The genus Rickettsia belongs to the Proteobacteria phylum and these bacteria infect animals and humans causing a range of diseases worldwide. The genus is divided into 4 groups and despite the public ...health threat and the knowledge accumulated so far, the mandatory intracellular bacteria behaviour and limitation for in vitro culture makes it difficult to create new vaccines and drug targets to these bacteria. In an attempt to overcome these limitations, pan-genomic approaches has used 47 genomes of the genus Rickettsia, in order to describe species similarities and genomics islands. Moreover, we conducted reverse vaccinology and docking analysis aiming the identification of proteins that have great potential to become vaccine and drug targets. We found out that the bacteria of the four Rickettsia groups have a high similarity with each other, with about 90 to 100% of identity. A pathogenicity island and a resistance island were predicted. In addition, 8 proteins were also predicted as strong candidates for vaccine and 9 as candidates for drug targets. The prediction of the proteins leads us to believe in a possibility of prospecting potential drugs or creating a polyvalent vaccine, which could reach most strains of this large group of bacteria.
Communicated by Ramaswamy H. Sarma
Pertussis is a highly contagious respiratory disease caused by Bordetella pertussis, a Gram-negative bacterium described over a century ago. Despite broad vaccine coverage and treatment options, the ...disease is remerging as a public health problem especially in infants and older children. Recent data indicate re-emergence of the disease is related to bacterial resistance to immune defences and decreased vaccine effectiveness, which obviously suggests the need of new effective vaccines and drugs. In an attempt to contribute with solutions to this great challenge, bioinformatics tools were used to genetically comprehend the species of these bacteria and predict new vaccines and drug targets. In fact, approaches were used to analysis genomic plasticity, gene synteny and species similarities between the 20 genomes of Bordetella pertussis already available. Furthermore, it was conducted reverse vaccinology and docking analysis to identify proteins with potential to become vaccine and drug targets, respectively. The analyses showed the 20 genomes belongs to a homogeneous group that has preserved most of the genes over time. Besides that, were found genomics islands and good proteins to be candidates for vaccine and drugs. Taken together, these results suggests new possibilities that may be useful to develop new vaccines and drugs that will help the prevention and treatment strategies of pertussis disease caused by these Bordetella strains.
Communicated by Ramaswamy H. Sarma
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•A Leishmania hypothetical protein, LiHyP, was evaluated as a vaccine candidate in mice.•It was administered as a recombinant protein plus saponin or in a DNA plasmid.•Both ...immunization strategies induced Th1 response in the vaccinated animals.•DNA LiHyP and rLiHyP/saponin induced partial protection in L. infantum-infected mice.•LiHyP was immunogenic in human PBMC from healthy subjects and VL patients.
Vaccination is one the most important strategies for the prevention of visceral leishmaniasis (VL). In the current study, a new Leishmania hypothetical protein, LiHyP, which was previously showed as antigenic in an immunoproteomic search in canine VL, was evaluated regarding its immunogenicity and protective efficacy against Leishmania infantum infection. The effects of the immunization using LiHyP were evaluated when administered as a DNA plasmid (DNA LiHyP) or recombinant protein (rLiHyP) associated with saponin. The immunity elicited by both vaccination regimens reduced the parasitism in liver, spleen, bone marrow and draining lymph nodes, being associated with high levels of IFN-γ, IL-12, GM-CSF, and specific IgG2a antibody, besides low production of IL-4, IL-10, and protein and parasite-specific IgG1 antibodies. CD4+ T cells contributed more significantly to IFN-γ production in the rLiHyP/saponin group, while CD8+ T cells were more important in the production of this cytokine in the DNA LiHyP group. In addition, increased IFN-γ secretion, along with low levels of IL-10, were found when PBMCs from treated VL subject and healthy individuals were stimulated with the recombinant protein. In conclusion, when administered either as a DNA plasmid or recombinant protein, LiHyP can direct the immune response towards a Th1 immune profile, protecting animals against L. infantum infection; therefore, it can be seen as a promising immunogen against human VL.
Several alkaline massifs on inland southeastern Brazil extend offshore, roughly parallel to ~20° S, through a seamount chain of the Vitoria-Trindade ridge. This paper presents the first extensive ...work on the Martin Vaz volcano through whole-rock and Sr and Nd isotopic composition of volcanic and subvolcanic lithotypes from the Martin Vaz Island, located at the easternmost of this volcanic chain. These alkaline rocks were generated during the Plio-Pleistocene (~0.47 My,
40
Ar/
39
Ar dating in whole-rock) and represent the crystallization of sodic magmas of nephelinitic composition that evolved through fractional crystallization towards phonolites. Calculations from P-T
Liquidus
using PELE software show temperatures of 1045°C and 818°C, viscosity of 2.47 log Poise and 5.02 log Poise, and densities of 2.57 g/cm
3
and 2.26 g/cm
3
for nephelinite and phonolite, respectively. Like in Trindade Island, the nephelinitic volcanism in Martin Vaz may represent a Strombolian and/or Hawaii-type eruption due to low viscosity magma according to its physical properties whereas phonolitic intrusions present higher viscosity characteristics forming lava domes. The
87
Sr/
86
Sr (~ 0.703800) and
143
Nd/
144
Nd (~ 0.512750) ratios of lavas from the seamounts and Martin Vaz do not vary significantly, pointing to partial melting process from a homogeneous mantle source showing isotope signature close to HIMU. Beside the restrict variation on these isotopic ratios, a conspicuous enrichment in incompatible trace elements, mainly LREE, indicates that metasomatism is a recent process and not a long-term source characteristic. Non-modal partial melting models (fractional melting and batch melting) suggest that the source of the Martin Vaz magmatism is consistent with the garnet-lherzolite mantle stability field (>90 km depth; Tb/Yb >0.7), generated about 3.0 GPa by very small degree of partial melting of an enriched wet mantle source (F = 0.03-0.04) with 2.5 wt. % of CO
2
.
