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https://www.readbyqxmd.com/read/27919346/disease-control-via-intensified-lipoprotein-apheresis-in-three-siblings-with-familial-hypercholesterolemia
#1
Christina Taylan, Andrea Schlune, Thomas Meissner, Karolis Ažukaitis, Floris E A Udink Ten Cate, Lutz T Weber
BACKGROUND: Familial hypercholesterolemia (FH), the prevalent monogenic form of hypercholesterolemia, carries the risk of premature coronary heart disease. Lipoprotein-apheresis is established in children with severe dyslipidemia. We present 3 siblings with a negative/negative residual low-density lipoprotein (LDL) receptor mutation (p.Trp577Arg), unresponsive to drug treatment. OBJECTIVE: Intensified lipoprotein-apheresis is well tolerated and results in permanently low lipid values without harming the health-related quality of life in children...
November 2016: Journal of Clinical Lipidology
https://www.readbyqxmd.com/read/27916408/safety-tolerability-and-immunogenicity-of-a-4-antigen-staphylococcus-aureus-vaccine-sa4ag-results-from-a-first-in-human-randomised-placebo-controlled-phase-1-2-study
#2
Robert W Frenck, C Buddy Creech, Eric A Sheldon, David J Seiden, Martin K Kankam, James Baber, Edward Zito, Robin Hubler, Joseph Eiden, Joseph M Severs, Shite Sebastian, Jasdeep Nanra, Kathrin U Jansen, William C Gruber, Annaliesa S Anderson, Douglas Girgenti
BACKGROUND: A prophylactic Staphylococcus aureus four-antigen vaccine (SA4Ag) is under development for prevention of invasive S. aureus disease. A preliminary S. aureus three-antigen vaccine (SA3Ag) was reformulated to include a novel manganese transporter protein (MntC or rP305A). This study describes the first-in-human dose-finding, safety, and immunogenicity results for SA4Ag. METHODS: In this double-blind, sponsor-unblind, placebo-controlled, phase 1/2 study, 454 healthy adults aged 18-64years were randomised to receive a single dose of one of three formulations of SA4Ag with escalating dose levels of rP305A or placebo...
December 1, 2016: Vaccine
https://www.readbyqxmd.com/read/27915287/light-induced-oxidation-of-the-telomeric-g4-dna-in-complex-with-zn-ii-tetracarboxymethyl-porphyrin
#3
Artemy D Beniaminov, Roman A Novikov, Olga K Mamaeva, Vladimir A Mitkevich, Igor P Smirnov, Mikhail A Livshits, Anna K Shchyolkina, Dmitry N Kaluzhny
Structure-specific ligands are convenient tools for the recognition, targeting or probing of non-canonical DNA structures. Porphyrin derivatives exhibit a preference for interaction with G-quadruplex (G4) structures over canonical duplex DNA and are able to cause photoinducible damage to nucleic acids. Here, we show that Zn(II) 5,10,15,20-tetrakis(N-carboxymethyl-4-pyridinium)porphyrin ( ZNP1: ) interacts with different conformations of the telomeric sequence d(TAGGG(TTAGGG)3) at submicromolar concentrations without any detectible disturbance of the particular fold...
December 1, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27914643/fate-and-effect-of-imidacloprid-on-vermicompost-amended-soils-under-dissimilar-conditions-risk-for-soil-functions-structure-and-bacterial-abundance
#4
Jean Manuel Castillo Diaz, Fabrice Martin-Laurent, Jérèmie Beguet, Rogelio Nogales, Esperanza Romero
The fate and impact of pesticide on soil depend partly on the agricultural practices, such as prior treatment with pesticide and/or organic amendments. As a means of determining how the previous soil conditions can affect the fate of imidacloprid (IMI) and its effect on soil functions, experiments were made with soil samples, double-amended or not with either vine-shoot (W) or olive cake (O) vermicompost or contaminated or not with IMI. These soil samples, incubated for 3months, were placed in two microcosms (M1 with the pre-amended soils and M2 with the pre-exposed soils), treated with IMI and amended with vermicomposts and then incubated for 3months...
November 30, 2016: Science of the Total Environment
https://www.readbyqxmd.com/read/27911725/the-multiple-roles-of-the-nucleocapsid-in-retroviral-rna-conversion-into-proviral-dna-by-reverse-transcriptase
#5
REVIEW
Jean-Luc Darlix, Hugues de Rocquigny, Yves Mély
Retroviruses are enveloped plus-strand RNA viruses that can cause cancer, immunodeficiency and neurological disorder in human and animals. Retroviruses have several unique properties, such as a genomic RNA in a dimeric form found in the virus, and a replication strategy called 'copy-and-paste' during which the plus-strand genomic RNA is converted into a double-stranded DNA, subsequently integrated into the cellular genome. Two essential viral enzymes, reverse transcriptase (RT) and integrase (IN), direct this 'copy-and-paste' replication...
