Metabolic control analysis of the transsulfuration pathway and the compensatory role of the cysteine transport in Trypanosoma cruzi.

Trypanosoma cruzi is the causal agent of American Trypanosomiasis or Chagas Disease in humans. The current drugs for its treatment benznidazole and nifurtimox have inconveniences of toxicity and efficacy; therefore, the search for new therapies continues. Validation through genetic strategies of new drug targets against the parasite metabolism have identified numerous essential genes. Target validation can be further narrowed by applying Metabolic Control Analysis (MCA) to determine the flux control coefficients of the pathway enzymes. That coefficient is a quantitative value that represents the degree in which an enzyme/transporter determines the flux of a metabolic pathway; those with the highest coefficients can be promising drug targets. Previous studies have demonstrated that cysteine (Cys) is a key precursor for the synthesis of trypanothione, the main antioxidant metabolite in the parasite. In this research, MCA was applied in an ex vivo system to the enzymes of the reverse transsulfuration pathway (RTP) for Cys synthesis composed by cystathionine beta synthase (CBS) and cystathionine gamma lyase (CGL). The results indicated that CGL has 90% of the control of the pathway flux. Inhibition of CGL with propargylglycine (PAG) decreased the levels of Cys and trypanothione and depleted those of glutathione in epimastigotes (proliferative stage in the insect vector); these metabolite changes were prevented by supplementing with Cys, suggesting a compensatory role of the Cys transport (CysT). Indeed, Cys supplementation (but not PAG treatment) increased the activity of the CysT in epimastigotes whereas in trypomastigotes (infective stage in mammals) CysT was increased when they were incubated with PAG. Our results suggested that CGL could be a potential drug target given its high control on the RTP flux and its effects on the parasite antioxidant defense. However, the redundant Cys supply pathways in the parasite may require inhibition of the CysT as well. Our findings also suggest differential responses of the Cys supply pathways in different parasite stages.

Dolor torácico agudo en pacientes jóvenes: reporte de dos casos / Acute chest pain in young patients: report of two cases

Se presentan dos casos clínicos de pacientes jóvenes con dolor torácico agudo, en ellos, el enfoque multidisciplinario y la resonancia magnética cardíaca jugaron un papel crucial en el diagnóstico y tratamiento. Presentación del caso 1. Un paciente de 20 años con dolor precordial y palpitaciones que mostró elevación de los niveles de enzimas cardíacas en los exámenes de laboratorio. La angiografía coronaria no reveló estenosis significativas. Sin embargo, se confirmó el diagnóstico de miocarditis a través de la resonancia magnética cardíaca, lo que llevó al inicio del tratamiento con medicamentos para lograr una función cardíaca adecuada y la prevención del progreso de la enfermedad. Su evolución clínica fue favorable. Presentación del caso 2. Un paciente de 19 años que presentó un dolor torácico intenso que se irradiaba al brazo izquierdo y mandíbula. Los exámenes de laboratorio reportaron elevación de los niveles de troponinas, que generaron la sospecha de un síndrome coronario agudo. La resonancia magnética cardíaca confirmó el diagnóstico de un infarto agudo de miocardio, y la angiografía coronaria reveló una estenosis significativa en la arteria descendente anterior y una ectasia subsiguiente. Durante la hospitalización, se brindó un enfoque terapéutico integral con la administración de medicamentos, monitoreo, control del dolor y prevención de complicaciones, y el paciente mostró una evolución clínica favorable

Two clinical cases of young patients with acute chest pain are presented, where the multidisciplinary approach and cardiac magnetic resonance played a crucial role in diagnosis and treatment. Case presentation 1. A 20 year old patient with precordial pain and palpitations showed elevated cardiac enzyme levels on laboratory examination. Coronary angiography revealed no significant stenosis. However, the diagnosis of myocarditis was confirmed by cardiac magnetic resonance imaging, which led to the initiation of drug treatment to achieve adequate cardiac function and prevention of disease progression. His clinical evolution was favorable. Case presentation 2. 19 year old patient presented with severe chest pain radiating to the left arm and jaw. Laboratory tests reported elevated troponin levels, which raised the suspicion of acute coronary syndrome. Cardiac magnetic resonance imaging confirmed the diagnosis of acute myocardial infarction, and coronary angiography revealed significant stenosis in the anterior descending artery and subsequent ectasia. During hospitalization, a comprehensive therapeutic approach with medication administration, monitoring, pain control, and prevention of complications was provided, and the patient showed a favorable clinical evolution

Machine learning and statistical classification of birdsong link vocal acoustic features with phylogeny.

