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https://www.readbyqxmd.com/read/28631612/wtf-genes-are-prolific-dual-poison-antidote-meiotic-drivers
#1
Nicole L Nuckolls, María Angélica Bravo Núñez, Michael T Eickbush, Janet M Young, Jeffrey J Lange, Jonathan S Yu, Gerald R Smith, Sue L Jaspersen, Harmit S Malik, Sarah E Zanders
Meiotic drivers are selfish genes that bias their transmission into gametes, defying Mendelian inheritance. Despite the significant impact of these genomic parasites on evolution and infertility, few meiotic drive loci have been identified or mechanistically characterized. Here, we demonstrate a complex landscape of meiotic drive genes on chromosome 3 of the fission yeasts Schizosaccharomyces kambucha and S. pombe. We identify S. kambucha wtf4 as one of these genes that acts to kill gametes (known as spores in yeast) that do not inherit the gene from heterozygotes...
June 20, 2017: ELife
https://www.readbyqxmd.com/read/28548315/aapm-medical-physics-practice-guideline-8-a-linear-accelerator-performance-tests
#2
Koren Smith, Peter Balter, John Duhon, Gerald A White, David L Vassy, Robin A Miller, Christopher F Serago, Lynne A Fairobent
PURPOSE: The purpose of this guideline is to provide a list of critical performance tests in order to assist the Qualified Medical Physicist (QMP) in establishing and maintaining a safe and effective quality assurance (QA) program. The performance tests on a linear accelerator (linac) should be selected to fit the clinical patterns of use of the accelerator and care should be given to perform tests which are relevant to detecting errors related to the specific use of the accelerator. METHODS: A risk assessment was performed on tests from current task group reports on linac QA to highlight those tests that are most effective at maintaining safety and quality for the patient...
May 26, 2017: Journal of Applied Clinical Medical Physics
https://www.readbyqxmd.com/read/28547032/car8-dorsal-root-ganglion-expression-and-genetic-regulation-of-analgesic-responses-are-associated-with-a-cis-eqtl-in-mice
#3
Roy C Levitt, Gerald Y Zhuang, Yuan Kang, Diana M Erasso, Udita Upadhyay, Mehtap Ozdemir, Eugene S Fu, Konstantinos D Sarantopoulos, Shad B Smith, William Maixner, Luda Diatchenko, Eden R Martin, Tim Wiltshire
Carbonic anhydrase-8 (Car8 mouse gene symbol) is devoid of enzymatic activity, but instead functions as an allosteric inhibitor of inositol trisphosphate receptor-1 (ITPR1) to regulate this intracellular calcium release channel important in synaptic functions and neuronal excitability. Causative mutations in ITPR1 and carbonic anhydrase-8 in mice and humans are associated with certain subtypes of spinal cerebellar ataxia (SCA). SCA mice are genetically deficient in dorsal root ganglia (DRG) Car8 expression and display mechanical and thermal hypersensitivity and susceptibility to subacute and chronic inflammatory pain behaviors...
May 25, 2017: Mammalian Genome: Official Journal of the International Mammalian Genome Society
https://www.readbyqxmd.com/read/28489971/phylogenetic-systematics-of-syncephalis-zoopagales-zoopagomycotina-a-genus-of-ubiquitous-mycoparasites
#4
Katherine L Lazarus, Gerald L Benny, Hsiao-Man Ho, Matthew E Smith
We examined phylogenetic relationships among species of the mycoparasite genus Syncephalis using sequences from three nuclear ribsosomal DNA genes (18S, 5.8S, and 28S nuc rDNA) and a gene encoding the largest subunit of RNA polymerase II (RPB1). Our data set included 88 Syncephalis isolates comprising 23 named species and several unnamed taxa. We also revived a culturing technique using beef liver and cellophane to grow several Syncephalis isolates without their host fungi to obtain pure parasite DNA. Most isolates, however, were grown in co-cultures with their host fungi, so we designed Syncephalis-specific primers to obtain sequence data...
