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Endogenously-expressed NH2-terminus of circumsporozoite protein interferes with sporozoite invasion of mosquito salivary glands
No full textAbstract\ud
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Background\ud
The circumsporozoite protein is the most abundant polypeptide expressed by sporozoites, the malaria parasite stage capable of infecting humans. Sporozoite invasion of mosquito salivary glands prior to transmission is likely mediated by a receptor/ligand-like interaction of the parasites with the target tissues, and the amino (NH2)-terminal portion of CSP is involved in this interaction but not the TSR region on the carboxyl (C)-terminus. Peptides based on the NH2-terminal domain could compete with the parasites for the salivary gland receptors and thus inhibit penetration.\ud
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Methods\ud
Peptides based on the NH2-terminus and TSR domains of the CSP from avian or human malaria parasites, Plasmodium gallinaceum and Plasmodium falciparum, respectively, were expressed endogenously in mosquito haemolymph using a transient (Sindbis virus-mediated) or stable (piggyBac-mediated transgenesis) system.\ud
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Results\ud
Transient endogenous expression of partial NH2-terminus peptide from P. falciparum CSP in P. gallinaceum-infected Aedes aegypti resulted in a reduced number of sporozoites in the salivary glands. When a transgenic approach was used to express a partial CSP NH2-terminal domain from P. gallinaceum the number of sporozoites in the salivary glands did not show a difference when compared to controls. However, a significant difference could be observed when mosquitoes with a lower infection were analysed. The same result could not be observed with mosquitoes endogenously expressing peptides based on the TSR domain from either P. gallinaceum or P. falciparum.\ud
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Conclusion\ud
These results support the conclusion that CSP partial NH2-terminal domain can be endogenously expressed to promote a competition for the receptor used by sporozoites to invade salivary glands, and they could be used to block this interaction and reduce parasite transmission. The same effect cannot be obtained with peptides based on the TSR domain.We thank Neuza Saraiva Fernandes and Ediane Saraiva Fernandes for technical\ud
assistance and Alexandre Santos de Moura for sample sequencing. This work\ud
was supported by FAPESP (Process#04/00889-9 and#00/12138-7). AAJ was\ud
supported in part by an award from the National Institute of Allergy and Infec‑\ud
tious Diseases (USA) (R37AI029746)
Amblyomma cajennense (Fabricius, 1787) (Acari: Ixodidae), the Cayenne tick: phylogeography and evidence for allopatric speciation
No full textAbstract
Background
Amblyomma cajennense F. is one of the best known and studied ticks in the New World because of its very wide distribution, its economical importance as pest of domestic ungulates, and its association with a variety of animal and human pathogens. Recent observations, however, have challenged the taxonomic status of this tick and indicated that intraspecific cryptic speciation might be occurring. In the present study, we investigate the evolutionary and demographic history of this tick and examine its genetic structure based on the analyses of three mitochondrial (12SrDNA, d-loop, and COII) and one nuclear (ITS2) genes. Because A. cajennense is characterized by a typical trans-Amazonian distribution, lineage divergence dating is also performed to establish whether genetic diversity can be linked to dated vicariant events which shaped the topology of the Neotropics.
Results
Total evidence analyses of the concatenated mtDNA and nuclear + mtDNA datasets resulted in well-resolved and fully congruent reconstructions of the relationships within A. cajennense. The phylogenetic analyses consistently found A. cajennense to be monophyletic and to be separated into six genetic units defined by mutually exclusive haplotype compositions and habitat associations. Also, genetic divergence values showed that these lineages are as distinct from each other as recognized separate species of the same genus. The six clades are deeply split and node dating indicates that they started diverging in the middle-late Miocene.
Conclusions
Behavioral differences and the results of laboratory cross-breeding experiments had already indicated that A. cajennense might be a complex of distinct taxonomic units. The combined and congruent mitochondrial and nuclear genetic evidence from this study reveals that A. cajennense is an assembly of six distinct species which have evolved separately from each other since at least 13.2 million years ago (Mya) in the earliest and 3.3 Mya in the latest lineages. The temporal and spatial diversification modes of the six lineages overlap the phylogeographical history of other organisms with similar extant trans-Amazonian distributions and are consistent with the present prevailing hypothesis that Neotropical diversity often finds its origins in the Miocene, after the Andean uplift changed the topology and consequently the climate and ecology of the Neotropics
Integrated health service delivery networks and tuberculosis avoidable hospitalizations: is there a relation between them in Brazil?
