Project description:Tendons play fundamental role in the musculoskeletal system and locomotion by transferring forces generated by muscles to the skeleton. Chronic tendon injuries and diseases are among the leading causes of musculoskeletal disability. For many types of tendinopathies, women have worse clinical outcomes than men. It is possible that tendon sex-based differences in protein composition are related to an altered injury response. The aim of this study was to compare the proteome of male and female tendon using label-free protein quantification. These data could provide new insight into pathways which may beinvolved in tendinopathies, and potentially in the differential injury response of female tendon.
Project description:Tendons play a critical role in the transmission of forces between muscles and bones, and chronic tendon injuries and diseases are among the leading causes of musculoskeletal disability. For many types of tendinopathies, women have worse clinical outcomes than men. It is possible that sex-based differences in tendon morphology, composition and mechanical properties may explain the greater susceptibility of women to develop tendinopathies. Our objective was to evaluate the mechanical properties, biochemical composition, transcriptome, and cellular activity of plantarflexor tendons from four month old male and female C57Bl/6 mice using in vitro biomechanics, mass spectrometry-based proteomics, genome-wide expression profiling, and cell culture techniques. Differences between groups were tested using t-tests (α=0.05). While the Achilles tendons of male mice were approximately 6% larger than female mice (P<0.05), the cell density of female mice was around 19% larger than males (P<0.05). No significant differences in the length (P=0.34), peak force (P=0.86), peak stress (P=0.52) or energy loss during stretch (P=0.94) of plantaris tendons were observed. Mass spectrometry proteomics analysis revealed no significant difference between sexes in the abundance of major extracellular matrix (ECM) proteins like collagen types I (P=0.30) and III (P=0.68), but female mice had approximately two-fold elevations (P<0.05) in different minor ECM proteins such as fibronectin, periostin, and tenascin. Using microarray analysis, there was no significant differences (P>0.05) in the expression of most major and minor ECM genes, and in the expression of genes involved in tendon fibroblast specification or proliferation. Whole tendon qPCR analysis showed significant expression differences in elastin, scleraxis, and tenomodulin. Cell culture techniques to test the effects of sex-specific extracellular environment on cellular activity show significant differences in gene expression of type I and III collagen, Ki67, scleraxis, and tenomodulin. Histologic analysis demonstrated that males have larger tendon cross-sectional area and lower cell density when compared to females. However, there were no differences between the sexes in the mechanical properties of tendons or in the majority of primary structural extracellular matrix proteins, although elevations were observed in some minor ECM proteins. Microarray analysis also showed no significant sex-based differences in the expression of major genes associated with collagen composition, extracellular components and turnover, and fibroblast proliferation. Cell culture tests of non-autonomous cellular activity show no major signals for ECM synthesis nor fibroblast proliferation. Our results indicate that while male mice expectedly had larger tendons, male and female mice have very similar mechanical properties and biochemical composition, with small increases in minor ECM proteins and proteoglycans in female tendons. The role that these minor ECM proteins and proteoglycans play in tendon repair should be evaluated in future studies. No treatment administered, study done to evaluate normal expression profiles of male and female tenocytes. This analysis is based on a Mouse Gene ST 2.1 strip that was processed in the microarray facility in May 2015 using the wt-pico kit.
Project description:Purpose: There is a need for point-of-care diagnostics for future mass casualty events involving radiation exposure. The development of radiation exposure and dose prediction algorithms for biodosimetry is needed for screening of large populations during these scenarios, and exploration of the potential effects which sex, age, genetic heterogeneity, and physiological comorbidities may have on the utility of biodosimetry diagnostics is needed. In the current study, proteomic profiling was used to examine sex specific differences in age matched C57BL6 mice on the blood proteome following radiation exposure and the usefulness of development and application of biodosimetry algorithms using both male and female samples. Methods: C57BL6 male and female mice between 9-11 weeks of age received a single total body radiation exposure of either 2, 4 or 8 Gy with plasma collection at days 1, 3 and 7 post-irradiation. Plasma was then screened using the SomaScan v4.1 assay for ~7000 protein analytes. A subset panel of protein biomarkers demonstrated significant (FDR<0.05 and |logFC|>0.2) changes in expression following radiation exposure. All proteins were used for feature selection to build predictive models of radiation exposure using different sample and sex specific cohorts. Both binary (prediction of any radiation exposure) and multidose (prediction of specific radiation dose) model series were developed using either female and male samples combined or only female or only male samples. The binary series (Models 1, 2 and 3) and multidose series (Models 4, 5 and 6) series included female/male combined, female only and male only respectively. Results: Detectable values were obtained for all ~7000 proteins included in the SomaScan assay for all samples. Each model algorithm built using a unique sample cohort was validated with a training set of samples and tested with a separate new sample series. Overall predictive accuracies in the binary model series was ~100% at the model training level and when tested with fresh samples 97.9% for Model 1(Female and Male) and 100% for Model 2 (Female only) and Model 3 (Male only). When sex specific Models’ 2 and 3 were tested with the opposite sex, the overall predictive accuracy rate dropped to 62.5% for Model 2 and remained 100% for Model 3. The overall predictive accuracy rate in the multidose model series was 100% for all models at the model training level and when tested with fresh samples 83.3%, 75% and 83.3% for Multidose Models 4-6 respectively. When sex specific Models’ 5 (Female only) and Model 6 (Male only) were tested with the opposite sex the overall predictive accuracy rate dropped to 52.1% and 68.8% respectively. Conclusion: These models represent novel predictive panels of radiation responsive proteomic biomarkers and illustrate the utility and necessity of considering sex specific differences in development of radiation biodosimetry prediction algorithms. As sex specific differences were observed in this study, and as use of point-of-care radiation diagnostics in future mass casualty settings will necessarily include persons of both sexes, consideration of sex specific variation is essential to ensure these diagnostic tools have practical utility in the field.