March 15, 2017: Mycologia
https://www.readbyqxmd.com/read/28469148/functional-organization-of-protein-determinants-of-meiotic-dna-break-hotspots
#5
Lijuan Ma, Kyle R Fowler, Cristina Martín-Castellanos, Gerald R Smith
During Schizosaccharomyces pombe meiotic prophase, homologous chromosomes are co-aligned by linear elements (LinEs) analogous to the axial elements of the synaptonemal complex (SC) in other organisms. LinE proteins also promote the formation of meiotic DNA double-strand breaks (DSBs), the precursors of cross-overs. Rec10 is required for essentially all DSBs and recombination, and three others (Rec25, Rec27, and Mug20) are protein determinants of DSB hotspots - they bind DSB hotspots with high specificity and are required for DSB formation there...
May 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28467880/teprotumumab-for-thyroid-associated-ophthalmopathy
#6
RANDOMIZED CONTROLLED TRIAL
Terry J Smith, George J Kahaly, Daniel G Ezra, James C Fleming, Roger A Dailey, Rosa A Tang, Gerald J Harris, Alessandro Antonelli, Mario Salvi, Robert A Goldberg, James W Gigantelli, Steven M Couch, Erin M Shriver, Brent R Hayek, Eric M Hink, Richard M Woodward, Kathleen Gabriel, Guido Magni, Raymond S Douglas
BACKGROUND: Thyroid-associated ophthalmopathy, a condition commonly associated with Graves' disease, remains inadequately treated. Current medical therapies, which primarily consist of glucocorticoids, have limited efficacy and present safety concerns. Inhibition of the insulin-like growth factor I receptor (IGF-IR) is a new therapeutic strategy to attenuate the underlying autoimmune pathogenesis of ophthalmopathy. METHODS: We conducted a multicenter, double-masked, randomized, placebo-controlled trial to determine the efficacy and safety of teprotumumab, a human monoclonal antibody inhibitor of IGF-IR, in patients with active, moderate-to-severe ophthalmopathy...
May 4, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28441961/the-influence-of-insulin-resistance-on-cerebrospinal-fluid-and-plasma-biomarkers-of-alzheimer-s-pathology
#7
REVIEW
Sarah Westwood, Benjamine Liu, Alison L Baird, Sneha Anand, Alejo J Nevado-Holgado, Danielle Newby, Maria Pikkarainen, Merja Hallikainen, Johanna Kuusisto, Johannes R Streffer, Gerald Novak, Kaj Blennow, Ulf Andreasson, Henrik Zetterberg, Ulf Smith, Markku Laakso, Hilkka Soininen, Simon Lovestone
BACKGROUND: Insulin resistance (IR) has previously been associated with an increased risk of developing Alzheimer's disease (AD), although the relationship between IR and AD is not yet clear. Here, we examined the influence of IR on AD using plasma and cerebrospinal fluid (CSF) biomarkers related to IR and AD in cognitively healthy men. We also aimed to characterise the shared protein signatures between IR and AD. METHODS: Fifty-eight cognitively healthy men, 28 IR and 30 non-IR (age and APOE ε4 matched), were drawn from the Metabolic Syndrome in Men study in Kuopio, Finland...
April 26, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28437190/consuming-a-ketogenic-diet-while-receiving-radiation-and-chemotherapy-for-locally-advanced-lung-cancer-and-pancreatic-cancer-the-university-of-iowa-experience-of-two-phase-1-clinical-trials
#8
Amir Zahra, Melissa A Fath, Emyleigh Opat, Kranti A Mapuskar, Sudershan K Bhatia, Daniel C Ma, Samuel N Rodman Iii, Travis P Snyders, Catherine A Chenard, Julie M Eichenberger-Gilmore, Kellie L Bodeker, Logan Ahmann, Brian J Smith, Sandy A Vollstedt, Heather A Brown, Taher Abu Hejleh, Gerald H Clamon, Daniel J Berg, Luke I Szweda, Douglas R Spitz, John M Buatti, Bryan G Allen
Ketogenic diets are low in carbohydrates and high in fat, which forces cells to rely more heavily upon mitochondrial oxidation of fatty acids for energy. Relative to normal cells, cancer cells are believed to exist under a condition of chronic mitochondrial oxidative stress that is compensated for by increases in glucose metabolism to generate reducing equivalents. In this study we tested the hypothesis that a ketogenic diet concurrent with radiation and chemotherapy would be clinically tolerable in locally advanced non-small cell lung cancer (NSCLC) and pancreatic cancer and could potentially exploit cancer cell oxidative metabolism to improve therapeutic outcomes...
