Developmental outcomes in children exposed to Zika virus in utero from a Brazilian urban slum cohort study

BackgroundThe prevalence of developmental alterations associated with in-utero Zika virus (ZIKV) exposure in children is not well understood. Furthermore, estimation of the Population Attributable Fraction (PAF) of developmental alterations attributed to ZIKV has not been performed due to lack of population-based cohorts with data on symptomatic and asymptomatic ZIKV exposures and an appropriate control group. The aim of this study was to characterize neurodevelopmental outcomes of children at 11 to 32 months of age with intrauterine ZIKV exposure and estimate the PAF of alterations secondary to ZIKV exposure.Methodology/Principal findingsWe performed a cohort of biannual community-based prospective serosurveys in a slum community in Salvador, Brazil. We recruited women participating in our cohort, with a documented pregnancy from January 2015 to December 2016 and children born to those mothers. Children were classified as ZIKV exposed in utero (born from women with ZIKV seroconversion during pregnancy) or unexposed (born from women without ZIKV seroconversion or that seroconverted before/after pregnancy) by using an IgG monoclonal antibody blockade-of-binding (BoB). We interviewed mothers and performed anthropometric, audiometric, ophthalmological, neurologic, and neurodevelopmental evaluations of their children at 11 to 32 months of age. Among the 655 women participating in the cohort, 66 (10%) were pregnant during the study period. 46 (70%) of them completed follow-up, of whom ZIKV seroconversion occurred before, during, and after pregnancy in 25 (54%), 13 (28%), and 1 (2%), respectively. The rest of women, 7 (21.2%), did not present ZIKV seroconversion. At 11 to 32 months of life, the 13 ZIKV-exposed children had increased risk of mild cognitive delay (RR 5.1; 95%CI 1.1–24.4) compared with the 33 children unexposed, with a PAF of 53.5%. Exposed children also had increased risk of altered auditory behavior (RR 6.0; 95%CI 1.3–26.9), with a PAF of 59.5%.ConclusionsA significant proportion of children exposed in utero to ZIKV developed mild cognitive delay and auditory behavioral abnormalities even in the absence of gross birth defects such as microcephaly and other neurodevelopmental domains. Furthermore, our findings suggest that over half of these abnormalities could be attributed to intrauterine ZIKV exposure.     

Coenzyme Q-10 improves preservation of mitochondrial functionality and actin structure of cryopreserved stallion sperm

Coenzyme Q-10 (CoQ-10) is a cofactor for mitochondrial electron transport chain and may be an alternative to improve sperm quality of cryopreserved equine semen. This work aimed to improve stallion semen quality after freezing by adding CoQ-10 to the cryopreservation protocol. Seven saddle stallions were utilized. Each animal was submitted to five semen collections and freezing procedures. For cryopreservation, each ejaculate was divided in three treatments: 1) Botucrio® diluent (control); 2) 50 μmol CoQ-10 added to Botucrio® diluent; 3) 1 mmol CoQ-10 added to Botucrio® diluent. Semen batches were analyzed for sperm motility characteristics (CASA), plasma and acrosomal membranes integrity and mitochondrial membrane potential (by fluorescence probes propidium iodide, Hoechst 33342, FITC-PSA and JC-1, respectively), alterations in cytoskeletal actin (phalloidin-FITC) and mitochondrial function (diaminobenzidine; DAB). The 1 mmol CoQ-10 treatment presented higher (P<0.05) amount (66.8%) of sperm cells with fully stained midpiece (indicating high mitochondrial activity) and higher (P<0.05) amount (81.6%) of cells without actin reorganization to the post-acrosomal region compared to control group (60.8% and 76.0%, respectively). It was concluded that the addition of 1 mmol CoQ-10 to the freezing diluent was more effective in preserving mitochondria functionality and cytoskeleton of sperm cells submitted to cryopreservation process.     

So alike yet so different. Differential expression of the long non-coding RNAs NORAD and HCG11 in breast cancer subtypes

Breast cancer (BC) is a heterogeneous disease, and it is the leading cause of death among women. NORAD and HCG11 are highly similar lncRNAs that present binding sites for PUMILIO proteins. PUMILIO acts on hundreds of mRNA targets, contributing to the modulation of gene expression. We analyzed the expression levels of NORAD and HCG11 in the BC subtypes luminal A (LA) and basal-like (BL), and the regulatory networks associated with these lncRNAs. In the analysis of TCGA cohort (n=329) and Brazilian BC samples (n=44), NORAD was up-regulated in LA while HCG11 was up-regulated in BL subtype. An increased expression of NORAD is associated with reduced disease-free survival in basal-like patients (p = 0.002), which suggests that its prognostic value could be different in specific subtypes. The biological pathways observed for the HCG11 network are linked to the epithelial-to-mesenchymal transition; while NORAD associated pathways appear to be related to luminal epithelial cell transformation. NORAD and HCG11 regulons respectively present 36% and 21.5% of PUMILIO targets, which suggests that these lncRNAs act as a decoy for PUMILIO. These lncRNAs seem to work as players in the differentiation process that drives breast cells to acquire distinct phenotypes related to a specific BC subtype.     

