disease-a-multicenter-study
#16
Amin Daoulah, Mushabab Al-Murayeh, Salem Al-Kaabi, Amir Lotfi, Osama E Elkhateeb, Salem M Al-Faifi, Saleh Alqahtani, James Stewart, Jon Heavey, William T Hurley, Mohamed N Alama, Mazen Faden, Mohamed Al-Shehri, Ali Youssef, Alawi A Alsheikh-Ali
The association between marital status and coronary artery disease (CAD) is supported by numerous epidemiological studies. While divorce may have an adverse effect on cardiac outcomes, the relationship between divorce and severe CAD is unclear. We conducted a multicenter, observational study of consecutive patients undergoing coronary angiography during the period between April 1, 2013, and March 30, 2014. Of 1,068 patients, 124 (12%) were divorced. Divorce was more frequent among women (27%) compared to men (6%)...
2017: Cardiology Research and Practice
https://www.readbyqxmd.com/read/28811350/defining-the-dna-binding-site-recognized-by-the-fission-yeast-zn2cys6-transcription-factor-pho7-and-its-role-in-phosphate-homeostasis
#17
Beate Schwer, Ana M Sanchez, Angad Garg, Debashree Chatterjee, Stewart Shuman
Fission yeast phosphate homeostasis entails transcriptional induction of genes encoding phosphate-mobilizing proteins under conditions of phosphate starvation. Transcription factor Pho7, a member of the Zn2Cys6 family of fungal transcription regulators, is the central player in the starvation response. The DNA binding sites in the promoters of phosphate-responsive genes have not been defined, nor have any structure-function relationships been established for the Pho7 protein. Here we narrow this knowledge gap by (i) delineating an autonomous DNA-binding domain (DBD) within Pho7 that includes the Zn2Cys6 module, (ii) deploying recombinant Pho7 DBD in DNase I footprinting and electrophoretic mobility shift assays (EMSAs) to map the Pho7 recognition sites in the promoters of the phosphate-regulated pho1 and tgp1 genes to a 12-nucleotide sequence motif [5'-TCG(G/C)(A/T)xxTTxAA], (iii) independently identifying the same motif as a Pho7 recognition element via in silico analysis of available genome-wide ChIP-seq data, (iv) affirming that mutations in the two Pho7 recognition sites in the pho1 promoter efface pho1 expression in vivo, and (v) establishing that the zinc-binding cysteines and a pair of conserved arginines in the DBD are essential for Pho7 activity in vivoIMPORTANCE Fungi respond to phosphate starvation by inducing the transcription of a set of phosphate acquisition genes that comprise a phosphate regulon...
August 15, 2017: MBio
https://www.readbyqxmd.com/read/28810853/acute-effects-of-reducing-sitting-time-in-adolescents-a-randomized-cross-over-study
#18
Anisse Penning, Anthony D Okely, Stewart G Trost, Jo Salmon, Dylan P Cliff, Marijka Batterham, Steven Howard, Anne-Maree Parrish
BACKGROUND: Levels of sitting among adolescents are high, especially during the school day. The acute cognitive and health consequences associated with prolonged sitting are poorly understood in adolescents. This randomized crossover design study examined the acute effects of a simulated school day with reduced sitting or usual sitting on adolescents' cognitive function and cardiometabolic biomarkers. METHODS: Eighteen healthy school aged adolescents were recruited from the community to the study (11 males; 7 females; mean age [SD] = 13...
August 15, 2017: BMC Public Health
https://www.readbyqxmd.com/read/28810463/body-image-in-adult-women-associations-with-health-behaviors-quality-of-life-and-functional-impairment
#19
Carolyn B Becker, Christina L Verzijl, Lisa S Kilpela, Salome A Wilfred, Tiffany Stewart
This study examined body image in adult women along with probable correlates including health behaviors, negative affect, quality of life, and functional impairment. Adult women ( N = 738, age = 25-86 years) completed an online survey assessing these domains. Women across all ages reported similar body image concerns. Negative body image significantly correlated with poorer wellness behaviors, negative affect, quality of life, and functional impairment. The inverse held for positive body image. The majority of correlations remained even when controlling for negative affect...
May 1, 2017: Journal of Health Psychology
https://www.readbyqxmd.com/read/28809565/dipicolinic-acid-derivatives-as-inhibitors-of-new-delhi-metallo-%C3%AE-lactamase-1
#20
Allie Y Chen, Pei W Thomas, Alesha C Stewart, Alexander Bergstrom, Zishuo Cheng, Callie Miller, Christopher R Bethel, Steven H Marshall, Cy V Credille, Christopher L Riley, Richard C Page, Robert A Bonomo, Michael W Crowder, David L Tierney, Walter Fast, Seth M Cohen
The efficacy of β-lactam antibiotics is threatened by the emergence and global spread of metallo-β-lactamase-(MBL) mediated resistance, specifically New Delhi-Metallo-β- lactamase-1 (NDM-1). Utilizing fragment-based drug discovery (FBDD), a new class of inhibitors for NDM-1 and two related β-lactamases, IMP-1 and VIM-2, was identified. Based on 2,6-dipicolinic acid (DPA), several libraries were synthesized for structure-activity relationship (SAR) analysis. Inhibitor 36 (IC50 = 80 nM) was identified to be highly selective for MBLs when compared to other Zn(II) metalloenzymes...
August 15, 2017: Journal of Medicinal Chemistry
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