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https://www.readbyqxmd.com/read/28934474/human-dna-polymerase-delta-double-mutant-d316a-e318a-interferes-with-dna-mismatch-repair-in-vitro
#1
Dekang Liu, Jane H Frederiksen, Sascha E Liberti, Anne Lützen, Guido Keijzers, Javier Pena-Diaz, Lene Juel Rasmussen
DNA mismatch repair (MMR) is a highly-conserved DNA repair mechanism, whose primary role is to remove DNA replication errors preventing them from manifesting as mutations, thereby increasing the overall genome stability. Defects in MMR are associated with increased cancer risk in humans and other organisms. Here, we characterize the interaction between MMR and a proofreading-deficient allele of the human replicative DNA polymerase delta, PolδD316A;E318A, which has a higher capacity for strand displacement DNA synthesis than wild type Polδ...
September 19, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28934390/protein-phosphatase-1-regulates-huntingtin-exon-1-aggregation-and-toxicity
#2
Joana Branco-Santos, Federico Herrera, Gonçalo M Poças, Yolanda Pires-Afonso, Flaviano Giorgini, Pedro M Domingos, Tiago F Outeiro
Huntington's disease is neurodegenerative disorder caused by a polyglutamine expansion in the N-terminal region of the huntingtin protein (N17). Here, we analysed the relative contribution of each phosphorylatable residue in the N17 region (T3, S13 and S16) towards huntingtin exon 1 (HTTex1) oligomerization, aggregation and toxicity in human cells and Drosophila neurons. We used bimolecular fluorescence complementation to show that expression of single phosphomimic mutations completely abolished HTTex1 aggregation in human cells...
October 1, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28934352/global-reaction-to-the-recent-outbreaks-of-zika-virus-insights-from-a-big-data-analysis
#3
Nicola Luigi Bragazzi, Cristiano Alicino, Cecilia Trucchi, Chiara Paganino, Ilaria Barberis, Mariano Martini, Laura Sticchi, Eugen Trinka, Francesco Brigo, Filippo Ansaldi, Giancarlo Icardi, Andrea Orsi
OBJECTIVE: The recent spreading of Zika virus represents an emerging global health threat. As such, it is attracting public interest worldwide, generating a great amount of related Internet searches and social media interactions. The aim of this research was to understand Zika-related digital behavior throughout the epidemic spreading and to assess its consistence with real-world epidemiological data, using a behavioral informatics and analytics approach. METHODS: In this study, the global web-interest and reaction to the recently occurred outbreaks of the Zika Virus were analyzed in terms of tweets and Google Trends (GT), Google News, YouTube, and Wikipedia search queries...
2017: PloS One
https://www.readbyqxmd.com/read/28934308/devices-and-tasks-involved-in-the-objective-assessment-of-standing-dynamic-balancing-a-systematic-literature-review
#4
Bálint Petró, Alexandra Papachatzopoulou, Rita M Kiss
BACKGROUND: Static balancing assessment is often complemented with dynamic balancing tasks. Numerous dynamic balancing assessment methods have been developed in recent decades with their corresponding balancing devices and tasks. OBJECTIVE: The aim of this systematic literature review is to identify and categorize existing objective methods of standing dynamic balancing ability assessment with an emphasis on the balancing devices and tasks being used. DATA SOURCES: Three major scientific literature databases (Science Direct, Web of Science, PLoS ONE) and additional sources were used...
2017: PloS One
https://www.readbyqxmd.com/read/28934227/hemorrhage-enhances-cytokine-complement-component-3-and-caspase-3-and-regulates-micrornas-associated-with-intestinal-damage-after-whole-body-gamma-irradiation-in-combined-injury
#5
Juliann G Kiang, Joan T Smith, Marsha N Anderson, Thomas B Elliott, Paridhi Gupta, Nagaraja S Balakathiresan, Radha K Maheshwari, Barbara Knollmann-Ritschel
Hemorrhage following whole-body γ-irradiation in a combined injury (CI) model increases mortality compared to whole-body γ-irradiation alone (RI). The decreased survival in CI is accompanied by increased bone marrow injury, decreased hematocrit, and alterations of miRNA in the kidney. In this study, our aim was to examine cytokine homeostasis, susceptibility to systemic bacterial infection, and intestinal injury. More specifically, we evaluated the interleukin-6 (IL-6)-induced stress proteins including C-reactive protein (CRP), complement 3 (C3), Flt-3 ligand, and corticosterone...