Project description:Tendons play a critical role in the transmission of forces between muscles and bones, and chronic tendon injuries and diseases are among the leading causes of musculoskeletal disability. For many types of tendinopathies, women have worse clinical outcomes than men. It is possible that sex-based differences in tendon morphology, composition and mechanical properties may explain the greater susceptibility of women to develop tendinopathies. Our objective was to evaluate the mechanical properties, biochemical composition, transcriptome, and cellular activity of plantarflexor tendons from four month old male and female C57Bl/6 mice using in vitro biomechanics, mass spectrometry-based proteomics, genome-wide expression profiling, and cell culture techniques. Differences between groups were tested using t-tests (α=0.05). While the Achilles tendons of male mice were approximately 6% larger than female mice (P<0.05), the cell density of female mice was around 19% larger than males (P<0.05). No significant differences in the length (P=0.34), peak force (P=0.86), peak stress (P=0.52) or energy loss during stretch (P=0.94) of plantaris tendons were observed. Mass spectrometry proteomics analysis revealed no significant difference between sexes in the abundance of major extracellular matrix (ECM) proteins like collagen types I (P=0.30) and III (P=0.68), but female mice had approximately two-fold elevations (P<0.05) in different minor ECM proteins such as fibronectin, periostin, and tenascin. Using microarray analysis, there was no significant differences (P>0.05) in the expression of most major and minor ECM genes, and in the expression of genes involved in tendon fibroblast specification or proliferation. Whole tendon qPCR analysis showed significant expression differences in elastin, scleraxis, and tenomodulin. Cell culture techniques to test the effects of sex-specific extracellular environment on cellular activity show significant differences in gene expression of type I and III collagen, Ki67, scleraxis, and tenomodulin. Histologic analysis demonstrated that males have larger tendon cross-sectional area and lower cell density when compared to females. However, there were no differences between the sexes in the mechanical properties of tendons or in the majority of primary structural extracellular matrix proteins, although elevations were observed in some minor ECM proteins. Microarray analysis also showed no significant sex-based differences in the expression of major genes associated with collagen composition, extracellular components and turnover, and fibroblast proliferation. Cell culture tests of non-autonomous cellular activity show no major signals for ECM synthesis nor fibroblast proliferation. Our results indicate that while male mice expectedly had larger tendons, male and female mice have very similar mechanical properties and biochemical composition, with small increases in minor ECM proteins and proteoglycans in female tendons. The role that these minor ECM proteins and proteoglycans play in tendon repair should be evaluated in future studies.
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:We utilised a 22,575 feature custom oligonucleotide DNA microarray designed from public domain databases of schistosome expressed sequence tags to explore differential gene expression between the Philippine (SJP) and Chinese (SJC) strains of S. japonicum, and between male and female S. japonicum. We found that 593, 664 and 426 probes were differentially expressed between the two geographical strains when we compared mix sexed adults, male worms and female worms. Additionally, the study revealed that 1,163 male- and 1,016 femaleassociated probes were differentially expressed in SJP whereas 1,047 male- and 897 female-associated probes were differentially expressed in SJC. Keywords: Strain and Gender Comparison
Project description:Aim of the present study is to identify sex-related sport adaptation proteins in female and male basketball players using proteomics approach on plasma samples withdraw from athletes during in-season training period but far from a competition. A cohort of 20 professional basketball players, 10 females (BF) and 10 males (BM), and 20 sedentary males (10 CM) and females (10 CF) as control, of comparable age and BMI were involved in this study. Protein profiles of plasma samples obtained from BM, BF, CM and CF were analysed by 2-DE. Differentially expressed proteins were identified by mass spectrometry. The computational 2-DE gel image analysis pointed out 33 differentially expressed protein spots (ANOVA p-value<0.05) and differences between male and female are more evident among the players than controls. The expression profile of 54.5% of the total proteins is affected by the sport activity. 14 proteins are differentially expressed in basket female players in comparison with their relative controls while 7 are differentially expressed in basket male players in comparison with their controls. In conclusion, we identify in female athletes a reduction in proteins related to transcription regulation, most of these modulate chronic inflammation confirming the anti-inflammatory effect of regular training in female muscle metabolism. In male and female athletes, we found a decrease in Transthyretin involved in muscle homeostasis and regeneration and Dermcidin a stress-induced myokine linked to inflammatory and it will be interesting to fully understand the role of its different isoforms in male and female skeletal muscle contraction.