Early-life nutrition interacts with developmental genes to shape the brain and sleep behavior in Drosophila melanogaster.

The mechanisms by which the genotype interacts with nutrition during development to contribute to the variation of complex behaviors and brain morphology of adults are not well understood. Here we use the Drosophila Genetic Reference Panel to identify genes and pathways underlying these interactions in sleep behavior and mushroom body morphology. We show that early-life nutritional restriction effects on sleep behavior and brain morphology depends on the genotype. We mapped genes associated with sleep sensitivity to early-life nutrition, which were enriched for protein-protein interactions responsible for translation, endocytosis regulation, ubiquitination, lipid metabolism, and neural development. By manipulating the expression of candidate genes in the mushroom bodies (MBs) and all neurons, we confirm that genes regulating neural development, translation and insulin signaling contribute to the variable response of sleep and brain morphology to early-life nutrition. We show that the interaction between differential expression of candidate genes with nutritional restriction in early life resides in the MBs or other neurons and that these effects are sex-specific. Natural variations in genes that control the systemic response to nutrition and brain development and function interact with early-life nutrition in different types of neurons to contribute to the variation of brain morphology and adult sleep behavior.

Pre-domestication bottlenecks of the cultivated seaweed Gracilaria chilensis.

Gracilaria chilensis is the main cultivated seaweed in Chile. The low genetic diversity observed in the Chilean populations has been associated with the over-exploitation of natural beds and/or the founder effect that occurred during post-glacial colonization from New Zealand. How these processes have affected its evolutionary trajectory before farming and incipient domestication is poorly understood. In this study, we used 2232 single nucleotide polymorphisms (SNPs) to assess how the species' evolutionary history in New Zealand (its region of origin), the founder effect linked to transoceanic dispersion and colonization of South America, and the recent over-exploitation of natural populations have influenced the genetic architecture of G. chilensis in Chile. The contrasting patterns of genetic diversity and structure observed between the two main islands in New Zealand attest to the important effects of Quaternary glacial cycles on G. chilensis. Approximate Bayesian Computation (ABC) analyses indicated that Chatham Island and South America were colonized independently near the end of the Last Glacial Maximum and emphasized the importance of coastal and oceanic currents during that period. Furthermore, ABC analyses inferred the existence of a recent and strong genetic bottleneck in Chile, matching the period of over-exploitation of the natural beds during the 1970s, followed by rapid demographic expansion linked to active clonal propagation used in farming. Recurrent genetic bottlenecks strongly eroded the genetic diversity of G. chilensis prior to its cultivation, raising important challenges for the management of genetic resources in this incipiently domesticated species.

Sobrevida en una cohorte con diagnóstico de tuberculosis en Colombia / Survival at cohort diagnosed with tuberculosis in Colombia

Introducción: La tuberculosis es una patología infecciosa crónica cuya incidencia es elevada en países en vía de desarrollo, sin embargo, es limitada la información y los estudios que analizan la mortalidad y sobrevida a largo plazo. Metodología: estudio de cohorte retrospectivo, en pacientes con diagnóstico de tuberculosis mayores de 18 años, el ingreso fue de manera consecutiva hasta completar el periodo de estudio. Se analizó la sobrevida y mortalidad a través del estimador Kaplan ­ Meier por la prueba de log Rank. Resultados: ingresaron 329 sujetos, la mortalidad a los 30 días fue de 11,9% y al año del 24,6%, la tuberculosis pulmonar fue el tipo más frecuente con en el 70,2%. Los hallazgos al examen físico relacionados con mortalidad fueron la caquexia (p<0,001) y el edema en extremidades (p<0,001). La sobrevida general fue del 87,2% a los 30 días y del 72,9% al año. En los pacientes con tuberculosis pulmonar la sobrevida fue del 85,8% a los 30 días y del 72,8% al año. Conclusión: La tasa de sobrevida a un año en pacientes hospitalizados por tuberculosis es baja, la edad avanzada, desnutrición, PaO2/FiO2 menor de 300, proteína c reactiva mayor de 45 mg/dL, enfermedad cerebrovascular y enfermedad vascular periférica fueron variables que se asociaron con una mayor mortalidad(AU)