Virological and immunological features of SARS-CoV-2-infected children who develop neutralizing antibodies

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Areas of endemism in the Espinhaço Range in Minas Gerais, Brazil

The Espinhaço Range, a mountain chain located in the Brazilian states of Minas Gerais and Bahia, contains one of the richest floras in Brazil, with a high frequency of endemic species. Since 2005 it is designated as UNESCO biosphere reserve and is situated at the joint border of two global hotspots for biodiversity conservation. Endemic species with congruent occurrence patterns were identified in order to establish areas of higher endemism within the Espinhaço Range. Taxonomic reviews were analyzed in order to identify endemic taxa and a dataset was elaborated containing 1765 records from 178 endemic species of vascular plants, representing 17 families and including the geographic coordinates for each record. Two maps were produced showing species richness and collection effort in 15′ quadrats. The congruent occurrences were identified and a third map was provided, delimiting 10 candidate areas of endemism for a “parsimony analysis of endemicity” (PAE). One most parsimonious cladogram is then retrieved, evidencing three major clades corresponding to the northern, central and southern portions of the Espinhaço, in addition to four subclades included into the central clade. We finally identified six major areas of endemism. Furthermore, there is a strong correlation between species richness and collector effort, revealing which areas are in need of further field inventories.     

Analysis of conversion and operation strategies for enzymatic hydrolysis of lignocellulosic biomass in a series of CSTRs with distributed feeding

Design considerations for enzymatic hydrolysis of lignocellulosic biomass in two and three continuous stirred tank reactors (CSTRs) in series with distributed feeding of substrate and enzyme, followed by a series of CSTRs, are discussed. A previously developed, fitted, and validated kinetic model is extended to accommodate distributed feeding and used along with the micromixing limiting situations of macrofluid and microfluid to describe the reaction system. The capabilities of the reaction system proposed are explored for a range of cumulative substrate concentration from 5 to 20% w/w (dry basis). Continuous distributed feeding does not show advantages in terms of cellulose conversion when compared with the operation where an equivalent mass of substrate is added at the first reactor of the series, but the potential to increase substrate concentration beyond the concentrations that can be handled in conventional CSTRs, and therefore, the volumetric productivity of reactors, is evident.     

Dysbiotic 1-carbon metabolism in cardiac muscle remodeling

Unless there is a genetic defect/mutation/deletion in a gene, the causation of a given disease is chronic dysregulation of gut metabolism. Most of the time, if not always, starts within the gut; that is what we eat. Recent research shows that the imbalance between good versus bad microbial population, especially in the gut, causes systemic diseases. Thus, an appropriate balance of the gut microbiota (eubiosis over dysbiosis) needs to be maintained for normal health (Veeranki and Tyagi, 2017, Journal of Cellular Physiology, 232, 2929–2930). However, during various diseases such as metabolic syndrome, inflammatory bowel disease, diabetes, obesity, and hypertension the dysbiotic gut environment tends to prevail. Our research focuses on homocysteine (Hcy) metabolism that occupies a center-stage in many biochemically relevant epigenetic mechanisms. For example, dysbiotic bacteria methylate promoters to inhibit gene activities. Interestingly, the product of the 1-carbon metabolism is Hcy, unequivocally. Emerging studies show that host resistance to various antibiotics occurs due to inverton promoter inhibition, presumably because of promoter methylation. This results from modification of host promoters by bacterial products leading to loss of host's ability to drug compatibility and system sensitivity. In this study, we focus on the role of high methionine diet (HMD), an ingredient rich in red meat and measure the effects of a probiotic on cardiac muscle remodeling and its functions. We employed wild type (WT) and cystathionine beta-synthase heterozygote knockout (CBS^+/−) mice with and without HMD and with and without a probiotic; PB (Lactobacillus) in drinking water for 16 weeks. Results indicate that matrix metalloproteinase-2 (MMP-2) activity was robust in CBS^+/− fed with HMD and that it was successfully attenuated by the PB treatment. Cardiomyocyte contractility and ECHO data revealed mitigation of the cardiac dysfunction in CBS^+/− + HMD mice treated with PB. In conclusion, our data suggest that probiotics can potentially reverse the Hcy-meditated cardiac dysfunction.     

Inhibition of liver protein degradation in vivo by intensive treatment with cycloheximide.

The AA in experiments performed on male rats treated with 0,5 mCi/kg of cycloheximide have observed an inhibition of liver protein degradation and have suggested two mechanism: 1) cycloheximide prevents the acute proteolytic response induced in fibroblast culture by exposure to serum-deficient media and in rat livers after perfusion probably by inhibiting the lysosomal - autophagic system, without modifications in total activity of lysosome proteinases. 2) It may be that protein degradation rate and level of lysosomal proteinases reinterrelated; the latter probably being a factor controlling the overall cell protein turnover rate.