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https://www.readbyqxmd.com/read/29054072/cysteine-perthiosulfenic-acid-cys-ssoh-a-novel-intermediate-in-thiol-based-redox-signaling
#1
David E Heppner, Milena Hristova, Tomoaki Ida, Ana Mijuskovic, Christopher M Dustin, Virág Bogdándi, Jon M Fukuto, Tobias P Dick, Péter Nagy, Jianing Li, Takaaki Akaike, Albert van der Vliet
The reversible oxidation of protein cysteine residues (Cys-SH) is a key reaction in cellular redox signaling involving initial formation of sulfenic acids (Cys-SOH), which are commonly detected using selective dimedone-based probes. Here, we report that significant portions of dimedone-tagged proteins are susceptible to cleavage by DTT reflecting the presence of perthiosulfenic acid species (Cys-SSOH) due to similar oxidation of hydropersulfides (Cys-SSH), since Cys-S-dimedone adducts are stable toward DTT...
October 9, 2017: Redox Biology
https://www.readbyqxmd.com/read/29053691/quantitative-whole-mount-immunofluorescence-analysis-of-cardiac-progenitor-populations-in-mouse-embryos
#2
Evan Bardot, Nikos Tzavaras, Deanna L Benson, Nicole C Dubois
The use of ever-advancing imaging techniques has contributed broadly to our increased understanding of embryonic development. Pre-implantation development and organogenesis are two areas of research that have benefitted greatly from these advances, due to the high quality of data that can be obtained directly from imaging pre-implantation embryos or ex vivo organs. While pre-implantation embryos have yielded data with especially high spatial resolution, later stages have been less amenable to three-dimensional reconstruction...
October 12, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29053207/dpp-4-inhibitors-moderate-the-risk-of-genitourinary-tract-infections-associated-with-sglt2-inhibitors
#3
Gian Paolo Fadini, Benedetta Maria Bonora, Mayur Sarangdhar, Mauro Rigato, Angelo Avogaro
Genito-urinary tract infections (GUTI) are the most common adverse event (AE) during therapy with sodium-glucose cotransporter 2 inhibitors (SGLT2i). We evaluated whether dipeptidyl peptidase 4 inhibitors (DPP4i) moderate the risk of GUTI during therapy with SGLT2i, using two approaches. First, we screened the literature for randomized controlled trials (RCTs) directly comparing the frequency of GUTI in patients receiving a DPP4i/SGLT2i combination therapy versus those receiving a SGLT2i only. In the 5 trials we retrieved, the pooled RR for genital tract infections (GTI) in patients on a DPP4i/SGLT2i combination therapy versus those on SGLT2i alone was 0...
October 20, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29052456/population-density-analysis-for-determining-the-protonation-state-of-the-catalytic-dyad-in-bace1-tertiary-carbinamine-based-inhibitor-complex
#4
Carlos Gueto-Tettay, Luis Pelaez-Bedoya, Juan Carlos Drosos-Ramirez
BACE1 is an aspartyl protease with a very relevant role in medicinal chemistry related to Alzheimer Disease since it has demonstrated to be a promising therapeutic target for inhibition and possible control for the progress of the peptide accumulation characteristic of this pathology. The enzymatic activity of this protein is given by the aspartic dyad, Asp93 and Asp289, which can adopt several protonation states depending on the chemical nature of its inhibitors, this is, monoprotonated, diprotonated and di-deprotonated states...
October 20, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/29052435/high-overall-cardiovascular-risk-and-mortality-in-patients-with-atrial-fibrillation-and-diabetes-a-nationwide-report
#5
Stelios Karayiannides, Pia Lundman, Leif Friberg, Anna Norhammar
AIM: To describe nationwide complication patterns in patients with atrial fibrillation and diabetes mellitus. METHODS: All ( n = 326,832) patients in Sweden with non-valvular atrial fibrillation during 2006-2012 were identified, and information on events, comorbidities and pharmacological therapy was extracted using nationwide mandatory registers. Patients were followed until 31 December 2013 and the mean follow-up time was 3.7 years (0.9-8 years). RESULTS: Diabetes was present in 17...
October 1, 2017: Diabetes & Vascular Disease Research
https://www.readbyqxmd.com/read/29052226/translational-high-dimensional-drug-interaction-discovery-and-validation-using-health-record-databases-and-pharmacokinetics-models
#6
Chien-Wei Chiang, Pengyue Zhang, Xueying Wang, Lei Wang, Shijun Zhang, Xia Ning, Li Shen, Sara K Quinney, Lang Li
Polypharmacy increases the risk of drug-drug interactions (DDI's). Combining epidemiological studies with pharmacokinetic modeling, we detected and evaluated high-dimensional DDI's among thirty frequent drugs. Multi-drug combinations that increased risk of myopathy were identified in the FDA Adverse Event Reporting System (FAERS) and electronic medical record (EMR) databases by a mixture drug-count response model. CYP450 inhibition was estimated among the 30 drugs in the presence of 1 to 4 inhibitors using in vitro in vivo extrapolation...