Background: Tuberculosis is a chronic infectious pathology whose incidence is high in developing countries, however, information and studies that analyze mortality and long-term survival are limited. Methodology: retrospective cohort study, in patients with a diagnosis of tuberculosis older than 18 years, admission was consecutive until completing the study period. Survival and mortality were analyzed using the Kaplan-Meier estimator by the log Rank test. Results: 329 subjects were admitted, mortality at 30 days was 11.9% and at one year 24.6%, pulmonary tuberculosis was the most frequent type with 70.2%. Physical examination findings related to mortality were cachexia (p<0.001) and extremity edema (p<0.001). Overall survival was 87.2% at 30 days and 72.9% at one year. In patients with pulmonary tuberculosis, survival was 85.8% at 30 days and 72.8% at one year. Conclusion: The one-year survival rate in patients hospitalized for tuberculosis is low, advanced age, malnutrition, PaO2/FiO2 less than 300, c-reactive protein greater than 45 mg/dL, cerebrovascular disease and peripheral vascular disease were variables that were associated with higher mortality(AU)

Percepciones sobre racismos en las universidades: experiencias de los laboratorios de Paz / Perceptions of racism in universities: experiences of the Peace Labs / Percepções de racismo nas universidades: experiências dos Laboratórios de Paz

El objetivo de este artículo es compartir las percepciones que jóvenes universitarios tienen sobre los conceptos de discriminación, clasismo y racismo, así como identificar las diversas manifestaciones que se visibilizan dentro de sus universidades. La experiencia es analizada desde el enfoque cualitativo, considerando la perspectiva fenomenológica descriptiva, ya que, desde las opiniones registradas, en videos y el llenado de instrumentos es posible reconocer de viva voz sus conceptos y experiencias sobre el tema. El trabajo documenta la participación de 102 estudiantes de pregrado y posgrado en dos laboratorios de paz realizados en dos universidades sede. Entre los resultados se puede apreciar que los estudiantes aprendieron a diferenciar los conceptos de discriminación, clasismo y racismo; así como darse cuenta de que la problemática está más presente de lo que pensaban. Además de estar interesados por conocer más sobre el tema y comprometerse en participar en actividades para erradicar el racismo en las Universidades.

The objective of this article is to share the perceptions that young university students have about the concepts of discrimination, classism and racism, as well as to identify the various manifestations that are visible within their universities. The experience is analyzed from a qualitative approach, considering the descriptive phenomenological perspective, since, from the opinions recorded in videos and the filling out of instruments, it is possible to recognize their concepts and experiences on the subject. The work documents the participation of 102 undergraduate and graduate students in two peace laboratories carried out in two host universities. Among the results, it can be seen that students learned to differentiate the concepts of discrimination, classism and racism, as well as to realize that the problem is more present than they thought. In addition to being interested in learning more about the subject and committing themselves to participate in activities to eradicate racism in universities.

O objetivo deste artigo é compartilhar as percepções que jovens universitários têm sobre os conceitos de discriminação, classismo e racismo, bem como identificar as diversas manifestações que são visíveis dentro de suas universidades. A experiência é analisada a partir de uma abordagem qualitativa, considerando a perspetiva fenomenológica descritiva, uma vez que, a partir das opiniões registradas em vídeos e do preenchimento de instrumentos, é possível reconhecer em suas próprias vozes seus conceitos e experiências sobre o tema. O trabalho documenta a participação de 102 alunos de graduação e pós-graduação em dois laboratórios de paz realizados em duas universidades anfitriãs. Os resultados mostram que os alunos aprenderam a diferenciar os conceitos de discriminação, classismo e racismo, além de perceberem que o problema é mais frequente do que pensavam. Além de se mostrarem interessados em aprender mais sobre o assunto e se comprometerem a participar de atividades para erradicar o racismo nas universidades.

Rho-kinase pathway activation and apoptosis in circulating leucocytes in patients with heart failure with reduced ejection fraction.

