Prokaryotic and eukaryotic skin microbiota modifications triggered by Leishmania infection in localized Cutaneous Leishmaniasis.

Cutaneous Leishmaniasis (CL) is a tropical disease characterized by cutaneous ulcers, sometimes with satellite lesions and nodular lymphangitis. Leishmania parasites, transmitted by sandfly vectors, cause this widespread public health challenge affecting millions worldwide. CL's complexity stems from diverse Leishmania species and intricate host interactions. Therefore, this study aims to shed light on the spatial-temporal distribution of Leishmania species and exploring the influence of skin microbiota on disease progression. We analyzed 40 samples from CL patients at three military bases across Colombia. Using Oxford Nanopore's Heat Shock Protein 70 sequencing, we identified Leishmania species and profiled microbiota in CL lesions and corresponding healthy limbs. Illumina sequencing of 16S-rRNA and 18S-rRNA genes helped analyze prokaryotic and eukaryotic communities. Our research uncovered a spatial-temporal overlap between regions of high CL incidence and our sampling locations, indicating the coexistence of various Leishmania species. L. naiffi emerged as a noteworthy discovery. In addition, our study delved into the changes in skin microbiota associated with CL lesions sampled by scraping compared with healthy skin sampled by brushing of upper and lower limbs. We observed alterations in microbial diversity, both in prokaryotic and eukaryotic communities, within the lesioned areas, signifying the potential role of microbiota in CL pathogenesis. The significant increase in specific bacterial families, such as Staphylococcaceae and Streptococcaceae, within CL lesions indicates their contribution to local inflammation. In essence, our study contributes to the ongoing research into CL, highlighting the need for a multifaceted approach to decipher the intricate interactions between Leishmaniasis and the skin microbiota.

Hormone profiles of the African pygmy mouse Mus minutoides, a species with XY female sex reversal.

In mammals, most sex differences in phenotype are controlled by gonadal hormones, but recent work on transgenic mice has shown that sex chromosomes can have a direct influence on sex-specific behaviors. In this study, we take advantage of the naturally occurring sex reversal in a mouse species, Mus minutoides, to investigate for the first time the relationship between sex chromosomes, hormones, and behaviors in a wild species. In this model, a feminizing variant of the X chromosome, named X*, produces three types of females with different sex chromosome complements (XX, XX*, and X*Y), associated with alternative behavioral phenotypes, while all males are XY. We thus compared the levels of three major circulating steroid hormones (testosterone, corticosterone, and estradiol) in the four sex genotypes to disentangle the influence of sex chromosomes and sex hormones on behavior. First, we did not find any difference in testosterone levels in the three female genotypes, although X*Y females are notoriously more aggressive. Second, in agreement with their lower anxiety-related behaviors, X*Y females and XY males display lower baseline corticosterone concentration than XX and XX* females. Instead of a direct hormonal influence, this result rather suggests that sex chromosomes may have an impact on the baseline corticosterone level, which in turn may influence behaviors. Third, estradiol concentrations do not explain the enhanced reproductive performance and maternal care behavior of the X*Y females compared to the XX and XX* females. Overall, this study highlights that most of the behaviors varying along with sex chromosome complement of this species are more likely driven by genetic factors rather than steroid hormone concentrations.

Genotypic sex shapes maternal care in the African pygmy mouse, Mus minutoides.

Sexually dimorphic behaviours, such as parental care, have long been thought to be mainly driven by gonadal hormones. In the past two decades, a few studies have challenged this view, highlighting the direct influence of the sex chromosome complement (XX versus XY or ZZ versus ZW). The African pygmy mouse, Mus minutoides, is a wild mouse species with naturally occurring XY sex reversal induced by a third, feminizing X* chromosome, leading to three female genotypes: XX, XX* and X*Y. Here, we show that sex reversal in X*Y females shapes a divergent maternal care strategy (maternal aggression, pup retrieval and nesting behaviours) from both XX and XX* females. Although neuroanatomical investigations were inconclusive, we show that the dopaminergic system in the anteroventral periventricular nucleus of the hypothalamus is worth investigating further as it may support differences in pup retrieval behaviour between females. Combining behaviours and neurobiology in a rodent subject to natural selection, we evaluate potential candidates for the neural basis of maternal behaviours and strengthen the underestimated role of the sex chromosomes in shaping sex differences in brain and behaviours. All things considered, we further highlight the emergence of a third sexual phenotype, challenging the binary view of phenotypic sexes.

