Infections with Plasmodium falciparum during pregnancy affect VAR2CSA DBL-5 domain-specific T cell cytokine responses

Background: Current knowledge of human immunological responses to pregnancy-associated malaria-specific Plasmodium falciparum protein VAR2CSA concerns almost exclusively B cell-driven antibody-mediated activity. Knowledge of VAR2CSA-specific T cell-mediated activity is minimal by comparison, with only a single published report of a study investigating VAR2CSA-derived peptide-specific T cell responses. The study described here represents an attempt to redress this balance. Methods: Within the framework of a cohort study of 1037 pregnant Beninese, sub-groups were selected on the basis of the documented presence/absence of infection with P. falciparum and conducted detailed immunological assessments both at inclusion into the study and at delivery. Peripheral blood mononuclear cells were isolated, stimulated in vitro, and VAR2CSA DBL-5 domain-specific, IFN-gamma-secreting T-cell frequencies and cytokine responses were quantified using flow cytometric techniques. Multivariate analyses were used to determine primarily whether the T cell-mediated DBL5-specific activity measured was associated with infection by P. falciparum adjusted for gravidity, anaemia and other cofactors. Results: Infections with P. falciparum detected at inclusion were associated with enhanced non-specific TNF responses, whilst diminished non-specific and DBL-5-specific IL-10 responses were associated with infections detected at delivery. Infections during pregnancy led to enhanced non-specific and DBL-5-specific IFN-gamma responses detectable at delivery but to concomitantly lower DBL-5-specific CD8+ IFN-gamma responses. Prospective assessments indicated that non-specific pro-inflammatory responses detectable at inclusion in the study were associated with the occurrence of infections subsequently during pregnancy. Conclusions: The findings represent a first step in elucidating the quantity and quality of cellular immunological responses to VAR2CSA, which will help in the development of the primary vaccine candidate for prevention of pregnancy-associated malaria

Findings of the Survey on Prevention of Plagiarism in Lithuanian Research Journals

AbstractAt the end of 2011, the Association of Lithuanian Serials initiated a survey, which aimed to ascertain whether Lithuanian journal editors, reviewers and authors encountered plagiarism, self-plagiarism and how they understood originality of a paper. Additionally, the survey looked at methods used for plagiarism prevention by editors and reviewers as well as ways, in which editors managed issues related to plagiarism. The survey suggests that no unanimous decision exists regarding the originality of a manuscript and that editors expect reviewers to identify plagiarism with little use of technologies. While answering to survey questions, respondents provided numerous comments. This demonstrates that plagiarism is a burning issue and scientific misconduct policy is needed in Lithuania. The survey was conducted during the period when the Lithuanian Research Council initiated the procedure for establishing the Ombudsman position. The Lithuanian Research Council funded several projects in 2012 and 2013, the aim of which was to familiarise the Lithuanian academic community with plagiarism prevention technologies and ethical aspects in academic publishing. The projects administrated by the Association of Lithuanian Serials provide research journal publishers and researchers related to journal publishing with a possibility of using CrossCheck system and discussing editorial policies

Ezrin interacts with the SARS coronavirus spike protein and restrains infection at the entry stage

© 2012 Millet et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Background: Entry of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) and its envelope fusion with host cell membrane are controlled by a series of complex molecular mechanisms, largely dependent on the viral envelope glycoprotein Spike (S). There are still many unknowns on the implication of cellular factors that regulate the entry process. Methodology/Principal Findings: We performed a yeast two-hybrid screen using as bait the carboxy-terminal endodomain of S, which faces the cytosol during and after opening of the fusion pore at early stages of the virus life cycle. Here we show that the ezrin membrane-actin linker interacts with S endodomain through the F1 lobe of its FERM domain and that both the eight carboxy-terminal amino-acids and a membrane-proximal cysteine cluster of S endodomain are important for this interaction in vitro. Interestingly, we found that ezrin is present at the site of entry of S-pseudotyped lentiviral particles in Vero E6 cells. Targeting ezrin function by small interfering RNA increased S-mediated entry of pseudotyped particles in epithelial cells. Furthermore, deletion of the eight carboxy-terminal amino acids of S enhanced S-pseudotyped particles infection. Expression of the ezrin dominant negative FERM domain enhanced cell susceptibility to infection by SARS-CoV and S pseudotyped particles and potentiated S-dependent membrane fusion. Conclusions/Significance: Ezrin interacts with SARS-CoV S endodomain and limits virus entry and fusion. Our data present a novel mechanism involving a cellular factor in the regulation of S-dependent early events of infection.This work was supported by the Research Grant Council of Hong Kong (RGC#760208)and the RESPARI project of the International Network of Pasteur Institutes

Shaping gold nanocomposites with tunable optical properties

We report the synthesis of morphological uniform composites using miniemulsions of poly(tert-butyl acrylate) or poly(styrene) containing organically capped gold nanocrystals (NCs). The optical features of such hybrid structures are dominated by plasmonic effects and depend critically on the morphology of the resulting nanocomposite. In particular, we demonstrate the ability to tune the overall optical response in the visible spectral region by varying the Au NCs arrangement within the polymer matrix, and therefore the interparticle plasmon coupling, using Au NCs resulting from the same batch of synthesis. This is a consequence of two well-known effects on the optical properties of Au particles: the variation of the surrounding dielectric refractive index and interparticle plasmonic coupling. The research reported here shows a general strategy to produce optical responsive nanocomposites via control of the morphology of submicrometric polymer particles containing metal nanocrystals and thus is an alternative to the more common strategy of size tuning metal nanoparticles used as nanofillers