June 2017: Radiation Research
https://www.readbyqxmd.com/read/28389324/comparing-the-incidence-of-bone-tumors-in-rats-chronically-exposed%C3%A2-to-the-selective-pth-type-1-receptor-agonist-abaloparatide%C3%A2-or%C3%A2-pth-1-34
#9
Jacquelin Jolette, Bassem Attalla, Aurore Varela, Gerald G Long, Nacera Mellal, Sabile Trimm, Susan Y Smith, Michael S Ominsky, Gary Hattersley
Prolonged treatment with human parathyroid hormone (hPTH) in rats results in development of bone tumors, though this finding has not been supported by clinical experience. The PTH type 1 receptor agonist abaloparatide, selected for its bone anabolic activity, is under clinical development to treat postmenopausal women with osteoporosis. To determine the carcinogenic potential of abaloparatide, Fischer (F344) rats were administered SC daily abaloparatide at doses of 0, 10, 25, and 50 μg/kg or 30 μg/kg hPTH(1-34) as a positive control for up to 2 years...
April 4, 2017: Regulatory Toxicology and Pharmacology: RTP
https://www.readbyqxmd.com/read/28384608/segmental-kinematic-analysis-of-planovalgus-feet-during-walking-in-children-with-cerebral-palsy
#10
Karen M Kruger, Katherine A Konop, Joseph J Krzak, Adam Graf, Haluk Altiok, Peter A Smith, Gerald F Harris
Pes planovalgus (flatfoot) is a common deformity among children with cerebral palsy. The Milwaukee Foot Model (MFM), a multi-segmental kinematic foot model, which uses radiography to align the underlying bony anatomy with reflective surface markers, was used to evaluate 20 pediatric participants (30feet) with planovalgus secondary to cerebral palsy prior to surgery. Three-dimensional kinematics of the tibia, hindfoot, forefoot, and hallux segments are reported and compared to an age-matched control set of typically-developing children...
March 23, 2017: Gait & Posture
https://www.readbyqxmd.com/read/28375222/light-losses-from-scattering-in-luminescent-solar-concentrator-waveguides
#11
Robert D Breukers, Gerald J Smith, Hedley L Stirrat, Adam J Swanson, Trevor A Smith, Kenneth P Ghiggino, Sebastiampillai G Raymond, Nicola M Winch, David J Clarke, Andrew J Kay
The reductions in the transmission of emission originating from a fluorophore dissolved in a polymer matrix due to light scattering were compared in two forms of planar waveguides used as luminescent solar concentrators: a thin film of poly(methylmethacrylate) (PMMA) spin-coated on a glass plate and a solid PMMA plate of the same dimensions. The losses attributable to light scattering encountered in the waveguide consisting of the thin film of polymer coated on a glass plate were not detectable within experimental uncertainty, whereas the losses in the solid polymer plate were significant...
April 1, 2017: Applied Optics
https://www.readbyqxmd.com/read/28366679/o2-%C3%A2-and-h2o2-mediated-disruption-of-fe-metabolism-causes-the-differential-susceptibility-of-nsclc-and-gbm-cancer-cells-to-pharmacological-ascorbate
#12
Joshua D Schoenfeld, Zita A Sibenaller, Kranti A Mapuskar, Brett A Wagner, Kimberly L Cramer-Morales, Muhammad Furqan, Sonia Sandhu, Thomas L Carlisle, Mark C Smith, Taher Abu Hejleh, Daniel J Berg, Jun Zhang, John Keech, Kalpaj R Parekh, Sudershan Bhatia, Varun Monga, Kellie L Bodeker, Logan Ahmann, Sandy Vollstedt, Heather Brown, Erin P Shanahan Kauffman, Mary E Schall, Ray J Hohl, Gerald H Clamon, Jeremy D Greenlee, Matthew A Howard, Michael K Shultz, Brian J Smith, Dennis P Riley, Frederick E Domann, Joseph J Cullen, Garry R Buettner, John M Buatti, Douglas R Spitz, Bryan G Allen
Pharmacological ascorbate has been proposed as a potential anti-cancer agent when combined with radiation and chemotherapy. The anti-cancer effects of ascorbate are hypothesized to involve the autoxidation of ascorbate leading to increased steady-state levels of H2O2; however, the mechanism(s) for cancer cell-selective toxicity remain unknown. The current study shows that alterations in cancer cell mitochondrial oxidative metabolism resulting in increased levels of O2(⋅-) and H2O2 are capable of disrupting intracellular iron metabolism, thereby selectively sensitizing non-small-cell lung cancer (NSCLC) and glioblastoma (GBM) cells to ascorbate through pro-oxidant chemistry involving redox-active labile iron and H2O2...