BACKGROUND: Increased Rho-kinase activity in circulating leucocytes is observed in heart failure with reduced ejection fraction (HFrEF). However, there is little information in HFrEF regarding other Rho-kinase pathway components an on the relationship between Rho-kinase and apoptosis. Here, Rho-kinase activation levels and phosphorylation of major downstream molecules and apoptosis levels were measured for the first time both in HFrEF patients and healthy individuals. METHODS: Cross-sectional study comparing HFrEF patients (n = 20) and healthy controls (n = 19). Rho-kinase activity in circulating leucocytes (peripheral blood mononuclear cells, PBMCs) was determined by myosin light chain phosphatase 1 (MYPT1) and ezrin-radixin-moesin (ERM) phosphorylation. Rho-kinase cascade proteins phosphorylation p38-MAPK, myosin light chain-2, JAK and JNK were also analysed along with apoptosis. RESULTS: MYPT1 and ERM phosphorylation were significantly elevated in HFrEF patients, (3.9- and 4.8-fold higher than in controls, respectively). JAK phosphorylation was significantly increased by 300% over controls. Phosphorylation of downstream molecules p38-MAPK and myosin light chain-2 was significantly higher by 360% and 490%, respectively, while JNK phosphorylation was reduced by 60%. Catecholamine and angiotensin II levels were significantly higher in HFrEF patients, while angiotensin-(1-9) levels were lower. Apoptosis in circulating leucocytes was significantly increased in HFrEF patients by 2.8-fold compared with controls and significantly correlated with Rho-kinase activation. CONCLUSION: Rho-kinase pathway is activated in PMBCs from HFrEF patients despite optimal treatment, and it is closely associated with neurohormonal activation and with apoptosis. ROCK cascade inhibition might induce clinical benefits in HFrEF patients, and its assessment in PMBCs could be useful to evaluate reverse remodelling and disease regression.

Development of an Isavirus minigenome system to study the function of the pocket RNA-binding domain of the viral nucleoprotein (NP) in salmon cells.

The Isavirus is an orthomyxovirus with a genome composed of eight segments of negative single-strand RNA (-ssRNA). It has been proposed that the eight genomic segments of the Isavirus are organized as a ribonucleoprotein (RNP) complex called a minigenome, which contains all the viral RNA segments, a viral heterotrimeric polymerase and multiple copies of the viral nucleoprotein (NP). Here, we develop an Isavirus minigenome system and show the importance of the formation of active RNPs and the role of viral NP R189, R194, R302 and K325 residues in the NP RNA-binding domain in the context of RNPs. The results indicate it is possible to generate a minigenome in salmon cells, a composite ISAV RNPs with EGFP-based chimeric vRNA with heterotrimeric polymerase (PB1, PB2, PA) and NP protein using CMV-based auxiliary plasmids. It was also shown that NP R189, R194, R302 and K325 residues are important to generate viral mRNA from the constituted RNPs and a detectable reporter protein. This work is the first salmon cell-based minigenome assay for the Isavirus, which was evaluated by a bioinformatic and functional study of the NP protein in viral RNPs, which showed that correct NP-vRNA interaction is key to the functioning of RNPs.

En el modelo preclínico de insuficiencia cardíaca por disfunción sistólica en ratón (coartación de aorta torácica) la velocidad de flujo carotídeo determinada precozmente se asocia a función ventricular izquierda tardía / Carotid flow velocity is associated to late ventricular function in mice with preclinic systolic dysfunction induced by thoracic aortic coarctation

