Next-Generation Leishmanization: Revisiting Molecular Targets for Selecting Genetically Engineered Live-Attenuated Leishmania.

Despite decades of research devoted to finding a vaccine against leishmaniasis, we are still lacking a safe and effective vaccine for humans. Given this scenario, the search for a new prophylaxis alternative for controlling leishmaniasis should be a global priority. Inspired by leishmanization-a first generation vaccine strategy where live L. major parasites are inoculated in the skin to protect against reinfection-live-attenuated Leishmania vaccine candidates are promising alternatives due to their robust elicited protective immune response. In addition, they do not cause disease and could provide long-term protection upon challenge with a virulent strain. The discovery of a precise and easy way to perform CRISPR/Cas-based gene editing allowed the selection of safer null mutant live-attenuated Leishmania parasites obtained by gene disruption. Here, we revisited molecular targets associated with the selection of live-attenuated vaccinal strains, discussing their function, their limiting factors and the ideal candidate for the next generation of genetically engineered live-attenuated Leishmania vaccines to control leishmaniasis.

Curcumin and Its Analogs as a Therapeutic Strategy in Infections Caused by RNA Genome Viruses.

The use of natural resources for the prevention and treatment of diseases considered fatal to humanity has evolved. Several medicinal plants have nutritional and pharmacological potential in the prevention and treatment of viral infections, among them, turmeric, which is recognized for its biological properties associated with curcuminoids, mainly represented by curcumin, and found mostly in rhizomes. The purpose of this review was to compile the pharmacological activities of curcumin and its analogs, aiming at stimulating their use as a therapeutic strategy to treat infections caused by RNA genome viruses. We revisited its historical application as an anti-inflammatory, antioxidant, and antiviral agent that combined with low toxicity, motivated research against viruses affecting the population for decades. Most findings concentrate particularly on arboviruses, HIV, and the recent SARS-CoV-2. As one of the main conclusions, associating curcuminoids with nanomaterials increases solubility, bioavailability, and antiviral effects, characterized by blocking the entry of the virus into the cell or by inhibiting key enzymes in viral replication and transcription.

Shear-wave corner retroreflector device for ultrasonic measurement of viscosity.

This work shows a novel ultrasonic viscosity measurement device with increased sensitivity. The measuring principle is based on the determination of the complex reflection coefficient of shear-waves at the solid-liquid interface. But the proposed approach is the replacement of the flat surface at the measurement interface with a grooved surface, which works in a similar way to an optical retroreflector. The complete reflection of the waves involves a double reflection with oblique incidence, where both phenomena increase sensitivity, in comparison with a plane surface. It is shown that a set of orthogonal flat interfaces reflects a well-defined ultrasonic pulse. The sensitivity is enough to measure the change in the magnitude and phase of the reflection coefficient even for the small portion of the energy transmitted to water. A model for calculating the viscosity and a calibration approach for the measurement were proposed. Results with samples of corn syrup-water mixture are reported.

Ichthyoplankton community structure on the shelf break off northeastern Brazil.

Oceanographic features influence the early stages of fish to a high degree. We investigated the influence of continental shelf-slope gradient on the ichthyoplankton composition and distribution off Northeastern Brazil. Two oceanographic campaigns were performed during July-August 2010 and 2012. The samplings were performed along three transects composed by three stations, covering the continental shelf and slope areas. Abiotic data were obtained by an ADCP and a CTD. The ichthyoplankton was sampled through diurnal and nocturnal hauls using a 500-µm bongo net from 200 m to the surface. A total of 1634 larvae and 4023 eggs, representing 91 genera and 76 species, were collected. Higher concentrations of fish eggs were found on the continental shelf, probably because of the North Brazil Undercurrent flux. Higher concentrations of larvae were found at night and could be associated with net avoidance or natural variation. Neritic, oceanic and transition groups of species association were determined. Larvae of neritic, demersal and pelagic fishes prevailed on the continental shelf, while larvae of oceanic, mesopelagic and bathypelagic fishes on the continental slope. Melanostomiidae, Scorpaena sp., Lestidium atlanticum, Lampadena sp. and Diaphus sp. were identified as indicators of the continental slope.

