Project description:To identify markers associated with inherent cellular sex-identity, we analysed macrophages from newly-hatched chicks. We found that male and female macrophages respond differently to stimulation by bacterial lipopolysaccharide and that female macrophages constitutively express higher levels of interferon target genes than male macrophages. Macrophages were collected from leg-bones of chickens between 1 and 3 days after hatch. Three pools of macrophage cells were made for male and female cultures. Cells were cultured in either standard medium or in medium containing lipopolysaccharide (LPS) to activate the macrophages. Macrophages were harvested and RNA collected for microarray analysis.
Project description:Simple Markov model.
There are 3 disease states: Healthy, Sick, and Dead, where the Dead state is terminal.
The yearly transition probabilities are:
Healthy to Dead: 0.01; Healthy to Sick: 0.2 for Male and 0.1 for Female; Sick to Healthy: 0.1; Sick to Dead: 0.3.
The transition probability now depends on the cohort (Male or Female) and can be expressed as a function of a Boolean covariate Male.
Initial conditions: Healthy = (50 Male, 50 Female), Sick = (0,0) and Dead = (0,0).
Output: Number of men and women in each disease state for years 1-10.
Project description:To identify markers associated with inherent cellular sex-identity, we analysed cultured macrophages from male and female chick embryos. We found that male and female macrophages respond differently to stimulation by bacterial lipopolysaccharide and that female macrophages constitutively express higher levels of interferon target genes than male macrophages. To determine whether these differences resulted from the actions of gonadal hormones, we induced gonadal sex-reversal to alter the hormonal environment of the developing chick and analysed different tissues and macrophages from male and female embryos.
Project description:To identify markers associated with inherent cellular sex-identity, we analysed macrophages from newly-hatched chicks. We found that male and female macrophages respond differently to stimulation by bacterial lipopolysaccharide and that female macrophages constitutively express higher levels of interferon target genes than male macrophages.
Project description:Cryptococcus neoformans (Cn) is a pathogenic yeast and the cause of cryptococcosis, a life-threatening fungal disease. Strikingly, ~70% of patients that develop cryptococcosis are male. Here, we investigated decreased Cn recognition by male macrophages and the impact on the subsequent innate immune response. Human PBMCs were isolated from healthy male and female donors, differentiated into macrophages, and tested for immune response differences. Cn incubated with female serum showed increased binding of the opsonin serum amyloid P component, possibly explaining the increased Cn phagocytosis in female macrophages. Cytokine analysis showed increased secretion of proinflammatory cytokines at 24 h in male macrophages that substantially decreased by 48 h. In contrast, female macrophages secreted fewer proinflammatory cytokines at both 24 and 48 h but had increased secretion of CCL5 (24 and 48 h) and IL-18 (48 h). As male macrophages rapidly downregulated proinflammatory immune responses after 24 h; we investigated the macrophage activation state. Male macrophages were alternatively activated at 48 h, with increased secretion of arginase 1 whereas female macrophages were classically activated, with increased secretion of nitric oxide at 24 and 48 h. Cn genes related to glucuronoxylomannan (GXM) biosynthesis were increased in Cn grown in male serum at 48 h. These data suggest that female macrophages better recognize Cn and become classically activated whereas male macrophages initiate an inflammatory response that is markedly reduced after 24 h, possibly due to testosterone-induced GXM secretion. Therefore, antifungal therapeutics targeting testosterone-induced GXM release may improve outcomes in male patients with cryptococcosis.
Project description:The genetic foundation of chicken tail feather color is not very well studied to date, though that of body feather color is extensively explored. In the present study, we used a synthetic chicken dwarf line (DW), which was originated from the hybrids between a black tail chicken breed, Rhode Island Red (RIR) and a white tail breed, Dwarf Layer (DL), to understand the genetic rules of the white/black tail color. The DW line still contain the individuals with black or white tails, even if the body feather are predominantly red, after more than ten generation of self-crossing and being selected for the body feather color. We firstly performed four crosses using the DW line chickens including black tail male to female, reciprocal crosses between the black and white, and white male to female to elucidate the inheritance pattern of the white/black tail. We found that (i) the white/black tail feather colors are independent of body feather color and (ii) the phenotype are autosomal simple trait and (iii) the white are dominant to the black in the DW lines. Furtherly, we performed a genome-wide association (GWA) analysis to determine the candidate genomic regions underlying the tail feather color by using black tail chickens from the RIR and DW chickens and white individuals from DW lines.
Project description:Model with functions depending on Age, Male, BP (Blood Pressure).
There are 3 disease states: Healthy, Sick, and Dead, where the Dead state is terminal. The yearly transition probabilities are: Healthy to Dead: Age/1000; Healthy to Sick: According to function F1 depending on Age and Male and BP; Sick to Healthy: 0.1; Sick to Dead: according to function F2 depending on Age and Male.
Pre-Transition Rules: Age increased by 1 and BP by Age/10 each simulation cycle. Post-Transition Rules: Treatment = BP>140 , becomes 1 when BP crosses 140 threshold; BP =BP-Treatment*10 , meaning a drop of 10 once treatment is applied; CostThisYear = Age + \Treatment*10 , cost depends on age and if treatment was taken; Cost= Cost + CostThisYear , it accumulates cost over time.
Initial conditions: Healthy = (50 Male, 50 Female with Age =1,2,...,50 for each individual), BP =120, Sick = (0,0) and Dead = (0,0).
Output: Number of men and women in each disease state for years 1-10 and their ages and costs in each state. A stratified report by male and female and young – up to age 30 and old above age 30 is produced.
Project description:Model dependent on changing parameters.
There are 3 disease states: Healthy, Sick, and Dead, where the Dead state is terminal.
The yearly transition probabilities are:
Healthy to Dead: Age/1000; Healthy to Sick: according to function F1 depending on Age and Male parameters; Sick to Healthy: 0.1; Sick to Dead: according to function F2 depending on Age and Male parameters. Pre-Transition Rules: Age increased by 1 each cycle.
Initial conditions: Healthy = (50 Male, 50 Female with Age =1,2,…,50 for each individual), Sick = (0,0) and Dead = (0,0).
Output: Number of men and women in each disease state for years 1-10 and their ages in each state.
Project description:Avian sex is determined by various factors, such as the dosage of DMRT1 and cell-autonomous mechanisms. While the sex-determination mechanism in gonads is well analyzed, the mechanism in germ cells remains unclear. In this study, we explored the gene expression profiles of male and female primordial germ cells (PGCs) during embryogenesis in chickens to predict the mechanism of sex-determination. Male and female PGCs were isolated from blood and gonads with a purity > 96% using flow cytometry and analyzed using RNA-seq. Prior to settlement in the gonads, female circulating PGCs (cPGCs) obtained from blood displayed sex-biased expression. Gonadal PGCs (gPGCs) also displayed sex-biased expression, and the number of female-biased genes detected was higher than male-biased genes. The female-biased genes in gPGCs were enriched in some metabolic processes. To reveal the mechanisms underlying the transcriptional regulation of female-biased genes in gPGCs, we performed stimulation tests. Stimulation with retinoic acid against cultured gPGCs derived from male embryos resulted in the upregulation of several female-biased genes. Overall, our results suggest that sex determination of avian PGCs possess aspects of both cell-autonomous and somatic cell regulation. Moreover, it appears that sex determination occurs earlier in females than in males.