Birdsong is a longstanding model system for studying evolution and biodiversity. Here, we collected and analyzed high quality song recordings from seven species in the family Estrildidae. We measured the acoustic features of syllables and then used dimensionality reduction and machine learning classifiers to identify features that accurately assigned syllables to species. Species differences were captured by the first 3 principal components, corresponding to basic frequency, power distribution, and spectrotemporal features. We then identified the measured features underlying classification accuracy. We found that fundamental frequency, mean frequency, spectral flatness, and syllable duration were the most informative features for species identification. Next, we tested whether specific acoustic features of species' songs predicted phylogenetic distance. We found significant phylogenetic signal in syllable frequency features, but not in power distribution or spectrotemporal features. Results suggest that frequency features are more constrained by species' genetics than are other features, and are the best signal features for identifying species from song recordings. The absence of phylogenetic signal in power distribution and spectrotemporal features suggests that these song features are labile, reflecting learning processes and individual recognition.

Auditory sensitivity and vocal acoustics in five species of estrildid songbirds.

Comparative studies of acoustic communication in clades with diverse signal features provide a powerful framework for testing relationships between perception and behaviour. We measured auditory sensitivity in five species of estrildid songbirds with acoustically distinct songs and tested whether differences aligned with species differences in song frequency content. Species were chosen based on phylogeny and differences in song acoustics. Behavioural audiograms were obtained using operant training and testing. Adult audiograms were compared across species and between sexes within a species. Juvenile and adult audiograms were compared in one species. The audiograms of adults reared by their own species and those reared and tutored by another species were compared in one species. Results showed that audiograms were similar across species and similar to previous reports of songbird auditory sensitivity. Species differed in the highest frequency detected and the frequency of peak sensitivity. While hearing frequency range was not correlated with song frequency bandwidth, the frequency of peak sensitivity was highly corelated with the frequency of peak energy in song. Sensitivity did not differ based on sex, age or tutoring experience. Our findings suggest that adaptations in songbird auditory sensitivity are largely constrained by shared peripheral and central encoding mechanisms, with species-specific perception appearing only at peak sensitivity.

Gestationally dependent immune organization at the maternal-fetal interface.

The immune system and placenta have a dynamic relationship across gestation to accommodate fetal growth and development. High-resolution characterization of this maternal-fetal interface is necessary to better understand the immunology of pregnancy and its complications. We developed a single-cell framework to simultaneously immuno-phenotype circulating, endovascular, and tissue-resident cells at the maternal-fetal interface throughout gestation, discriminating maternal and fetal contributions. Our data reveal distinct immune profiles across the endovascular and tissue compartments with tractable dynamics throughout gestation that respond to a systemic immune challenge in a gestationally dependent manner. We uncover a significant role for the innate immune system where phagocytes and neutrophils drive temporal organization of the placenta through remarkably diverse populations, including PD-L1+ subsets having compartmental and early gestational bias. Our approach and accompanying datasets provide a resource for additional investigations into gestational immunology and evoke a more significant role for the innate immune system in establishing the microenvironment of early pregnancy.

Neural activation in response to conspecific songs in zebra finch (Taeniopygia guttata) embryos and nestlings.

Classic studies on the effects of auditory stimulation in embryonic birds have largely been limited to precocial taxa. In altricial taxa, physiological responses of embryos and, subsequently, the behavioral responses of nestlings have begun to receive increasing attention, yet it remains unclear whether and to what specificity neural responses are generated in ovo. Using in-situ hybridization for an immediate early gene, ZENK, we detected significant neural activation in both the embryos and nestlings of an altricial songbird, the zebra finch (Taeniopygia guttata) when exposed to conspecific song playbacks relative to silence. In turn, embryonic ZENK responses to heterospecific songs were intermediate in strength. These results are consistent with physiological evidence for conspecific song selectivity in embryos of other altricial songbird taxa.

