Project description:Preterm birth is a major cause of infant mortality and morbidity. The rate of preterm birth is 5-9% in most developed countries and 12% in the United States with approximately 15 million children born prematurely each year. Globally, prematurity is the second most common cause of death in children under the age of five years. To characterize the transcriptomic changes between preterm and full term neonates, RNA-sequencing was applied altogether to 14 cord blood samples. The analysis of the RNA-sequencing data revealed that the spontaneous preterm delivery resulted in systemic inflammatory responses at the gene and pathway level in the fetus.
Project description:We measured expression profiles of skin fibroblasts harvested during lip cleft surgery of neonates (until 16 days after birth) and children (until 10 years after birth) and compared them to fibroblast isolated from adult skin of breast, scar, and face. We observed clear differences between the cleft and facial fibroblasts and the fibroblasts of breast, as the former originate from the neural crest. Further, we observed differences between adult face fibroblasts and children fibroblasts.
Project description:Human blood plasma is a complex biological fluid containing soluble proteins, sugars, hormones, electrolytes, and dissolved gasses. As plasma interacts with a wide array of bodily systems, changes in protein expression, or the presence or absence of specific proteins are regularly used in the clinic as a molecular biomarker tool. A large body of literature exists detailing proteomic changes in pathologic contexts, however little research has been conducted on the quantitation of the plasma proteome in age-specific, healthy subjects, especially in pediatrics. In this study, we utilized SWATH-MS to identify and quantify proteins in the blood plasma of healthy neonates, infants under 1 year of age, children between 1-5 years, and adults. We identified more than 100 proteins that showed significant differential expression levels across these age groups, and we analyzed variation in protein expression across the age spectrum. The plasma proteomic profiles of neonates were strikingly dissimilar to the older children and adults. By extracting the SWATH data against a large human spectral library we increased protein identification more than 6-fold (940 proteins) and confirmed the concentrations of several of these using ELISA. The results of this study map the variation in expression of proteins and pathways often implicated in disease, and so have significant clinical implication.
2017-03-27 | PXD005661 | Pride
Project description:The nasopharyngeal microbiota of children under 5 years
Project description:We performed reduced-representation bisulfite sequencing (RRBS) on 137 umbilical cord blood (UCB) samples and 158 parental peripheral blood (PPB) samples from nuclear families with either singletons or twins. The samples were classified into five groups based on the mode of conception: spontaneous (CTRL), IVF-ET, IVF-FET, ICSI-ET and ICSI-FET. There were no significant differences in the clinical features of the neonates among the different groups; in addition, maternal ages were under 35 years old and parental body mass index (BMI) values were comparable in general. In addition, we performed chromatin immunoprecipitation sequencing (ChIP-seq) on 33 UCB samples to examine histone modifications (H3K4me1, H3K4me3, H3K27ac, and H3K27me3) and RNA sequencing (RNA-seq) on 32 UCB samples to examine the transcriptomes of neonates.
Project description:Bothrops moojeni has a wide distribution in Brazil and represents a serious medical concern at some localities. Previous works reported that the manifestations of snakebites caused by B. moojeni juveniles were mainly related to coagulation, while those caused by adults had more prominent local damage. In this work, we aimed to analyze the venoms of B. moojeni at different life stages to better understand how the venom shifts along the ontogeny. Snakes were grouped by age and sex, and venom pools were formed accordingly. Compositional analyses by one-dimensional electrophoresis (1-DE), chromatography and mass spectrometry revealed that ontogenetic changes may be mostly related to phospholipase A2 (PLA2) and metalloproteases. Regarding the functional aspect of the venoms, in vitro assays of proteolytic, L-amino acid oxidase, PLA2 and coagulant activities were assayed, but only the first and the last showed age-related changes, with the venom of younger snakes displaying lower proteolytic and higher coagulant activities up to 1 year-old; from 2 years-old onward, the venoms presented the opposite relation. The venoms of 3 years-old snakes were exceptions to the compositional and functional pattern of adults. Sex-related differences were observed at specific groups and not related to age. In vivo experiments (median lethal dose and hemorrhagic activity) were statistically similar between neonates and adults, but observation of the time each venom took to kill the mice revealed that the adult one seemed to act faster than the venoms of the neonates. All venoms were mostly recognized by the antibothropic serum and displayed similar profiles to 1-DE in western blotting. In conclusion, the venoms showed ontogenetic shift in composition and activities. Furthermore, this change occurred from 1 to 2 years-old, and interestingly the 3 years-old pools had particular characteristics, which highlight the importance of extending the studies to better understand venom variability.
