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https://www.readbyqxmd.com/read/28816084/adenoviral-type-35-and-26-vectors-with-a-bidirectional-expression-cassette-in-the-e1-region-show-an-improved-genetic-stability-profile-and-potent-transgene-specific-immune-response
#1
Marija Vujadinovic, Kerstin Wunderlich, Benoit Callendret, Marina Koning, Mark Vermeulen, Barbara Sanders, Esmeralda van der Helm, Adile Gecgel, Dirk Spek, Karin de Boer, Masha Stalknecht, Jan Serroyen, Maria Grazia Pau, Hanneke Schuitemaker, Roland Zahn, Jerome Custers, Jort Vellinga
Genetic vaccines based on replication-incompetent adenoviral (AdV) vectors are currently in clinical development. Monovalent AdV vectors express one antigen from an expression cassette placed in most cases in the E1 region. For many vaccines, inclusion of several antigens is necessary in order to raise protective immunity and/or target more than one pathogen or pathogen strain. Based on the current technology, a mix of several monovalent vectors can be employed. However, a mix of the standard monovalent AdV may not be optimal with respect to manufacturing costs and the final dose per vector in humans...
August 17, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28803330/bime2-a-novel-gene-required-for-interhomolog-meiotic-recombination-in-the-protist-model-organism-tetrahymena
#2
Anura Shodhan, Maria Novatchkova, Josef Loidl
Meiotic recombination is initiated by DNA double-strand breaks (DSBs). Most DSBs are converted into nonreciprocal exchanges (gene conversions) or crossovers (COs) between sister chromatids. Only a minority of DSBs are processed toward interhomolog COs, the precursors of the chiasmata that connect homologous chromosomes. Dmc1, the meiosis-specific paralog of the universal recombination protein Rad51, is required for interhomolog COs; in its absence, univalents are primarily formed. Here, we report a ciliate-specific novel meiotic gene, BIME2, which also promotes interhomolog crossing over...
August 12, 2017: Chromosome Research
https://www.readbyqxmd.com/read/28796844/genome-wide-identification-of-autosomal-genes-with-allelic-imbalance-of-chromatin-state
#3
Andrej J Savol, Peggy I Wang, Yesu Jeon, David Colognori, Eda Yildirim, Stefan F Pinter, Bernhard Payer, Jeannie T Lee, Ruslan I Sadreyev
In mammals, monoallelic gene expression can result from X-chromosome inactivation, genomic imprinting, and random monoallelic expression (RMAE). Epigenetic regulation of RMAE is not fully understood. Here we analyze allelic imbalance in chromatin state of autosomal genes using ChIP-seq in a clonal cell line. We identify approximately 3.7% of autosomal genes that show significant differences between chromatin states of two alleles. Allelic regulation is represented among several functional gene categories including histones, chromatin modifiers, and multiple early developmental regulators...
2017: PloS One
https://www.readbyqxmd.com/read/28794452/the-anti-influenza-m2e-antibody-response-is-promoted-by-xcr1-targeting-in-pig-skin
#4
Charlotte Deloizy, Even Fossum, Christophe Barnier-Quer, Céline Urien, Tiphany Chrun, Audrey Duval, Maelle Codjovi, Edwige Bouguyon, Pauline Maisonnasse, Pierre-Louis Hervé, Céline Barc, Olivier Boulesteix, Jérémy Pezant, Christophe Chevalier, Nicolas Collin, Marc Dalod, Bjarne Bogen, Nicolas Bertho, Isabelle Schwartz-Cornil
XCR1 is selectively expressed on a conventional dendritic cell subset, the cDC1 subset, through phylogenetically distant species. The outcome of antigen-targeting to XCR1 may therefore be similar across species, permitting the translation of results from experimental models to human and veterinary applications. Here we evaluated in pigs the immunogenicity of bivalent protein structures made of XCL1 fused to the external portion of the influenza virus M2 proton pump, which is conserved through strains and a candidate for universal influenza vaccines...
August 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28794021/structure-based-design-of-hepatitis-c-virus-vaccines-that-elicit-neutralizing-antibody-responses-to-a-conserved-epitope
#5
Brian G Pierce, Elisabeth N Boucher, Kurt H Piepenbrink, Monir Ejemel, Chelsea A Rapp, William D Thomas, Eric J Sundberg, Zhiping Weng, Yang Wang
Despite recent advances in therapeutic options, hepatitis C virus (HCV) remains a severe global disease burden, and a vaccine can substantially reduce its incidence. Due to its extremely high sequence variability, HCV can readily escape the immune response, thus an effective vaccine must target conserved, functionally important epitopes. Using the structure of a broadly neutralizing antibody in complex with a conserved linear epitope from the HCV E2 envelope glycoprotein (residues 412-423; epitope I), we performed structure-based design of immunogens to induce antibody responses to this epitope...