No full textAbstract\ud
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Background\ud
The early identification of the Breathing Symptoms within the scope of Primary Health Care is recommended, and is also one of the strategies of national sanitary authorities for reaching the elimination of tuberculosis. The purpose of this study is to consider which attributes and which territories have shown the most significant progress in Primary Health Care, in terms of coordination of Health Care Networks, and also check if those areas of Primary Health Care that are most critical regarding coordination, there were more or less cases of avoidable hospitalizations for tuberculosis.\ud
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Methods\ud
This is an ecological study that uses primary and secondary data. For analysis, coropletic maps were developed through the ArcGIS software, version 10.2. There was also the calculation of gross annual and Bayesian rates for hospitalizations for tuberculosis, for each Primary Health Care territory.\ud
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Results\ud
There were satisfactory results for attributes such as Population (n = 37; 80.4 %), Primary Health Care (n = 43; 93.5 %), Support System (n = 45; 97.8 %); the exceptions were Logistics System (n = 32; 76.0 %) and Governance System, with fewer units in good condition (n = 31; 67.3 %). There is no evidence of any connection between networks’ coordination by Primary Health Care and tuberculosis avoidable admissions.\ud
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Conclusion\ud
The results show that progress has been made regarding the coordination of the Health Care Networks, and a positive trend has been shown, even though the levels are not excellent. It was found no relationship between the critical areas of Primary Health Care and tuberculosis avoidable hospitalizations, possibly because other variables necessary to comprehend the phenomena.We are grateful to the Municipal Secretariat for Health, for the partnership\ud
and support they have provided in the materialization of the study. We also\ud
thank the coordinators of the Health Districts, for the articulation with the\ud
managers of the Units and also as they have made it possible for us to\ud
participate in the Ordinary General Meeting for the presentation of the\ud
study. We thank the managers of the Health Units who have so kindly\ud
opened the doors of their Units to our team, also encouraging the\ud
participation of their employees. We thank the health workers for having\ud
agreed to participate in the study, essentially as they have believed in the\ud
potential of Primary Health Care for a change in model. Last but not least, to\ud
the team from the Reference Hospital for making available the secondary\ud
data. The Foundation of Support for Research of the State of São Paulo\ud
(Fundação de Amparo e Apoio à Pesquisa do Estado de São Paulo - FAPESP)\ud
(Processes No. 2012/51235-5 and No. 2013/22486-2)
The capability of endophytic fungi for production of hemicellulases and related enzymes
No full textAbstract
Background
There is an imperative necessity for alternative sources of energy able to reduce the world dependence of fossil oil. One of the most successful options is ethanol obtained mainly from sugarcane and corn fermentation. The foremost residue from sugarcane industry is the bagasse, a rich lignocellulosic raw material uses for the production of ethanol second generation (2G). New cellulolytic and hemicellulytic enzymes are needed, in order to optimize the degradation of bagasse and production of ethanol 2G.
Results
The ability to produce hemicellulases and related enzymes, suitable for lignocellulosic biomass deconstruction, was explored using 110 endophytic fungi and 9 fungi isolated from spoiled books in Brazil. Two initial selections were performed, one employing the esculin gel diffusion assay, and the other by culturing on agar plate media with beechwood xylan and liquor from the hydrothermal pretreatment of sugar cane bagasse. A total of 56 isolates were then grown at 29°C on steam-exploded delignified sugar cane bagasse (DEB) plus soybean bran (SB) (3:1), with measurement of the xylanase, pectinase, β-glucosidase, CMCase, and FPase activities. Twelve strains were selected, and their enzyme extracts were assessed using different substrates. Finally, the best six strains were grown under xylan and pectin, and several glycohydrolases activities were also assessed. These strains were identified morphologically and by sequencing the internal transcribed spacer (ITS) regions and the partial β-tubulin gene (BT2). The best six strains were identified as Aspergillus niger DR02, Trichoderma atroviride DR17 and DR19, Alternaria sp. DR45, Annulohypoxylon stigyum DR47 and Talaromyces wortmannii DR49. These strains produced glycohydrolases with different profiles, and production was highly influenced by the carbon sources in the media.
