StreptInCor: A Candidate Vaccine Epitope against S. pyogenes Infections Induces Protection in Outbred Mice

Infection with Streptococcus pyogenes (S. pyogenes) can result in several diseases, particularly in children. S. pyogenes M protein is the major virulence factor, and certain regions of its N-terminus can trigger autoimmune sequelae such as rheumatic fever in susceptible individuals with untreated group A streptococcal pharyngitis. In a previous study, we utilized a large panel of human peripheral blood cells to define the C-terminal protective epitope StreptInCor (medical identity), which does not induce autoimmune reactions. We recently confirmed the results in HLA-transgenic mice. In the present study, we extended the experimental assays to outbred animals (Swiss mice). Herein, we demonstrate high titers of StreptInCor-specific antibodies, as well as appropriate T-cell immune responses. No cross-reaction to cardiac myosin was detected. Additionally, immunized Swiss mice exhibited 87% survival one month after challenge with S. pyogenes. In conclusion, the data presented herein reinforce previous results in humans and animals and further emphasize that StreptInCor could be an effective and safe vaccine for the prevention of S. pyogenes infections.     

Slow clearance of Plasmodium vivax with chloroquine amongst children younger than six months of age in the Brazilian Amazon

Plasmodium vivax is the most widespread parasite causing malaria, being especially prevalent in the Americas and Southeast Asia. Children are one of the most affected populations, especially in highly endemic areas. However, there are few studies evaluating the therapeutic response of infants with vivax malaria. This study retrospectively evaluated the parasitaemia clearance in children diagnosed with vivax malaria during the first five days of exclusive treatment with chloroquine (CQ). Infants aged less than six months old had a significantly slower parasitaemia clearance time compared to the group of infants and children between six months and 12 years old (Kaplan-Meier survival analysis; Wilcoxon test; p = 0.004). The impaired clearance of parasitaemia in younger children with vivax malaria is shown for the first time in Latin America. It is speculated that CQ pharmacokinetics in young children with vivax malaria is distinct, but this specific population may also allow the detection of CQ-resistant parasites during follow-up, due to the lack of previous immunity.     

Two species of swimming crabs of the genus Achelous (Crustacea,Brachyura): environmental requirements determining the niche

Some holoplanktonic species are cosmopolitan and have continuous distribution in the world’s oceans. For most of these species it is not clear whether there is unhampered gene flow between far distant populations or they represent a complex of cryptic species. In the present study we investigated genetic diversity of the cosmopolitan chaetognath Eukrohnia hamata in order to identify its spatial structure. DNA-barcode fragment of the mitochondrial COI gene was determined and analyzed for E. hamata specimens collected in the Arctic Ocean, Atlantic Ocean, and Atlantic sector of the Southern Ocean. Five lineages were determined by the phylogenetic analysis with robust statistical support. Three lineages: Antarctic (Eh-1), Subantarctic (Eh-2), and Arctic (Eh-3) had significant genetic differences and were geographically separated. Two other lineages: Eh-4 and Eh-5, that had the smallest genetic difference, were observed together in tropical waters, but they were geographically separated from the other lineages. We suppose that geographical distribution of most of the E. hamata lineages is shaped by the large-scale oceanic fronts, considered as biogeographic boundaries for numerous zooplankton species. Genetic homogeneity of Arctic, Subantarctic, and Antarctic lineages was also shown, each within its regions of inhabit.     

Freshwater sponge spicules: a new agent of ocular pathology

In a recent outbreak of human ocular injuries that occurred in the town of Araguatins, at the right bank of Araguaia river, state of Tocantins, Brazil, along the low water period of 2005, two patients (8 and 12-year-old boys) presented inferior adherent leukoma in the left eye (OS), and peripherical uveites, with snowbanking in the inferior pars plana. The third one (13-year-old girl) showed posterior uveites in OS, also with snowbanking. Histopathological analysis of lensectomy material from the three patients and vitrectomy from the last one revealed several silicious spicules (gemmoscleres) of the freshwater sponges Drulia uruguayensis and D. ctenosclera. This work brings material evidences, for the first time in the literature, that freshwater sponge spicules may be a surprising new etiological agent of ocular pathology.     

