Growth differentiation factor 9 (GDF9) is an oocyte-derived growth factor that plays a critical role in ovarian folliculogenesis and oocyte developmental competence and belongs to the TGF-β family of proteins. Recombinant human GDF9 (hGDF9) is secreted in a latent form, which in the case of the fully processed protein, has the proregion noncovalently associated with the mature region. In this study, we investigated a number of amino acid residues in the mature region of hGDF9 that are different from the corresponding residues in the mouse protein, which is not latent. We designed, expressed, and purified 4 forms of chimeric hGDF9 (M1-M4) that we found to be active in a granulosa cell bioassay. Using a porcine in vitro maturation model with inherent low developmental competence (yielding 10%-20% blastocysts), we tested the ability of the chimeric hGDF9 proteins to improve oocyte maturation and developmental competence. Interestingly, one of the chimeric proteins, M3, was able to significantly increase the level of embryo production using such low competence oocytes. Our molecular modeling studies suggest that in the case of hGDF9 the Gly(391)Arg mutation probably increases receptor binding affinity, thereby creating an active protein for granulosa cells in vitro. However, for an improvement in oocyte developmental competence, a second mutation (Ser(412)Pro), which potentially decreases the affinity of the mature region for the proregion, is also required.
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http://dx.doi.org/10.1210/me.2014-1173 | DOI Listing |
J Mammary Gland Biol Neoplasia
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Department of Histology and Embryology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.
Fluorescent biosensors offer a powerful tool for tracking and quantifying protein activity in living systems with high temporospatial resolution. However, the expression of genetically encoded fluorescent proteins can interfere with endogenous signaling pathways, potentially leading to developmental and physiological abnormalities. The EKAREV-NLS mouse model, which carries a FRET-based biosensor for monitoring extracellular signal-regulated kinase (ERK) activity, has been widely utilized both in vivo and in vitro across various cell types and organs.
View Article and Find Full Text PDFJ Youth Adolesc
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Manchester Institute of Education, University of Manchester, Manchester, UK.
Current understanding of the longitudinal relationships between different aspects of peer relationships and mental health problems in early- to mid-adolescence is limited. In particular, the role played by gender in these developmental cascades processes is unclear, little is known about within-person effects between bullying victimization and internalizing symptoms, and the theorized benefits of friendship and social support are largely untested. Addressing these important research gaps, this study tested a number of theory-driven hypotheses (e.
View Article and Find Full Text PDFJ Youth Adolesc
January 2025
Research Center of Adolescent Psychology and Behavior, School of Education, Guangzhou University, Guangzhou, China.
Risk-taking is a concerning yet prevalent issue during adolescence and can be life-threatening. Examining its etiological sources and evolving pathways helps inform strategies to mitigate adolescents' risk-taking behavior. Studies have found that unfavorable environmental factors, such as adverse childhood experiences (ACEs), are associated with momentary levels of risk-taking in adolescents, but little is known about whether ACEs shape the developmental trajectory of risk-taking.
View Article and Find Full Text PDFEur Child Adolesc Psychiatry
January 2025
School of Psychology, Centre for Innovation in Mental Health, University of Southampton, University Road, Southampton, SO17 1BJ, UK.
The directionality of the relationship between adolescent alcohol consumption and mental health difficulties remains poorly understood. This study investigates the longitudinal relationship between alcohol use frequency, internalizing and externalizing symptoms from the ages of 11 to 17. We conducted a random-intercept cross-lagged panel model across three timepoints (ages: 11yrs, 14yrs, 17yrs; 50.
View Article and Find Full Text PDFJ Mol Evol
January 2025
Faculty of Biology, Institute of Evolutionary Biology, University of Warsaw, Ul. Żwirki I Wigury 101, 02-089, Warsaw, Poland.
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