Resumen: Los modelos experimentales de falla cardíaca con fracción de eyección disminuida en murinos son pocos. Uno de estos modelos es el de coartación de la aorta torácica en el arco aórtico (COA) en ratones. Un aspecto importante en su desarrollo es la evaluación precoz del procedimiento y su relación con la función sistólica posterior. En este sentido, las velocidades de flujo carotídeo y la relación entre ambos flujos (derecho, pre-coartación; izquierdo post coartación) pueden permitir evaluar tempranamente la precisión del procedimiento y relacionarse más tardíamente con la función sistólica VI. Nuestro objetivo fue comparar precozmente (semana 2 post operatoria) las velocidades de flujo en ambas carótidas (Doppler continuo) y tardíamente (semana 5 postoperatoria) la función sistólica VI (Ecocardiograma de superficie) en ratones seudocoartados o sham (n= 6) vs ratones COA (n = 12). Se confirmó una diferencia estadísticamente significativa en la relación de velocidades de flujo entre ambas carótidas medida precozmente entre los ratones sham y COA (1,1 ± 0,1 vs 2,5 ± 0,5, p< 0,001), lo que se correlacionó con un deterioro significativo de la función sistólica del ventrículo izquierdo evaluada a las 5 semanas en los ratones COA. Conclusión: En este modelo preclínico de falla cardíaca por sobrecarga de presión con fracción de eyección VI disminuida en ratón, el aumento precoz de la velocidad de flujo en la arteria carótida derecha (pre-coartación en el modelo COA) y sobre todo de la relación entre las velocidades de flujo carotídeo entre ambas carótidas se asocia a deterioro importante de la función sistólica VI cinco semanas después de efectuada la COA, lo que permite predecir la efectividad del procedimiento en este modelo experimental.

Abstract: There are few experimental models of heart failure with reduced ejection fraction in murines. One of these models is transverse aortic coarctation (TAC) in mice. However, an important challenge in its development is the early evaluation of the procedure and its relationship with late systolic LV function. In this sense, carotid flow velocities and the relationship between both (right, precoarctation, left post-coarctation) may allow early evaluation of the accuracy of the procedure and be related to late LV systolic function. The aim was to compare early (week 2 post-operative) flow velocities determined in both carotid arteries (by continuous Doppler) with late (week 5 postoperative) LV systolic function (by echocardiogram) in sham (n= 6) vs. TAC (n: 12) mice. We confirmed a statistically significant difference in the early ratio of carotid flow velocities (left/right common carotid velocity ratio) between sham and TAC mice (1.1 ± 0.1 vs 2.5 ± 0.5, p< 0.001) and this correlated well with a deteriorated left ventricular function in the TAC mice after 5 weeks. In this preclinical model of cardiac failure due to pressure overload with reduced LV ejection fraction in the mouse, the early increase in right carotid flow velocity (precoarctation) and especially the relationship between precoarctation/postcoarctation carotid flow velocities is associated with significant impairment of LV systolic function five weeks after the TAC, which allows to predict the effectiveness of the procedure in this experimental model.

A functional transcriptomic analysis in the relict marsupial Dromiciops gliroides reveals adaptive regulation of protective functions during hibernation.

The small South American marsupial, Dromiciops gliroides, known as the missing link between the American and the Australian marsupials, is one of the few South American mammals known to hibernate. Expressing both daily torpor and seasonal hibernation, this species may provide crucial information about the mechanisms and the evolutionary origins of marsupial hibernation. Here, we compared torpid and active individuals, applying high-throughput sequencing technologies (RNA-seq) to profile gene expression in three D. gliroides tissues and determine whether hibernation induces tissue-specific differential gene expression. We found 566 transcripts that were significantly up-regulated during hibernation (369 in brain, 147 in liver and 50 in skeletal muscle) and 339 that were down-regulated (225 in brain, 79 in liver and 35 in muscle). The proteins encoded by these differentially expressed genes orchestrate multiple metabolic changes during hibernation, such as inhibition of angiogenesis, prevention of muscle disuse atrophy, fuel switch from carbohydrate to lipid metabolism, protection against reactive oxygen species and repair of damaged DNA. According to the global enrichment analysis, brain cells seem to differentially regulate a complex array of biological functions (e.g., cold sensitivity, circadian perception, stress response), whereas liver and muscle cells prioritize fuel switch and heat production for rewarming. Interestingly, transcripts of thioredoxin-interacting protein (TXNIP), a potent antioxidant, were significantly over-expressed during torpor in all three tissues. These results suggest that marsupial hibernation is a controlled process where selected metabolic pathways show adaptive modulation that can help to maintain homeostasis and enhance cytoprotection in the hypometabolic state.

Rho kinase activation in circulating leukocytes is related to hypertensive myocardial remodeling.