Prospecting candidate SNPs for backfat in Canchim beef cattle

Canchim is a composite cattle breed developed in Brazil for beef production. One of the breeding objectives is to increase fat deposition. QTLs for fat thickness and/or marbling have been reported on BTA4 and BTA14. The IGFBP3 and DDEF1 genes, mapped to BTA4 and BTA14, respectively, affect adipogenesis. We looked for SNPs in the IGFBP3 and DDEF1 genes that could be associated with backfat thickness in Canchim beef cattle. For SNP identification, sires with the highest accuracy were ranked according to expected breeding value for fat thickness; the 12 extremes (six sires with the highest and six with the lowest expected breeding value for the trait) were chosen. Six regions of the IGFBP3 and 14 regions of the DDEF1 were sequenced using the Sanger method. Nine SNPs were identified in IGFBP3 and 76 in the DDEF1. After an initial analysis, two SNPs were selected to be genotyped for the whole population; these were DDEF1g.279401A>G and IGFBP3c.4394T>C(Trp>Arg). We found a significant effect (P ≤ 0.05) of allele substitution on backfat thickness; however, the IGFBP3 SNP did not significantly affect this trait.     

First Description of a Cluster of Acute/Subacute Paracoccidioidomycosis Cases and Its Association with a Climatic Anomaly

Background

Identifying clusters of acute paracoccidioidomycosis cases could potentially help in identifying the environmental factors that influence the incidence of this mycosis. However, unlike other endemic mycoses, there are no published reports of clusters of paracoccidioidomycosis.

Methodology/Principal Findings

A retrospective cluster detection test was applied to verify if an excess of acute form (AF) paracoccidioidomycosis cases in time and/or space occurred in Botucatu, an endemic area in São Paulo State. The scan-test SaTScan v7.0.3 was set to find clusters for the maximum temporal period of 1 year. The temporal test indicated a significant cluster in 1985 (P<0.005). This cluster comprised 10 cases, although 2.19 were expected for this year in this area. Age and clinical presentation of these cases were typical of AF paracccidioidomycosis. The space-time test confirmed the temporal cluster in 1985 and showed the localities where the risk was higher in that year. The cluster suggests that some particularities took place in the antecedent years in those localities. Analysis of climate variables showed that soil water storage was atypically high in 1982/83 (∼2.11/2.5 SD above mean), and the absolute air humidity in 1984, the year preceding the cluster, was much higher than normal (∼1.6 SD above mean), conditions that may have favored, respectively, antecedent fungal growth in the soil and conidia liberation in 1984, the probable year of exposure. These climatic anomalies in this area was due to the 1982/83 El Niño event, the strongest in the last 50 years.

Conclusions/Significance

We describe the first cluster of AF paracoccidioidomycosis, which was potentially linked to a climatic anomaly caused by the 1982/83 El Niño Southern Oscillation. This finding is important because it may help to clarify the conditions that favor Paracoccidioides brasiliensis survival and growth in the environment and that enhance human exposure, thus allowing the development of preventive measures.     

Molecular phylogeography of Carapichea ipecacuanha,an amphitropical shrub that occurs in the understory of both semideciduous and evergreen forests

The medicinal shrub Carapichea ipecacuanha (ipecac) is an amphitropic species with three disjunct areas of distribution. In the Brazilian Atlantic and Amazonian ranges, the species was associated mostly with the understory of seasonal semideciduous forests, whereas in the Central American–Colombian range, the species occurred in the understory of moist evergreen forests. We examined the phylogeographic structure of ipecac using chloroplast trnT‐trnL and nuclear internal transcribed spacer (ITS) sequences from 120 and 46 specimens, respectively. To complement existing data on root alkaloid profiles, we used high‐performance liquid chromatography to assess the levels of emetine and cephaeline in 33 specimens from the two Brazilian ranges. The three ranges shared neither nuclear nor chloroplast haplotypes. The phylogeographic structures showed an uneven distribution of genetic diversity, sharp breaks and high levels of genetic differentiation among ranges. Our results suggest that the extant populations are descendents of at least four distinct ancestral lineages. The Atlantic ipecacs showed higher levels of genetic diversity than ipecacs from the other two ranges; it is likely that they derive from two ancestral lineages, with long‐term persistence in that region. The Amazonian ipecacs were monomorphic with respect to the ITS and cpDNA sequences, which supports the view that there was a recent expansion from a single parental source after a strong genetic bottleneck. The existence of a fourth distinct lineage is apparent from the high levels of genetic and chemical differentiation that we identified in the Central American–Columbian ipecacs.     

