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https://www.readbyqxmd.com/read/28346571/is-the-ergogenicity-of-caffeine-affected-by-increasing-age-the-direct-effect-of-a-physiological-concentration-of-caffeine-on-the-power-output-of-maximally-stimulated-edl-and-diaphragm-muscle-isolated-from-the-mouse
#1
J Tallis, R S James, V M Cox, M J Duncan
INTRODUCTION: Caffeine is a well-established performance enhancing nutritional supplement in a young healthy population, however far less is known about how its ergogenicity is affected by increasing age. A recent review has highlighted the value of studies examining the direct effect of caffeine on isolated skeletal muscle contractility, but the present work is the first to assess the direct effect of 70µM caffeine (physiological maximum) on the maximal power output of isolated mammalian muscle from an age range representing developmental to early ageing...
2017: Journal of Nutrition, Health & Aging
https://www.readbyqxmd.com/read/28345008/insights-into-the-mechanism-of-membrane-pyrophosphatases-by-combining-experiment-and-computer-simulation
#2
Nita R Shah, Craig Wilkinson, Steven P D Harborne, Ainoleena Turku, Kun-Mou Li, Yuh-Ju Sun, Sarah Harris, Adrian Goldman
Membrane-integral pyrophosphatases (mPPases) couple the hydrolysis of pyrophosphate (PPi) to the pumping of Na(+), H(+), or both these ions across a membrane. Recently solved structures of the Na(+)-pumping Thermotoga maritima mPPase (TmPPase) and H(+)-pumping Vigna radiata mPPase revealed the basis of ion selectivity between these enzymes and provided evidence for the mechanisms of substrate hydrolysis and ion-pumping. Our atomistic molecular dynamics (MD) simulations of TmPPase demonstrate that loop 5-6 is mobile in the absence of the substrate or substrate-analogue bound to the active site, explaining the lack of electron density for this loop in resting state structures...
May 2017: Structural Dynamics (Melville, N.Y.)
https://www.readbyqxmd.com/read/28343630/de-novo-truncating-mutations-in-the-last-and-penultimate-exons-of-ppm1d-cause-an-intellectual-disability-syndrome
#3
Sandra Jansen, Sinje Geuer, Rolph Pfundt, Rachel Brough, Priyanka Ghongane, Johanna C Herkert, Elysa J Marco, Marjolein H Willemsen, Tjitske Kleefstra, Mark Hannibal, Joseph T Shieh, Sally Ann Lynch, Frances Flinter, David R FitzPatrick, Alice Gardham, Birgitta Bernhard, Nicola Ragge, Ruth Newbury-Ecob, Raphael Bernier, Malin Kvarnung, E A Helena Magnusson, Marja W Wessels, Marjon A van Slegtenhorst, Kristin G Monaghan, Petra de Vries, Joris A Veltman, Christopher J Lord, Lisenka E L M Vissers, Bert B A de Vries
Intellectual disability (ID) is a highly heterogeneous disorder involving at least 600 genes, yet a genetic diagnosis remains elusive in ∼35%-40% of individuals with moderate to severe ID. Recent meta-analyses statistically analyzing de novo mutations in >7,000 individuals with neurodevelopmental disorders highlighted mutations in PPM1D as a possible cause of ID. PPM1D is a type 2C phosphatase that functions as a negative regulator of cellular stress-response pathways by mediating a feedback loop of p38-p53 signaling, thereby contributing to growth inhibition and suppression of stress-induced apoptosis...
March 18, 2017: American Journal of Human Genetics
https://www.readbyqxmd.com/read/28341774/rna-dna-hybrid-r-loop-immunoprecipitation-mapping-an-analytical-workflow-to-evaluate-inherent-biases
#4
László Halász, Zsolt Karányi, Beáta Boros-Oláh, Tímea Rózsa, Éva Sipos, Éva Nagy, Ágnes Mosolygó-L, Anett Mázló, Éva Rajnavölgyi, Gábor Halmos, Lóránt Székvölgyi
The impact of R-loops on the physiology and pathology of chromosomes has been demonstrated extensively by chromatin biology research. The progress in this field has been driven by technological advancement of R-loop mapping methods that largely relied on a single approach, DNA-RNA immunoprecipitation (DRIP). Most of the DRIP protocols use the experimental design that was developed by a few laboratories, without paying attention to the potential caveats that might affect the outcome of RNA-DNA hybrid mapping...