Rho-kinase has relevant functions in blood pressure modulation and cardiovascular remodeling. Rho-kinase activity is determined in circulating leukocytes measuring phosphorylation of its target myosin phosphatase target subunit 1 (MYPT1), but its relationship with Rho-kinase activity in the myocardium and in vasculature in hypertension has not been evaluated.The aim was to determine the degree of association between Rho-kinase cascade activation in circulating leukocytes with cardiac and aortic Rho-kinase pathway activation in a model of hypertension and to analyze it with a cause-effect perspective.Hypertensive deoxycorticosterone (DOCA)-salt rats received the Rho-kinase antagonist fasudil (DOCA-Fas, 100 mg/kg/day, 3 weeks). Results were compared with an untreated DOCA-salt and a sham group.Rho-kinase inhibition reduced significantly blood pressure, cardiac hypertrophy, myocardial collagen and macrophage infiltration, but not aortic wall hypertrophy. Fasudil decreased significantly Rho-kinase activity in peripheral blood mononucleated cells (PBMC), myocardium and aortic wall to similar levels as in the sham group. A significant correlation was found between PBMC Rho-kinase activity and cardiac remodeling, specifically with hypertrophy (r = 0.51, P≤0.01), myocardial collagen (r = 0.40, P≤0.05) and ED1 immunostaining (r = 0.48, P≤0.01). In the untreated hypertensive group, increased levels (P<0.05) of the proinflammatory molecules p65 NF-κB, vascular cell adhesion molecule 1 and interleukin-6 antibody in the myocardium, aortic wall and PBMC were observed and were reduced with fasudil (P<0.05).In conclusion, in this hypertension model, Rho-kinase and its pathway activation determined in circulating leukocytes reflect the activation of this pathway in the myocardium and in the aortic wall and are significantly related to myocardial remodeling (hypertrophy, fibrosis and inflammation).

Comparative Pan-Genome Analysis of Piscirickettsia salmonis Reveals Genomic Divergences within Genogroups.

Piscirickettsia salmonis is the etiological agent of salmonid rickettsial septicemia, a disease that seriously affects the salmonid industry. Despite efforts to genomically characterize P. salmonis, functional information on the life cycle, pathogenesis mechanisms, diagnosis, treatment, and control of this fish pathogen remain lacking. To address this knowledge gap, the present study conducted an in silico pan-genome analysis of 19 P. salmonis strains from distinct geographic locations and genogroups. Results revealed an expected open pan-genome of 3,463 genes and a core-genome of 1,732 genes. Two marked genogroups were identified, as confirmed by phylogenetic and phylogenomic relationships to the LF-89 and EM-90 reference strains, as well as by assessments of genomic structures. Different structural configurations were found for the six identified copies of the ribosomal operon in the P. salmonis genome, indicating translocation throughout the genetic material. Chromosomal divergences in genomic localization and quantity of genetic cassettes were also found for the Dot/Icm type IVB secretion system. To determine divergences between core-genomes, additional pan-genome descriptions were compiled for the so-termed LF and EM genogroups. Open pan-genomes composed of 2,924 and 2,778 genes and core-genomes composed of 2,170 and 2,228 genes were respectively found for the LF and EM genogroups. The core-genomes were functionally annotated using the Gene Ontology, KEGG, and Virulence Factor databases, revealing the presence of several shared groups of genes related to basic function of intracellular survival and bacterial pathogenesis. Additionally, the specific pan-genomes for the LF and EM genogroups were defined, resulting in the identification of 148 and 273 exclusive proteins, respectively. Notably, specific virulence factors linked to adherence, colonization, invasion factors, and endotoxins were established. The obtained data suggest that these genes could be directly associated with inter-genogroup differences in pathogenesis and host-pathogen interactions, information that could be useful in designing novel strategies for diagnosing and controlling P. salmonis infection.

