A role for tumor necrosis factor-alpha in remodeling the splenic marginal zone during Leishmania donovani infection.

The development of secondary lymphoid organs is a highly regulated process, mediated by tumor necrosis factor (TNF) family cytokines. In contrast, the mechanisms controlling changes in lymphoid architecture that occur during infectious disease are poorly understood. Here we demonstrate that during infection with Leishmania donovani, the marginal zone of mice undergoes extensive remodeling, similar in extent to developmental abnormalities in mice lacking some TNF family cytokines. This process is selective, comprising a dramatic and rapid loss of marginal zone macrophages (MZMs). As a functional consequence, lymphocyte traffic into the white pulp is impaired during chronic leishmaniasis. Significantly, MZMs were preserved in L. donovani-infected B6.TNF-alpha(-/-) mice or mice that received anti-TNF-alpha antibodies, whereas studies in CD8(+) T-cell-deficient mice and in mice lacking functional CD95L, excluded a direct role for either cytotoxic T lymphocyte activity or CD95-mediated apoptosis in this process. Loss of MZMs was independent of parasite burden, yet could be partially prevented by chemotherapy, which in turn reduced endogenous TNF-alpha levels. This is the first report of an infectious agent causing selective and long-lasting changes to the marginal zone via TNF-alpha-mediated mechanisms, and illustrates that those cytokines involved in establishing lymphoid architecture during development, may also play a role in infection-induced lymphoid tissue remodeling

Pengembangan kualitas sumber daya manusia di Sentra Industri Sanitair Kelurahan Karangbesuki Kecamatan Sukun Malang

INDONESIA: Dalam prakteknya, penelitian ini dilakukan di Sentra Industri Sanitair yang berada di kelurahan Karangbesuki Malang. Sentra industri ini cukup berkembang di kota Malang, yang perkembangannya meliputi beberapa aspek, baik aspek usahanya maupun aspek tenaga kerjanya (sumber daya manusia). Dan penelitian ini bertujuan untuk mendeskripsikan kualitas sumber daya manusia di industri sanitair Karangbesuki dan strategi yang diterapkan dalam pengembangan kualitas sumber daya manusia di Sentra Industri Sanitair Karangbesuki Jenis penelitian ini adalah penelitian kualitatif deskriftif. Penelitian dilaksanakan di Sentra Industri Sanitair Kelurahan Karangbesuki Kecamatan Sukun Malang dengan metode pengumpulan data menggunakan observasi, wawancara dan dokumentasi, teknik analisis data pelaksanaanya ada tiga tahapan yaitu penyederhanaan, penyajian data, penarikan dan kesimpulan. Hasil penelitian di lapangan bahwa dalam pengembangan kualiatas sumber daya manusia sentra industri sanitair telah ditemukan strategi dalam pengembangan kualiatas sumber daya manusia dalam strategi pengembangan sumber daya manusia menggunakan metode pembelajaran langsung dan metode on the job training dengan bimbingan salah seorang karyawan yang pengetahuan dan kemampuannya sudah cukup mumpuni dalam bidang tersebut, namun yang disayangkan dalam pengembangan sumber daya manusia di sentra industri sanitair ini tidak adanya pelatihan khusus dan berkala untuk beberapa karyawan yang tidak memiliki kemampuan dalam bidang kerajinan. ENGLISH: In practice, this research conducted at the Sanitary Industry Centers located in the village of Malang Karangbesuki. Industrial district is quite developed in the city of Malang, the development includes several aspects, both aspects of its business and labor aspects (human resources). And this study aimed to describe the quality of human resources in the industry sanitair Karangbesuki and strategies applied in the development of human resources in the Sanitary Industry Centers Karangbesuki. This research is descriptive qualitative research. The experiment was conducted at the Center for Urban Sanitary Industry Karangbesuki Breadfruit District of Malang with the data collection method using observations, interviews and documentation, implementation of data analysis techniques, there are three stages namely simplification, data presentation, drawing and conclusions. The results of research in the field that the human resource development kualiatas sanitair industrial centers have been found in the strategy of human resource development kualiatas in human resource development strategy using the direct method and the method of learning on the job training with the guidance of one of the employees who had enough knowledge and ability qualified in the field, but the unfortunate in the development of human resources in the industrial district sanitair absence of special and regular training for some employees who do not have the ability in the field of handicrafts