March 24, 2017: Genome Research
https://www.readbyqxmd.com/read/28340353/molecular-structure-of-the-human-cftr-ion-channel
#5
Fangyu Liu, Zhe Zhang, László Csanády, David C Gadsby, Jue Chen
The cystic fibrosis transmembrane conductance regulator (CFTR) is an ATP-binding cassette (ABC) transporter that uniquely functions as an ion channel. Here, we present a 3.9 Å structure of dephosphorylated human CFTR without nucleotides, determined by electron cryomicroscopy (cryo-EM). Close resemblance of this human CFTR structure to zebrafish CFTR under identical conditions reinforces its relevance for understanding CFTR function. The human CFTR structure reveals a previously unresolved helix belonging to the R domain docked inside the intracellular vestibule, precluding channel opening...
March 23, 2017: Cell
https://www.readbyqxmd.com/read/28337838/the-selective-metabotropic-glutamate-receptor-5-antagonist-mavoglurant-afq056-reduces-the-incidence-of-reflux-episodes-in-dogs-and-patients-with-moderate-to-severe-gastroesophageal-reflux-disease
#6
M-L Rouzade-Dominguez, N Pezous, O J David, R Tutuian, S Bruley des Varannes, J Tack, P Malfertheiner, H-D Allescher, M Ufer, A Rühl
BACKGROUND: Transient lower esophageal sphincter relaxations (TLESRs) induced by gastric distension are modulated by the metabotropic glutamate receptor 5 (mGluR5) that influences the vagal reflex loop. We therefore aimed to examine the effects of the selective mGluR5 antagonist mavoglurant (AFQ056) on the number of TLESRs in dogs and reflux episodes in patients with gastroesophageal reflux disease (GERD). METHODS: In a dog model, the number of meal-induced TLESRs was determined after intravenous (0...
March 23, 2017: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
https://www.readbyqxmd.com/read/28337027/obesity-induced-decreases-in-muscle-performance-are-not-reversed-by-weight-loss
#7
F Seebacher, J Tallis, K McShea, R S James
BACKGROUND/OBJECTIVES: Obesity can affect muscle phenotypes, and may thereby constrain movement and energy expenditure. Weight loss is a common and intuitive intervention for obesity, but it is not known whether the effects of obesity on muscle function are reversible by weight loss. Here we tested whether obesity-induced changes in muscle metabolic and contractile phenotypes are reversible by weight loss. SUBJECTS/METHODS: We used zebrafish (Danio rerio) in a factorial design to compare energy metabolism, locomotor capacity, muscle isometric force and work-loop power output, and myosin heavy chain composition between lean fish, diet-induced obese fish, and fish that were obese and then returned to lean body mass following diet restriction...
March 24, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28336549/eavk-segment-c-sequence-confers-ca-2-dependent-changes-to-the-kinetics-of-full-length-human-ano1
#8
Peter R Strege, Simon J Gibbons, Amelia Mazzone, Cheryl E Bernard, Arthur Beyder, Gianrico Farrugia
Anoctamin1 (Ano1, TMEM16A) is a calcium-activated chloride channel specifically expressed in interstitial cells of Cajal (ICC) of the gastrointestinal (GI) tract muscularis propria. Ano1 is necessary for normal electrical slow waves and ICC proliferation. The full length human Ano1 sequence includes an additional exon, exon "0," at the N-terminus. Ano1 with exon "0" (Ano1(0)) had a lower EC50 for intracellular calcium ([Ca(2+)]i) and faster chloride current (ICl) kinetics. The Ano1 alternative splice variant with segment "c" encoding exon 13 expresses on the first intracellular loop four additional amino acid residues, EAVK, which alter ICl at low [Ca(2+)]i Exon 13 is expressed in 75-100% of Ano1 transcripts in most human tissues but only 25% in human stomach...
March 23, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28334742/recognition-but-no-repair-of-abasic-site-in-single-stranded-dna-by-human-ribosomal-us3-protein-residing-within-intact-40s-subunit
#9
Anastasia S Grosheva, Dmitry O Zharkov, Joachim Stahl, Alexander V Gopanenko, Alexey E Tupikin, Marsel R Kabilov, Dmitri M Graifer, Galina G Karpova
Isolated human ribosomal protein uS3 has extra-ribosomal functions including those related to base excision DNA repair, e.g. AP lyase activity that nicks double-stranded (ds) DNA 3΄ to the abasic (AP) site. However, the ability of uS3 residing within ribosome to recognize and cleave damaged DNA has never been addressed. Here, we compare interactions of single-stranded (ss) DNA and dsDNA bearing AP site with human ribosome-bound uS3 and with the isolated protein, whose interactions with ssDNA were not yet studied...
January 30, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28327421/adult-intussusceptions-clinical-presentation-diagnosis-and-therapeutic-management
#10
H Maghrebi, A Makni, R Rhaiem, S Atri, M Ayadi, M Jrad, M Jouini, M Kacem, Z Bensafta
BACKGROUND: Adult intussusception is a rare clinical entity. It is an uncommon cause of intestinal obstruction in adult. It often presents with nonspecific symptoms and preoperative diagnosis remains difficult. The purpose of this study was to determine the clinical entity and surgical approach of adult intussusception. METHODS: We have conducted a retrospective descriptive study starting from 2006 until 2014. We reviewed data for all patients that had been admitted to our department for intestinal intussusception...
