Nutrient supply affects the mRNA expression profile of the porcine skeletal muscle

Background: The genetic basis of muscle fat deposition in pigs is not well known. So far, we have only identified a limited number of genes involved in the absorption, transport, storage and catabolism of lipids. Such information is crucial to interpret, from a biological perspective, the results of genome-wide association analyses for intramuscular fat content and composition traits. Herewith, we have investigated how the ingestion of food changes gene expression in the gluteus medius muscle of Duroc pigs. Results: By comparing the muscle mRNA expression of fasted pigs (T0) with that of pigs sampled 5 h (T1) and 7 h (T2) after food intake, we have detected differential expression (DE) for 148 (T0-T1), 520 (T0-T2) and 135 (T1-T2) genes (q-value of 1.5). Many of these DE genes were transcription factors, suggesting that we have detected the coordinated response of the skeletal muscle to nutrient supply. We also found DE genes with a dual role in oxidative stress and angiogenesis (THBS1, THBS2 and TXNIP), two biological processes that are probably activated in the post-prandial state. Finally, we have identified several loci playing a key role in the modulation of circadian rhythms (ARNTL, PER1, PER2, BHLHE40, NR1D1, SIK1, CIART and CRY2), a result that indicates that the porcine muscle circadian clock is modulated by nutrition. Conclusion: We have shown that hundreds of genes change their expression in the porcine skeletal muscle in response to nutrient intake. Many of these loci do not have a known metabolic role, a result that suggests that our knowledge about the genetic basis of muscle energy homeostasis is still incomplete

The trans-ancestral genomic architecture of glycemic traits

Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 x 10(-8)), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution. A trans-ancestry meta-analysis of GWAS of glycemic traits in up to 281,416 individuals identifies 99 novel loci, of which one quarter was found due to the multi-ancestry approach, which also improves fine-mapping of credible variant sets.Peer reviewe

does participating in national and ethnic associations promote migrant integration a study with young first and second generation migrants

On arrival to a new country, migrants usually face language barriers, cultural barriers, discrimination, and other sources of unjust contextual conditions that lower their chances of a successful life (Handy and Greenspan, Nonprofit Volunt Sect Q 38:956–982, 2009). This scenario compromises their levels of well-being and supports a tendency toward social fragmentation in places of settlement (Garcia-Ramirez et al., Am J Community Psychol 47(1–2), 86–97, 2011). In response to this situation, migrants' engagement in civic life has been identified as an important element for developing both individual well-being and cohesive communities (Gilster, J Community Psychol 40(7), 769–784, 2012) (Stoll and Wong, Int Migr Rev 41(4), 880–908, 2007). Using a qualitative study, the present work explores the effects of activism on youth of sub-Saharan African origin, of the first and second generations, who are active in national and ethnic associations. The work aims to explore (1) through narratives the meaning that integration has for young migrants; (2) how integrated they feel; and (3) the role of the association, both national and ethnic, in the perception of integration of these young people

Perceptions and experiences of (in)fertility, contraception, and reproductive health outcomes: A mixed methods study among women and men in Malawi

Globally, more than 180 million people experience infertility, the condition of being unable to conceive a pregnancy within 1-2 years of attempting to do so (Inhorn &amp; Patrizio, 2015). In Malawi, a small country in south-eastern Africa, approximately 20% of women reported experiencing difficulty becoming pregnant or infertility in studies conducted in 2005 and 2014-2015 (Barden-O’Fallon, 2005b; Rao et al., 2017). At the same time, 40% of pregnancies in Malawi are considered unintended (National Statistics Office (NSO) [Malawi] and ICF, 2017). This dissertation uses a hybrid exploratory-explanatory mixed methods study design. The first study uses qualitative in-depth interview data from the Umoyo Wa Thanzi (UTHA) research program in a rural area of Central Malawi, and the second and third studies use quantitative cross-sectional and longitudinal survey data from the same population. Together, the three studies explore how infertility and perceived fecundity influence how women make reproductive decisions with their current and future fertility desires in mind. The three studies provide insight into how perceptions of fecundity (ability to become pregnant) and experiences of infertility (not conceiving a pregnancy after two or more years of trying), influence women’s contraceptive use, incidence of a subsequent pregnancies, and pregnancy planning/intention. The first study, which analyzed 20 in-depth interviews from women in the UTHA cohort, showed how women’s perceptions of fecundity and experiences of infertility influenced not only whether she used contraception or not, but how she used contraception in an effort to manage her fertility. The second study explored the association between ever experiencing infertility, perceived certainty of pregnancy, and contraceptive use. Women who reported ever experiencing infertility had 44% lower odds of current contraceptive use than women who did not report infertility (AOR: 0.56; 95% CI: 0.39-0.83). Women who reported ‘no chance/unlikely’ that they would become pregnant within one year of not using contraception had 70% lower odds of contraceptive use compared to women who were ‘certain’ they would become pregnant within a year (AOR: 0.30; 95% CI: 0.10-0.92). These findings led to the third study, which explored associations between ever experiencing infertility at Wave 1 (2014-15) and reporting a subsequent pregnancy by the final wave of data collection in 2019. In this study, women’s reports of ever experiencing infertility did not have a significant relationship with reporting a subsequent pregnancy (AOR: 0.89; p&gt;0.05). Additionally, there were no statistically significant differences in retrospective pregnancy planning/intentions between women who did and did not report ever experiencing infertility (p&gt;0.05). Together, the three studies reveal the importance of perceptions and experiences of fecundity and infertility in influencing women’s reproductive decisions