Therapeutic Efficacy of a Mixed Formulation of Conventional and PEGylated Liposomes Containing Meglumine Antimoniate, Combined with Allopurinol, in Dogs Naturally Infected with Leishmania infantum.

The treatment of dogs naturally infected with Leishmania infantum using meglumine antimoniate (MA) encapsulated in conventional liposomes (LC) in association with allopurinol has been previously reported to promote a marked reduction in the parasite burden in the main infection sites. Here, a new assay in naturally infected dogs was performed using a novel liposome formulation of MA consisting of a mixture of conventional and long-circulating (PEGylated) liposomes (LCP), with expected broader distribution among affected tissues of the mononuclear phagocyte system. Experimental groups of naturally infected dogs were as follows: LCP plus Allop, receiving LCP intravenously as 2 cycles of 6 doses (6.5 mg Sb/kg of body weight/dose) at 4-day intervals plus allopurinol at 30 mg/kg/12 h per os (p.o.) during 130 days (LCP+Allop); LC plus Allop, receiving LC intravenously as 2 cycles of 6 doses (6.5 mg Sb/kg/dose) plus allopurinol during 130 days (LC+Allop); Allop, treated with allopurinol only; and a nontreated control. Parasite loads were evaluated by quantitative PCR in liver, spleen, and bone marrow tissue and by immunohistochemistry in the ear skin, before treatment, just after treatment, and 4 months later. The LCP+Allop and LC+Allop groups, but not the Allop group, showed significant suppression of the parasites in the liver, spleen, and bone marrow 4 months after treatment compared to the pretreatment period or the control group. Only LCP+Allop group showed significantly lower parasite burden in the skin in comparison to the control group. On the basis of clinical staging and parasitological evaluations, the LCP formulation exhibited a more favorable therapeutic profile than the LC one, being therefore promising for the treatment of canine visceral leishmaniasis.

Dynamic torque analysis of rotary and reciprocating instruments during root canal instrumentation in simulated canals by an endodontist or a general dentist.

BACKGROUND: Excessive torque is associated with engine-driven file fracture. AIMS: The aim of this study to evaluate the real-time torque of rotary and reciprocating instruments, working time, and the occurrence of procedural errors during root canal preparation of simulated canals by an endodontist and a general dentist. METHODS: Thirty-six commercially available simulated "J-shaped" root canals in resin blocks were used. Instrumentation was performed using WaveOne, WaveOne Gold, ProTaper Next, Reciproc, Reciproc Blue, and Mtwo. The real-time torque analysis and the number of times the maximum torque applied to the instrument were evaluated. Images were obtained to assess the occurrence of procedural errors, and working time was recorded. STATISTICAL ANALYSIS: The one-way analysis of variance with a Bonferroni post hoc test, Mann Whitney test and the t-test was used for statistical analysis (P < 0.05). RESULTS: Reciprocating instruments showed lower values in the number of times that reached maximum torque and percentage time in the area of critical torque, with significant differences compared to rotary instruments (P < 0.05). Operators influenced torque values only with rotary motion instruments. There was no significant difference in mean working time between the operators or instruments. No fracture of instruments or canal transportation occurred. CONCLUSIONS: Rotary instruments were associated with higher peaks in real-time torque variation during the preparation of simulated root canals.

Comparison of body composition analysis methods among centenary women: Seeking simpler methods.