Generating Edge Cases for Testing Autonomous Vehicles Using Real-World Data.

In the past decade, automotive companies have invested significantly in autonomous vehicles (AV), but achieving widespread deployment remains a challenge in part due to the complexities of safety evaluation. Traditional distance-based testing has been shown to be expensive and time-consuming. To address this, experts have proposed scenario-based testing (SBT), which simulates detailed real-world driving scenarios to assess vehicle responses efficiently. This paper introduces a method that builds a parametric representation of a driving scenario using collected driving data. By adopting a data-driven approach, we are then able to generate realistic, concrete scenarios that correspond to high-risk situations. A reinforcement learning technique is used to identify the combination of parameter values that result in the failure of a system under test (SUT). The proposed method generates novel, simulated high-risk scenarios, thereby offering a meaningful and focused assessment of AV systems.

Epidemiological Dynamics of SARS-CoV-2 Variants During Social Protests in Cali, Colombia.

Background: The third wave of the global health crisis attributed to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus reached Colombia in March 2021. Over the following 6 months, it was interpolated by manifestations of popular disapproval to the actual political regime-with multiple protests sprouting throughout the country. Large social gatherings seeded novel coronavirus disease 2019 (COVID-19) variants in big cities and propagated their facile spread, leading to increased rates of hospitalizations and deaths. Methods: In this article, we evaluate the effective reproduction number (Rt) dynamics of SARS-CoV-2 in Cali, Colombia, between 4 April 2021 and 31 July 2021 based on the analysis of 228 genomes. Results: Our results showed clear contrast in Rt values between the period of frequent protests (Rt > 1), and the preceding and following months (Rt < 1). Genomic analyses revealed 16 circulating SARS-CoV-2 lineages during the initial period-including variants of concern (VOCs) (Alpha, Gamma, and Delta) and variants of interest (VOIs) (Lambda and Mu). Furthermore, we noticed the Mu variant dominating the COVID-19 distribution schema as the months progressed. We identified four principal clusters through phylogenomic analyses-each one of potentially independent introduction to the city. Two of these were associated with the Mu variant, one associated with the Gamma variant, and one with the Lambda variant. Conclusion: Our results chronicle the impact of large group assemblies on the epidemiology of COVID-19 during this intersection of political turmoil and sanitary crisis in Cali, Colombia. We emphasize upon the effects of limited biosecurity strategies (which had characterized this time period), on the spread of highly virulent strains throughout Cali and greater Colombia.

Impact of SARS-CoV-2 Mu variant on vaccine effectiveness: A comparative genomics study at the peak of the third wave in Bogota, Colombia.

We assessed the circulation of severe acute respiratory syndrome coronavirus-2 variants amongst vaccinated military personnel in Bogotá, Colombia to evaluate the mutations of certain variants and their potential for breakthrough infection in vaccinated subjects. We observed that in vaccinated individuals the most frequent infecting lineage was Mu (B.1.621 and B.1.621.1). The above is possibly associated with specific mutations that confer it with vaccine-induced immune escape ability. Our findings highlight the importance of how genomic tracking coupled with epidemiological surveillance can assist in the study of novel emerging variants (e.g., Omicron) and their impact on vaccination efforts worldwide.

Multiple sex chromosome drivers in a mammal with three sex chromosomes.