Discrimination of water quality monitoring sites in River Vouga using a mixed-effect state space model

The surface water quality monitoring is an important concern of public organizations due to its relevance to the public health. Statistical methods are taken as consistent and essential tools in the monitoring procedures in order to prevent and identify environmental problems. This work presents the study case of the hydrological basin of the river Vouga, in Portugal. The main goal is discriminate the water monitoring sites using the monthly dissolved oxygen concentration dataset between January 2002 and May 2013. This is achieved through the extraction of trend and seasonal components in a linear mixed-effect state space model. The parameters estimation is performed with both maximum likelihood method and distribution-free estimators in a two-step procedure. The application of the Kalman smoother algorithm allows to obtain predictions of the structural components as trend and seasonality. The water monitoring sites are discriminated through the structural components by a hierarchical agglomerative clustering procedure. This procedure identified different homogenous groups relatively to the trend and seasonality components and some characteristics of the hydrological basin are presented in order to support the results

High-throughput 18K SNP array to assess genetic variability of the main grapevine cultivars from Sicily

The viticulture of Sicily, for its vocation, is one of the most important and ancient forms in Italy. Autochthonous grapevine cultivars, many of which known throughout the world, have always been cultivated in the island from many centuries. With the aim to preserve this large grapevine diversity, previous studies have already started to assess the genetic variability among the Sicilian cultivars by using morphological and microsatellite markers. In this study, simple sequence repeat (SSR) were utilized to verify the true-to-typeness of a large clone collection (101) belonging to 21 biotypes of the most 10 cultivated Sicilian cultivars. Afterwards, 42 Organization Internationale de la Vigne et du Vin (OIV) descriptors and a high-throughput single nucleotide polymorphism (SNP) genotyping array (Vitis18kSNP) were applied to assess genetic variability among cultivars and biotypes of the same cultivar. Ampelographic traits and high-throughput SNP genotyping platforms provided an accuracy estimation of genetic diversity in the Sicilian germplasm, showing the relationships among cultivars by cluster and multivariate analyses. The large SNP panel defined sub-clusters unable to discern among biotypes, previously classified by ampelographic analysis, belonging to each cultivar. These results suggested that a very large number of SNP did not cover the genome regions harboring few morphological traits. Genetic structure of the collection revealed a clear optimum number of groups for K = 3, clustering in the same group a significant portion of family-related genotypes. Parentage analysis highlighted significant relationships among Sicilian grape cultivars and Sangiovese, as already reported, but also the first evidences of the relationships between Nero d’Avola and both Inzolia and Catarratto. Finally, a small panel of highly informative markers (12 SNPs) allowed us to isolate a private profile for each Sicilian cultivar, providing a new tool for cultivar identification

Revisiting the B-cell compartment in mouse and humans: more than one B-cell subset exists in the marginal zone and beyond.

International audienceABSTRACT: The immunological roles of B-cells are being revealed as increasingly complex by functions that are largely beyond their commitment to differentiate into plasma cells and produce antibodies, the key molecular protagonists of innate immunity, and also by their compartmentalisation, a more recently acknowledged property of this immune cell category. For decades, B-cells have been recognised by their expression of an immunoglobulin that serves the function of an antigen receptor, which mediates intracellular signalling assisted by companion molecules. As such, B-cells were considered simple in their functioning compared to the other major type of immune cell, the T-lymphocytes, which comprise conventional T-lymphocyte subsets with seminal roles in homeostasis and pathology, and non-conventional T-lymphocyte subsets for which increasing knowledge is accumulating. Since the discovery that the B-cell family included two distinct categories - the non-conventional, or extrafollicular, B1 cells, that have mainly been characterised in the mouse; and the conventional, or lymph node type, B2 cells - plus the detailed description of the main B-cell regulator, FcγRIIb, and the function of CD40+ antigen presenting cells as committed/memory B-cells, progress in B-cell physiology has been slower than in other areas of immunology. Cellular and molecular tools have enabled the revival of innate immunity by allowing almost all aspects of cellular immunology to be re-visited. As such, B-cells were found to express "Pathogen Recognition Receptors" such as TLRs, and use them in concert with B-cell signalling during innate and adaptive immunity. An era of B-cell phenotypic and functional analysis thus began that encompassed the study of B-cell microanatomy principally in the lymph nodes, spleen and mucosae. The novel discovery of the differential localisation of B-cells with distinct phenotypes and functions revealed the compartmentalisation of B-cells. This review thus aims to describe novel findings regarding the B-cell compartments found in the mouse as a model organism, and in human physiology and pathology. It must be emphasised that some differences are noticeable between the mouse and human systems, thus increasing the complexity of B-cell compartmentalisation. Special attention will be given to the (lymph node and spleen) marginal zones, which represent major crossroads for B-cell types and functions and a challenge for understanding better the role of B-cell specificities in innate and adaptive immunology