Семантичні зміни в лексичному складі російської та української мов

Использование вычислительной техники и радиоэлектроники способствовало формированию специальной группы лексических единиц. Номинация новых явлений и понятий является актуальной проблемой нынешнего этапа развития языка. Изменение семантического наполнения – это один из способов решения данной проблемы. Расширение или сужение семантического объема слов способствует обогащению лексической системы, а именно терминологии.Використання обчислювальної техніки та радіоелектроніки спричинило формування спеціальної групи лексичних одиниць. Номінація нових явищ та понять є актуальною проблемою теперішнього етапу розвитку мови. Зміна семантичного об'єму – це один із засобів вирішення даної проблеми. Звуження або розширення семантичного наповнення сприяє збагаченню лексичної системи, а саме термінології.Using of radio-electronic devices forced the formation of a special group of lexical units. The nomination of new processes and notions is an actual problem of today's language development. Semantic changes of existing units is one of the decisions of the problem. Widening and narrowing of semantic meanings promotes the enrichment of lexical system, especially the system of terminology

High production of pro-inflammatory cytokines by maternal blood mononuclear cells is associated with reduced maternal malaria but increased cord blood infection

BACKGROUND: Increased susceptibility to malaria during pregnancy is not completely understood. Cellular immune responses mediate both pathology and immunity but the effector responses involved in these processes have not been fully characterized. Maternal and fetal cytokine and chemokine responses to malaria at delivery, and their association with pregnancy and childhood outcomes, were investigated in 174 samples from a mother and child cohort from Mozambique. Peripheral and cord mononuclear cells were stimulated with Plasmodium falciparum lysate and secretion of IL-12p70, IFN-gamma, IL-2, IL-10, IL-8, IL-6, IL-4, IL-5, IL-1beta, TNF, TNF-beta was quantified in culture supernatants by multiplex flow cytometry while cellular mRNA expression of IFN-gamma, TNF, IL-2, IL-4, IL-6, IL-10 and IL-13 was measured by quantitative PCR. RESULTS: Higher concentrations of IL-6 and IL-1beta were associated with a reduced risk of P. falciparum infection in pregnant women (p < 0.049). Pro-inflammatory cytokines IL-6, IL-1beta and TNF strongly correlated among themselves (rho > 0.5, p < 0.001). Higher production of IL-1beta was significantly associated with congenital malaria (p < 0.046) and excessive TNF was associated with peripheral infection and placental lesions (p < 0.044). CONCLUSIONS: Complex network of immuno-pathological cytokine mechanisms in the placental and utero environments showed a potential trade-off between positive and negative effects on mother and newborn susceptibility to infection

Roles for Drosophila melanogaster myosin IB in maintenance of enterocyte brush-border structure and resistance to the bacterial pathogen Pseudomonas entomophila

Author Posting. © American Society for Cell Biology, 2007. This article is posted here by permission of American Society for Cell Biology for personal use, not for redistribution. The definitive version was published in Molecular Biology of the Cell 18 (2007): 4625-4636, doi:10.1091/mbc.E07-02-0191.Drosophila myosin IB (Myo1B) is one of two class I myosins in the Drosophila genome. In the larval and adult midgut enterocyte, Myo1B is present within the microvillus (MV) of the apical brush border (BB) where it forms lateral tethers between the MV membrane and underlying actin filament core. Expression of green fluorescent protein-Myo1B tail domain in the larval gut showed that the tail domain is sufficient for localization of Myo1B to the BB. A Myo1B deletion mutation exhibited normal larval gut physiology with respect to food uptake, clearance, and pH regulation. However, there is a threefold increase in terminal deoxynucleotidyl transferase dUTP nick-end labeling-positive enterocyte nuclei in the Myo1B mutant. Ultrastructural analysis of mutant midgut revealed many perturbations in the BB, including membrane tethering defects, MV vesiculation, and membrane shedding. The apical localization of both singed (fascin) and Dmoesin is impaired. BBs isolated from mutant and control midgut revealed that the loss of Myo1B causes the BB membrane and underlying cytoskeleton to become destabilized. Myo1B mutant larvae also exhibit enhanced sensitivity to oral infection by the bacterial pathogen Pseudomonas entomophila, and severe cytoskeletal defects are observed in the BB of proximal midgut epithelial cells soon after infection. Resistance to P. entomophila infection is restored in Myo1B mutant larvae expressing a Myo1B transgene. These results indicate that Myo1B may play a role in the local midgut response pathway of the Imd innate immune response to Gram-negative bacterial infection.This work was supported by National Institutes of Health grants DK-25387 (to M.S.M.), DK-55389 (to Jon Morrow, Yale School of Medicine), and GM-52857 (to L.G.T.) and a research grant from the Crohns and Colitis Foundation of America (to M.S.M.)