Eukaryotes with separate males and females display a great diversity in the way they determine sex, but it is still unclear what evolutionary forces cause transitions between sex-determining systems. Rather that the lack of hypotheses, the problem is the scarcity of adequate biological systems to test them. Here, we take advantage of the recent evolution of a feminizing X chromosome (called X∗) in the African pygmy mouse Mus minutoides to investigate one of the evolutionary forces hypothesized to cause such transitions, namely sex chromosome drive (i.e., biased transmission of sex chromosomes to the next generation). Through extensive molecular sexing of pups at weaning, we reveal the existence of a remarkable male sex chromosome drive system in this species, whereby direction and strength of drive are conditional upon the genotype of males' partners: males transmit their Y at a rate close to 80% when mating with XX or XX∗ females and only 36% when mating with X∗Y females. Using mathematical modeling, we explore the joint evolution of these unusual sex-determining and drive systems, revealing that different sequences of events could have led to the evolution of this bizarre system and that the "conditional" nature of sex chromosome drive plays a crucial role in the short- and long-term maintenance of the three sex chromosomes.

Epidemiological Indicators of SARS-CoV-2 (COVID-19) and Vaccination Effectiveness on the Report of Positive Cases in the Colombian Army.

The description of the epidemiological indicators of SARS-CoV-2 (COVID-19), such as the mortality rate (MR), the case fatality rate (CFR), and the attack rate (AR), as well as the geographical distribution and daily case reports, are used to evaluate the impact that this virus has had within the Colombian Army and its health system. As military forces around the world represent the force that defends sovereignty, independence, the integrity of the national territory, and the constitutional order, while maintaining migration controls in blocked border areas during this critical pandemic times, they must carry out strict epidemiological surveillance to control the situation among the servicemen. Up to date, the Colombian Army has faced a very high attack rate (AR = 8.55%) due, among others, to living conditions where active military personnel share bedrooms, bathrooms, and dining facilities, which facilitate the spread of the virus. However, being a mainly young and healthy population, the MR was 1.82 deaths/1,000 ha, while the CFR = 2.13% indexes consistently low if compared with those values reported for the national population. In addition, the effectiveness of vaccination is shown in daily cases of COVID-19, where, for the third peak, the active military population presented a decrease of positive patients compared to the dynamics of national transmission and the total population of the military forces (active, retired, and beneficiaries).

A supernumerary "B-sex" chromosome drives male sex determination in the Pachón cavefish, Astyanax mexicanus.

Sex chromosomes are generally derived from a pair of classical type-A chromosomes, and relatively few alternative models have been proposed up to now.1,2 B chromosomes (Bs) are supernumerary and dispensable chromosomes with non-Mendelian inheritance found in many plant and animal species3,4 that have often been considered as selfish genetic elements that behave as genome parasites.5,6 The observation that in some species Bs can be either restricted or predominant in one sex7-14 raised the interesting hypothesis that Bs could play a role in sex determination.15 The characterization of putative B master sex-determining (MSD) genes, however, has not yet been provided to support this hypothesis. Here, in Astyanax mexicanus cavefish originating from Pachón cave, we show that Bs are strongly male predominant. Based on a high-quality genome assembly of a B-carrying male, we characterized the Pachón cavefish B sequence and found that it contains two duplicated loci of the putative MSD gene growth differentiation factor 6b (gdf6b). Supporting its role as an MSD gene, we found that the Pachón cavefish gdf6b gene is expressed specifically in differentiating male gonads, and that its knockout induces male-to-female sex reversal in B-carrying males. This demonstrates that gdf6b is necessary for triggering male sex determination in Pachón cavefish. Altogether these results bring multiple and independent lines of evidence supporting the conclusion that the Pachón cavefish B is a "B-sex" chromosome that contains duplicated copies of the gdf6b gene, which can promote male sex determination in this species.

Phylogenomic Evidence of Reinfection and Persistence of SARS-CoV-2: First Report from Colombia.