October 20, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29052211/technical-review-cytogenetic-tools-for-studying-mitotic-chromosomes
#7
Václaclav Bačovský, Roman Hobza, Boris Vyskot
Significant advances in chromosome preparation and other techniques have greatly increased the potential of plant cytogenetics in recent years. Increase in longitudinal resolution using DNA extended fibers as well as new developments in imaging and signal amplification technologies have enhanced the ability of FISH to detect small gene targets. The combination of fluorescence in situ hybridization with immunocytochemistry allows the investigation of cell events, chromosomal rearrangements and chromatin features typical for plant nuclei...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29052102/changes-in-cerebellar-functional-connectivity-and-autonomic-regulation-in-cancer-patients-treated-with-the-neuro-emotional-technique-for-traumatic-stress-symptoms
#8
Daniel A Monti, Anna Tobia, Marie Stoner, Nancy Wintering, Michael Matthews, Chris J Conklin, Feroze B Mohamed, Inna Chervoneva, Andrew B Newberg
PURPOSE: A growing number of research studies have implicated the cerebellum in emotional processing and regulation, especially with regard to negative emotional memories. However, there currently are no studies showing functional changes in the cerebellum as a result of treatment for traumatic stress symptoms. The Neuro Emotional Technique (NET) is an intervention designed to help improve symptoms related to traumatic stress using an integrative approach that combines emotional, cognitive, and motor processing, with a particular focus on autonomic nervous system regulation...
October 19, 2017: Journal of Cancer Survivorship: Research and Practice
https://www.readbyqxmd.com/read/29051781/prediction-of-adverse-pregnancy-outcomes-by-extreme-values-of-first-trimester-screening-markers
#9
Marina S Gomes, Mariana Carlos-Alves, Vera Trocado, Diana Arteiro, Paula Pinheiro
BACKGROUND: To determine the association between extreme values of first trimester markers and adverse pregnancy outcomes. METHODS: A retrospective cohort study of 916 women who underwent first-trimester combined screening during 2015 was performed. Extreme values of NT, pregnancy-associated plasma protein-A (PAPP-A) and free β-hCG, and their association with adverse pregnancy outcomes were analyzed. RESULTS: Low PAPP-A (<10th percentile) was associated with an increased risk for preeclampsia (adjusted odds ratio (AOR) 4...
September 2017: Obstetric Medicine
https://www.readbyqxmd.com/read/29051533/microtome-integrated-microscope-system-for-high-sensitivity-tracking-of-in-resin-fluorescence-in-blocks-and-ultrathin-sections-for-correlative-microscopy
#10
Nicolas Lemercier, Volker Middel, Didier Hentsch, Serge Taubert, Masanari Takamiya, Tanja Beil, Jean-Luc Vonesch, Tilo Baumbach, Patrick Schultz, Claude Antony, Uwe Strähle
Many areas of biological research demand the combined use of different imaging modalities to cover a wide range of magnifications and measurements or to place fluorescent patterns into an ultrastructural context. A technically difficult problem is the efficient specimen transfer between different imaging modalities without losing the coordinates of the regions-of-interest (ROI). Here, we report a new and highly sensitive integrated system that combines a custom designed microscope with an ultramicrotome for in-resin-fluorescence detection in blocks, ribbons and sections on EM-grids...
October 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29051523/emotion-regulating-attentional-control-abnormalities-in-major-depressive-disorder-an-event-related-potential-study
#11
Bin Hu, Juan Rao, Xiaowei Li, Tong Cao, Jianxiu Li, Dennis Majoe, Jürg Gutknecht
Major depressive disorders (MDD) exhibit cognitive dysfunction with respect to attention. The deficiencies in cognitive control of emotional information are associated with MDD as compared to healthy controls (HC). However, the brain mechanism underlying emotion that influences the attentional control in MDD necessitates further research. The present study explores the emotion-regulated cognitive competence in MDD at a dynamic attentional stage. Event-Related Potentials (ERPs) were recorded from 35 clinical MDD outpatients and matched HCs by applying a modified affective priming dot-probe paradigm, which consisted of various emotional facial expression pairs...