Conclusions
The selected endophytic fungi Aspergillus niger DR02, Trichoderma atroviride DR17 and DR19, Alternaria sp. DR45, Annulohypoxylon stigyum DR47 and Talaromyces wortmannii DR49 are excellent producers of hydrolytic enzymes to be used as part of blends to decompose sugarcane biomass at industrial level
Sintering and nanostability: The thermodynamic perspective.
No full textSintering and nanostability (defined as the stability against sintering) are critical phenomena present in the processing and application of nanoparticles. With important implications in obtaining high-quality dense ceramics with fine grains or in enabling high surface areas in nanoparticles for catalytic applications, the control of these interrelated phenomena has been the focuses of several studies. From a thermodynamic perspective, it is recognized that surface energy is a fundamental parameter in both cases, since it is the main driving force for sintering and also the reason that nanoparticles are thermodynamically unstable and have the tendency to coarsen at elevated temperatures. The role of grain-boundary energies is less recognized as relevant, but is also connected to densification, grain growth, and nanoparticle stability. In this paper, we review the critical aspects of the role of interfacial energies in the microstructure evolution, in particular addressing them as parameters to allow better control in addition to more conventional kinetic parameters. The concept is based on the nonsingularity of interfacial energies in a given system, which varies with temperature, atmosphere, and most importantly, chemical composition-this last offering a method to induce particular microstructural evolutions. While the model assumes isotropic grain boundaries but consequences to anisotropy are also discussed. The paper presents examples of the role of dopants on interfacial energies, how this is quantitatively related to their segregation at the interfaces, and the impact in sintering and nanostability. Given the importance of interface energetics to these phenomena, we also present a short review on the current methods used to obtain reliable interface thermodynamic data.FAPESPCNP
ACTN3 R577X and ACE I/D gene variants influence performance in elite sprinters: a multi-cohort study
No full textAbstract\ud
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Background\ud
To date, studies investigating the association between ACTN3 R577X and ACE I/D gene variants and elite sprint/power performance have been limited by small cohorts from mixed sport disciplines, without quantitative measures of performance. Aim: To examine the association between these variants and sprint time in elite athletes.\ud
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Methods\ud
We collected a total of 555 best personal 100-, 200-, and 400-m times of 346 elite sprinters in a large cohort of elite Caucasian or African origin sprinters from 10 different countries. Sprinters were genotyped for ACTN3 R577X and ACE ID variants.\ud
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Results\ud
On average, male Caucasian sprinters with the ACTN3 577RR or the ACE DD genotype had faster best 200-m sprint time than their 577XX (21.19 ± 0.53 s vs. 21.86 ± 0.54 s, p = 0.016) and ACE II (21.33 ± 0.56 vs. 21.93 ± 0.67 sec, p = 0.004) counterparts and only one case of ACE II, and no cases of ACTN3 577XX, had a faster 200-m time than the 2012 London Olympics qualifying (vs. 12 qualified sprinters with 577RR or 577RX genotype). Caucasian sprinters with the ACE DD genotype had faster best 400-m sprint time than their ACE II counterparts (46.94 ± 1.19 s vs. 48.50 ± 1.07 s, p = 0.003). Using genetic models we found that the ACTN3 577R allele and ACE D allele dominant model account for 0.92 % and 1.48 % of sprint time variance, respectively.\ud
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Conclusions\ud
Despite sprint performance relying on many gene variants and environment, the % sprint time variance explained by ACE and ACTN3 is substantial at the elite level and might be the difference between a world record and only making the final
The risk of dengue for non-immune foreign visitors to the 2016 summer olympic games in Rio de Janeiro, Brazil
No full textAbstract\ud
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Background\ud
Rio de Janeiro in Brazil will host the Summer Olympic Games in 2016. About 400,000 non-immune foreign tourists are expected to attend the games. As Brazil is the country with the highest number of dengue cases worldwide, concern about the risk of dengue for travelers is justified.\ud
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Methods\ud