OBJECTIVES: The aim of this study was to evaluate the most commonly used body composition tools in clinical practice, such as anthropometry and electrical bioimpedance, and compare it with deuterium oxide. METHODS: An exploratory cross-sectional study was conducted on women aged 100 years or above at home. Body composition was determined by measuring skinfolds (Jackson and Pollock and Durnin and Womersley equations), by bioimpedance, and by the deuterium oxide method. RESULTS: Body mass index values were lower than 22 kg/m2 in 64% of the subjects. When the various methods used were compared with deuterium oxide, there was better agreement for the determination of fat mass than lean mass. For fat mass, agreement was better when using bioimpedance (Lin's coefficient = 0.70), whereas for lean mass, agreement was better using the Durnin and Womersley equation (Lin's coefficient = 0.51). CONCLUSION: It is possible to use bioimpedance and skinfolds to evaluate fat mass and lean mass, respectively, in centenarians.

Large-Scale Spatial and Temporal Variability of Larval Fish Assemblages in the Tropical Atlantic Ocean.

This study investigated the large-scale spatial and temporal variability of larval fish assemblages in the west tropical Atlantic Ocean. The sampling was performed during four expeditions. Identification resulted in 100 taxa (64 families, 19 orders and 17 suborders). During the four periods, 80% of the total larvae taken represented eight characteristics families (Scombridae, Carangidae, Paralepididae, Bothidae, Gonostomatidae, Scaridae, Gobiidae and Myctophidae). Fish larvae showed a rather heterogeneous distribution with density at each station ranging from 0.5 to 2000 larvae per 100m3. A general trend was observed, lower densities at oceanic area and higher densities in the seamounts and islands. A gradient in temperature, salinity, phytoplankton biomass, zooplankton biomass and station depth was strongly correlated with changes in ichthyoplankton structure. Myctophidae, and Paralepididae presented increased abundance at high salinities and temperatures. Bothidae and Gobiidae were more abundant at higher phytoplankton biomass and zooplankton biomass. Scaridae, Scombridae and Gonostomatidae had higher abundances at deep offshore stations. Different events might be responsible for the formation, maintenance and breakdown of fish larvae assemblage in the tropical oceanic area of Brazil. The results suggested that the oceanographic variables (temperature, salinity, phytoplankton biomass, zooplankton biomass and station depth) played an important role on the distribution patterns of ichthyoplankton.

Novel Symmetrical 1,4-Disubstituted-bis-1,2,3-Triazoles: Synthesis by Double CuAAC and Cytotoxicity Evaluation.

BACKGROUND: A series of symmetrical 1,4-disubstituted bis-1,2,3-triazoles was prepared by double copper catalyzed Azide-alkyne Cycloaddition (CuAAC) from aliphatic bis-azides and a tetraethylene glycol bis-azide derivative. The eighteen novel compounds were evaluated in vitro for their cytotoxic activity against two human tumor cell lines: Human breast adenocarcinoma (MDA-MB 231) and ovarian adenocarcinoma (TOV-21G). RESULTS AND CONCLUSION: The results of colorimetric MTT assays showed that compounds 4j and 4q exhibited a better selectivity index and cell viability comparable with the standard drug doxorubicin. These compounds induced apoptosis in both tested cell lines, as assessed by BrdU assay. The results suggest that these structurally simple compounds may be promising prototypes for antitumoral agents.

The relative isotopic abundance (δ13C, δ15N) during composting of agricultural wastes in relation to compost quality and feedstock.

Variations in the relative isotopic abundance of C and N (δ13C and δ15N) were measured during the composting of different agricultural wastes using bench-scale bioreactors. Different mixtures of agricultural wastes (horse bedding manure + legume residues; dairy manure + jatropha mill cake; dairy manure + sugarcane residues; dairy manure alone) were used for aerobic-thermophilic composting. No significant differences were found between the δ13C values of the feedstock and the final compost, except for dairy manure + sugarcane residues (from initial ratio of -13.6 ± 0.2 ‰ to final ratio of -14.4 ± 0.2 ‰). δ15N values increased significantly in composts of horse bedding manure + legumes residues (from initial ratio of +5.9 ± 0.1 ‰ to final ratio of +8.2 ± 0.5 ‰) and dairy manure + jatropha mill cake (from initial ratio of +9.5 ± 0.2 ‰ to final ratio of +12.8 ± 0.7 ‰) and was related to the total N loss (mass balance). δ13C can be used to differentiate composts from different feedstock (e.g. C3 or C4 sources). The quantitative relationship between N loss and δ15N variation should be determined.