Regulation of immunity during visceral Leishmania infection

Unicellular eukaryotes of the genus Leishmania are collectively responsible for a heterogeneous group of diseases known as leishmaniasis. The visceral form of leishmaniasis, caused by L. donovani or L. infantum, is a devastating condition, claiming 20,000 to 40,000 lives annually, with particular incidence in some of the poorest regions of the world. Immunity to Leishmania depends on the development of protective type I immune responses capable of activating infected phagocytes to kill intracellular amastigotes. However, despite the induction of protective responses, disease progresses due to a multitude of factors that impede an optimal response. These include the action of suppressive cytokines, exhaustion of specific T cells, loss of lymphoid tissue architecture and a defective humoral response. We will review how these responses are orchestrated during the course of infection, including both early and chronic stages, focusing on the spleen and the liver, which are the main target organs of visceral Leishmania in the host. A comprehensive understanding of the immune events that occur during visceral Leishmania infection is crucial for the implementation of immunotherapeutic approaches that complement the current anti-Leishmania chemotherapy and the development of effective vaccines to prevent disease.The research leading to these results has received funding from the European Community’s Seventh Framework Programme under grant agreement No.602773 (Project KINDRED). VR is supported by a post-doctoral fellowship granted by the KINDReD consortium. RS thanks the Foundation for Science and Technology (FCT) for an Investigator Grant (IF/00021/2014). This work was supported by grants to JE from ANR (LEISH-APO, France), Partenariat Hubert Curien (PHC) (program Volubilis, MA/11/262). JE acknowledges the support of the Canada Research Chair Program

Improving COVID-19 vaccine uptake among Black populations : a systematic review of strategies

Given the growing body of evidence on COVID-19 vaccine hesitancy among Black populations, the aim of this systematic review was to identify the interventions and strategies used to improve COVID-19 vaccine confidence and uptake among Black populations globally. To identify relevant studies, we conducted a systematic review of the literature based on a systematic search of 10 electronic databases: MEDLINE, Embase, PsycINFO, CINAHL, Scopus, Cochrane Library, Web of Science, Sociological Abstracts, Dissertations and Theses Global, and SocINDEX. We screened a total of 1728 records and included 14 peer-reviewed interventional studies that were conducted to address COVID-19 vaccine hesitancy among Black populations. A critical appraisal of the included studies was performed using the Newcastle-Ottawa Quality Assessment Scale. The intervention strategies for increasing COVID-19 vaccine uptake were synthesized into three major categories: communication and information-based interventions, mandate-based interventions, and incentive-based interventions. Interventions that incorporated communication, community engagement, and culturally inclusive resources significantly improved vaccine uptake among Black populations, while incentive- and mandate-based interventions had less impact. Overall, this systematic review revealed that consideration of the sociocultural, historical, and political contexts of Black populations is important, but tailored interventions that integrate culture-affirming strategies are more likely to decrease COVID-19 vaccine hesitancy and increase uptake among Black populations

Immune engineering enhances H7N9 vaccine immunogenicity by regulatory T cell epitope deletion in hemagglutinin