October 15, 2016: Biochemical Society Transactions
https://www.readbyqxmd.com/read/27909291/engineering-of-a-thermostable-esterase-est816-to-improve-its-quorum-quenching-activity-and-the-underlying-structural-basis
#6
Xiwen Liu, Li-Chuang Cao, Xin-Jiong Fan, Yu-Huan Liu, Wei Xie
N-acyl-homoserine lactones (AHLs) are small diffusible molecules called autoinducers that mediate cell-to-cell communications. Enzymatic degradation of AHLs is a promising bio-control strategy known as quorum-quenching. To improve the quorum-quenching activity of a thermostable esterase Est816, which had been previously cloned, we have engineered the enzyme by random mutagenesis. One of the mutants M2 with double amino acid substitutions (A216V/K238N) showed 3-fold improvement on catalytic efficiency. Based on the crystal structure determined at 2...
December 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27908199/hemoglobin-extravasation-in-the-brain-of-rats-exchange-transfused-with-hemoglobin-based-oxygen-carriers
#7
Laura Terraneo, Paola Bianciardi, Ashok Malavalli, Gnel Mkrtchyan, Stephanie N Spann, Jeff Lohman, Michele Samaja, Kim D Vandegriff
Haemoglobin (Hb)-based oxygen carriers are under consideration as oxygen therapeutics. Their effect on apoptosis is critical, because the onset of pro-apoptotic pathways may lead to tissue damage. MP4OX, a polyethylene glycol-conjugated human Hb preserves the baseline level of neuron apoptosis with respect to sham. Here we develop a method for measuring Hb extravasation in brain. We exchange transfused rats by haemorrhaging 50% of their blood with simultaneous, isovolemic replacement with Hextend (negative control), MP4OX, or αα-cross-linked Hb...
December 1, 2016: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/27903487/disturbed-p53-mdm2-feedback-loop-contributes-to-thoracic-aortic-dissection-formation-and-may-be-a-result-of-trim-25-overexpression
#8
Bin Gong, Zhiwei Wang, Min Zhang, Zhipeng Hu, Zongli Ren, Zheng Tang, Wanli Jiang, Lianghao Cheng, Jun Huang, Wei Ren, Qingtao Wang
BACKGROUND: The development of thoracic aortic dissection (TAD) is attributed to a broad range of degenerative, genetic, structural, oxidative, apoptotic, and acquired disease states. In this study, we examined the role of the disturbed p53-MDM2 feed-back loop in the formation of TAD, and one of a potential feed-back loop regulator, TRIM-25. METHODS: Surgical specimens of the aorta from TAD patients (n=10) and controls (n=10) were tested for α-smooth muscle actin (α-SMA),p53,murine double minute2(MDM2) and tripartite motif protein-25(TRIM-25) by western blot, immunohistochemical staining and quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) , respectively...
November 26, 2016: Annals of Vascular Surgery
https://www.readbyqxmd.com/read/27903094/effects-of-self-complementarity-codon-optimization-transgene-and-dose-on-liver-transduction-with-aav8
#9
Peter Bell, Lili Wang, Shu-Jen Chen, Hongwei Yu, Yanqing Zhu, Mohamad Nayal, Zhenning He, John White, Deborah Lebel-Hagan, James M Wilson
Numerous methods of vector design and delivery have been employed in an attempt to increase transgene expression following AAV-based gene therapy. Here, we conducted a gene transfer study in mice to compare the effects of vector self-complementarity (double- or single-stranded DNA), codon optimization of the transgene, and vector dose on transgene expression levels in liver. Two different reporter genes were used: human ornithine transcarbamylase (hOTC) detected by immunofluorescence, and enhanced green fluorescent protein (EGFP) detected by direct fluorescence...
November 30, 2016: Human Gene Therapy Methods
https://www.readbyqxmd.com/read/27899264/cyclic-ferrocenylnaphthalene-diimide-derivative-as-a-new-class-of-g-quadruplex-dna-binding-ligand
#10
Md Monirul Islam, Shinobu Sato, Shingo Shinozaki, Shigeori Takenaka
To identify an effective ligand that binds to a G-quadruplex structure but not a double-stranded DNA (dsDNA), a set of biophysical and biochemical experiments were carried out using newly synthesized cyclic ferrocenylnaphthalene diimide (cFNDI, 1) or the non-cyclic derivative (2) with various structures of G-quadruplex DNAs and dsDNA. Compound 1 bound strongly to G-quadruplexes DNAs (10(6)M(-1) order) with diminished binding to dsDNA (10(4)M(-1) order) in 100mM AcOH-AcOK buffer (pH 5.5) containing 100mM KCl...
