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https://www.readbyqxmd.com/read/28437834/elucidation-of-factor-viii-activity-pharmacokinetics-a-pooled-population-analysis-in-hemophilia-a-patients-treated-with-moroctocog-alfa
#1
João A Abrantes, Elisabet I Nielsen, Joan Korth-Bradley, Lutz Harnisch, Siv Jönsson
This study investigated the disposition of coagulation factor VIII activity in 754 moderate to severe hemophilia A patients following the administration of moroctocog alfa, a B-domain deleted recombinant factor VIII. Data analyzed included patients aged 1 day to 73 years enrolled in 13 studies conducted over a period of 20 years in 25 countries. A two-compartment population pharmacokinetic model with a baseline model described the pooled data well. Body size, age, inhibitors, race and analytical assay were identified as significant predictors of factor VIII disposition...
April 24, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28437463/relationship-of-the-crebc-two-component-regulatory-system-and-inner-membrane-protein-cred-with-swimming-motility-in-stenotrophomonas-maltophilia
#2
Hsin-Hui Huang, Wei-Ching Chen, Cheng-Wen Lin, Yi-Tsung Lin, Hsiao-Chen Ning, Yi-Chih Chang, Tsuey-Ching Yang
The CreBC two-component system (TCS) is a conserved regulatory system found in Escherichia coli, Aeromonas spp., Pseudomonas aeruginosa, and Stenotrophomonas maltophilia. In this study, we determined how CreBC TCS regulates secreted protease activities and swimming motility using creB, creC, and creBC in-frame deletion mutants (KJΔCreB, KJΔCreC, and KJΔBC) of S. maltophilia KJ. Compared to wild-type KJ, KJΔCreB had a comparable secreted protease activity; however, the secreted protease activities were obviously reduced in KJΔCreC and KJΔBC, suggesting that CreC works together with another unidentified response regulator (not CreB) to regulate secreted protease activity...
2017: PloS One
https://www.readbyqxmd.com/read/28437377/microrna-21-is-required-for-local-and-remote-ischemic-preconditioning-in-multiple-organ-protection-against-sepsis
#3
Ping Jia, Xiaoli Wu, Yan Dai, Jie Teng, Yi Fang, Jiachang Hu, Jianzhou Zou, Mingyu Liang, Xiaoqiang Ding
OBJECTIVE: Sepsis, triggered by microbial infection, is a common and life-threatening systemic illness, often leads to impaired function of vital organs. Ischemic preconditioning induced by transient brief episodes of ischemia is a powerful innate mechanism of organ protection. We have reported that a 15-minute renal ischemic preconditioning substantially attenuated subsequent renal ischemia-reperfusion injury. Here, we investigate whether a brief ischemia and reperfusion in kidney can provide protection at local and remote sites against sepsis-induced organ injury, and whether this protection is microRNA-21 dependent...
April 21, 2017: Critical Care Medicine
https://www.readbyqxmd.com/read/28437167/the-fgvps39-fgvam7-fgsso1-complex-mediates-vesicle-trafficking-and-is-important-for-the-development-and-virulence-of-fusarium-graminearum
#4
Bing Li, Luping Liu, Ying Li, Xin Dong, Haifeng Zhang, Huaigu Chen, Xiaobo Zheng, Zhengguang Zhang
Vesicle trafficking is an important event in eukaryotic organisms. Many proteins and lipids transported between different organelles or compartments are essential for survival. These processes are mediated by soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins, Rab-GTPases, and multisubunit tethering complexes such as class C core vacuole or endosome tethering and homotypic fusion or vacuole protein sorting (HOPS). Our previous study has demonstrated that FgVam7, which encodes a SNARE protein involving in vesicle trafficking, plays crucial roles in growth, asexual or sexual development, deoxynivalenol production, and pathogenicity in Fusarium graminearum...
April 24, 2017: Molecular Plant-microbe Interactions: MPMI
https://www.readbyqxmd.com/read/28436956/identification-of-subepithelial-mesenchymal-cells-that-induce-iga-and-diversify-gut-microbiota
#5
Kazuki Nagashima, Shinichiro Sawa, Takeshi Nitta, Masanori Tsutsumi, Tadashi Okamura, Josef M Penninger, Tomoki Nakashima, Hiroshi Takayanagi
Immunoglobulin A (IgA) maintains a symbiotic equilibrium with intestinal microbes. IgA induction in the gut-associated lymphoid tissues (GALTs) is dependent on microbial sampling and cellular interaction in the subepithelial dome (SED). However it is unclear how IgA induction is predominantly initiated in the SED. Here we show that previously unrecognized mesenchymal cells in the SED of GALTs regulate bacteria-specific IgA production and diversify the gut microbiota. Mesenchymal cells expressing the cytokine RANKL directly interact with the gut epithelium to control CCL20 expression and microfold (M) cell differentiation...