The continuing evolution of SARS-CoV-2 and the emergence of novel variants have raised concerns about possible reinfection events and potential changes in the coronavirus disease 2019 (COVID-19) transmission dynamics. Utilizing Oxford Nanopore technologies, we sequenced paired samples of three patients with positive RT-PCR results in a 1-2-month window period, and subsequent phylogenetics and genetic polymorphism analysis of these genomes was performed. Herein, we report, for the first time, genomic evidence of one case of reinfection in Colombia, exhibiting different SARS-CoV-2 lineage classifications between samples (B.1 and B.1.1.269). Furthermore, we report two cases of possible viral persistence, highlighting the importance of deepening our understanding on the evolutionary intra-host traits of this virus throughout different timeframes of disease progression. These results emphasize the relevance of genomic surveillance as a tool for understanding SARS-CoV-2 infection dynamics, and how this may translate effectively to future control and mitigations efforts, such as the national vaccination program.

Distribution, treatment outcome and genetic diversity of Leishmania species in military personnel from Colombia with cutaneous leishmaniasis.

BACKGROUND: Leishmaniasis is one of the most important infectious diseases affecting the Colombian National Army due to the high number of reported cases and exposure throughout military operations in endemic areas. The main aim of this study was to estimate the geographical distribution along with the genetic diversity and treatment outcome of Leishmania species in Colombian military personnel. METHODS: Skin lesion samples by smear and aspirate were collected in 136 patients having parasitological cutaneous leishmaniasis (CL) diagnosis. DNA was extracted, the nuclear marker heat shock protein 70 (HSP70) was amplified by PCR and sequenced. Leishmania species were identified by BLASTn. The geo-spatial distribution of the identified parasites was determined according to the possible site of infection. Gene tree was constructed by maximum likelihood (ML), diversity indices (π, h) were estimated and haplotype network was constructed under the Templeton-Crandall-Sing algorithm in order to determine the geographic relationships of the genetic variants of Leishmania species circulating in Colombian military population. RESULTS: The species were identified in 77.94% of the samples, with a predominance of L. braziliensis (65.09%), followed by L. panamensis (31.13%), L. naiffi by the first time reported in Colombia in two patients (1.89%) as well as L. lindenbergi in a single patient (0.945%) with possible infection in the municipality of Miraflores, Guaviare and L. infantum in a single patient (0.945%) notified with CL in the municipality of Tumaco, Nariño. The phylogenetic analysis was consistent according to bootstrap, showing four strongly differentiated clades. CONCLUSIONS: The geo-spatial distribution suggested that L. braziliensis has a greater abundance, while L. panamensis has a greater dispersion. The phylogenetic relationships of Leishmania species in Colombian military personnel was estimated with the confirmation of two new species circulating without prior report in the country and a species with no background for CL in the Colombian army. A substantial genetic diversity of Leishmania braziliensis was defined. This study contributes through the understanding of the molecular epidemiology to the CL transmission in Colombia.

Prevalence of Trypanosoma cruzi infection in active military population of The Colombian National Army gathered in five departments.

BACKGROUND: The National Army of Colombia is present in all of the national territory, focused in sylvatic zones where they are exposed continually to potential risk of transmission of Trypanosoma cruzi, the etiological agent of the Chagas disease. People of this study were active personal that were born and lived during their first years in endemic areas of transmission through domiciled vectors as Rhodnius prolixus. AIM: The main aim of this study was to estimate the prevalence of Chagas disease in the active military population of the National Army, gathered in five departments. METHODS: An observational and descriptive study with cross-sectional analysis was carried out. Blood sample each patient in order to apply serological diagnosis by two different Enzyme Linked ImmunoSorbent Assay tests, following the algorithm of National Institute of Health, Colombia. In cases of serum results with inconsistencies, a Hemagglutination Inhibition test and Indirect Immunofluorescence assay test were performed to solve inconclusiveness. Positive samples by two different tests were considered seropositive. Additionally, to each positive sample by at least one serological test, we did extraction of DNA for molecular diagnosis. RESULTS: 295 serums were analyzed and two of them were positive in order to get a prevalence of 0.68%. Two samples analyzed by molecular diagnosis were negative. CONCLUSION: The prevalence was < 1% It is probable the infection in the seropositive individuals occurred before enlisting in the military service due to origin locations with transmission such as Casanare and Boyacá. These findings allow defining the prevention and control programs of chronic cases and reduction in the disease burden.