Hybrid Geoid Model: Theory and Application in Brazil.

Determination of the ellipsoidal height by Global Navigation Satellite Systems (GNSS) is becoming better known and used for purposes of leveling with the aid of geoid models. However, the disadvantage of this method is the quality of the geoid models, which degrade heights and limit the application of the method. In order to provide better quality in transforming height using GNSS leveling, this research aims to develop a hybridization methodology of gravimetric geoid models EGM08, MAPGEO2015 and GEOIDSP2014 for the State of São Paulo, providing more consistent models with GNSS technology. Radial Basis Function (RBF) neural networks were used to obtain the corrector surface, based on differences between geoid model undulations and the undulations obtained by GNSS tracking in benchmarks. The experiments showed that the most suitable interpolation for correction modeling is the linear RBF. Checkpoints indicate that the geoid hybrid models feature root mean square deviation ± 0.107, ± 0.104 and ± 0.098 m, respectively. The results shows an improvement of 30 to 40% in consistencies compared with the gravimetric geoids, providing users with better quality in transformation of geometric to orthometric heights.

Hybrid Geoid Model: Theory and Application in Brazil

Determination of the ellipsoidal height by Global Navigation Satellite Systems (GNSS) is becoming better known and used for purposes of leveling with the aid of geoid models. However, the disadvantage of this method is the quality of the geoid models, which degrade heights and limit the application of the method. In order to provide better quality in transforming height using GNSS leveling, this research aims to develop a hybridization methodology of gravimetric geoid models EGM08, MAPGEO2015 and GEOIDSP2014 for the State of São Paulo, providing more consistent models with GNSS technology. Radial Basis Function (RBF) neural networks were used to obtain the corrector surface, based on differences between geoid model undulations and the undulations obtained by GNSS tracking in benchmarks. The experiments showed that the most suitable interpolation for correction modeling is the linear RBF. Checkpoints indicate that the geoid hybrid models feature root mean square deviation ± 0.107, ± 0.104 and ± 0.098 m, respectively. The results shows an improvement of 30 to 40% in consistencies compared with the gravimetric geoids, providing users with better quality in transformation of geometric to orthometric heights.

Numerical Simulations to Assess ART and MART Performance for Ionospheric Tomography of Chapman Profiles

ABSTRACT The incomplete geometrical coverage of the Global Navigation Satellite System (GNSS) makes the ionospheric tomographic system an ill-conditioned problem for ionospheric imaging. In order to detect the principal limitations of the ill-conditioned tomographic solutions, numerical simulations of the ionosphere are under constant investigation. In this paper, we show an investigation of the accuracy of Algebraic Reconstruction Technique (ART) and Multiplicative ART (MART) for performing tomographic reconstruction of Chapman profiles using a simulated optimum scenario of GNSS signals tracked by ground-based receivers. Chapman functions were used to represent the ionospheric morphology and a set of analyses was conducted to assess ART and MART performance for estimating the Total Electron Content (TEC) and parameters that describes the Chapman function. The results showed that MART performed better in the reconstruction of the electron density peak and ART gave a better representation for estimating TEC and the shape of the ionosphere. Since we used an optimum scenario of the GNSS signals, the analyses indicate the intrinsic problems that may occur with ART and MART to recover valuable information for many applications of Telecommunication, Spatial Geodesy and Space Weather.

Numerical Simulations to Assess ART and MART Performance for Ionospheric Tomography of Chapman Profiles.