February 20, 2017: International Journal of Surgery Case Reports
https://www.readbyqxmd.com/read/28325187/postgastrectomy-syndromes-and-nutritional-considerations-following-gastric-surgery
#11
REVIEW
Jeremy L Davis, R Taylor Ripley
Postgastrectomy syndromes result from altered form and function of the stomach. Gastrectomy disrupts reservoir capacity, mechanical digestion and gastric emptying. Early recognition of symptoms with prompt evaluation and treatment is essential. Many syndromes resolve with minimal intervention or dietary modifications. Re-operation is not common but often warranted for afferent and efferent loop syndromes and bile reflux gastritis. Preoperative nutritional assessment and treatment of common vitamin and mineral deficiencies after gastrectomy can reduce the incidence of chronic complications...
April 2017: Surgical Clinics of North America
https://www.readbyqxmd.com/read/28323788/traumatic-colon-injury-in-damage-control-laparotomy-a-multicenter-trial-is-it-safe-to-do-a-delayed-anastomosis
#12
Leah Carey Tatebe, Andrew Jennings, Ken Tatebe, Alexandra Handy, Purvi Prajapati, Michael Smith, Tai Do, Gerald O Ogola, Rajesh R Gandhi, Therese M Duane, Stephen Luk, Laura Bruce Petrey
BACKGROUND: Delayed colonic anastomosis after damage control laparotomy (DCL) is an alternative to colostomies during a single laparotomy (SL) in high-risk patients. However, literature suggests increased colonic leak rates up to 27% with DCL, and various reported risk factors. We evaluated our regional experience to determine if delayed colonic anastomosis was associated with worse outcomes. METHODS: A multicenter retrospective cohort study was performed across three Level I trauma centers encompassing traumatic colon injuries from January 2006 through June 2014...
April 2017: Journal of Trauma and Acute Care Surgery
https://www.readbyqxmd.com/read/28322945/bifunctional-role-of-leucine-300-of-firefly-luciferase-in-structural-rigidity
#13
Farzad Yousefi, Farangis Ataei, Mojtaba Mortazavi, Saman Hosseinkhani
Firefly luciferase is susceptible to thermal inactivation, thereby its intracellular half-life decreased. Previous reports indicated that L(300)R mutation (LRR mutant) in E(354)R/Arg(356) double mutant (ERR mutant) from Lampyris turkestanicus luciferase has increased its thermal stability and rigidity through induction of some ionic bonds with Asp 270 and 271. Disruption of the deduced ionic bonds in an ultra-rigid mutant of firefly luciferase did not reverse the flexibility of the protein. In this study, we investigated the effects of this residue to find the truth behind an extraordinary increase in thermal stability and rigidity of luciferase after replacement of leucine 300 by arginine based on previous reports...
March 18, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28321285/role-of-preliminary-registry-data-in-development-of-a-clinical-trial-for-an-innovative-device-a-small-but-integral-piece-of-a-health-policy-initiative
#14
Donald R Ricci, Joost de Vries, Raphael Blanc
Establishing a national health policy at a macro level involves the integration of a series of health initiatives across a spectrum of activities, including clinical care. Evaluation of the safety and efficacy of a new medical device ultimately evolves to testing in humans. The pathway to a formal prospective clinical trial includes a stepwise appreciation of pre-clinical data and detailed analysis of data obtained from preliminary registries, where information about appropriate patient selection and use of the device is obtained...
2017: Journal of Market Access & Health Policy
https://www.readbyqxmd.com/read/28320386/delayed-gastric-emptying-following-pancreatoduodenectomy-with-alimentary-reconstruction-according-to-roux-en-y-or-billroth-ii
#15
Tim R Glowka, Markus Webler, Hanno Matthaei, Nico Schäfer, Volker Schmitz, Jörg C Kalff, Jens Standop, Steffen Manekeller
BACKGROUND: Delayed gastric emptying (DGE) remains the most frequent complication following pancreatoduodenectomy (PD) with published incidences as high as 61%. The present study investigates the impact of bowel reconstruction techniques on DGE following classic PD (Whipple-Kausch procedure) with pancreatogastrostomy (PG). METHODS: We included 168 consecutive patients who underwent PD with PG with either Billroth II type (BII, n = 78) or Roux-en-Y type reconstruction (ReY, n = 90) between 2004 and 2015...