April 10, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28349389/quantitative-genome-wide-measurements-of-meiotic-dna-double-strand-breaks-and-protein-binding-in-s-pombe
#13
Randy W Hyppa, Kyle R Fowler, Gerald R Smith
The fission yeast Schizosaccharomyces pombe is especially well suited for studying meiosis in molecular detail. Experiments with S. pombe strains that undergo a nearly synchronous meiosis-at variable temperatures-have elucidated the mechanisms of meiotic progression and the proteins that are involved. For example, studies focused on the initiation of meiotic recombination by programmed DNA double-strand breaks (DSBs) have proven exceptionally informative. In meiosis, some regions of DNA have more frequent DSBs than the surrounding regions...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28339906/interstitial-fibrosis-scored-on-whole-slide-digital-imaging-of-kidney-biopsies-is-a-predictor-of-outcome-in-proteinuric-glomerulopathies
#14
Laura H Mariani, Sebastian Martini, Laura Barisoni, Pietro A Canetta, Jonathan P Troost, Jeffrey B Hodgin, Matthew Palmer, Avi Z Rosenberg, Kevin V Lemley, Hui-Ping Chien, Jarcy Zee, Abigail Smith, Gerald B Appel, Howard Trachtman, Stephen M Hewitt, Matthias Kretzler, Serena M Bagnasco
Background.: Interstitial fibrosis (IF), tubular atrophy (TA) and interstitial inflammation (II) are known determinants of progression of renal disease. Standardized quantification of these features could add value to current classification of glomerulopathies. Methods.: We studied 315 participants in the Nephrotic Syndrome Study Network (NEPTUNE) study, including biopsy-proven minimal change disease (MCD = 98), focal segmental glomerulosclerosis (FSGS = 121), membranous nephropathy (MN = 59) and IgA nephropathy (IgAN = 37)...
February 27, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28336910/populus-trichocarpa-encodes-small-effector-like-secreted-proteins-that-are-highly-induced-during-mutualistic-symbiosis
#15
Jonathan M Plett, Hengfu Yin, Ritesh Mewalal, Rongbin Hu, Ting Li, Priya Ranjan, Sara Jawdy, Henrique C De Paoli, George Butler, Tessa Maureen Burch-Smith, Hao-Bo Guo, Chun Ju Chen, Annegret Kohler, Ian C Anderson, Jessy L Labbé, Francis Martin, Gerald A Tuskan, Xiaohan Yang
During symbiosis, organisms use a range of metabolic and protein-based signals to communicate. Of these protein signals, one class is defined as 'effectors', i.e., small secreted proteins (SSPs) that cause phenotypical and physiological changes in another organism. To date, protein-based effectors have been described in aphids, nematodes, fungi and bacteria. Using RNA sequencing of Populus trichocarpa roots in mutualistic symbiosis with the ectomycorrhizal fungus Laccaria bicolor, we sought to determine if host plants also contain genes encoding effector-like proteins...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28330793/outcomes-in-transcatheter-aortic-valve-replacement-for-bicuspid-versus-tricuspid%C3%A2-aortic%C3%A2-valve-stenosis
#16
Sung-Han Yoon, Sabine Bleiziffer, Ole De Backer, Victoria Delgado, Takahide Arai, Johannes Ziegelmueller, Marco Barbanti, Rahul Sharma, Gidon Y Perlman, Omar K Khalique, Erik W Holy, Smriti Saraf, Florian Deuschl, Buntaro Fujita, Philipp Ruile, Franz-Josef Neumann, Gregor Pache, Masao Takahashi, Hidehiro Kaneko, Tobias Schmidt, Yohei Ohno, Niklas Schofer, William K F Kong, Edgar Tay, Daisuke Sugiyama, Hiroyuki Kawamori, Yoshio Maeno, Yigal Abramowitz, Tarun Chakravarty, Mamoo Nakamura, Shingo Kuwata, Gerald Yong, Hsien-Li Kao, Michael Lee, Hyo-Soo Kim, Thomas Modine, S Chiu Wong, Francesco Bedgoni, Luca Testa, Emmanuel Teiger, Christian Butter, Stephan M Ensminger, Ulrich Schaefer, Danny Dvir, Philipp Blanke, Jonathon Leipsic, Fabian Nietlispach, Mohamed Abdel-Wahab, Bernard Chevalier, Corrado Tamburino, David Hildick-Smith, Brian K Whisenant, Seung-Jung Park, Antonio Colombo, Azeem Latib, Susheel K Kodali, Jeroen J Bax, Lars Søndergaard, John G Webb, Thierry Lefèvre, Martin B Leon, Raj Makkar
BACKGROUND: Transcatheter aortic valve replacement (TAVR) is being increasingly performed in patients with bicuspid aortic valve stenosis (AS). OBJECTIVES: This study sought to compare the procedural and clinical outcomes in patients with bicuspid versus tricuspid AS from the Bicuspid AS TAVR multicenter registry. METHODS: Outcomes of 561 patients with bicuspid AS and 4,546 patients with tricuspid AS were compared after propensity score matching, assembling 546 pairs of patients with similar baseline characteristics...