A mathematical model to calculate the risk of developing dengue for foreign tourists attending the Olympic Games in Rio de Janeiro in 2016 is proposed. A system of differential equation models the spread of dengue amongst the resident population and a stochastic approximation is used to assess the risk to tourists. Historical reported dengue time series in Rio de Janeiro for the years 2000-2015 is used to find out the time dependent force of infection, which is then used to estimate the potential risks to a large tourist cohort. The worst outbreak of dengue occurred in 2012 and this and the other years in the history of Dengue in Rio are used to discuss potential risks to tourists amongst visitors to the forthcoming Rio Olympics.\ud
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Results\ud
The individual risk to be infected by dengue is very much dependent on the ratio asymptomatic/symptomatic considered but independently of this the worst month of August in the period studied in terms of dengue transmission, occurred in 2007.\ud
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Conclusions\ud
If dengue returns in 2016 with the pattern observed in the worst month of August in history (2007), the expected number of symptomatic and asymptomatic dengue cases among tourists will be 23 and 206 cases, respectively. This worst case scenario would have an incidence of 5.75 (symptomatic) and 51.5 (asymptomatic) per 100,000 individuals.We thank Paulo Cesar Costa Santos for computational support.\ud
Funding\ud
This study received partial funding from LIM01-HCFMUSP, CNPq (grant\ud
300981/2014-7), FAPESP (grant 2012/18463-4), Brazilian Ministry of Health\ud
(Fundo Nacional de Saúde, grant 777588/2012), Dengue Tools under the\ud
Health theme of the Seventh Framework Programme of the European Community\ud
(Grant Agreement Number 282589) and was also partially funded by\ud
Leverhulme Trust Research Fellowship grant (RF-2015-88) (DG)
Impaired CD8+ T cell responses upon Toll-like receptor activation in common variable immunodeficiency
No full textAbstract\ud
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Background\ud
Infections caused by bacteria or viruses are frequent in common variable immunodeficiency (CVID) patients due to antibody deficiencies, which may be associated with altered T cell function. CVID patients are frequently in contact with pathogen-associated molecular patterns (PAMPs), leading to the activation of innate immunity through Toll-like receptors (TLR) affecting T cell activation. We evaluated the effect of TLR activation on T cells in CVID patients undergoing intravenous immunoglobulin (IVIg) replacement using synthetic ligands.\ud
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Methods\ud
Expression of exhaustion, activation and maturation markers on T cells from peripheral blood as well as regulatory T cells and follicular T cells in peripheral blood mononuclear cells (PBMCs) from CVID and healthy individuals were evaluated by flow cytometry. PBMCs cultured with TLR agonists were assessed for intracellular IFN-γ, TNF, IL-10, IL-17a or IL-22 secretion as monofunctional or polyfunctional T cells (simultaneous cytokine secretion) by flow cytometry.\ud
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Results\ud
We found increased expression of the exhaustion marker PD-1 on effector memory CD4+ T cells (CD45RA−CCR7−) in the peripheral blood and increased expression of CD38 in terminally differentiated CD8+ T cells (CD45RA+CCR7−). Furthermore, a decreased frequency of naïve regulatory T cells (CD45RA+Foxp3low), but not of activated regulatory T cells (CD45RA−Foxp3high) was detected in CVID patients with splenomegaly, the non-infectious manifestation in this CVID cohort (43.7 %). Moreover, the frequency of peripheral blood follicular helper T cells (CD3+CD4+CXCR5+PD-1+ICOS+) was similar between the CVID and control groups. Upon in vitro TLR3 activation, a decreased frequency of CD8+ T cells secreting IFN-γ, IL-17a or IL-22 was detected in the CVID group compared to the control group. However, a TLR7/TLR8 agonist and staphylococcal enterotoxin B induced an increased Th22/Tc22 (IL-22+, IFN-γ−, IL-17a−) response in CVID patients. Both TLR2 and TLR7/8/CL097 activation induced an increased response of CD4+ T cells secreting three cytokines (IL-17a, IL-22 and TNF)in CVID patients, whereas CD8+ T cells were unresponsive to these stimuli.\ud
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Conclusion\ud
The data show that despite the unresponsive profile of CD8+ T cells to TLR activation, CD4+ T cells and Tc22/Th22 cells are responsive, suggesting that activation of innate immunity by TLRs could be a strategy to stimulate CD4+ T cells in CVID.We are grateful to all individuals who participated in the study. This work\ud