April 24, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28436605/digeorge-like-syndrome-in-a-child-with-a-3p12-3-deletion-involving-mir4273-gene-born-to-a-mother-with-gestational-diabetes-mellitus
#6
Emilia Cirillo, Giuliana Giardino, Vera Gallo, Giovanni Galasso, Roberta Romano, Roberta D'Assante, Giulia Scalia, Luigi Del Vecchio, Lucio Nitsch, Rita Genesio, Claudio Pignata
Chromosome 22q11.2 deletion is the most common chromosomal alteration associated with DiGeorge syndrome (DGS), even though this is not the only underlying cause of DGS. In rare patients, mutations in a single gene, TBX1, have been described resulting in a DGS phenotype. Recently, it has been reported that at least part of the TBX1 mutant phenotype is due to excessive bone morphogenetic proteins (BMP) signaling. Evidence suggests that miRNA may modulate the expression of critical T-box transcriptional regulators during midface development and Bmp-signaling...
April 24, 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28436537/error-prone-replication-bypass-of-the-imidazole-ring-opened-formamidopyrimidine-deoxyguanosine-adduct
#7
Yan Sha, Irina G Minko, Chanchal K Malik, Carmelo J Rizzo, R Stephen Lloyd
Addition of hydroxyl radicals to the C8 position of 2'-deoxyguanosine generates an 8-hydroxyguanyl radical that can be converted into either 8-oxo-7,8-dihydro-2'-deoxyguanosine or N-(2-deoxy-d-pentofuranosyl)-N-(2,6-diamino-4-hydroxy-5-formamidopyrimidine) (Fapy-dG). The Fapy-dG adduct can adopt different conformations and in particular, can exist in an unnatural α anomeric configuration in addition to canonical β configuration. Previous studies reported that in 5'-TGN-3' sequences, Fapy-dG predominantly induced G → T transversions in both mammalian cells and Escherichia coli, suggesting that mutations could be formed either via insertion of a dA opposite the 5' dT due to primer/template misalignment or as result of direct miscoding...
April 24, 2017: Environmental and Molecular Mutagenesis
https://www.readbyqxmd.com/read/28436452/disrupted-neuronal-maturation-in-angelman-syndrome-derived-induced-pluripotent-stem-cells
#8
James J Fink, Tiwanna M Robinson, Noelle D Germain, Carissa L Sirois, Kaitlyn A Bolduc, Amanda J Ward, Frank Rigo, Stormy J Chamberlain, Eric S Levine
Angelman syndrome (AS) is a neurogenetic disorder caused by deletion of the maternally inherited UBE3A allele and is characterized by developmental delay, intellectual disability, ataxia, seizures and a happy affect. Here, we explored the underlying pathophysiology using induced pluripotent stem cell-derived neurons from AS patients and unaffected controls. AS-derived neurons showed impaired maturation of resting membrane potential and action potential firing, decreased synaptic activity and reduced synaptic plasticity...
April 24, 2017: Nature Communications
https://www.readbyqxmd.com/read/28436431/dna-single-strand-break-induced-dna-damage-response-causes-heart-failure
#9
Tomoaki Higo, Atsuhiko T Naito, Tomokazu Sumida, Masato Shibamoto, Katsuki Okada, Seitaro Nomura, Akito Nakagawa, Toshihiro Yamaguchi, Taku Sakai, Akihito Hashimoto, Yuki Kuramoto, Masamichi Ito, Shungo Hikoso, Hiroshi Akazawa, Jong-Kook Lee, Ichiro Shiojima, Peter J McKinnon, Yasushi Sakata, Issei Komuro
The DNA damage response (DDR) plays a pivotal role in maintaining genome integrity. DNA damage and DDR activation are observed in the failing heart, however, the type of DNA damage and its role in the pathogenesis of heart failure remain elusive. Here we show the critical role of DNA single-strand break (SSB) in the pathogenesis of pressure overload-induced heart failure. Accumulation of unrepaired SSB is observed in cardiomyocytes of the failing heart. Unrepaired SSB activates DDR and increases the expression of inflammatory cytokines through NF-κB signalling...
April 24, 2017: Nature Communications
https://www.readbyqxmd.com/read/28436127/tip110-deletion-impaired-embryonic-and-stem-cell-development-involving-down-regulation-of-stem-cell-factors-nanog-oct4-and-sox2
#10
Amanda Whitmill, Ying Liu, Khalid Amine Timani, Yinghua Niu, Johnny J He
HIV-1 Tat-interacting protein of 110 kDa, Tip110, plays important roles in multiple biological processes. In this study, we aimed to characterize the function of Tip110 in embryonic development. Transgenic mice lacking expression of a functional Tip110 gene (Tip110(-/-) ) died post-implantation, and Tip110(-/-) embryos exhibited developmental arrest between 8.5 and 9.5 days post coitum. However, in vitro cultures of Tip110(-/-) embryos showed that Tip110 loss did not impair embryo growth from the zygote to the blastocyst...