Efectividad a 3 y 6 meses de una intervención integral para caries dental en escolares de Sitio del Niño, La Libertad; San Cayetano Istepeque, San Vicente; Ilopango y Ciudad Delgado, San Salvador / Effectiveness at 3 and 6 months of an integral intervention for dental caries in schoolchildren from Sitio del Niño, La Libertad; San Cayetano Istepeque, San Vicente; Ilopango and Ciudad Delgado, San Salvador

El objetivo es determinar la efectividad a 3 y 6 meses de una intervención integral para caries dental en escolares de Sitio del Niño, La Libertad; San Cayetano Istepeque, San Vicente; Ilopango y Ciudad Delgado, San Salvador. Es una intervención comunitaria cuasi experimental con grupo control pre-post realizado en los niños de los centros escolares dentro de la cobertura de las Unidades Comunitarias de Salud Familiar, durante el período comprendido entre abril y diciembre de 2017 y primer trimestre del 2018, con una muestra total de 120 pacientes. Se realizó una evaluación diagnóstica para determinar las necesidades de tratamientos, registrándose los hallazgos en una ficha clínica. Se ejecutaron los tratamientos y posteriormente se determinó la efectividad a tres y seis meses con la disminución de la placa dentobacteriana, las lesiones de caries activas y la sobrevivencia de los tratamientos. El procesamiento y análisis de los datos se realizó en la herramienta informática S-DENT y SPSS. Al inicio de la investigación, se determinó una prevalencia de caries de 3.72; dando una disminución de caries de 0.91 a 3 meses y 0.58 a 6 meses. Así mismo, se evaluó el índice de higiene oral simplificado mostrando que el 40 % de la población estaba clasificada en nivel óptimo y a los 6 meses el porcentaje subió a 83%, con diferencia significativa p< 0.05. La supervivencia de sellantes de fosas y fisuras fue de 82% y de obturaciones fue de 92%. La intervención integral fue efectiva al disminuir el índice de placa dentobacteriana y de caries; así como el alto porcentaje de supervivencia de SFF y obturaciones.

The aim of the study is to determine the effectiveness at 3 and 6 months intervals of an integral intervention for dental caries in school children from Sitio del Niño, La Libertad; San Cayetano Istepeque, San Vicente; Ilopango and Ciudad Delgado, San Salvador. It is a quasy- experimental community intervention treatment with a pre-post control group, carried out among children of school centers within the coverage of the Family Health Community Units, between Apil and December of 2017 and the first trimester of 2018, with a total sample of 120 patients. A diagnostic evaluation was made to determine the necessities of treatments, and the findings were recorded in a clinical record card. The treatments were implemented and later their effectiveness was determined at three and six month intervals with the diminishing of the dento-bacterial plaque, active carious lesions and the survival of the treatments. The processing and analysis of the data were made using the S-DENT and SPDD Programs. At the beginning of the research, a dental caries prevalence of 3.72 was determined; resulting in a caries reduction of 0.91 at 3 months and 0.58 at six months. In the same way, the index of simplified oral hygiene was evaluated, showing that the 40% of the population was classified within the optimal level and in 6 months the percentage increased to 83%, with a significant difference of P< 0.05. The survival of the sealants of pits and fissures was the 82% and of the obturations was the 92%. The integral intervention was effective at decreasing the level of the dentobacterial plaque and caries; as well as the high percentage of survival of the SFFi and obturations.

Stereotypical alterations in cortical patterning are associated with maternal illness-induced placental dysfunction.

We have previously shown in mice that cytokine-mediated damage to the placenta can temporarily limit the flow of nutrients and oxygen to the fetus. The placental vulnerability is pronounced before embryonic day 11, when even mild immune challenge results in fetal loss. As gestation progresses, the placenta becomes increasingly resilient to maternal inflammation, but there is a narrow window in gestation when the placenta is still vulnerable to immune challenge yet resistant enough to allow for fetal survival. This gestational window correlates with early cortical neurogenesis in the fetal brain. Here, we show that maternal illness during this period selectively alters the abundance and laminar positioning of neuronal subtypes influenced by the Tbr1, Satb2, and Ctip2/Fezf2 patterning axis. The disturbances also lead to a laminar imbalance in the proportions of projection neurons and interneurons in the adult and are sufficient to cause changes in social behavior and cognition. These data illustrate how the timing of an illness-related placental vulnerability causes developmental alterations in neuroanatomical systems and behaviors that are relevant to autism spectrum disorders.