November 15, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27894690/a-systematic-review-of-the-association-between-occupational-exposure-to-formaldehyde-and-effects-on-chromosomal-dna-damage-measured-using-the-cytokinesis-block-micronucleus-assay-in-lymphocytes
#11
REVIEW
Michael Fenech, Armen Nersesyan, Siegfried Knasmueller
Formaldehyde (FAL) is classified as a Class I carcinogen by the WHO International Agency for Research on Cancer. Therefore, there is a need to validate appropriate methods for detecting its genotoxic effects in vivo in humans. One of the most commonly used methods to measure the genotoxic effects of exposure to environmental chemicals is the lymphocyte cytokinesis-block micronucleus (L-CBMN assay). We performed a systematic review and statistical analysis of the results from all of the published studies in which the L-CBMN assay was used to measure the genotoxic effects of human exposure to FAL...
October 2016: Mutation Research
https://www.readbyqxmd.com/read/27889450/rpa-mediates-recruitment-of-mrx-to-forks-and-double-strand-breaks-to-hold-sister-chromatids-together
#12
Andrew Seeber, Anna Maria Hegnauer, Nicole Hustedt, Ishan Deshpande, Jérôme Poli, Jan Eglinger, Philippe Pasero, Heinz Gut, Miki Shinohara, Karl-Peter Hopfner, Kenji Shimada, Susan M Gasser
The Mre11-Rad50-Xrs2 (MRX) complex is related to SMC complexes that form rings capable of holding two distinct DNA strands together. MRX functions at stalled replication forks and double-strand breaks (DSBs). A mutation in the N-terminal OB fold of the 70 kDa subunit of yeast replication protein A, rfa1-t11, abrogates MRX recruitment to both types of DNA damage. The rfa1 mutation is functionally epistatic with loss of any of the MRX subunits for survival of replication fork stress or DSB recovery, although it does not compromise end-resection...
December 1, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27888074/toxoplasma-gondii-immune-mapped-protein-1-is-anchored-to-the-inner-leaflet-of-the-plasma-membrane-and-adopts-a-novel-protein-fold
#13
Yonggen Jia, Stefi Benjamin, Qun Liu, Yingqi Xu, Sunil Kumar Dogga, Jing Liu, Stephen Matthews, Dominique Soldati-Favre
The immune mapped protein 1 (IMP1) was first identified as a protective antigen in Eimeria maxima and described as vaccine candidate and invasion factor in Toxoplasma gondii. We show here that TgIMP1 localizes to the inner leaflet of plasma membrane (PM) via dual acylation. Mutations either in the N-terminal myristoylation or palmitoylation sites (G2 and C5) cause relocalization of TgIMP1 to the cytosol. The first 11 amino acids are sufficient for PM targeting and the presence of lysine (K7) is critical. Disruption of TgIMP1 gene by double homologous recombination revealed no invasion defect or any measurable alteration in the lytic cycle of tachyzoites...
November 22, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27886064/probiotic-supplements-beneficially-affect-tryptophan-kynurenine-metabolism-and-reduce-the-incidence-of-upper-respiratory-tract-infections-in-trained-athletes-a-randomized-double-blinded-placebo-controlled-trial
#14
Barbara Strasser, Daniela Geiger, Markus Schauer, Johanna M Gostner, Hannes Gatterer, Martin Burtscher, Dietmar Fuchs
BACKGROUND: Prolonged intense exercise has been associated with transient suppression of immune function and an increased risk of infections. In this context, the catabolism of amino acid tryptophan via kynurenine may play an important role. The present study examined the effect of a probiotic supplement on the incidence of upper respiratory tract infections (URTI) and the metabolism of aromatic amino acids after exhaustive aerobic exercise in trained athletes during three months of winter training...
November 23, 2016: Nutrients
https://www.readbyqxmd.com/read/27880793/seed-quality-traits-can-be-predicted-with-high-accuracy-in-brassica-napus-using-genomic-data
#15
Jun Zou, Yusheng Zhao, Peifa Liu, Lei Shi, Xiaohua Wang, Meng Wang, Jinling Meng, Jochen Christoph Reif
Improving seed oil yield and quality are central targets in rapeseed (Brassica napus) breeding. The primary goal of our study was to examine and compare the potential and the limits of marker-assisted selection and genome-wide prediction of six important seed quality traits of B. napus. Our study is based on a bi-parental population comprising 202 doubled haploid lines and a diverse validation set including 117 B. napus inbred lines derived from interspecific crosses between B. rapa and B. carinata. We used phenotypic data for seed oil, protein, erucic acid, linolenic acid, stearic acid, and glucosinolate content...