Presentación tomográfica inusual, con crazy-paving, en insuflciencia cardíaca / Unusual tomographic presentation, with crazy-paving, in heart failure

Paciente masculino de 50 años ingresó a nuestra institución por sufrir un infarto agudo de miocardio. Durante su estadía en unidad coronaria se evidenció una fracción de eyección de 40% con aquinesia anterior medial, anterior apical, septal anterior medial, septal y lateral. Se realizó una cinecoronariografía con compromiso de la coronaria descendente anterior y circunfleja con colocación de un stent. En su evolución presentó edemas de miembros inferiores, presión venosa central elevada, registro febril y leucocitosis con progresión del cuadro a insuficiencia respiratoria, por lo que inició esquema antibiótico de amplio espectro y requirió intubación orotraqueal. A la auscultación, presentó hipoventilación en bases de ambos hemitórax. En la radiografía de tórax, se observaron ambas playas pulmonares ocupadas por infiltrado algodonoso parcheado con mayor compromiso y confluencia en campo medio izquierdo y mala delimitación de los hilios. Se realizó TAC de tórax simple (Figuras 1 y 2) con presencia de un patrón heterogéneo, compuesto por áreas de engrosamiento de septos interlobulillares asociado a tenue incremento de la densidad pulmonar (crazy paving), asociado a imágenes de mayor densidad, de ocupación alveolar, confluentes a nivel de campo medio izquierdo. Presencia de hilios prominentes vasculares y derrame pleural bilateral a predominio derecho

Next-generation transcriptome characterization in three Nacella species (Patellogastropoda: Nacellidae) from South America and Antarctica.

The southern tip of South America and Antarctica are particularly interesting due to many genera and also species currently sharing between both areas. The genus Nacella (Patellogastropoda: Nacellidae) is distributed in different regions of South America and Antarctica living preferentially on rocks and boulders and grazing on algae, diatoms and bacterial films. We described the transcriptomes of three Nacella species, Nacella concinna (Strebel, 1908), inhabiting the Antarctic Peninsula; Nacella magallanica (Gmelin, 1791), from Patagonia and Nacella clypeater (Lesson, 1831), from central Chile. In total, we obtained over 20,000 contigs with an average length of 583bp. Homologous protein coding genes (PCGs) for mitochondrial genome of the three species were characterized and a database of molecular markers was also generated. This study represents the first publicly available report on pyrosequencing data for patellogastropod species, and provides an important comparative resource for studies in ecophysiology and evolutionary adaptation in marine invertebrate species.

Molecular phylodynamics and protein modeling of infectious salmon anemia virus (ISAV).

BACKGROUND: ISAV is a member of the Orthomyxoviridae family that affects salmonids with disastrous results. It was first detected in 1984 in Norway and from then on it has been reported in Canada, United States, Scotland and the Faroe Islands. Recently, an outbreak was recorded in Chile with negative consequences for the local fishing industry. However, few studies have examined available data to test hypotheses associated with the phylogeographic partitioning of the infecting viral population, the population dynamics, or the evolutionary rates and demographic history of ISAV. To explore these issues, we collected relevant sequences of genes coding for both surface proteins from Chile, Canada, and Norway. We addressed questions regarding their phylogenetic relationships, evolutionary rates, and demographic history using modern phylogenetic methods. RESULTS: A recombination breakpoint was consistently detected in the Hemagglutinin-Esterase (he) gene at either side of the Highly Polymorphic Region (HPR), whereas no recombination breakpoints were detected in Fusion protein (f) gene. Evolutionary relationships of ISAV revealed the 2007 Chilean outbreak group as a monophyletic clade for f that has a sister relationship to the Norwegian isolates. Their tMRCA is consistent with epidemiological data and demographic history was successfully recovered showing a profound bottleneck with further population expansion. Finally, selection analyses detected ongoing diversifying selection in f and he codons associated with protease processing and the HPR region, respectively. CONCLUSIONS: Our results are consistent with the Norwegian origin hypothesis for the Chilean outbreak clade. In particular, ISAV HPR0 genotype is not the ancestor of all ISAV strains, although SK779/06 (HPR0) shares a common ancestor with the Chilean outbreak clade. Our analyses suggest that ISAV shows hallmarks typical of RNA viruses that can be exploited in epidemiological and surveillance settings. In addition, we hypothesized that genetic diversity of the HPR region is governed by recombination, probably due to template switching and that novel fusion gene proteolytic sites confer a selective advantage for the isolates that carry them. Additionally, protein modeling allowed us to relate the results of phylogenetic studies with the predicted structures. This study demonstrates that phylogenetic methods are important tools to predict future outbreaks of ISAV and other salmon pathogens.