The incomplete geometrical coverage of the Global Navigation Satellite System (GNSS) makes the ionospheric tomographic system an ill-conditioned problem for ionospheric imaging. In order to detect the principal limitations of the ill-conditioned tomographic solutions, numerical simulations of the ionosphere are under constant investigation. In this paper, we show an investigation of the accuracy of Algebraic Reconstruction Technique (ART) and Multiplicative ART (MART) for performing tomographic reconstruction of Chapman profiles using a simulated optimum scenario of GNSS signals tracked by ground-based receivers. Chapman functions were used to represent the ionospheric morphology and a set of analyses was conducted to assess ART and MART performance for estimating the Total Electron Content (TEC) and parameters that describes the Chapman function. The results showed that MART performed better in the reconstruction of the electron density peak and ART gave a better representation for estimating TEC and the shape of the ionosphere. Since we used an optimum scenario of the GNSS signals, the analyses indicate the intrinsic problems that may occur with ART and MART to recover valuable information for many applications of Telecommunication, Spatial Geodesy and Space Weather.

Effect of heavy-equipment aided environmental nebulization on Aedes aegypti vectors of Dengue, Zika and Chikungunya in São Paulo, Brazil.

The control of dengue constitutes a great challenge for public health; however, the methods normally used have shown themselves to be insufficient to keep the indices of infestation of Aedes aegypti under control. Recently, beyond the large number of cases and deaths associated with dengue, new risks have arisen such as those represented by chikungunya fever and Zika. In the light of the great significance of these problems within the public health context, two areas in a municipality in the interior of the State of São Paulo, Brazil were selected in 2014. One of them, Bairro Cidade Nova, was submitted to the conventional method of nebulization with portable equipment, and the other, Bairro Jardim Europa, received the application of the insecticide by means of heavy-equipment coupled to the vehicle. During the project, 1355 mosquito eggs were collected, 1105 of them in Bairro Cidade Nova and 205 in Bairro Jardim Europa. After the applications with heavy-equipment in the months of March and April, the number of cases of the disease reported in the month of April for Bairro Jardim Europa was less than half that of Bairro Cidade Nova, which had received the conventional treatment. The nebulization with the heavy-equipment may constitute a viable and effective strategy for achieving better results in the control of Ae. aegypti.

White matter abnormalities in the fornix are linked to cognitive performance in SZ but not in BD disorder: An exploratory analysis with DTI deterministic tractography.

BACKGROUND: In psychosis, white matter (WM) microstructural changes have been detected previously; however, direct comparisons of findings between bipolar (BD) and schizophrenia (SZ) patients are scarce. In this study, we employed deterministic tractography to reconstruct WM tracts in BD and SZ patients. METHODS: Diffusion tensor imaging (DTI) data was carried out with n=32 euthymic BD type I patients, n=26 SZ patients and 30 matched healthy controls. Deterministic tractography using multiple indices of diffusion (fractional anisotropy (FA), tract volume (Vol), tract length (Le) and number of tracts (NofT)) were obtained from the fornix, the cingulum, the anterior thalamic radiation, and the corpus callosum bilaterally. RESULTS: We showed widespread WM microstructural changes in SZ, and changes in the corpus callosum, the left cingulum and the fornix in BD. Fornix fiber tracking scores were associated with cognitive performance in SZ, and with age and age at disease onset in the BD patient group. LIMITATIONS: Although the influence of psychopharmacological drugs as biasing variables on morphological alterations has been discussed for SZ and BD, we did not observe a clear influence of drug exposure on our findings. CONCLUSIONS: These results confirm the assumption that SZ patients have more severe WM changes than BD patients. The findings also suggest a major role of WM changes in the fornix as important fronto-limbic connections in the etiology of cognitive symptoms in SZ, but not in BD.

p53 gene discriminates two ecologically divergent sister species of pine voles.