August 9, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28793256/dynamics-of-rna-polymerase-ii-pausing-and-bivalent-histone-h3-methylation-during-neuronal-differentiation-in-brain-development
#6
Jiancheng Liu, Xiwei Wu, Heying Zhang, Gerd P Pfeifer, Qiang Lu
During cellular differentiation, genes important for differentiation are expected to be silent in stem/progenitor cells yet can be readily activated. RNA polymerase II (Pol II) pausing and bivalent chromatin marks are two paradigms suited for establishing such a poised state of gene expression; however, their specific contributions in development are not well understood. Here we characterized Pol II pausing and H3K4me3/H3K27me3 marks in neural progenitor cells (NPCs) and their daughter neurons purified from the developing mouse cortex...
August 8, 2017: Cell Reports
https://www.readbyqxmd.com/read/28783324/a-noncanonical-binding-site-in-the-evh1-domain-of-vasp-regulates-its-interactions-with-the-proline-rich-region-of-zyxin
#7
Lucila Andrea Acevedo, Alexander Ian Greenwood, Linda K Nicholson
Vasodilator-Stimulated Phosphoprotein, VASP, is a processive actin polymerase with roles in the control of cell shape and cell migration. Through interaction with the cytoskeletal adaptor protein Zyxin, VASP can localize to damaged stress fibers where it serves to repair and reinforce these structures. VASP localization is mediated by its N-terminal Ena/VASP Homology domain (EVH1), which binds to the motif (W/F)PxφP (most commonly occurring as FPPPP) found in cytoskeletal proteins such as vinculin, lamellipodin, and Zyxin...
August 7, 2017: Biochemistry
https://www.readbyqxmd.com/read/28776396/paclitaxel-loaded-nanoparticles-decorated-with-bivalent-fragment-hab18-f-ab-2-and-cell-penetrating-peptide-for-improved-therapeutic-effect-on-hepatocellular-carcinoma
#8
Cheng Jin, Ling Bai, Lemin Lin, Shuangquan Wang, Xiaolong Yin
Hepatocellular carcinoma (HCC) shows low response to most conventional treatment strategies. Therefore, there is an urgent need for new and effective chemotherapies. Nanotechnology gives a dramatic impact on medicine. In this work, paclitaxel loaded nanoparticles (NPs) decorated with bivalent fragment HAb18 F(ab')2 and/or cell penetrating peptide (CPP) were developed and evaluated. NPs were prepared by emulsification-solvent evaporation method and decorated by carbodiimide chemistry. The physicochemical characteristics of NPs (i...
August 4, 2017: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/28774624/capability-of-cation-exchange-technology-to-remove-proven-n-nitrosodimethylamine-precursors
#9
Shixiang Li, Xulan Zhang, Er Bei, Huihui Yue, Pengfei Lin, Jun Wang, Xiaojian Zhang, Chao Chen
N-nitrosodimethylamine (NDMA) precursors consist of a positively charged dimethylamine group and a non-polar moiety, which inspired us to develop a targeted cation exchange technology to remove NDMA precursors. In this study, we tested the removal of two representative NDMA precursors, dimethylamine (DMA) and ranitidine (RNTD), by strong acidic cation exchange resin. The results showed that pH greatly affected the exchange efficiency, with high removal (DMA>78% and RNTD>94%) observed at pH<pka-1 when the molar ratio of exchange capacity to precursor was 4...
August 2017: Journal of Environmental Sciences (China)
https://www.readbyqxmd.com/read/28772266/evolution-of-the-sex-chromosomes-in-beetles-i-the-loss-of-the-y-chromosome
#10
Anne-Marie Dutrillaux, Bernard Dutrillaux
In the males of Coleoptera, the most frequent sex chromosome constitution is XY. At metaphase I of meiosis, the X and Y are linked by nucleolar proteins, forming the so-called parachute bivalent (Xyp), which is assumed to allow the non-synapsed X and Y to segregate correctly at anaphase I. However, X0 males are not exceptional, and we explored the relationships between the X and nucleolar proteins in the absence of the Y chromosome in 6 species belonging to different families/subfamilies. Using C-banding and silver staining, we show that nucleolar proteins always remain in contact with the X until anaphase I...