Dynamics of HIV-Containing Compartments in Macrophages Reveal Sequestration of Virions and Transient Surface Connections

During HIV pathogenesis, infected macrophages behave as “viral reservoirs” that accumulate and retain virions within dedicated internal Virus-Containing Compartments (VCCs). The nature of VCCs remains ill characterized and controversial. Using wild-type HIV-1 and a replication-competent HIV-1 carrying GFP internal to the Gag precursor, we analyzed the biogenesis and evolution of VCCs in primary human macrophages. VCCs appear roughly 14 hours after viral protein synthesis is detected, initially contain few motile viral particles, and then mature to fill up with virions that become packed and immobile. The amount of intracellular Gag, the proportion of dense VCCs, and the density of viral particles in their lumen increased with time post-infection. In contrast, the secretion of virions, their infectivity and their transmission to T cells decreased overtime, suggesting that HIV-infected macrophages tend to pack and retain newly formed virions into dense compartments. A minor proportion of VCCs remains connected to the plasma membrane overtime. Surprisingly, live cell imaging combined with correlative light and electron microscopy revealed that such connections can be transient, highlighting their dynamic nature. Together, our results shed light on the late phases of the HIV-1 cycle and reveal some of its macrophage specific features.     

Influence of Maternal Height and Weight on Low Birth Weight: A Cross-Sectional Study in Poor Communities of Northeastern Brazil

Background

Low birth weight (LBW) is associated with an increased risk of mortality, adverse metabolic conditions, and long-term chronic morbidities. The relationship between LWB and short maternal stature coupled with nutritional status was investigated in poor communities.

Methods/Principal Findings

A cross-sectional population-based study involving 2226 mother-child pairs was conducted during the period 2009-2010 in shantytowns of Maceió, Alagoas, Brazil. Associations between LBW and maternal sociodemographics, stature and nutritional status were investigated. The outcome variable was birth weight (< 2500g and ≥ 2500g). The independent variables were the age, income, educational background, stature and nutritional status (eutrophic, underweight, overweight and obese) of the mother. The frequency of LBW was 10%. Short-statured mothers (1^st quartile of stature ≤ 152cm) showed a tendency of increased risk of LBW children compared to mothers in the 4^th quartile of stature (>160.4cm) (OR: 1.42, 95% CI: 0.96 - 1.09, p = 0.078). Children from short-statured mothers weighed an average of 125g less than those from taller mothers (3.18±0.56kg vs. 3.30±0.58kg, respectively p = 0.002). Multivariate analyses showed that short stature, age < 20y (OR: 3.05, 95% CI:1.44 - 6.47) or were underweight (OR: 2.26, 95% CI:0.92 - 5.95) increased the risk of LBW, while overweight (OR: 0.38, 95% CI:0.16 - 0.95) and obesity (OR: 0.39, 95% CI:0.11 - 1.31) had lower risk for LBW. In taller mothers, lower income and underweight were associated with LBW (OR: 1.88, 95% CI: 1.07 - 3.29 and 2.85, 95% CI:1.09 - 7.47, respectively), and obese mothers showed a trend of increased risk of LBW (OR: 1.66, 95% CI:0.84 - 3.25).

Conclusions/Significance

Overweight was found to have a protective effect in short-statured mothers, indicating that a surplus of energy may diminish the risk of LBW. Short-statured younger mothers, but not taller ones, showed higher risk of LBW. The mother being underweight, regardless of stature, was associated with LBW.     

Increased Na+ and Cl− accumulation induced by NaCl salinity inhibits cotyledonary reserve mobilization and alters the source-sink relationship in establishing dwarf cashew seedlings

We studied the NaCl-induced changes in cotyledons and the embryonic axis of establishing dwarf cashew (Anacardium occidentale) seedlings. The salt stress reduced the growth of dwarf cashew seedlings, and this response was related to the inhibition of cotyledonary reserve depletion. Lipid mobilization was inhibited by NaCl due to reduced lipase activity in the emerging and establishing seedlings. Additionally, there was reduced transient starch accumulation in the cotyledons of the salt-stressed seedlings that was associated with lower starch synthase activity at the early developmental stages and inhibited amylolytic and starch phosphorylase activities at the established seedling stage. The NaCl-induced changes in lipid and starch metabolism influenced the soluble sugar content in the cotyledons. Protein mobilization was inhibited by NaCl, and we observed the accumulation of amino acids and the inhibition of proteolytic activity in the cotyledons of the salt-stressed established seedlings. Salinity significantly reduced the free amino acid and reducing sugar contents in the embryonic axes of both emerged and established seedlings, whereas the non-reducing sugar content was affected by this stress only in the established seedlings. The Na⁺ and Cl^? contents progressively increased in the cotyledons and embryonic axis of the seedlings as the salinity increased. We conclude that salt stress inhibits dwarf cashew seedling establishment by inhibiting the mobilization of reserves, an inhibition that was related to increased Na⁺ and Cl^? accumulation in the cotyledons. Additionally, these toxic ions reduced the sink strength of the embryonic axis with regard to the products of cotyledonary reserve mobilization.