The present study examines racial, ethnic, and gender disparities in career self-efficacy amongst 6077 US citizens and US naturalized graduate and postdoctoral trainees. Respondents from biomedical fields completed surveys Graduate and postdoctoral demographic and survey response data were examined to evaluate the impact of intersectional identities on trainee career self-efficacy. l-fucose hypothesized that race, ethnicity and gender, and the relations between these identities, would impact trainee career self-efficacy. The analysis demonstrated that racial and ethnic group, gender, specific career interests , and seniority were, to various degrees, all associated with trainee career self-efficacy and the effects were consistent across graduate and postdoctoral respondents. Implications for differing levels of self-efficacy are discussed, including factors and events during training that may contribute to career self-efficacy. The importance of mentorship for building research and career self-efficacy of trainees is discussed, especially with respect to those identifying as women and belonging to racial/ethnic populations underrepresented in biomedical sciences. The results underscore the need for change in the biomedical academic research community in order to retain a diverse under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. of New Jersey, New Brunswick, New Jersey, NJ, United States of America. Polycystic Ovarian Syndrome: A Case-Control Study and In Silico Analyses. Polycystic ovarian syndrome is a complex endocrine and metabolic condition with several potential causes. Insulin resistance is a hallmark of PCOS that often coexists with hirsutism, hyperandrogenism, being overweight, and hormonal imbalances. The functioning of multiple replication and transcription factors is regulated by tumor suppressor genes , which play a crucial role in maintaining genomic integrity and controlling the cell cycle of granulosa cells. In the present study, we examined how three single nucleotide polymorphisms in TP53, a cell cycle regulatory gene, affect the risk of developing PCOS in a sample of an Iranian population. Genomic DNA was extracted from 200 PCOS patients and 200 healthy women to analyze TP53 rs17880604, rs1625895, and rs1042522 SNPs using the polymerase chain reaction-restriction fragment length polymorphism method. Our findings revealed that the majority of PCOS cases were overweight [25 < body mass index < 30]. A positive association was observed between the TP53 rs1042522 SNP and the risk of PCOS under codominant heterozygous and overdominant genetic patterns . Meanwhile, a negative association was observed between TP53 SNPs and susceptibility to PCOS under codominant heterozygous and dominant models of inheritance . Moreover, different genotype and haplotype combinations of rs17880604/rs1625895/rs1042522 conferred a decreased risk of PCOS in our population. We found no statistical difference in the frequency of TP53 genotypes between PCOS cases and/or controls in terms of BMI, waist circumference, prolactin level, and markers of lipid and carbohydrate profile . Molecular dynamic prediction showed that the missense substitution in the 17p1 position could change the properties and secondary structure of the p53 protein. As inherited risk factors, TP53 variations may play a pivotal role in the pathogenesis of PCOS among Iranian women. Replicated population-based studies on other ethnicities are required to find the genetic contribution of variants of TP53, or SNPs located in other TSGs, to the etiology BACKGROUND: Oncogenic mutations in BRAF genes are found in approximately 5- of colorectal cancers. The majority of BRAF mutations are located within exons 11-15 of the catalytic kinase domains, with BRAF V600E accounting for more than of the observed BRAF mutations. Sensitivity to BRAF- and mitogen-activated protein kinase inhibitors varies depending on BRAF mutations and tumor cell types. Previously, we newly identified, BRAF L525R-mutation, in the activation segment of the kinase in colorectal cancer patient. Here, we characterized the function of the BRAF L525R mutation. METHODS: HEK293 cells harboring a BRAF mutation were first characterized and then treated with cetuximab, dabrafenib, and selumetinib. Cell viability was measured using WST-1 assay and the expression of proteins involved in the extracellular signal-regulated kinase and protein kinase B signaling pathways was evaluated using western blot analysis. RESULTS: The MEK inhibitor selumetinib effectively inhibited cell proliferation and ERK phosphorylation in BRAF L525R cells but not in BRAF V600E cells. Further studies revealed that AKT phosphorylation was reduced by selumetinib in BRAF L525R cells but not in BRAF V600E cells or selumetinib-resistant BRAF L525R cells. Moreover, the AKT inhibitor overcame the selumetinib resistance. CONCLUSIONS: We established a model system harboring BRAF L525R using HEK293 cells. BRAF L525R constitutively activated ERK.
l-fucose
