Project description:Indisulam is an abandoned drug that acts as a molecular glue, inducing degradation of splicing factor RBM39 through interaction with CRL4DCAF15. We combined indisulam with sphinx 31 (a splicing factor inhibitor) and evaluated their combined activity in inducing splicing errors.
Project description:All but the most basal Lepidopteran species produce two sperm morphs. Only one of these morphs is capable of completing karyogamy and producing offspring, this morph contains the correct genetic complement and is termed eupyrene sperm. Apyrene sperm, on the other hand, is completely devoid of nuclear DNA and fertilisation incompetent. Despite the fact apyrene sperm is believed to be functional, the function of this sperm type is largely unknown. Here we apply tandem mass spectrometry based proteomics to the two sperm types independently in the monarch butterfly (Danaus plexippus) and the carolina sphinx moth (Manduca sexta). Comparative analysis between sperm morphs and species shows a reduced complexity and greater divergence in apyrene sperm relative to eupyrene consistent across the two species.
Project description:The fundamental interaction between the immune and skeletal systems, termed as osteoimmunology, has been demonstrated to play indispensable roles in the maintenance of balance between bone resorption and formation. The pleiotropic sphingolipid metabolite, sphingosine 1-phosphate (S1P), together with its cognate receptor, sphingosine-1-phosphate receptor-1 (S1PR1), are known as key players in osteoimmunology due to the regulation on both immune system and bone remodeling. The role of S1P-S1PR1 signaling in bone remodeling can be directly targeting both osteoclastogenesis and osteogenesis. Meanwhile, inflammatory cell function and polarization in both adaptive immune (T cell subsets) and innate immune cells (macrophages) are also regulated by this signaling axis, suggesting that S1P-S1PR1 signaling could aslo indirectly regulate bone remodeling via modulating the immune system. Therefore, it could be likely that S1P-S1PR1 signaling might take part in the maintenance of continuous bone turnover under physiological conditions, while lead to the pathogenesis of bone deformities during inflammation. In this review, we summarized the immunological regulation of S1P-S1PR1 signal axis during bone remodeling with an emphasis on how osteo-immune regulators are affected by inflammation, an issue with relevance to chronical bone disorders such as rheumatoid arthritis, spondyloarthritis and periodontitis.
Project description:Recent studies of wild animal populations have shown that estimators of neutral genetic diversity, such as mean heterozygosity, are often correlated with various fitness traits, such as survival, disease susceptibility, or reproductive success. We used two estimators of genetic diversity to explore the relationship between heterozygosity and reproductive success in male and female mandrills (Mandrillus sphinx) living in a semifree ranging setting in Gabon. Because social rank is known to influence reproductive success in both sexes, we also examined the correlation between genetic diversity and social rank in females, and acquisition of alpha status in males, as well as length of alpha male tenure. We found that heterozygous individuals showed greater reproductive success, with both females and males producing more offspring. However, heterozygosity influenced reproductive success only in dominant males, not in subordinates. Neither the acquisition of alpha status in males, nor social rank in females, was significantly correlated with heterozygosity, although more heterozygous alpha males showed longer tenure than homozygous ones. We also tested whether the benefits of greater genetic diversity were due mainly to a genome-wide effect of inbreeding depression or to heterosis at one or a few loci. Multilocus effects best explained the correlation between heterozygosity and reproductive success and tenure, indicating the occurrence of inbreeding depression in this mandrill colony.