2016: PloS One
https://www.readbyqxmd.com/read/27880071/interplay-of-cis-and-trans-regulatory-mechanisms-in-the-spliceosomal-rna-helicase-brr2
#16
Eva Absmeier, Christian Becke, Jan Wollenhaupt, Karine F Santos, Markus C Wahl
RNA helicase Brr2 is implicated in multiple phases of pre-mRNA splicing and thus requires tight regulation. Brr2 can be auto-inhibited via a large N-terminal region folding back onto its helicase core and auto-activated by a catalytically inactive C-terminal helicase cassette. Furthermore, it can be regulated in trans by the Jab1 domain of the Prp8 protein, which can inhibit Brr2 by intermittently inserting a C-terminal tail in the enzyme's RNA-binding tunnel or activate the helicase after removal of this tail...
November 23, 2016: Cell Cycle
https://www.readbyqxmd.com/read/27878566/pharmacokinetic-and-pharmacodynamic-properties-of-faster-acting-insulin-aspart-versus-insulin-aspart-across-a-clinically-relevant-dose-range-in-subjects-with-type-1-diabetes-mellitus
#17
Tim Heise, Kirstine Stender-Petersen, Ulrike Hövelmann, Jacob Bonde Jacobsen, Leszek Nosek, Eric Zijlstra, Hanne Haahr
BACKGROUND: Absorption of current rapid-acting insulins is too slow for patients with diabetes mellitus to achieve optimal postprandial glucose control. Faster-acting insulin aspart (faster aspart) is insulin aspart in a new formulation with faster early absorption. We compared the pharmacokinetic/pharmacodynamic properties of faster aspart and insulin aspart across a clinically relevant dose range. METHODS: In this randomised, double-blind, crossover trial, 46 subjects with type 1 diabetes mellitus received single subcutaneous doses of faster aspart and insulin aspart at 0...
November 22, 2016: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/27878457/poorly-understood-and-often-miscategorized-congenital-umbilical-cord-hernia-an-alternative-repair-method
#18
E İnce, A Temiz, S S Ezer, H Ö Gezer, A Hiçsönmez
PURPOSE: Umbilical cord hernia is poorly understood and often miscategorized as "omphalocele minor". Careless clamping of the cord leads to iatrogenic gut injury in the situation of umbilical cord hernia. This study aimed to determine the characteristics and outcomes of umbilical cord hernias. We also highlight an alternative repair method for umbilical cord hernias. METHODS: We recorded 15 cases of umbilical cord hernias over 10 years. The patients' data were retrospectively reviewed, and preoperative preparation of the newborn, gestational age, birth weight, other associated malformations, surgical technique used, enteral nutrition, and length of hospitalization were recorded...
November 22, 2016: Hernia: the Journal of Hernias and Abdominal Wall Surgery
https://www.readbyqxmd.com/read/27875568/gated-volumetric-modulated-arc-therapy-vs-tumor-tracking-cyberknife-radiotherapy-as-stereotactic-body-radiotherapy-for-hepatocellular-carcinoma-a-dosimetric-comparison-study-focused-on-the-impact-of-respiratory-motion-managements
#19
KyoungJun Yoon, Jungwon Kwak, Byungchul Cho, Jin-Hong Park, Sang Min Yoon, Sang-Wook Lee, Jong Hoon Kim
PURPOSE: To assess the potential dosimetric benefits associated with the CyberKnife (CK) tumor tracking capability, wherein an extra margin for respiratory tumor motion is not required, when compared to respiratory-gated volumetric-modulated arc therapy (VMAT) for hepatocellular carcinoma (HCC). METHODS: Twenty-nine HCC patients previously treated with double-arc VMAT were enrolled. In each VMAT plan, the individual internal target volume (ITV) margin around the tumor was determined by measuring its motion over 30-70% of respiratory phases using four-dimensional computed tomography, followed by a 5-mm isotropic margin for the planning target volume (PTV)...
2016: PloS One
https://www.readbyqxmd.com/read/27874035/p53-isoform-%C3%AE-133p53-promotes-efficiency-of-induced-pluripotent-stem-cells-and-ensures-genomic-integrity-during-reprogramming
#20
Lu Gong, Xiao Pan, Haide Chen, Lingjun Rao, Yelin Zeng, Honghui Hang, Jinrong Peng, Lei Xiao, Jun Chen
Human induced pluripotent stem (iPS) cells have great potential in regenerative medicine, but this depends on the integrity of their genomes. iPS cells have been found to contain a large number of de novo genetic alterations due to DNA damage response during reprogramming. Thus, to maintain the genetic stability of iPS cells is an important goal in iPS cell technology. DNA damage response can trigger tumor suppressor p53 activation, which ensures genome integrity of reprogramming cells by inducing apoptosis and senescence...
November 22, 2016: Scientific Reports
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