C18 core-shell column with in-series absorbance and fluorescence detection for simultaneous monitoring of changes in stilbenoid and proanthocyanidin concentrations during grape cane storage.

Grape canes, the residues from the annual pruning of vines, contain high levels of inducible (E)-resveratrol and also oligomeric stilbenoids and proanthocyanidins. These two families of phenolic compounds are bioactive, but to quantify them in a single chromatographic run using only ultraviolet detection is a difficult task. To overcome this limitation, a chromatographic method was developed using a core shell column for separation, an ultraviolet-visible diode array detector (DAD) and a fluorescence (FL) detector connected in series for quantification, with an electrospray ionization interface (ESI) and a triple quadrupole mass spectrometric detector (MS/MS) added for identification of the analytes. The proanthocyanidins (+)-catechin, (-)-epicatechin, procyanidins B1, B2, and C1, an unknown dimer and trimer, two prodelphinidin dimers, and monogallate procyanidin dimers were detected in the tested grape cane samples. The stilbenoids detected were (E)-resveratrol, (E)-piceatannol, (E)-piceid, (E)-ε-viniferin, vitisin B, a glycosylated monomer, three oxidized dimers, an unknown dimer and a tetramer, pallidol, hopeaphenol, (E)-δ-viniferin, and (E)-ω-viniferin. However, this method required 60min for each analysis. A faster and more efficient method for quantitative analysis was developed based on HPLC-DAD-FL, reducing the time required to 24min for the simultaneous quantification of proanthocyanidins and stilbenoids in Cabernet Sauvignon, Pinot Noir, and Tintorera grape canes stored at controlled temperatures and relativity humidities for 134days after pruning. To the best of our knowledge, this is the first time a prodelphinidin dimer has been quantified in grape canes. The incorporation of fluorescence detection in series with DAD not only allowed the quantification of proanthocyanidins, it also improved the detectability of some minor stilbenoids present in the canes, such as (E)-piceid. The (E)-resveratrol and (E)-piceatannol levels increased significantly during cane storage, while those of (E)-ε-viniferin and ampelopsin A did not show significant increases. The relative humidity had a determining effect on the levels of (E)-resveratrol and (E)-piceatannol in the canes of all varieties studied; their concentrations were higher at a relative humidity of 60% than at 70%. This is the first time that the proanthocyanidin profiles of canes stored after pruning were monitored under controlled conditions of temperature, time and relative humidity. The concentration of (-)-epicatechin decreased during storage under both relative humidities. Furthermore, the levels of proanthocyanidin B1 and the prodelphinidin dimer also decreased to a certain extent.

X inactivation in a mammal species with three sex chromosomes.

X inactivation is a fundamental mechanism in eutherian mammals to restore a balance of X-linked gene products between XY males and XX females. However, it has never been extensively studied in a eutherian species with a sex determination system that deviates from the ubiquitous XX/XY. In this study, we explore the X inactivation process in the African pygmy mouse Mus minutoides, that harbours a polygenic sex determination with three sex chromosomes: Y, X, and a feminizing mutant X, named X*; females can thus be XX, XX*, or X*Y, and all males are XY. Using immunofluorescence, we investigated histone modification patterns between the two X chromosome types. We found that the X and X* chromosomes are randomly inactivated in XX* females, while no histone modifications were detected in X*Y females. Furthermore, in M. minutoides, X and X* chromosomes are fused to different autosomes, and we were able to show that the X inactivation never spreads into the autosomal segments. Evaluation of X inactivation by immunofluorescence is an excellent quantitative procedure, but it is only applicable when there is a structural difference between the two chromosomes that allows them to be distinguished.

Spatial distribution, Leishmania species and clinical traits of Cutaneous Leishmaniasis cases in the Colombian army.