October 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29051384/taxon-restricted-genes-at-the-origin-of-a-novel-trait-allowing-access-to-a-new-environment
#12
M Emília Santos, Augustin Le Bouquin, Antonin J J Crumière, Abderrahman Khila
Taxon-restricted genes make up a considerable proportion of genomes, yet their contribution to phenotypic evolution is poorly understood. We combined gene expression with functional and behavioral assays to study the origin and adaptive value of an evolutionary innovation exclusive to the water strider genus Rhagovelia: the propelling fan. We discovered that two taxon-restricted genes, which we named geisha and mother-of-geisha, specifically control fan development. geisha originated through a duplication event at the base of the Rhagovelia lineage, and both duplicates acquired a novel expression in a specific cell population prefiguring fan development...
October 20, 2017: Science
https://www.readbyqxmd.com/read/29051322/a-multicenter-phase-i-study-evaluating-dual-pi3k-and-braf-inhibition-with-px-866-and-vemurafenib-in-patients-with-advanced-braf-v600-mutant-solid-tumors
#13
Clinton Yam, Xiaowei Xu, Michael A Davies, Phyllis A Gimotty, Jennifer Jd Morrissette, Michael T Tetzlaff, Khalida Wani, Shujing Liu, Wanleng Deng, Meghan Buckley, Jianhua Zhao, Ravi K Amaravadi, Naomi Haas, Ragini R Kudchadkar, Anna Pavlick, Jeffrey A Sosman, Hussein Tawbi, Luke Walker, Lynn M Schuchter, Giorgos C Karakousis, Tara C Gangadhar
PURPOSE: The objectives of the study were to evaluate the safety of daily oral PX-866 in combination with twice daily vemurafenib and to identify potential predictive biomarkers for this novel combination. EXPERIMENTAL DESIGN: We conducted a phase I, open-label, dose escalation study in patients with advanced BRAF V600 mutant solid tumors. PX-866 was administered on a continuous schedule in combination with vemurafenib. Patients underwent a baseline and on-treatment biopsy after 1-week of PX-866 monotherapy for biomarker assessment...
October 19, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29050991/mycophenolate-mofetil-in-autoimmune-hepatitis-patients-with-suboptimal-outcomes-to-standard-therapy-the-tapestry-study
#14
Stuart K Roberts, Ricky Lim, Simone Strasser, Amanda Nicoll, Alessia Gazzola, Joanne Mitchell, Way Siow, Tiffany Khoo, Zaki Hamarneh, Martin Weltman, Paul Gow, Natasha Janko, Edmund Tse, Gauri Mishra, En-Hsiang Cheng, Miriam Levy, Wendy Cheng, Siddarth Sood, Richard Skoien, Jonathan Mitchell, Amany Zekry, Jacob George, Gerry MacQuillan, Alan Wigg, Katherine Stuart, William Sievert, Geoffrey McCaughan
BACKGROUND AND AIMS: The outcomes of mycophenolate mofetil (MMF) as rescue therapy for AIH patients who have a suboptimal outcome to standard therapy remain unclear. We evaluated the efficacy and safety of MMF in patients who had failed or were intolerant to corticosteroids with/without azathioprine. METHODS: A retrospective study was performed of AIH patients who received MMF after an inadequate response or intolerance to standard therapy. Patients were recruited from 17 liver clinics via the Australian Liver Association Clinical Research Network...
October 16, 2017: Clinical Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/29050959/sequential-proton-boost-after-standard-chemoradiation-for-high-grade-glioma
#15
Sebastian Adeberg, Denise Bernhardt, Semi Ben Harrabi, Matthias Uhl, Angela Paul, Nina Bougatf, Vivek Verma, Andreas Unterberg, Wolfgang Wick, Thomas Haberer, Stephanie E Combs, Klaus Herfarth, Juergen Debus, Stefan Rieken
PURPOSE: To retrospectively assess the feasibility and safety of a sequential proton boost following conventional chemoradiation in high-grade glioma (HGG). METHOD AND MATERIALS: Sixty-six consecutive patients with HGG were treated with 50.0 Gy photons (50.0-50.4 Gy) in 2.0 Gy (1.8-2.0 Gy) fractions, followed by a proton boost with 10 Gy equivalent (Gy(RBE)) in 2.0 Gy(RBE) fractions. Patients were matched one to one with 66 patients with HGG undergoing conventional radiation therapy (RT) with 60...