May 30, 2017: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/28323788/traumatic-colon-injury-in-damage-control-laparotomy-a-multicenter-trial-is-it-safe-to-do-a-delayed-anastomosis
#17
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/28303498/validation-of-a-preclinical-drug-screening-platform-for-pharmacoresistant-epilepsy
#18
Melissa L Barker-Haliski, Kristina Johnson, Peggy Billingsley, Jennifer Huff, Laura J Handy, Rizvana Khaleel, Zhenmei Lu, Matthew J Mau, Timothy H Pruess, Carlos Rueda, Gerald Saunders, Tristan K Underwood, Fabiola Vanegas, Misty D Smith, Peter J West, Karen S Wilcox
The successful identification of promising investigational therapies for the treatment of epilepsy can be credited to the use of numerous animal models of seizure and epilepsy for over 80 years. In this time, the maximal electroshock test in mice and rats, the subcutaneous pentylenetetrazol test in mice and rats, and more recently the 6 Hz assay in mice, have been utilized as primary models of electrically or chemically-evoked seizures in neurologically intact rodents. In addition, rodent kindling models, in which chronic network hyperexcitability has developed, have been used to identify new agents...
March 16, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28254760/personal-model-assisted-identification-of-nad-and%C3%A2-glutathione-metabolism-as-intervention-target-in-nafld
#19
Adil Mardinoglu, Elias Bjornson, Cheng Zhang, Martina Klevstig, Sanni Söderlund, Marcus Ståhlman, Martin Adiels, Antti Hakkarainen, Nina Lundbom, Murat Kilicarslan, Björn M Hallström, Jesper Lundbom, Bruno Vergès, Peter Hugh R Barrett, Gerald F Watts, Mireille J Serlie, Jens Nielsen, Mathias Uhlén, Ulf Smith, Hanns-Ulrich Marschall, Marja-Riitta Taskinen, Jan Boren
To elucidate the molecular mechanisms underlying non-alcoholic fatty liver disease (NAFLD), we recruited 86 subjects with varying degrees of hepatic steatosis (HS). We obtained experimental data on lipoprotein fluxes and used these individual measurements as personalized constraints of a hepatocyte genome-scale metabolic model to investigate metabolic differences in liver, taking into account its interactions with other tissues. Our systems level analysis predicted an altered demand for NAD(+) and glutathione (GSH) in subjects with high HS Our analysis and metabolomic measurements showed that plasma levels of glycine, serine, and associated metabolites are negatively correlated with HS, suggesting that these GSH metabolism precursors might be limiting...
March 2, 2017: Molecular Systems Biology
https://www.readbyqxmd.com/read/28185296/a-report-of-cerebral-malaria-treated-with-automated-red-blood-cell-exchange
#20
Waseem Q Anani, Gerald P Smith, Mehraboon Irani, Kathleen E Puca
BACKGROUND: Adjunctive automated whole blood or red blood cell exchange (RBCEx) can rapidly decrease malarial hyperparasitemia. Several case reports and series suggest improvement in clinical symptomatology; however, recent Centers of Disease Control and Prevention (CDC) recommendations concluded that RBCEx has no efficacy as an adjunctive therapy. We present a case of mental status changes secondary to cerebral malaria treated with automated RBCEx resulting in rapid and dramatic neurologic improvement...
April 2017: Transfusion
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