Avian-origin H7N9 influenza is a novel influenza group A virus that emerged in humans in China in 2013. H7N9 influenza hemagglutinin (HA) elicits weak neutralizing antibody responses in natural infection and vaccination. Limited helper T cell response could explain the poor immunogenicity observed [1]. We hypothesize a T cell epitope in H7-HA stimulates regulatory T cells (Tregs) capable of suppressing crucial signals needed for protective antibody production. Furthermore, deletion of the epitope without perturbing neutralizing B cell epitope structures may increase H7-HA immunogenicity to produce an optimized vaccine. Immunoinformatics tools were used to identify H7N9 class II HLA epitopes with high potential to cross-react with Tregs educated on human antigens. In peripheral blood leukocyte cultures, H7N9 epitopes with significant human homology expanded CD4+CD25+FoxP3+CD39+ Tregs and reduced IFNγ secretion when co-incubated with other H7N9 epitopes with low potential cross-reactivity [2]. We applied this finding to design an antigenically improved H7-HA based on Anhui/01 by introducing three modifications to recombinant HA (rHA) that delete a highly conserved Treg activating epitope. Engineered rHA (Opt1 rH7-HA) demonstrated both preserved antigenicity and improved immunogenicity in humanized mice. Monoclonal antibodies raised against wild type H7-HA recognized Opt1 rH7-HA with affinity equivalent to the wild type protein, suggesting that modifications did not induce significant structural perturbations. Similarly, human polyclonal sera demonstrated identical binding profiles against Opt1 and wild type rH7-HA. Vaccination of immunodeficient mice reconstituted with human PBMCs (N=8) using non-adjuvanted Opt1 rH7-HA stimulated higher anti-H7-HA IgG titers and higher frequencies of anti-H7-HA plasma cells than mice immunized with wild-type protein. In a related study, HLA-DR3 transgenic mice were immunized with Alum-formulated H7N9 virus-like particles containing either Opt1 or wild-type H7-HA and hemagglutinin inhibition (HAI) titers were measured. Opt1 rH7-HA stimulated protective levels of HAI antibodies suggesting that modifications of H7-HA preserved neutralizing epitopes. The Opt1 H7N9 VLP vaccine raised HAI antibodies sooner and at lower doses than wild-type vaccine. Epitope-driven approaches to vaccine design that carefully consider T cell subsets primed in immunization promise to enhance vaccine efficacy. 1. De Groot AS, Ardito M, Terry F, Levitz L, Ross T, Moise L, Martin W. Low immunogenicity predicted for emerging avian-origin H7N9: implication for influenza vaccine design. Hum Vaccin Immunother. 2013 May;9(5):950-6. 2. Liu R, Moise L, Tassone R, Gutierrez AH, Terry FE, Sangare K, Ardito MT, Martin WD, De Groot AS. H7N9 T-cell epitopes that mimic human sequences are less immunogenic and may induce Treg-mediated tolerance. Hum Vaccin Immunother. 2015;11(9):2241-52

Antimicrobial resistance profiling of Salmonella enterica distinct serotypes isolated from pork in São Paulo

Salmonellosis still is one of the most important worldwide zoonosis due to its high endemicity, mortality, and difficulty in control (Stevens et al., 2009). In the São Paulo city, different realities regarding good production practices and quality control of animal products coexists, especially when considering points of direct consumer sales. The aim of this study was to evaluate the antimicrobial resistance profiles of Salmonella enterica distinct serotypes isolated from pork in São Paulo

Highly Frequent Mutations in Negative Regulators of Multiple Virulence Genes in Group A Streptococcal Toxic Shock Syndrome Isolates

Streptococcal toxic shock syndrome (STSS) is a severe invasive infection characterized by the sudden onset of shock and multiorgan failure; it has a high mortality rate. Although a number of studies have attempted to determine the crucial factors behind the onset of STSS, the responsible genes in group A Streptococcus have not been clarified. We previously reported that mutations of csrS/csrR genes, a two-component negative regulator system for multiple virulence genes of Streptococcus pyogenes, are found among the isolates from STSS patients. In the present study, mutations of another negative regulator, rgg, were also found in clinical isolates of STSS patients. The rgg mutants from STSS clinical isolates enhanced lethality and impaired various organs in the mouse models, similar to the csrS mutants, and precluded their being killed by human neutrophils, mainly due to an overproduction of SLO. When we assessed the mutation frequency of csrS, csrR, and rgg genes among S. pyogenes isolates from STSS (164 isolates) and non-invasive infections (59 isolates), 57.3% of the STSS isolates had mutations of one or more genes among three genes, while isolates from patients with non-invasive disease had significantly fewer mutations in these genes (1.7%). The results of the present study suggest that mutations in the negative regulators csrS/csrR and rgg of S. pyogenes are crucial factors in the pathogenesis of STSS, as they lead to the overproduction of multiple virulence factors