August 4, 2017: Cytogenetic and Genome Research
https://www.readbyqxmd.com/read/28771339/specific-acetylation-patterns-of-h2a-z-form-transient-interactions-with-the-bptf-bromodomain
#11
Gabriella T Perell, Neeraj K Mishra, Babu Sudhamalla, Peter D Ycas, Kabirul Islam, William C K Pomerantz
Post-translational lysine acetylation of histone tails affect both chromatin accessibility and recruitment of multi-functional bromodomain-containing proteins for modulating transcription. Bromodomain and PHD finger-containing protein (BPTF) regulates transcription, but has also been implicated with high gene expression levels in a variety of cancers. In this report, the histone variant H2A.Z, which replaces H2A in chromatin, is evaluated for affinity towards BPTF with a specific recognition pattern of acetylated lysine residues of the N-terminal tail region...
August 3, 2017: Biochemistry
https://www.readbyqxmd.com/read/28769084/antibody-induced-dimerization-of-fgfr1-promotes-receptor-endocytosis-independently-of-its-kinase-activity
#12
Łukasz Opaliński, Aleksandra Sokołowska-Wędzina, Martyna Szczepara, Małgorzata Zakrzewska, Jacek Otlewski
Fibroblast growth factors (FGFs) and their plasma membrane-localized receptors (FGFRs) play a key role in the regulation of developmental processes and metabolism. Aberrant FGFR signaling is associated with the progression of serious metabolic diseases and human cancer. Binding of FGFs to FGFRs induces receptor dimerization and transphosphorylation of FGFR kinase domains that triggers activation of intracellular signaling pathways. Following activation, FGFRs undergo internalization and subsequent lysosomal degradation, which terminates transmission of signals...
August 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28768817/cxcr4-specific-nanobodies-as-potential-therapeutics-for-whim-syndrome
#13
Raymond H de Wit, Raimond Heukers, Hendrik Brink, Angela Arsova, David Maussang, Pasquale Cutolo, Beatrijs Strubbe, Henry Vischer, Francoise Bachelerie, Martine J Smit
WHIM syndrome is a rare congenital immunodeficiency disease, named after its main clinical manifestations: Warts, Hypogammaglobulinemia, Infections and Myelokathexis. The disease is primarily caused by C-terminal truncation mutations of the chemokine receptor CXCR4. Consequently, these CXCR4-WHIM mutants have a gain of function in response to its ligand CXCL12, which results in abnormal leukocyte migration and thereby immune system dysfunctions. Treatment of WHIM patients currently consists of symptom relief, leading to unsatisfactory clinical responses...
August 2, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28767218/selective-binders-of-the-tandem-sh2-domains-in-syk-and-zap-70-kinases-by-dna-programmed-spatial-screening
#14
Michaela Marczynke, Katharina Groeger, Oliver Seitz
Members of the Syk family of tyrosine kinases arrange Src homology 2 (SH2) domains in tandem to allow firm binding of immunoreceptor tyrosine-based interaction motifs (ITAMs). While the advantages provided by the bivalency enhanced interactions are evident, the impact on binding specificity is less clear. For example, the Spleen tyrosine kinase (Syk) and the Zeta-chain-associated protein kinase (ZAP-70) recognize the consensus sequence pYXXI/L(X)6-8 pYXXI/L with near identical nanomolar affinity. The non-discriminatory recognition on the one hand poses a specificity challenge for the design of sub-type selective protein binders and, on the other hand, raises the question as to how differential activation of Syk and ZAP-70 is ensured when both kinases are co-expressed...
August 2, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28759852/the-role-of-different-network-modifying-cations-on-the-speciation-of-the-co-2-complex-in-silicates-and-implication-in-the-investigation-of-historical-glasses
#15
Cristina Fornacelli, Andrea Ceglia, Susanna Bracci, Marcia Vilarigues
In the last decades the speciation of the cobalt complex in a glass matrix has been extensively studied. Bivalent cobalt ions in glasses of different composition commonly adopt a tetrahedral coordination, though hexa- or penta-coordinated species are also possible. Changes in the absorbance spectrum of Co-doped glasses were attested in previous studies according to the introduction of different modifying cations. A shifting of the first sub-band characterizing the typical triplets of tetrahedral Co(2+) ions in both the visible and near infrared regions was observed, but discrepancies in literature suggested a relevant role of glass composition on the definition of the optical signature of cobalt...