2017: PloS One
https://www.readbyqxmd.com/read/28934168/role-of-the-genes-of-type-vi-secretion-system-in-virulence-of-rice-bacterial-brown-stripe-pathogen-acidovorax-avenae-subsp-avenae-strain-rs-2
#6
Md Mahidul Islam Masum, Yingzi Yang, Bin Li, Ogunyemi Solabomi Olaitan, Jie Chen, Yang Zhang, Yushi Fang, Wen Qiu, Yanli Wang, Guochang Sun
The Type VI secretion system (T6SS) is a class of macromolecular machine that is required for the virulence of gram-negative bacteria. However, it is still not clear what the role of T6SS in the virulence of rice bacterial brown stripe pathogen Acidovorax avenae subsp. avenae (Aaa) is. The aim of the current study was to investigate the contribution of T6SS in Aaa strain RS2 virulence using insertional deletion mutation and complementation approaches. This strain produced weak virulence but contains a complete T6SS gene cluster based on a genome-wide analysis...
September 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28934165/salmonella-o48-serum-resistance-is-connected-with-the-elongation-of-the-lipopolysaccharide-o-antigen-containing-sialic-acid
#7
Aleksandra Pawlak, Jacek Rybka, Bartłomiej Dudek, Eva Krzyżewska, Wojciech Rybka, Anna Kędziora, Elżbieta Klausa, Gabriela Bugla-Płoskońska
Complement is one of the most important parts of the innate immune system. Some bacteria can gain resistance against the bactericidal action of complement by decorating their outer cell surface with lipopolysaccharides (LPSs) containing a very long O-antigen or with specific outer membrane proteins. Additionally, the presence of sialic acid in the LPS molecules can provide a level of protection for bacteria, likening them to human cells, a phenomenon known as molecular mimicry. Salmonella O48, which contains sialic acid in the O-antigen, is the major cause of reptile-associated salmonellosis, a worldwide public health problem...
September 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28934145/spectroscopic-electrochemical-and-dft-studies-of-phosphorescent-homoleptic-cyclometalated-iridium-iii-complexes-based-on-substituted-4-fluorophenylvinyl-and-4-methoxyphenylvinylquinolines
#8
Adewale O Adeloye, Malose J Mphahlele, Abolanle S Adekunle, Lydia Rhyman, Ponnadurai Ramasami
This study reports the synthesis and comparative investigation of the substituent effects of a new series of highly luminescent homoleptic tris-cyclometalated iridium(III) complexes of the type [Ir(N(˄)C)₃]. These are based on two ligand type derivatives comprising of 4-fluorophenylvinylquinolines and 4-methoxyphenylvinylquinolines with electron-donating and/or electron-withdrawing groups as aryl substituents at 2-position. The structures of the ligands and their complexes were characterized by means of FT-IR, UV-Vis and NMR spectrometry complemented with photoluminescence and cyclic voltammetry...
September 21, 2017: Materials
https://www.readbyqxmd.com/read/28934066/characterization-of-t-cell-immune-responses-in-clinical-trials-of-the-candidate-rts-s-malaria-vaccine
#9
Philippe Moris, Erik Jongert, Robbert G van der Most
The candidate malaria vaccine RTS,S has demonstrated 45.7% efficacy over 18 months against all clinical disease in a phase-III field study of African children. RTS,S targets the circumsporozoite protein (CSP), which is expressed on the Plasmodium sporozoite during the pre-erythrocyte stage of its life-cycle; the stage between mosquito bite and liver infection. Early in the development of RTS,S, it was recognized that CSP-specific cell-mediated immunity (CMI) was required to complement CSP-specific antibody-mediated immunity...
September 21, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28933919/re-chinese-tcm-renaissance-and-the-global-movement-for-integrative-health-and-medicine-by-weeks-j-altern-complement-med-2017-23-79-81
#10
Arthur Yin Fan, Sarah Faggert
No abstract text is available yet for this article.