March 20, 2017: BMC Surgery
https://www.readbyqxmd.com/read/28320323/changes-in-duration-of-action-of-rocuronium-following-decrease-in-hepatic-blood-flow-during-pneumoperitoneum-for-laparoscopic-gynaecological-surgery
#16
Yang Liu, Wen Cao, Yu Liu, Yun Wang, Ren Lang, Yun Yue, An-Shi Wu
BACKGROUND: A moderate insufflation pressure and deep neuromuscular blockade (NMB) have been recommended in laparoscopic surgery in consideration of the possible reduction in splanchnic perfusion due to the CO2-pneumoperitoneum. Since the liver is the major organ for rocuronium metabolism, the question of whether NMB of rocuronium would change with the variation of liver perfusion during pneumoperitoneum during laparoscopic surgery merits investigation. METHODS: In this prospective study, a total of sixty female patients scheduled for either selective laparoscopic gynaecological surgery (group laparoscopy) or laparotomy for gynaecological surgery (group control) were analyzed...
March 20, 2017: BMC Anesthesiology
https://www.readbyqxmd.com/read/28318821/snf2-family-protein-fft3-suppresses-nucleosome-turnover-to-promote-epigenetic-inheritance-and-proper-replication
#17
Nitika Taneja, Martin Zofall, Vanivilasini Balachandran, Gobi Thillainadesan, Tomoyasu Sugiyama, David Wheeler, Ming Zhou, Shiv I S Grewal
Heterochromatin can be epigenetically inherited in cis, leading to stable gene silencing. However, the mechanisms underlying heterochromatin inheritance remain unclear. Here, we identify Fft3, a fission yeast homolog of the mammalian SMARCAD1 SNF2 chromatin remodeler, as a factor uniquely required for heterochromatin inheritance, rather than for de novo assembly. Importantly, we find that Fft3 suppresses turnover of histones at heterochromatic loci to facilitate epigenetic transmission of heterochromatin in cycling cells...
March 8, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28317311/novel-pathogenic-variants-in-foxp3-in-fetuses-with-echogenic-bowel-and-skin-desquamation-identified-by-ultrasound
#18
Raymond J Louie, Queenie K-G Tan, Jennifer B Gilner, R Curtis Rogers, Noelle Younge, Stephanie B Wechsler, Marie T McDonald, Barbara Gordon, Christopher A Saski, Julie R Jones, Shelley J Chapman, Roger E Stevenson, John W Sleasman, Michael J Friez
Immunodysregulation, Polyendocrinopathy, Enteropathy, X-linked (IPEX) syndrome is a rare, X-linked recessive disease that affects regulatory T cells (Tregs) resulting in diarrhea, enteropathy, eczema, and insulin-dependent diabetes mellitus. IPEX syndrome is caused by pathogenic alterations in FOXP3 located at Xp11.23. FOXP3 encodes a transcription factor that interacts with several partners, including NFAT and NF-κB, and is necessary for the proper cellular differentiation of Tregs. Although variable, the vast majority of IPEX syndrome patients have onset of disease during infancy with severe enteropathy...
March 20, 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28316873/nonholonomic-closed-loop-velocity-control-of-a-soft-tethered-magnetic-capsule-endoscope
#19
Addisu Z Taddese, Piotr R Slawinski, Keith L Obstein, Pietro Valdastri
In this paper, we demonstrate velocity-level closed-loop control of a tethered magnetic capsule endoscope that is actuated via serial manipulator with a permanent magnet at its end-effector. Closed-loop control (2 degrees-of-freedom in position, and 2 in orientation) is made possible with the use of a real-time magnetic localization algorithm that utilizes the actuating magnetic field and thus does not require additional hardware. Velocity control is implemented to create smooth motion that is clinically necessary for colorectal cancer diagnostics...
October 2016: Proceedings of the ... IEEE/RSJ International Conference on Intelligent Robots and Systems
https://www.readbyqxmd.com/read/28314855/def6-restrains-osteoclastogenesis-and-inflammatory-bone-resorption
#20
Nikolaus Binder, Christine Miller, Masaki Yoshida, Kazuki Inoue, Shinichi Nakano, Xiaoyu Hu, Lionel B Ivashkiv, Georg Schett, Alessandra Pernis, Steven R Goldring, F Patrick Ross, Baohong Zhao
Inflammatory bone resorption mediated by osteoclasts is a major cause of morbidity and disability in many inflammatory disorders, including rheumatoid arthritis (RA). The mechanisms that regulate osteoclastogenesis and bone resorption in inflammatory settings are complex and have not been well elucidated. In this study, we identify the immunoregulator differentially expressed in FDCP 6 homolog (Def6) as a novel inhibitor of osteoclastogenesis in physiological and inflammatory conditions. Def6 deficiency in Def6(-/-) mice enhanced the sensitivity of osteoclast precursors to the physiological osteoclastogenic inducer receptor activator for NF-κB ligand, and Def6(-/-) osteoclasts formed actin rings...
March 17, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
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