Loss of function of ribosomal protein L13a blocks blastocyst formation and reveals a potential nuclear role in gene expression.

Ribosomal proteins play diverse roles in development and disease. Most ribosomal proteins have canonical roles in protein synthesis, while some exhibit extra-ribosomal functions. Previous studies in our laboratory revealed that ribosomal protein L13a (RPL13a) is involved in the translational silencing of a cohort of inflammatory proteins in myeloid cells. This prompted us to investigate the role of RPL13a in embryonic development. Here we report that RPL13a is required for early development in mice. Crosses between Rpl13a+/- mice resulted in no Rpl13a-/- offspring. Closer examination revealed that Rpl13a-/- embryos were arrested at the morula stage during preimplantation development. RNA sequencing analysis of Rpl13a-/- morulae revealed widespread alterations in gene expression, including but not limited to several genes encoding proteins involved in the inflammatory response, embryogenesis, oocyte maturation, stemness, and pluripotency. Ex vivo analysis revealed that RPL13a was localized to the cytoplasm and nucleus between the two-cell and morula stages. RNAi-mediated depletion of RPL13a phenocopied Rpl13a-/- embryos and knockdown embryos exhibited increased expression of IL-7 and IL-17 and decreased expression of the lineage specifier genes Sox2, Pou5f1, and Cdx2. Lastly, a protein-protein interaction assay revealed that RPL13a is associated with chromatin, suggesting an extra ribosomal function in transcription. In summary, our data demonstrate that RPL13a is essential for the completion of preimplantation embryo development. The mechanistic basis of the absence of RPL13a-mediated embryonic lethality will be addressed in the future through follow-up studies on ribosome biogenesis, global protein synthesis, and identification of RPL13a target genes using chromatin immunoprecipitation and RNA-immunoprecipitation-based sequencing.

Bicyclic (alkyl)(amino)carbene (BICAAC) in a dual role: activation of primary amides and CO2 towards catalytic N-methylation.

Herein, we report the first catalytic methylation of primary amides using CO2 as a C1 source. A bicyclic (alkyl)(amino)carbene (BICAAC) exhibits dual role by activating both primary amide and CO2 to carry out this catalytic transformation which enables the formation of a new C-N bond in the presence of pinacolborane. This protocol was applicable to a wide range of substrate scopes, including aromatic, heteroaromatic, and aliphatic amides. We successfully used this procedure in the diversification of drug and bioactive molecules. Moreover, this method was explored for isotope labelling using 13CO2 for a few biologically important molecules. A detailed study of the mechanism was carried out with the help of spectroscopic studies and DFT calculations.

Prevalence and correlates of knowledge and practices regarding infection prevention and control, and triage in primary healthcare settings: A cross-sectional study in Bangladesh.

Background: Despite the high prevalence of healthcare-acquired infection in resource-limited settings, healthcare workers' (HCWs') knowledge and practices of infection prevention and control (IPC) and triage are not well-researched. We examined thisin Bangladesh's primary healthcare facilities (HCFs) during the COVID-19 pandemic. Methods: We surveyed 312 HCWs in 94 community clinics (CCs) and 90 family welfare centres (FWCs) in six districts from February to April 2021. We assessed HCWs' self-reported knowledge and observed practices in four domains: personal hygiene, medical instrument processing, waste management, and triage. We constructed a weighted composite knowledge score and estimated the association between knowledge and background characteristics using a generalised linear mixed effects model. Practices were described through univariate analysis. Findings: On a scale of 100, the mean composite knowledge score was 38.3 (SD: 13.3) overall and 44.0 (SD: 13.1) and 33.8 (SD: 11.6) for FWCs and CCs, respectively. The HCWs of FWCs were more aged, experienced, and educated than those of CCs. Knowledge score was the highest in personal hygiene and the lowest in medical waste segregation. Knowledge was significantly associated with HCWs' designation and education. Concerning practices, not more than one-third of the HCWs or HCFs, on average, followed the recommended protocols, except for wearing face masks while on duty (87.1%) and referring potential COVID-19 patients to higher-level facilities (68.3%). Conclusions: HCWs' capacity in instrument processing, waste management, and triage needs to be improved through formal education and training initiatives. Our study can contribute to the under-researched IPC and triage domains in resource-limited settings.

Implementation of an aggressive random drug-testing policy in a rural school district: Student attitudes regarding program fairness and effectiveness.

School districts are increasingly initiating random drug-testing (RDT) programs in an effort to curb substance-use rates among students, yet little is known about student attitudes toward RDT and potential obstacles to program acceptance and effectiveness. The authors surveyed 1011 9th through 11th grade students in 2 rural high schools in North Florida regarding the pending implementation of one of the most aggressive RDT programs in the nation. A significant majority of students predicted that RDT would be effective, yet students were more clearly divided in their perceptions of the fairness and the accuracy of testing. Student perceptions of whether there is a drug problem at their school proved to be a robust predictor of perceptions of policy fairness. Student substance-use rates were more limited predictors of policy effectiveness and fairness. These results may prove useful to school administrators, health professionals, and policy makers seeking to build acceptance for RDT in their schools.