September 21, 2017: Journal of Alternative and Complementary Medicine: Research on Paradigm, Practice, and Policy
https://www.readbyqxmd.com/read/28933846/inhibition-of-calcium-dependent-protein-kinase-1-cdpk1-by-pyrazolopyrimidine-analogs-decreases-establishment-and-reoccurrence-of-central-nervous-system-disease-by-toxoplasma-gondii
#11
Florentine U Rutaganira, Jennifer Barks, Mary Savari Dhason, Qiuling Wang, Michael Steven Lopez, Shaojun Long, Joshua B Radke, Nathaniel G Jones, Amarendar R Maddirala, James W Janetka, Majida El Bakkouri, Raymond Hui, Kevan M Shokat, L David Sibley
Calcium dependent protein kinase 1 (CDPK1) is an essential enzyme in the opportunistic pathogen Toxoplasma gondii. CDPK1 controls multiple processes that are essential to the intracellular replicative cycle of T. gondii including secretion of adhesins, motility, invasion, and egress. Remarkably, CDPK1 contains a small glycine gatekeeper residue in the ATP binding pocket making it sensitive to ATP-competitive inhibitors with bulky substituents that complement this expanded binding pocket. Here we explored structure-activity relationships of a series of pyrazolopyrimidine inhibitors of CDPK1 with the goals of increasing selectivity over host enzymes, improving anti-parasite potency, and improving metabolic stability...
September 21, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28933676/bringing-humanity-into-view-action-research-with-qatar-s-ambulance-service
#12
Gill Coleman, Liz Wiggins
Purpose The purpose of this paper is to argue for the widening of attention in healthcare improvement efforts, to include an awareness of the humanity of people who work in the sector and an appreciation of the part human connection plays in engagement around good quality work. Theoretical frameworks and research approaches which draw on action-based, interpretive and systemic thinking are proposed, as a complement to current practices. Design/methodology/approach The paper describes the early stages of an action research (AR) project, which used the appreciative inquiry "4D" framework to conduct participative inquiry in Hamad Medical Corporation's ambulance service in Qatar, in which staff became co-researchers...
August 21, 2017: Journal of Health Organization and Management
https://www.readbyqxmd.com/read/28933673/making-history-critical
#13
Mark Learmonth
Purpose The purpose of this paper is to explore a possible discursive history of National Health Service (NHS) "management" (with management, for reasons that will become evident, very much in scare quotes). Such a history is offered as a complement, as well as a counterpoint, to the more traditional approaches that have already been taken to the history of the issue. Design/methodology/approach Document analysis and interviews with UK NHS trust chief executives. Findings After explicating the assumptions of the method it suggests, through a range of empirical sources that the NHS has undergone an era of administration, an era of management and an era of leadership...
August 21, 2017: Journal of Health Organization and Management
https://www.readbyqxmd.com/read/28933663/type-iii-hypersensitivity-reactions-to-a-b-cell-epitope-antigen-are-abrogated-using-a-depot-forming-vaccine-platform
#14
Lisa D MacDonald, Alecia MacKay, Valarmathy Kaliaperumal, Genevieve Weir, Andrea Penwell, Rajkannan Rajagopalan, Joanne Langley, Scott Halperin, Marc Mansour, Marianne M Stanford
Peptide antigens are combined with an adjuvant in order to increase immunogenicity in vivo. The immunogenicity and safety of a RSV vaccine formulated in a novel oil-based platform, DepoVax™ (DPX), was compared to an alum formulation. A peptide B cell epitope derived from RSV small hydrophobic ectodomain (SHe) served as the antigen. Both vaccines induced SHe-specific antibodies after immunization of mice. A single dose of the DPX-based formulation resulted in anti-SHe titres for up to 20 weeks. Boosting with Alum-SHe, but not with DPX-SHe, led to unexpected clinical signs such as decreased activity, cyanosis and drop in body temperature in mice but not in rabbits...
September 21, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28933647/identification-of-regions-responsible-for-the-function-of-the-plant-k-channels-kat1-and-akt2-in-saccharomyces-cerevisiae-and-xenopus-laevis-oocytes
#15
Shunya Saito, Naomi Hoshi, Lalu Zulkifli, Sri Widyastuti, Shinobu Goshima, Ingo Dreyer, Nobuyuki Uozumi
The Arabidopsis K(+) channel KAT1 complements in K(+)-limited medium the growth of the K(+) uptake defective Saccharomyces cerevisiae mutant strain CY162, while another K(+) channel, AKT2, does not. To gain insight into the structural basis for this difference, we constructed 12 recombinant chimeric channels from these two genes. When expressed in CY162, only three of these chimeras fully rescued the growth of CY162 under K(+)-limited conditions. We conclude that the transmembrane core region of KAT1 is important for its activity in S...