April 24, 2017: Stem Cells
https://www.readbyqxmd.com/read/28435970/-amp-activated-kinase-activation-inhibits-transforming-growth-factor-%C3%AE-1-production-in-cardiac-fibroblasts-via-targeting-c-ebp%C3%AE
#11
Han Xiao, Cheng-Shi Piao, Rui-Fei Chen, You-Yi Zhang
AMP-activated protein kinase (AMPK) activation has been shown to protect against fibrosis. However, the underlying mechanism remains unclear. Here we explored the effect of AMPK activation on transforming growth factor-β1 (TGFβ1) production induced by angiotensin II (AngII) in cardiac fibroblasts and the underlying mechanisms. Adult mouse cardiac fibroblasts were isolated. TGFβ1 and AMPK activity were determined by ELISA and Western blots, respectively. Pretreatment of AMPK activator AICAR inhibited TGFβ1 production induced by AngII in cardiac fibroblasts, which was reversed by AMPK inhibitor compound C...
April 25, 2017: Sheng Li Xue Bao: [Acta Physiologica Sinica]
https://www.readbyqxmd.com/read/28435893/opacification-domain-of-serum-opacity-factor-inhibits-beta-hemolysis-and-contributes-to-virulence-of-streptococcus-pyogenes
#12
Luchang Zhu, Randall J Olsen, James M Musser
Serum opacity factor (SOF) is a cell surface virulence factor made by the human pathogen Streptococcus pyogenes. We found that S. pyogenes strains with naturally occurring truncation mutations in the sof gene have markedly enhanced beta-hemolysis. Moreover, deletion of the sof gene in a SOF-positive parental strain resulted in significantly increased beta-hemolysis. Together, these observations suggest that SOF is an inhibitor of beta-hemolysis. SOF has two major functional domains, including an opacification domain and a fibronectin-binding domain...
March 2017: MSphere
https://www.readbyqxmd.com/read/28435444/role-of-trichoderma-reesei-mitogen-activated-protein-kinases-mapks-in-cellulase-formation
#13
Mingyu Wang, Meiling Zhang, Ling Li, Yanmei Dong, Yi Jiang, Kuimei Liu, Ruiqin Zhang, Baojie Jiang, Kangle Niu, Xu Fang
BACKGROUND: Despite being the most important cellulase producer, the cellulase-regulating carbon source signal transduction processes in Trichoderma reesei are largely unknown. Elucidating these processes is the key for unveiling how external carbon sources regulate cellulase formation, and ultimately for the improvement of cellulase production and biofuel production from lignocellulose. RESULTS: In this work, the role of the mitogen-activated protein kinase (MAPK) signal transduction pathways on cellulase formation was investigated...
2017: Biotechnology for Biofuels
https://www.readbyqxmd.com/read/28435344/development-of-performance-and-error-metrics-for-ultrasound-guided-axillary-brachial-plexus-block
#14
Osman M Ahmed, Brian D O'Donnell, Anthony G Gallagher, George D Shorten
PURPOSE: Change in the landscape of medical education coupled with a paradigm shift toward outcome-based training mandates the trainee to demonstrate specific predefined performance benchmarks in order to progress through training. A valid and reliable assessment tool is a prerequisite for this process. The objective of this study was to characterize ultrasound-guided axillary brachial plexus block to develop performance and error metrics and to verify face and content validity using a modified Delphi method...
2017: Advances in Medical Education and Practice
https://www.readbyqxmd.com/read/28435285/exploratory-cohort-study-and-meta-analysis-of-bim-deletion-polymorphism-in-patients-with-epidermal-growth-factor-receptor-mutant-non-small-cell-lung-cancer-treated-with-epidermal-growth-factor-receptor-tyrosine-kinase-inhibitors
#15
Si Sun, Hui Yu, Huijie Wang, Xinmin Zhao, Xintai Zhao, Xianghua Wu, Jie Qiao, Jianhua Chang, Jialei Wang
BACKGROUND: Non-small-cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations might develop primary and secondary resistance to tyrosine kinase inhibitors (TKIs). The proapoptotic protein Bcl-2-like 11 (BIM) is a key modulator of apoptosis triggered by EGFR-TKIs. The recent studies have indicated that some patients with positive EGFR mutations were refractory to EGFR-TKIs if they harbored a BIM deletion polymorphism. The purpose of this study was to investigate whether BIM polymorphism predicts treatment efficacy of EGFR-TKIs in Chinese NSCLC patients...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28435024/lkb1-deletion-in-murine-b-lymphocytes-promotes-cell-death-and-cancer
#16
George P Souroullas, Yuri Fedoriw, Louis M Staudt, Norman E Sharpless
LKB1 (aka STK11) is a potent tumor suppressor in solid tumors such as melanoma and lung adenocarcinoma, but inactivation in hematopoietic cells causes cell death, without signs of tumorigenesis. We noted somatic LKB1 deletion or mutation at low frequency in human B cell lymphoma. In order to determine if LKB1 inactivation is a passenger or driver event in lymphoid cancers, we examined the effects of conditional inactivation of Lkb1 in murine lymphocytes. Consistent with prior reports, Lkb1 deletion in either T or B cells resulted in massive, lineage-specific apoptosis...