October 16, 2017: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
https://www.readbyqxmd.com/read/29050588/sequential-one-pot-multienzyme-synthesis-of-hyaluronan-and-its-derivative
#16
Shuang Li, Shuaishuai Wang, Xuan Fu, Xian-Wei Liu, Peng George Wang, Junqiang Fang
Hyaluronan (HA) is a linear polysaccharide composed of repeating disaccharide units. It has been well documented to play an array of biological functions in cancer events. Here, we reported a sequential one-pot multienzyme (OPME) strategy for in vitro synthesis of HA and its derivatives. The strategy, which combined in situ sugar nucleotides generation with HA chain polymerization, could convert cheap monosaccharides into HA polymers without consuming exogenous sugar nucleotide donors. HA polymers (number-average molecular weight ranged from 1...
December 15, 2017: Carbohydrate Polymers
https://www.readbyqxmd.com/read/29050517/the-safety-and-efficacy-of-dabrafenib-and-trametinib-for-the-treatment-of-melanoma
#17
Sarah Knispel, Lisa Zimmer, Theodora Kanaki, Selma Ugurel, Dirk Schadendorf, Elisabeth Livingstone
The introduction of BRAF and MEK inhibitors into clinical practice improved the prognosis of metastatic melanoma patients. The combination of BRAF inhibitor dabrafenib with MEK inhibitor trametinib has shown its superiority to single agent therapy and is characterized by a tolerable spectrum of adverse events which shows a decrease in incidence over time on treatment. Areas covered: The current scientific literature on safety and adverse events (AEs) related to BRAF and MEK-inhibition has been investigated with special focus on the large phase 3 studies (COMBI-v, COMBI-d and CoBRIM) as well as recent updates presented at oncology and melanoma meetings...
October 20, 2017: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/29050354/phase-i-study-of-nivolumab-combined-with-ifn-%C3%AE-for-patients-with-advanced-melanoma
#18
Taku Fujimura, Takanori Hidaka, Yumi Kambayashi, Sadanori Furudate, Aya Kakizaki, Hisayuki Tono, Akira Tsukada, Takahiro Haga, Akira Hashimoto, Ryo Morimoto, Takuhiro Yamaguchi, Tadao Takano, Setsuya Aiba
The efficacy of nivolumab is greater than that of other anti-melanoma drugs, so nivolumab-based combined therapies that enhance anti-tumor immune responses in patients with metastatic melanoma are of great interest to dermato-oncologists. As we have previously reported, IFN-β enhances the anti-tumor immune response of anti-PD-1 antibodies against B16F10 melanoma in vivo. To explore the potential of this property of IFN-β as part of a combination therapy for the treatment of metastatic melanoma patients, we performed a phase 1 trial, using a traditional rule-based 3 + 3 design, on patients with advanced melanoma...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29050316/pharmacokinetics-and-drug-drug-interaction-between-enalapril-enalaprilat-and-felodipine-extended-release-er-in-healthy-subjects
#19
Dai Li, Sumei Xu, Yulu Wang, Dan Li, Xiaomin Li, Jing Pan, Pingsheng Xu
Since angiotensin-converting enzyme (ACE) inhibitors and calcium antagonists have complimentary mechanisms of action, enalapril, an ACE inhibitor, is used in combination with felodipine, a vascular selective dihydropyridine calcium antagonist, for the treatment of hypertension. The present study was designed to investigate the possible drug-drug interaction between these two agents in Chinese healthy subjects. A randomized, open-label, multiple-dose, 3-treatment, 3-period, 6-sequence cross-over study enrolling 12 healthy subjects (six male and six female subjects) was performed...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29050231/a-phase-i-study-of-foretinib-plus-erlotinib-in-patients-with-previously-treated-advanced-non-small-cell-lung-cancer-canadian-cancer-trials-group-ind-196
#20
Natasha B Leighl, Ming-Sound Tsao, Geoffrey Liu, Dongsheng Tu, Cheryl Ho, Frances A Shepherd, Nevin Murray, John R Goffin, Garth Nicholas, Shingo Sakashita, Zhuo Chen, Lucia Kim, Jean Powers, Lesley Seymour, Glenwood Goss, Penelope A Bradbury
PURPOSE: MET and AXL mediate resistance to EGFR TKI in NSCLC. Foretinib, a MET/RON/AXL/TIE-2/VEGFR kinase inhibitor may overcome EGFR kinase resistance. This dose escalation study combined foretinib and erlotinib in advanced pretreated NSCLC patients. EXPERIMENTAL DESIGN: The primary endpoint was to define the RP2D of foretinib plus erlotinib as continuous oral daily dosing. Secondary objectives included safety, pharmacokinetics, response and potential biomarkers of response including EGFR, KRAS genotype, MET, AXL expression, and circulating HGF levels...
September 19, 2017: Oncotarget
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