September 21, 2017: Channels
https://www.readbyqxmd.com/read/28933634/development-of-a-multiplexed-opsonophagocytic-killing-assay-mopa-for-group-b-streptococcus
#16
Min Joo Choi, Ji Yun Noh, Hee Jin Cheong, Woo Joo Kim, Shun-Mei Lin, Yong Zhi, Jae Hyang Lim, Sangyong Lim, Ho Seong Seo, Joon Young Song
Group B Streptococcus (GBS) is a leading cause of sepsis in infants as well as chorioamnionitis in pregnant women. Opsonophagocytic killing assays (OPAs) are an essential technique in vaccine studies of encapsulated bacteria for estimating serotype-specific functional antibody levels in vitro. Here, we developed a three-fold multiplexed OPA (MOPA) to enable practical, large-scale assessment of GBS vaccine immunogenicity, including against serotypes Ia, III, and V. First, three target bacteria strains resistant to streptomycin, spectinomycin, or kanamycin were generated by natural selection through exposure to increasing antibiotic concentrations...
September 21, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28933277/identification-of-an-interaction-between-a-histidine-kinase-response-regulator-hybrid-protein-and-2-keto-3-deoxy-d-manno-octulosonate-8-phosphate-synthase-in-gluconobacter-oxydans
#17
Cuijuan Yuan, Yangchen Lin, Yushu Ma, Dongzhi Wei
The histidine kinase response regulator hybrid protein was identified as a member of two-component signaling systems in Gluconobacter oxydans by gene annotation, but the function of this protein remains unknown. In this research, its specific interaction with a 2-keto-3-deoxy-D-manno-octulosonate-8-phosphate synthase was screened by yeast two-hybrid assay. The interaction between the two proteins was further identified by GST pull-down assay and bimolecular fluorescence complementation assay in vitro and in vivo, respectively...
September 19, 2017: Protein and Peptide Letters
https://www.readbyqxmd.com/read/28933170/-pcr-diagnosis-of-infectious-diseases
#18
Tomáš Freiberger
The practices based on microbe cultivation are the corner stone of laboratory diagnostics of infectious diseases etiology. However, cultivation-independent molecular methods for microorganism detection are increasingly being used in a routine clinical setting as an important complement to the conventional procedures and, in some cases, they have already become the golden diagnostic standard. The PCR-based methods are used the most frequently.Key words: molecular genetic detection of microorganisms - polymerase chain reaction (PCR)...
2017: Vnitr̆ní Lékar̆ství
https://www.readbyqxmd.com/read/28933003/research-costs-investigated-a-study-into-the-budgets-of-dutch-publicly-funded-drug-related-research
#19
Thea van Asselt, Bram Ramaekers, Isaac Corro Ramos, Manuela Joore, Maiwenn Al, Ivonne Lesman-Leegte, Maarten Postma, Pepijn Vemer, Talitha Feenstra
BACKGROUND: The costs of performing research are an important input in value of information (VOI) analyses but are difficult to assess. OBJECTIVE: The aim of this study was to investigate the costs of research, serving two purposes: (1) estimating research costs for use in VOI analyses; and (2) developing a costing tool to support reviewers of grant proposals in assessing whether the proposed budget is realistic. METHODS: For granted study proposals from the Netherlands Organization for Health Research and Development (ZonMw), type of study, potential cost drivers, proposed budget, and general characteristics were extracted...
September 20, 2017: PharmacoEconomics
https://www.readbyqxmd.com/read/28932632/local-endothelial-complement-activation-reverses-endothelial-quiescence-enabling-t-cell-homing-and-tumor-control-during-t-cell-immunotherapy
#20
Andrea Facciabene, Francesco De Sanctis, Stefano Pierini, Edimara S Reis, Klara Balint, John Facciponte, Jens Rueter, Masahiro Kagabu, Paola Magotti, Evripidis Lanitis, Robert A DeAngelis, Ronald J Buckanovich, Wenchao C Song, John D Lambris, George Coukos
Cancer immunotherapy relies upon the ability of T cells to infiltrate tumors. The endothelium constitutes a barrier between the tumor and effector T cells, and the ability to manipulate local vascular permeability could be translated into effective immunotherapy. Here, we show that in the context of adoptive T cell therapy, antitumor T cells, delivered at high enough doses, can overcome the endothelial barrier and infiltrate tumors, a process that requires local production of C3, complement activation on tumor endothelium and release of C5a...
2017: Oncoimmunology
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