Apolipoprotein E controls Dectin-1-dependent development of monocyte-derived alveolar macrophages upon pulmonary ß-glucan-induced inflammatory adaptation.

The lung is constantly exposed to the outside world and optimal adaptation of immune responses is crucial for efficient pathogen clearance. However, mechanisms that lead to lung-associated macrophages' functional and developmental adaptation remain elusive. To reveal such mechanisms, we developed a reductionist model of environmental intranasal ß-glucan exposure, allowing for the detailed interrogation of molecular mechanisms of pulmonary macrophage adaptation. Employing single-cell transcriptomics, high-dimensional imaging and flow cytometric characterization paired with in vivo and ex vivo challenge models, we reveal that pulmonary low-grade inflammation results in the development of apolipoprotein E (ApoE)-dependent monocyte-derived alveolar macrophages (ApoE+CD11b+ AMs). ApoE+CD11b+ AMs expressed high levels of CD11b, ApoE, Gpnmb and Ccl6, were glycolytic, highly phagocytic and produced large amounts of interleukin-6 upon restimulation. Functional differences were cell intrinsic, and myeloid cell-specific ApoE ablation inhibited Ly6c+ monocyte to ApoE+CD11b+ AM differentiation dependent on macrophage colony-stimulating factor secretion, promoting ApoE+CD11b+ AM cell death and thus impeding ApoE+CD11b+ AM maintenance. In vivo, ß-glucan-elicited ApoE+CD11b+ AMs limited the bacterial burden of Legionella pneumophilia after infection and improved the disease outcome in vivo and ex vivo in a murine lung fibrosis model. Collectively these data identify ApoE+CD11b+ AMs generated upon environmental cues, under the control of ApoE signaling, as an essential determinant for lung adaptation enhancing tissue resilience.

Consensus on the management of complications of cirrhosis of the liver in pediatrics.

The Asociación Mexicana de Hepatología A.C. carried out the Consensus on the Management of Complications of Cirrhosis of the Liver in Pediatrics to provide physicians with useful information for treating said complications. A group of pediatric gastroenterologists and experts in nutrition, nephrology, and infectious diseases participated and reviewed the medical literature. The Delphi method was applied to obtain the level of agreement on the statements that were formulated. The statements were sent to the participants to be analyzed and voted upon, after which they were discussed in virtual sessions, and the final versions were produced. The aim of the consensus results was to issue indications for the management of pediatric patients with liver cirrhosis, to prevent or control complications.

The electronic nose as a rule-out test for tuberculosis in an indigenous population.

INTRODUCTION: To end the tuberculosis (TB) epidemic, efficient diagnostic tools are needed. In a previous calibration study, a portable 'point of care' electronic nose device (AeonoseTM ) proved to be a promising tool in a hospital setting. We evaluated this technology to detect TB in an indigenous population in Paraguay. METHODS: A total of 131 participants were enrolled. eNose results were compared with anamnesis, physical examinations, chest radiography and mycobacterial cultures in individuals with signs and symptoms compatible with TB. The eNose analysis was performed in two stages: first, the training with a combination of a previous study population plus 47 participants from the new cohort (total n = 153), and second, the 'blind prediction' of 84 participants. RESULTS: 21% of all participants (n = 131) showed symptoms and/or chest radiography abnormalities suspicious of TB. No sputum samples resulted culture positive for Mycobacterium tuberculosis complex. Only one patient had a positive smell print analysis. In the training model, the specificity was 92% (95% confidence interval (CI): 85%-96%) and the negative predictive value (NPV) was 95%. In the blind prediction model, the specificity and the NPV were 99% (95% CI: 93%-99%) and 100%, respectively. Although the sensitivity and positive predictive value of the eNose could not be assessed in this cohort due to the small sample size, no active TB cases were found during a one year of follow-up period. CONCLUSION: The eNose showed promising specificity and negative predictive value and might therefore be developed as a rule-out test for TB in vulnerable populations.

Identification of SNPs in growth-related genes in Colombian creole cattle.

Colombian creole cattle have important adaptation traits related to heat tolerance and reproductive and productive efficiency. Romosinuano (ROMO) and Blanco Orejinegro (BON) are the most common breeds used by Colombian cattle breeders. Growth traits are of prime importance in these animals, which are mainly raised for beef production. Genes encoding growth hormone, growth hormone receptor, homeobox protein, insulin growth factor binding protein 3, leptin, and myostatin have been associated with physiological growth pathways in cattle and other species. We therefore aimed to identify single nucleotide polymorphisms (SNPs) within these genes in ROMO, BON, and Zebu cattle. DNA regions of these genes were sequenced in 386 animals; 47 new SNPs were found, of which 14 were located in the exonic regions, thereby changing the protein sequence. An association of SNPs with weaning weight (WW), daily weight gain at weaning (DWG), and weight at 16 months (W16M) traits was deduced. The genetic analysis revealed several SNPs related to these traits. The SNP GhRE06.2 had a significant association with WW and the SNP Lep03.4 was highly associated with DWG and W16M. Other polymorphisms were significantly associated with WW and DWG, although they did not surpass the Bonferroni significance threshold. The new mutations identified may indicate important points of genetic control in the DNA that could be responsible for changes in the expression of the analyzed traits. These SNPs might be used in future breeding programs to improve the productive performance of cattle in beef farms.

Direct and maternal genetic effects on growth, reproduction, and ultrasound traits in zebu Brahman cattle in Colombia.

Covariance components and genetic parameters were estimated for birth weight (BiW); adjusted weights at 4, 7, 12, and 18 mo; and ADG between 0 and 4 mo, between 4 and 7 mo, between 7 and 12 mo, and between 12 and 18 mo. Additionally, reproductive traits, calving interval, and age at first calving were analyzed, together with traits measured by ultrasound: loin eye area, deep fat mean, back fat, and rump fat. Analyses were performed using an animal model, considering the fixed effects of the farm ( = 37), year and month of birth, sex, calving number (1 to 7), season (dry and rainy seasons), region (North Coast, Andean Region, and Oriental Savannas), and conception (natural mating or AI), whereas the age of the cows at calving was considered a polynomial covariate with linear and quadratic effects. Three different models were used to find the one with the best fit for each trait: a single-trait model with an additive direct genetic effect, a single-trait model with additive direct and maternal genetic effects, and finally, a multitrait model with an additive direct genetic effect. For the growth traits, the heritability was between 0.24 and 0.47, with the lowest value for weight at 7 mo and the greatest value for BiW, and the maternal heritability was found to be between 0.15 and 0.21 but did not decrease later on. The correlation between direct and maternal effects was high and negative (-0.59 to -0.76). With ultrasound traits, a model with only direct effects was used. The heritability was between 0.13 and 0.28 for back fat and loin eye area, respectively. The heritabilities for deep fat mean and rump fat were similar, being 0.19 and 0.21, respectively. The reproductive traits showed high residual variance. In particular, the heritability of calving interval was low (0.06). The results showed that the growth traits have an important genetic component, which is a favorable indicator for obtaining improvement progress in the zebu Brahman breed for beef production in tropical regions of Colombia. The maternal effects influenced the weight performance from 4 to 18 mo and should be taken into account in genetic analyses. In general, the direct heritability of medium magnitude estimated for growth and traits measured by ultrasound suggests that individual selection for these traits will be effective.