In Colombia, the cutaneous leishmaniasis (CL) is the most common manifestation across the army personnel. Hence, it is mandatory to determine the species associated with the disease as well as the association with the clinical traits. A total of 273 samples of male patients with CL were included in the study and clinical data of the patients was studied. PCR and sequencing analyses (Cytb and HSP70 genes) were performed to identify the species and the intra-specific genetic variability. A georeferenced database was constructed to identify the spatial distribution of Leishmania species isolated. The identification of five species of Leishmania that circulate in the areas where army personnel are deployed is described. Predominant infecting Leishmania species corresponds to L. braziliensis (61.1%), followed by Leishmania panamensis (33.5%), with a high distribution of both species at geographical and municipal level. The species L. guyanensis, L. mexicana and L. lainsoni were also detected at lower frequency. We also showed the identification of different genotypes within L. braziliensis and L. panamensis. In conclusion, we identified the Leishmania species circulating in the areas where Colombian army personnel are deployed, as well as the high intra-specific genetic variability of L. braziliensis and L. panamensis and how these genotypes are distributed at the geographic level.

Sex reversal induces size and performance differences among females of the African pygmy mouse, Mus minutoides.

Differences in biological performance, at both intra- and inter-specific levels, have often been linked to morphology but seldom to behavioural or genotypic effects. We tested performance at the intraspecific level by measuring bite force in the African pygmy mouse, Mus minutoides. This species displays an unusual sex determination system, with sex-reversed, X*Y females carrying a feminizing X* chromosome. X*Y females cannot be differentiated from XX females based on external or gonadal morphology; however, they are known to be more aggressive. We found that bite force was higher in X*Y females than in other females and males. We then performed geometric morphometric analyses on their skulls and mandibles and found that the higher performance of X*Y females was mainly explained by a greater overall skull size. The effects of the X* chromosome thus go beyond feminization, and extend to whole-organism performance and morphology. Our results also suggest limited effects of behaviour on bite force.

Respostas ao tráfico no norte global: o caso de Portugal e Espanha / Responses to trafficking in the global north: the case of Portugal and Spain

Países desenvolvidos usam ações e discursos contra o tráfico de seres humanos como uma maneira mais palatável de impor políticas que restringem a migração e o trabalho sexual. Ainda que suas metas e resultados sejam similares, a maneira como Estados individuais elaboram e utilizam suas estruturas antitráfico varia e gera consequentemente repercussões distintas. Podemos considerar, por exemplo, que ainda que as políticas ibéricas sejam similares, a Espanha tem um sistema mais duramente criticado do que o de Portugal, pois seus métodos violam direitos de maneira mais clara.(AU)

Developed countries use anti-trafficking actions and discourses as a more palatable way of imposing polices that restrict migration and sex work. Although their aims and results are similar, the way individual States elaborate and use their anti-trafficking frameworks differs and therefore leads to different repercussions. We may consider, for instance, that while Iberian policies are similar, Spain’s system is much more harshly criticized than Portugal’s as its methods violate rights in a clearer manner.(AU)

An ace-1 gene duplication resorbs the fitness cost associated with resistance in Anopheles gambiae, the main malaria mosquito.

Widespread resistance to pyrethroids threatens malaria control in Africa. Consequently, several countries switched to carbamates and organophophates insecticides for indoor residual spraying. However, a mutation in the ace-1 gene conferring resistance to these compounds (ace-1(R) allele), is already present. Furthermore, a duplicated allele (ace-1(D)) recently appeared; characterizing its selective advantage is mandatory to evaluate the threat. Our data revealed that a unique duplication event, pairing a susceptible and a resistant copy of the ace-1 gene spread through West Africa. Further investigations revealed that, while ace-1(D) confers less resistance than ace-1(R), the high fitness cost associated with ace-1(R) is almost completely suppressed by the duplication for all traits studied. ace-1 duplication thus represents a permanent heterozygote phenotype, selected, and thus spreading, due to the mosaic nature of mosquito control. It provides malaria mosquito with a new evolutionary path that could hamper resistance management.