Objective: To describe and compare energy expenditure (EE)/minute walking and in different body postures in individuals with COPD; and to investigate if EE/minute walking is a predictor of their ...classification as physically active or inactive. Methods: Physical activity (PA) in daily life was objectively assessed using two PA monitors for 7 days and data were analyzed on a minute-by-minute basis. Predominant minutes were separated into walking, standing, sitting, and reclined, and EE/minute (a reflection of PA intensity) was then calculated in each of these four activities and postures. Participants were classified as active and inactive according to the criteria proposed by the American College of Sports Medicine (ACSM). Results: 43 individuals were evaluated (65±8 years; FEV1 50±14% predicted). A binary logistic regression model yielded that, regardless of the time spent walking/day, EE/minute walking was a significant predictor of the classification as physically active (OR=18.2 2 – 165; p=0.01), together with BMI (OR=0.68 0.5 - 0.9; p=0.008) (model: Chi-square = 22.431, p< 0.05; R2 Nagelkerke = 0.556). In the active group, significantly higher EE/minute was observed for walking and standing in comparison both to sitting and reclined. However, in the inactive group, there were significant differences in EE/minute only when comparing walking versus reclined and standing versus reclined. Conclusion: In individuals, with COPD, EE/minute walking is a significant predictor of being classified as physically active, independently of the time spent walking/day. Each additional kilocalorie/minute spent walking increases in 18 times the chances to be classified as physically active in daily life.
The classic monitoring methods for detecting faults in automotive vehicles based on on-board diagnostics (OBD) are insufficient when diagnosing several mechanical failures. Other sensing techniques ...present drawbacks such as high invasiveness and limited physical range. The present work presents a fully noninvasive system for fault detection and isolation in internal combustion engines through sound signals processing. An acquisition system was developed, whose data are transmitted to a smartphone in which the signal is processed, and the user has access to the information. A study of the chaotic behavior of the vehicle was carried out, and the feasibility of using fractal dimensions as a tool to diagnose engine misfire and problems in the alternator belt was verified. An artificial neural network was used for fault classification using the fractal dimension data extracted from the sound of the engine. For comparison purposes, a strategy based on wavelet multiresolution analysis was also implemented. The proposed solution allows a diagnosis without having any contact with the vehicle, with low computational cost, without the need for installing sensors, and in real time. The system and method were validated through experimental tests, with a success rate of 99% for the faults under consideration.
Summary
Current therapies for inflammatory bowel diseases (IBD) are aimed at controlling the exacerbated response in the gut, but no treatment is fully effective for many refractory patients. ...Mesenchymal stromal cells (MSC) are multi‐potent cells with regulatory immunosuppressive activity that may control inflammatory diseases. In this study, we investigated the short‐ and especially the long‐term protective effects of MSC on experimental colitis. We show that MSC elicited protection to acute intestinal inflammation with gain of weight, improvement in the clinical disease score and expressive reduction in the mortality rate of treated mice. MSC changed the population of neutrophils, eosinophils and augmented the frequency of CD4 T lymphocytes in the gut‐draining lymph nodes, together with reduced accumulation of these cells in the colon intraepithelial compartment. Interestingly, there were increased levels of programmed death 1 (PD‐1) and glucocorticoid‐induced tumour necrosis factor receptor family‐related receptor (GITR) in the spleen regulatory T cells of mice that received MSC treatment, which also presented a reversal in the pattern of immune response in the gut, with diminished inflammatory, T helper type 1 (Th1) and Th17 profile, in contrast to augmented Th2 responses. Most strikingly, this balanced response elicited by a single administration of MSC during the acute colitis persisted long‐term, with restored goblet cells, eosinophils and maintenance of elevated gut interleukin (IL)‐4, besides increased CD4+CD25+PD‐1+ cells in the spleen and reduced Th17 response in mesenteric lymph nodes (MLN) of treated mice on day 60. Taken together, our findings provided a significant contribution to translational immunology by pointing human adipose tissue‐derived MSC as a novel therapeutic approach with long‐term beneficial regulatory effects in experimental colitis.
An early and unique administration of adipose tissue‐derived mesenchymal stromal cells produced persistent protective effects on experimental colitis
Abstract
Phospholipases A
2
(
PLA
2
s) overexpression is closely associated with the malignant potential of breast cancers. Here, we showed for the first the antitumoral effects of γCdcPLI, a PLA
2
...inhibitor from
Crotalus durissus collilineatus
via PI3K/Akt pathway on MDA-MB-231 cell. Firstly, γCdcPLI was more cytotoxic to MDA-MB-231 breast cancer cells than other cell lines (MCF-7, HeLa, PC3 and A549) and did not affect the viability of non-tumorigenic breast cell (MCF 10A). In addition, γCdcPLI induced modulation of important mediators of apoptosis pathways such as p53, MAPK-ERK, BIRC5 and MDM2. γCdcPLI decreased MDA-MB-231 adhesion, migration and invasion. Interestingly, the γCdcPLI also inhibited the adhesion and migration of endothelial cells and blocked angiogenesis by inhibiting tube formation by HUVECs
in vitro
and sprouting elongation on aortic ring assay
ex vivo
. Furthermore, γCdcPLI reduced the production of vascular endothelial growth factor (VEGF). γCdcPLI was also able to decrease PGE2 levels in MDA-MB-231 and inhibited gene and protein expression of the PI3K/Akt pathway. In conclusion, γCdcPLI showed
in vitro
antitumoral, antimestatatic and anti-angiogenic potential effects and could be an attractive approach for futures studies in cancer therapy.
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