Genes with relevant roles in the differentiation of closely-related species are likely to have diverged simultaneously with the species and more accurately reproduce the species tree. The Lusitanian (Microtus lusitanicus) and Mediterranean (M. duodecimcostatus) pine voles are two recently separated sister species with fossorial lifestyles whose different ecological, physiological and morphological phenotypes reflect the better adaptation of M. duodecimcostatus to the underground habitat. Here we asked whether the differentiation of M. lusitanicus and M. duodecimcostatus involved genetic variations within the tumour suppressor p53 gene, given its role in stress-associated responses. We performed a population-genetic analysis through sequencing of exons and introns of p53 in individuals from sympatric and allopatric populations of both the species in the Iberian Peninsula in which a unidirectional introgression of mitochondrial DNA was previously observed. We were able to discriminate the two species to a large extent. We show that M. duodecimcostatus is composed of one genetically unstructured group of populations sharing a P53 protein that carries a mutation in the DNA-binding region not observed in M. lusitanicus, raising the possibility that this mutation may have been central in the evolutionary history of M. duodecimcostatus. Our results provide suggestive evidence for the involvement of a master transcription factor in the separation of M. lusitanicus and M. duodecimcostatus during Microtus radiation in the Quaternary presumably via a differential adaptive role of the novel p53 in M. duodecimcostatus.

Identifying N fertilizer regime and vegetable production system in tropical Brazil using (15) N natural abundance.

BACKGROUND: This study was conducted in areas of vegetable production in tropical Brazil, with the objectives of (i) measuring the variation in δ(15) N in soils, organic N fertilizer sources and lettuce (Lactuca sativa L.) from different farming systems, (ii) measuring whether plant δ(15) N can differentiate organic versus conventional lettuce and (iii) identifying the factors affecting lettuce δ(15) N. RESULTS: Samples of soil, lettuce and organic inputs were taken from two organic, one conventional and one hydroponic farm. The two organic farms had different N-sources with δ(15) N values ranging from 0.0 to +14.9‰ (e.g. leguminous green manure and animal manure compost, respectively), and differed significantly (P < 0.05) in lettuce δ(15) N (+9.2 ± 1.1‰ and +14.3 ± 1.0‰). Conventional lettuce δ(15) N (+8.5 ± 2.7‰) differed from hydroponic lettuce δ(15) N (+4.5 ± 0.2‰) due to manure inputs. The N from leguminous green manure made a small contribution to the N nutrition of lettuce in the multi-N-source organic farm. CONCLUSION: To differentiate organic versus conventional farms using δ(15) N the several subsets of mode of fertilization should be considered. Comparisons of δ(15) N of soil, organic inputs and lettuce allowed a qualitative analysis of the relative importance of different N inputs.

Relationship between spatial distribution of chaetognaths and hydrographic conditions around seamounts and islands of the tropical southwestern Atlantic.

Relationship between spatial distribution of chaetognaths and hydrographic conditions around seamounts and islands off Northeastern Brazil were analyzed from 133 oceanographic stations during the months of January - April of 1997 and April - July of 1998. Oblique zooplankton tows, using 50 cm diameter Bongo nets with 500µm mesh with a flowmeter to determine the filtered volume, were carried out to a maximum of 200m depth. The Superficial Equatorial Water, which had a salinity > 36 PSU and temperature > 20°C, occupied the top 80 to 200m depth. Below this water mass was the South Atlantic Central Water with salinity ranging from 34.5 to 36 PSU and temperature from 6 to 20°C. The community of chaetognaths showed six species: Pterosagitta draco, Flaccisagitta enflata, Flaccisagitta hexaptera, Pseudosagitta lyra, Serratosagitta serratodentata, and Sagitta helenae. Of these species, F. enflata was the most abundant (32.05% in 1997 and 42.18% in 1998) and the most frequent (87.88% in 1997 and 95% in 1998) during both periods. A mesopelagic specie was identified (P. lyra). This specie was more abundant in 1997 (3.42%), when the upwelling was more intense. P. lyra occurred in 22% of the samples during 1997. The abundance of F. enflata, an epiplanktonic species, increased, associated with greater water-column stability.