was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo\ud
(2012/14110-0) and the Laboratório de Investigação Médica, Unidade 56 do\ud
Hospital das Clínicas da Faculdade de Medicina de São Paulo. The funders had\ud
no role in the study design, data collection and analysis, decision to publish or\ud
manuscript preparation
Global liver gene expression differences in Nelore steers with divergent residual feed intake phenotypes
No full textAbstract\ud
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Background\ud
Efficiency of feed utilization is important for animal production because it can reduce greenhouse gas emissions and improve industry profitability. However, the genetic basis of feed utilization in livestock remains poorly understood. Recent developments in molecular genetics, such as platforms for genome-wide genotyping and sequencing, provide an opportunity to identify genes and pathways that influence production traits. It is known that transcriptional networks influence feed efficiency-related traits such as growth and energy balance. This study sought to identify differentially expressed genes in animals genetically divergent for Residual Feed Intake (RFI), using RNA sequencing methodology (RNA-seq) to obtain information from genome-wide expression profiles in the liver tissues of Nelore cattle.\ud
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Results\ud
Differential gene expression analysis between high Residual Feed Intake (HRFI, inefficient) and low Residual Feed Intake (LRFI, efficient) groups was performed to provide insights into the molecular mechanisms that underlie feed efficiency-related traits in beef cattle. A total of 112 annotated genes were identified as being differentially expressed between animals with divergent RFI phenotypes. These genes are involved in ion transport and metal ion binding; act as membrane or transmembrane proteins; and belong to gene clusters that are likely related to the transport and catalysis of molecules through the cell membrane and essential mechanisms of nutrient absorption. Genes with functions in cellular signaling, growth and proliferation, cell death and survival were also differentially expressed. Among the over-represented pathways were drug or xenobiotic metabolism, complement and coagulation cascades, NRF2-mediated oxidative stress, melatonin degradation and glutathione metabolism.\ud
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Conclusions\ud
Our data provide new insights and perspectives on the genetic basis of feed efficiency in cattle. Some previously identified mechanisms were supported and new pathways controlling feed efficiency in Nelore cattle were discovered. We potentially identified genes and pathways that play key roles in hepatic metabolic adaptations to oxidative stress such as those involved in antioxidant mechanisms. These results improve our understanding of the metabolic mechanisms underlying feed efficiency in beef cattle and will help develop strategies for selection towards the desired phenotype
Perceived neighborhood problems: multilevel analysis to evaluate psychometric properties in a Southern adult Brazilian population
No full textAbstract
Background
Physical attributes of the places in which people live, as well as their perceptions of them, may be important health determinants. The perception of place in which people dwell may impact on individual health and may be a more telling indicator for individual health than objective neighborhood characteristics. This paper aims to evaluate psychometric and ecometric properties of a scale on the perceptions of neighborhood problems in adults from Florianopolis, Southern Brazil.
Methods
Individual, census tract level (per capita monthly familiar income) and neighborhood problems perception (physical and social disorders) variables were investigated. Multilevel models (items nested within persons, persons nested within neighborhoods) were run to assess ecometric properties of variables assessing neighborhood problems.
Results
The response rate was 85.3%, (1,720 adults). Participants were distributed in 63 census tracts. Two scales were identified using 16 items: Physical Problems and Social Disorder. The ecometric properties of the scales satisfactory: 0.24 to 0.28 for the intra-class correlation and 0.94 to 0.96 for reliability. Higher values on the scales of problems in the physical and social domains were associated with younger age, more length of time residing in the same neighborhood and lower census tract income level.
Conclusions
The findings support the usefulness of these scales to measure physical and social disorder problems in neighborhoods