We previously showed that, during mouse oocyte maturation, specific maternal mRNAs (actins) are deadenylated, while others (hypoxanthine phosphoribosyltransferase:HPRT) are adenylated. As in other systems, these changes can be correlated with changes in translational activities. Maturation-specific polyadenylation in Xenopus depends on the presence of a U-rich cytoplasmic polyadenylation element (CPE) close to the 3' end of the RNA. RNAs that lack CPEs appear to be deadenylated by default when meiosis resumes. We show here that this default program also applies to maturing mouse oocytes. Microinjected beta- and gamma-actin 3' UTR (untranslated region) transcripts lacking CPEs but including polyA tails (100-200 N) behave as endogenous maternal actin mRNAs and are deadenylated by maturing oocytes. "Nonsense" transcripts that do not include CPEs, but that do contain polyA tails, are also deadenylated. beta- and gamma-Actin 3' UTRs with short polyA tails (50-80 N) are stable and exhibit no detectable change in adenylation when injected into growing, full-grown, or maturing oocytes. In contrast, HPRT 3' UTRs, which include the CPE UUUUAAAU and a short polyA tail (50 N), are polyadenylated during maturation. HPRT 3' UTR transcripts with long polyA tails (100-200 N) are more extensively deadenylated by growing and full-grown oocytes that retain germinal vesicles than by maturing oocytes. The presence of CPEs may be required for polyA tail shortening and translational inactivation of stable mRNAs during oocyte growth and subsequent selective readenylation and translation during meiotic maturation.(ABSTRACT TRUNCATED AT 250 WORDS)
The immune and skeletal systems are known to interact. We have repeatedly shown that in contrast to in vitro data, the administration of T lymphocyte immunosuppressants, such as cyclosporin A, leads to an increase in bone resorption and a high turnover osteopenia. The purpose of this study was to characterize the bone metabolism of the T lymphocyte deficient Rowett athymic homozygous (rnu/rnu) nude rat. We wished to determine whether these rats share the bone abnormalities of cyclosporin A-treated rats. Eleven 10-week-old Sprague-Dawley rats and 12 similarly aged nude rats were studied over a 4-week period. Metaphyseal cancellous bone histomorphometry was similar in the two groups of rats and only differed with regard to percentage eroded perimeter (lower in nude rats, p = 0.0008) and longitudinal growth rate (49% lower in nude rats, p < 0.001). The nude rats had less body mass (p < 0.001) but nevertheless gained the same percentage of their body weight over the study period. The athymic rats had lower levels of serum, 1,25-dihydroxyvitamin D (p < 0.014) and serum osteocalcin(p < 0.009), and at the age of 14 weeks the nude rats had lower concentrations of serum creatinine (p = 0.001) and blood ionized calcium (p = 0.0002), yet serum PTH was similar throughout. RNA isolated from the contralateral tibias revealed that the nude group had lower steady-state levels of osteocalcin mRNA despite similar rates of bone formation. In its entirety, the data suggest that T cell deficiency per se is not necessarily associated with high turnover osteopenia.
Fentanyl has been implicated as a major contributor to the increased number of opioid overdose deaths. Surprisingly, little is known about the pharmacogenetic influences on fentanyl pharmacokinetics or pharmacodynamics. Pharmacogenetic studies of fentanyl are based largely on small sample sizes and have examined the potential association of only a small number of high frequency variants in selected candidate genes primarily with postoperative pain. Few data are available on low frequency variants, variants from racially/ethnically diverse populations, or on other phenotypes. Given the genetic diversity of low frequency variants, DNA sequencing may be needed to determine whether pharmacogenetic differences may contribute to lethal opioid overdoses.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.