Performance of LBSap Vaccine after Intradermal Challenge with L. infantum and Saliva of Lu. longipalpis: Immunogenicity and Parasitological Evaluation

In the last decade, the search for new vaccines against canine visceral leishmaniasis has intensified. However, the pattern related to immune protection during long periods after experimental infection in vaccine trials is still not fully understood. Herein, we investigated the immunogenicity and parasitological levels after intradermal challenge with Leishmania infantum plus salivary gland extract in dogs immunized with a vaccine composed of L. braziliensis antigens plus saponin as an adjuvant (LBSap vaccine). The LBSap vaccine elicited higher levels of total anti-Leishmania IgG as well as both IgG1 and IgG2. Furthermore, dogs vaccinated had increased levels of lymphocytes, particularly circulating B cells (CD21⁺) and both CD4⁺ and CD8⁺ T lymphocytes. LBSap also elicited an intense in vitro cell proliferation associated with higher levels of CD4⁺ T lymphocytes specific for vaccine soluble antigen and soluble lysate of L. infantum antigen even 885 days after experimental challenge. Furthermore, LBSap vaccinated dogs presented high IFN-γ and low IL-10 and TGF-β1 expression in spleen with significant reduction of parasite load in this tissue. Overall, our results validate the potential of LBSap vaccine to protect against L. infantum experimental infection and strongly support further evaluation of efficiency of LBSap against CVL in natural infection conditions.     

Protist Biodiversity and Biogeography in Lakes From Four Brazilian River–Floodplain Systems

The biodiversity and biogeography of protists inhabiting many ecosystems have been intensely studied using different sequencing approaches, but tropical ecosystems are relatively under‐studied. Here, we sampled planktonic waters from 32 lakes associated with four different river–floodplains systems in Brazil, and sequenced the DNA using a metabarcoding approach with general eukaryotic primers. The lakes were dominated by the largely free‐living Discoba (mostly the Euglenida), Ciliophora, and Ochrophyta. There was low community similarity between lakes even within the same river–floodplain. The protists inhabiting these floodplain systems comprise part of the large and relatively undiscovered diversity in the tropics.     

Metabolomic Profile of the Genus Inula

Plants have a long history as therapeutics in the treatment of human diseases and have been used as source of medicines for ages. Searching for new biologically active natural products, many plants and herbs are screened for natural products with pharmacological activities. In this field, the genus Inula, which comprises more than 100 species, several of them being used in traditional medicine, is very important, especially due to the finding that several of the isolated pure secondary metabolites proved to possess important biological activities. Inula species have been reported as rich sources of sesquiterpene lactones, including eudesmanes, germacranes, guaianes, and dimeric structures, and since 2006 ca. 400 secondary metabolites, including more than 100 new natural products, some of them with relevant pharmacological activities, have been identified. Herein, we critically compile and update the information regarding the types of secondary metabolites found in the genus Inula and the progress in their isolation.     

IFN-γ Production to Leishmania Antigen Supplements the Leishmania Skin Test in Identifying Exposure to L. braziliensis Infection

Background

Cutaneous leishmaniasis due to L. braziliensis (CL) is characterized by a positive delayed type hypersensitivity test (DTH) leishmania skin test (LST) and high IFN-γ production to soluble leishmania antigen (SLA). The LST is used for diagnosis of CL and for identification of individuals exposed to leishmania infection but without disease. The main aim of the present study was to identify markers of exposure to L. braziliensis infection.

Methodolgy/Principal Findings

This cohort study enrolled 308 household contacts (HC) of 76 CL index cases. HC had no active or past history of leishmaniasis. For the present cross-sectional study cytokines and chemokines were determined in supernatants of whole blood culture stimulated with SLA. Of the 308 HC, 36 (11.7%) had a positive LST but in these IFN-γ was only detected in 22 (61.1%). Moreover of the 40 HC with evidence of IFN-γ production only 22 (55%) had a positive LST. A total of 54 (17.5%) of 308 HC had specific immune response to SLA. Only a moderate agreement (Kappa = 0.52; 95% CI: 0.36–0.66) was found between LST and IFN-γ production. Moreover while enhancement of CXCL10 in cultures stimulated with SLA was observed in HC with DTH+ and IFN-γ+ and in patients with IFN-γ⁺ and DTH⁻, no enhancement of this chemokine was observed in supernatants of cells of HC with DTH⁺ and IFN-γ⁻.

Conclusions/Significance

This study shows that in addition of LST, the evaluation of antigen specific IFN-γ production should be performed to determine evidence of exposure to leishmania infection. Moreover it suggests that in some HC production of IFN-γ and CXCL10 are performed by cells not involved with DTH reaction.     