Perceptions and experiences of (in)fertility, contraception, and reproductive health outcomes: A mixed methods study among women and men in Malawi

Globally, more than 180 million people experience infertility, the condition of being unable to conceive a pregnancy within 1-2 years of attempting to do so (Inhorn &amp; Patrizio, 2015). In Malawi, a small country in south-eastern Africa, approximately 20% of women reported experiencing difficulty becoming pregnant or infertility in studies conducted in 2005 and 2014-2015 (Barden-O’Fallon, 2005b; Rao et al., 2017). At the same time, 40% of pregnancies in Malawi are considered unintended (National Statistics Office (NSO) [Malawi] and ICF, 2017). This dissertation uses a hybrid exploratory-explanatory mixed methods study design. The first study uses qualitative in-depth interview data from the Umoyo Wa Thanzi (UTHA) research program in a rural area of Central Malawi, and the second and third studies use quantitative cross-sectional and longitudinal survey data from the same population. Together, the three studies explore how infertility and perceived fecundity influence how women make reproductive decisions with their current and future fertility desires in mind. The three studies provide insight into how perceptions of fecundity (ability to become pregnant) and experiences of infertility (not conceiving a pregnancy after two or more years of trying), influence women’s contraceptive use, incidence of a subsequent pregnancies, and pregnancy planning/intention. The first study, which analyzed 20 in-depth interviews from women in the UTHA cohort, showed how women’s perceptions of fecundity and experiences of infertility influenced not only whether she used contraception or not, but how she used contraception in an effort to manage her fertility. The second study explored the association between ever experiencing infertility, perceived certainty of pregnancy, and contraceptive use. Women who reported ever experiencing infertility had 44% lower odds of current contraceptive use than women who did not report infertility (AOR: 0.56; 95% CI: 0.39-0.83). Women who reported ‘no chance/unlikely’ that they would become pregnant within one year of not using contraception had 70% lower odds of contraceptive use compared to women who were ‘certain’ they would become pregnant within a year (AOR: 0.30; 95% CI: 0.10-0.92). These findings led to the third study, which explored associations between ever experiencing infertility at Wave 1 (2014-15) and reporting a subsequent pregnancy by the final wave of data collection in 2019. In this study, women’s reports of ever experiencing infertility did not have a significant relationship with reporting a subsequent pregnancy (AOR: 0.89; p&gt;0.05). Additionally, there were no statistically significant differences in retrospective pregnancy planning/intentions between women who did and did not report ever experiencing infertility (p&gt;0.05). Together, the three studies reveal the importance of perceptions and experiences of fecundity and infertility in influencing women’s reproductive decisions

Metformin alters an anti-proliferative effect of Mitotane in a human adrenocortical cancer (H295R) cell line- preliminary results.pdf

Introduction: Metformin is used as a first-line treatment in type 2 diabetes. Several studies suggest that patients with type 2 diabetes treated with metformin may have a reduced cancer risk. Recently it has been shown that metformin acts directly on mitochondria to alter cellular bioenergetics and reduce tumorigenesis. We have shown that anti-proliferative effect of mitotane is related to changes in expression of the genes involved in mitochondrial metabolism in human adrenocortical (H295R), breast, lung and colon cancer (ENDO 2015). Aim: As both metformin and mitotane affect mitochondrial metabolism, the objective of the study was to assess the impact of combined treatment with metformin and mitotane on H295R cell line proliferation. Material and Methods: Human adrenocortical cancer cell lines (H295R) were cultured in 96 well plates, and cell proliferation rate was assessed by resazurin assay. Results: The maximum effect of metformin was observed at 48-hours of incubation, resulting in cytotoxicity of 6, 16, 28 and 55% at the concentration of 5, 10, 20 and 40mM, respectively. The maximum effect of mitotane (10uM) was observed at 24-hours of incubation, resulting in 30% of cytotoxicity and this concentration was used in combined treatments with metformin. Even though both compounds inhibited proliferation separately, combined treatment led to either total loss of their anti-proliferative effect (metformin at the concentration of 5 and 10mM) or a significant decrease in cytotoxicity to 9 (p<0.001) and 44% (p<0.001) for metformin at the concentration of 20 and 40mM, respectively. Conclusions: Those preliminary results shows that even though metformin alone can have an anti-proliferative effect on H295R cell line, it should be added to mitotane with caution as it can negatively alter the cytotoxic effect of mitotane. The studies require further exploration to understand this unexpected mechanism. - See more at http://press.endocrine.org/doi/abs/10.1210/endo-meetings.2016.AHPAA.3.SAT-411#sthash.qoPhRUpy.dpu