July 22, 2017: Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy
https://www.readbyqxmd.com/read/28756395/the-impact-of-bivalent-hpv-vaccine-on-cervical-intraepithelial-neoplasia-by-deprivation-in-scotland-reducing-the-gap
#16
Ross L Cameron, Kimberley Kavanagh, D Cameron Watt, Chris Robertson, Kate Cuschieri, Syed Ahmed, Kevin G Pollock
BACKGROUND: Cervical cancer disproportionately affects women from lower socioeconomic backgrounds. A human papillomavirus (HPV) vaccination programme was introduced in Scotland in 2008 with uptake being lower and inequitable in a catch-up cohort run for the first three years of the programme compared with the routine programme. The socioeconomic differences in vaccine uptake have the potential to further increase the inequality gap in regards to cervical disease. METHODS: Vaccination status was linked to demographic, cytological and colposcopic data, which are routinely collected by the Scottish HPV surveillance system...
July 29, 2017: Journal of Epidemiology and Community Health
https://www.readbyqxmd.com/read/28754985/epigenetic-changes-in-myelofibrosis-distinct-methylation-changes-in-the-myeloid-compartments-and-in-cases-with-asxl1-mutations
#17
Helene Myrtue Nielsen, Christen Lykkegaard Andersen, Maj Westman, Lasse Sommer Kristensen, Fazila Asmar, Torben Arvid Kruse, Mads Thomassen, Thomas Stauffer Larsen, Vibe Skov, Lise Lotte Hansen, Ole Weis Bjerrum, Hans Carl Hasselbalch, Vasu Punj, Kirsten Grønbæk
This is the first study to compare genome-wide DNA methylation profiles of sorted blood cells from myelofibrosis (MF) patients and healthy controls. We found that differentially methylated CpG sites located to genes involved in 'cancer' and 'embryonic development' in MF CD34+ cells, in 'inflammatory disease' in MF mononuclear cells, and in 'immunological diseases' in MF granulocytes. Only few differentially methylated CpG sites were common among the three cell populations. Mutations in the epigenetic regulators ASXL1 (47%) and TET2 (20%) were not associated with a specific DNA methylation pattern using an unsupervised approach...
July 28, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28754982/recombinant-attenuated-salmonella-typhimurium-with-heterologous-expression-of-the-salmonella-choleraesuis-o-polysaccharide-high-immunogenicity-and-protection
#18
Xinxin Zhao, Qinlong Dai, Dekang Zhu, Mafeng Liu, Shun Chen, Kunfeng Sun, Qiao Yang, Ying Wu, Qingke Kong, Renyong Jia
Non-typhoidal Salmonella are associated with gastrointestinal disease worldwide and invasive disease in Africa. We constructed novel bivalent vaccines through the recombinant expression of heterologous O-antigens from Salmonella Choleraesuis in Salmonella Typhimurium. A recombinant Asd(+) plasmid pCZ1 with the cloned Salmonella Choleraesuis O-antigen gene cluster was introduced into three constructed Salmonella Typhimurium Δasd mutants: SLT11 (ΔrfbP), SLT12 (ΔrmlB-rfbP) and SLT16 (ΔrfbP ∆pagL::TT araCPBAD rfbP)...
July 28, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28753028/general-linker-diversification-approach-to-bivalent-ligand-assembly-generation-of-an-array-of-ligands-for-the-cation-independent-mannose-6-phosphate-receptor
#19
Xiang Fei, Megan E Zavorka, Guillaume Malik, Christopher M Connelly, Richard G MacDonald, David B Berkowitz
A generalized strategy is presented for the rapid assembly of a set of bivalent ligands with a variety of linking functionalities from a common monomer. Herein, an array of phosphatase-inert mannose-6-phosphonate-presenting ligands for the cation-independent-mannose 6-phosphate receptor (CI-MPR) is constructed. Receptor binding affinity varies with linking functionality-the simple amide and 1,5-triazole(tetrazole) being preferred over the 1,4-triazole. This approach is expected to find application across chemical biology, particularly in glycoscience, wherein multivalency often governs molecular recognition...
July 28, 2017: Organic Letters
https://www.readbyqxmd.com/read/28748840/cardiovascular-involvement-in-severe-malaria-a-prospective-study-in-ranchi-jharkhand
#20
Hemant Narayan Ray, Darshit Doshi, Appu Rajan, Amit K Singh, S B Singh, M K Das
BACKGROUND & OBJECTIVES: Malaria is considered as the most important parasitic disease of humans, causing seri- ous illness that can be fatal, if not diagnosed and treated immediately. It is a multisystem disorder affecting nearly every system of the body. The aim of the present study was to evaluate the involvement of cardiovascular system in severe malaria using non-invasive methods. METHODS: This prospective study was conducted on patients of severe malaria who were admitted between June and November 2015 in the Department of Medicine, Rajendra Institute of Medical Sciences and Hospital, Ranchi, Jharkhand, India...
April 2017: Journal of Vector Borne Diseases
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