Project description:Bacterial pulmonary infections are a major cause of morbidity and mortality in neonates, with less severity in older children (juveniles). Previous studies demonstrated that CD4+ T cells in the mouse lung, whose primary responsibility is coordinating the immune response foreign pathogens, are differentially methylated in neonates compared with juveniles. Nevertheless, the effect of this differential methylation on CD4+ T cell gene expression and response to infection remains unclear. We treated E. coli-infected neonatal (4-day-old) and juvenile (13-day-old) mice with decitabine (DAC), a DNA methyltransferase inhibitor with broad-spectrum DNA demethylating activity, and performed simultaneous genome-wide DNA methylation and transcriptional profiling on lung CD4+ T cells. Juvenile and neonatal mice experienced differential demethylation in response to DAC treatment, with larger methylation differences observed in neonates. By cross-filtering differentially expressed genes between juveniles and neonates with those sites that were demethylated in neonates, we found that interferon-responsive genes such as Ifit1 are the most down-regulated methylation-sensitive genes in neonatal mice. DAC treatment shifted neonatal lung CD4+ T cells toward a gene expression program similar to that of juveniles. Following lung infection with E. coli, lung CD4+ T cells in neonatal mice exhibit epigenetic repression of important host defense pathways, which are activated by inhibition of DNA methyltransferase activity to resemble a more mature profile.
Project description:Bacterial pulmonary infections are a major cause of morbidity and mortality in neonates, with less severity in older children (juveniles). Previous studies demonstrated that CD4+ T cells in the mouse lung, whose primary responsibility is coordinating the immune response foreign pathogens, are differentially methylated in neonates compared with juveniles. Nevertheless, the effect of this differential methylation on CD4+ T cell gene expression and response to infection remains unclear. We treated E. coli-infected neonatal (4-day-old) and juvenile (13-day-old) mice with decitabine (DAC), a DNA methyltransferase inhibitor with broad-spectrum DNA demethylating activity, and performed simultaneous genome-wide DNA methylation and transcriptional profiling on lung CD4+ T cells. Juvenile and neonatal mice experienced differential demethylation in response to DAC treatment, with larger methylation differences observed in neonates. By cross-filtering differentially expressed genes between juveniles and neonates with those sites that were demethylated in neonates, we found that interferon-responsive genes such as Ifit1 are the most down-regulated methylation-sensitive genes in neonatal mice. DAC treatment shifted neonatal lung CD4+ T cells toward a gene expression program similar to that of juveniles. Following lung infection with E. coli, lung CD4+ T cells in neonatal mice exhibit epigenetic repression of important host defense pathways, which are activated by inhibition of DNA methyltransferase activity to resemble a more mature profile.
Project description:Patients with sickle cell anemia (SCA) show higher levels of circulating pro-inflammatory cytokines and endothelial activation markers compared to healthy peers and altered blood transcriptome profiles. However, the characterization of the whole-blood transcriptome profile in response to exercise has not been evaluated in children with SCA. Twenty-three children/adolescents with SCA (10-19 years old) and 17 healthy controls (10-22 years old) performed eight 2-min bouts of cycle ergometry interspersed with 1-min rest intervals (50% or 70% of the peak workload achieved during the cardiopulmonary exercise test). Whole-blood transcriptome profile (RNA-seq) was performed before and after the exercise protocol. Following exercise, gene pathways associated with innate immunity were altered in both children with SCA and controls. Our results shed light on the common and different immune responses to acute exercise at the molecular level in children with SCA and healthy controls.
2024-05-24 | GSE244401 | GEO
Project description:Fecal microbiotia compositions from Ugandan children of 2 and 3 years old