April 20, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28435021/the-mtorc2-pkc-pathway-sustains-compensatory-insulin-secretion-of-pancreatic-%C3%AE-cells-in-response-to-metabolic-stress
#17
Yun Xie, Canqi Cui, Aifang Nie, Yan Wang, Qicheng Ni, Yun Liu, Qinglei Yin, Hongli Zhang, Yong Li, Qidi Wang, Yanyun Gu, Guang Ning
BACKGROUND: Compensation of the pancreatic β cell functional mass in response to metabolic stress is key to the pathogenesis of Type 2 Diabetes. The mTORC2 pathway governs fuel metabolism and β cell functional mass. It is unknown whether mTORC2 is required for regulating metabolic stress-induced β cell compensation. METHODS: We challenged four-week-old β-cell-specific Rictor (a key component of mTORC2)-knockout mice with a high fat diet (HFD) for 4weeks and measured metabolic and pancreatic morphological parameters...
April 20, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28434922/association-of-autoimmune-thyroiditis-and-celiac-disease-with-juvenile-polyposis-due-to-10q23-1q23-31-deletion-potential-role-of-pi3k-akt-pathway-dysregulation
#18
Federica Guaraldi, Giovanni Di Nardo, Luigi Tarani, Luca Bertelli, Francesco Claudio Susca, Rosanna Bagnulo, Nicoletta Resta
Juvenile Polyposis (JP) is a rare hereditary condition characterized by diffuse hamartomatous gastrointestinal polyposis, associated with a significantly increased risk of neoplastic transformation. Most of the cases are caused by SMAD and BMPR1A mutations, while 10q23 microdeletions, encompassing both PTEN and BMPR1A oncogenes, are extremely rare, typically associated with more aggressive JP, and extraintestinal features overlapping with PTEN Hamartoma Tumor Syndrome. We present the first case of a young female with multiple autoimmune disorders (i...
April 18, 2017: European Journal of Medical Genetics
https://www.readbyqxmd.com/read/28434908/duchenne-muscular-dystrophy-in-a-female-with-compound-heterozygous-contiguous-exon-deletions
#19
Eri Takeshita, Narihiro Minami, Kumiko Minami, Mikiya Suzuki, Takeya Awashima, Akihiko Ishiyama, Hirofumi Komaki, Ichizo Nishino, Masayuki Sasaki
Females with Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) mutations rarely exhibit clinical symptoms from childhood, although potential mechanisms for symptoms associated with DMD and BMD in females have been reported. We report the case of a female DMD patient with a clinical course indistinguishable from that of a male DMD patient, and who possessed compound heterozygous contiguous exon deletions in the dystrophin gene. She exhibited Gowers' sign, calf muscle hypertrophy, and a high serum creatine kinase level at 2 years...
April 3, 2017: Neuromuscular Disorders: NMD
https://www.readbyqxmd.com/read/28434899/mechanisms-responsible-for-imipenem-resistance-among-pseudomonas-aeruginosa-clinical-isolates-exposed-to-imipenem-concentrations-within-the-mutant-selection-window
#20
Foula Vassilara, Irene Galani, Maria Souli, Konstantinos Papanikolaou, Helen Giamarellou, Antonios Papadopoulos
The aim of this study was to determine the propensities of imipenem to select for resistant Pseudomonas aeruginosa mutants by determining the mutant prevention concentrations (MPCs) for 9 unrelated clinical isolates and the accession of any relationship with mechanisms of resistance development. The MPC/MIC ratios ranged from 4 to 16. Detection of resistance mechanisms in the mutant derivatives of the nine isolates mainly revealed inactivating mutations in the gene coding for outer membrane protein OprD. Point mutations leading to premature stop codons or amino acid substitution S278P, ≥1bp deletion leading to frameshift mutations and interruption of the oprD by an insertion sequence, were observed...
April 12, 2017: Diagnostic Microbiology and Infectious Disease
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