Computer Simulation of Magnetic Resonance Angiography Imaging: Model Description and Validation

With the development of medical imaging modalities and image processing algorithms, there arises a need for methods of their comprehensive quantitative evaluation. In particular, this concerns the algorithms for vessel tracking and segmentation in magnetic resonance angiography images. The problem can be approached by using synthetic images, where true geometry of vessels is known. This paper presents a framework for computer modeling of MRA imaging and the results of its validation. A new model incorporates blood flow simulation within MR signal computation kernel. The proposed solution is unique, especially with respect to the interface between flow and image formation processes. Furthermore it utilizes the concept of particle tracing. The particles reflect the flow of fluid they are immersed in and they are assigned magnetization vectors with temporal evolution controlled by MR physics. Such an approach ensures flexibility as the designed simulator is able to reconstruct flow profiles of any type. The proposed model is validated in a series of experiments with physical and digital flow phantoms. The synthesized 3D images contain various features (including artifacts) characteristic for the time-of-flight protocol and exhibit remarkable correlation with the data acquired in a real MR scanner. The obtained results support the primary goal of the conducted research, i.e. establishing a reference technique for a quantified validation of MR angiography image processing algorithms.     

Polymorphisms in the TNFA and IL6 Genes Represent Risk Factors for Autoimmune Thyroid Disease

Background

Autoimmune thyroid disease (AITD) comprises diseases including Hashimoto''s thyroiditis and Graves'' disease, both characterized by reactivity to autoantigens causing, respectively, inflammatory destruction and autoimmune stimulation of the thyroid-stimulating hormone receptor. AITD is the most common thyroid disease and the leading form of autoimmune disease in women. Cytokines are key regulators of the immune and inflammatory responses; therefore, genetic variants at cytokine-encoding genes are potential risk factors for AITD.

Methods

Polymorphisms in the IL6-174 G/C (rs1800795), TNFA-308 G/A (rs1800629), IL1B-511 C/T (rs16944), and IFNGR1-56 T/C (rs2234711) genes were assessed in a case-control study comprising 420 Hashimoto''s thyroiditis patients, 111 Graves'' disease patients and 735 unrelated controls from Portugal. Genetic variants were discriminated by real-time PCR using TaqMan SNP genotyping assays.

Results

A significant association was found between the allele A in TNFA-308 G/A and Hashimoto''s thyroiditis, both in the dominant (OR = 1.82, CI = 1.37–2.43, p-value = 4.4×10⁻⁵) and log-additive (OR = 1.64, CI = 1.28–2.10, p-value = 8.2×10⁻⁵) models. The allele C in IL6-174 G/C is also associated with Hashimoto''s thyroiditis, however, only retained significance after multiple testing correction in the log-additive model (OR = 1.28, CI = 1.06–1.54, p-value = 8.9×10⁻³). The group with Graves'' disease also registered a higher frequency of the allele A in TNFA-308 G/A compared with controls both in the dominant (OR = 1.85, CI = 1.19–2.87, p-value = 7.0×10⁻³) and log-additive (OR = 1.69, CI = 1.17–2.44, p-value = 6.6×10⁻³) models. The risk for Hashimoto''s thyroiditis and Graves'' disease increases with the number of risk alleles (OR for two risk alleles is, respectively, 2.27 and 2.59).

Conclusions

This study reports significant associations of genetic variants in TNFA and IL6 with the risk for AITD, highlighting the relevance of polymorphisms in inflammation-related genes in the etiopathogenesis of AITD.     

Global patterns in anuran–prey networks: structure mediated by latitude

Life on Earth is supported by an infinite number of interactions among organisms. Species interactions in these networks are influenced by latitude, evolutionary history and species traits. We performed a global‐scale literature analysis to build up a database of interactions between anuran communities and their preys, from a wide range of geographical areas, using a network approach. For this purpose, we compiled a total of 55 weighted anuran–prey interaction networks, 39 located in the tropics and 16 in temperate areas. We tested the influence of latitude, as well as anuran taxonomic, functional and phylogenetic richness on network metrics. We found that anuran–prey networks are not nested, exhibit low complementary specialization and modularity and high connectance when compared to other types of networks. The main effects on network metrics were related to latitude, followed by anuran taxonomic, functional and phylogenetic richness, a pattern similar to the emerging in mutualistic networks. Our study is the first integrated analysis of the structural patterns in anuran–prey antagonistic interaction networks in different parts of the world. We suggest that different processes, mediated mainly by latitude, are modeling the architecture of anuran–prey networks across the globe.