Developmental Regulation of Alternative Polyadenylation in an Adult Stem Cell Lineage.

Co-transcriptional alternate processing of nascent mRNA molecules can make major contributions to cell type specific gene expression programs as proliferating precursor cells initiate terminal differentiation. Alternative Cleavage and Polyadenylation (APA) can result in the production of mRNA isoforms from the same gene locus with either longer or shorter 3'UTRs. In Drosophila spermatogenesis, approximately 500 genes undergo APA as proliferating spermatogonia differentiate into spermatocytes, producing transcript isoforms with shortened 3'UTRs, and resulting in profound stage specific changes in the proteins expressed. The molecular mechanisms that specify usage of upstream polyadenylation sites in spermatocytes are thus key to understanding the changes in cell state. Here, we show that PCF11 and Cbc, the two components of Cleavage factor II (CFII), orchestrate APA switching during Drosophila spermatogenesis. Knockdown of PCF11 or cbc in spermatocytes caused dysregulation of APA, with many transcripts normally cleaved at a proximal site in spermatocytes now cleaved at their distal site, as in spermatogonia. Although PCF11 is widely expressed, cbc is strongly upregulated in spermatocytes. Our findings reveal a developmental mechanism where changes in activity of specific cleavage factors can direct cell type specific APA at selected genes, presenting CFII as a key developmental regulator of APA during spermatogenesis.

SARS-CoV-2 IgG Antibodies Seroprevalence and Sera Neutralizing Activity in MEXICO: A National Cross-Sectional Study during 2020.

Until recently, the incidence of COVID-19 was primarily estimated using molecular diagnostic methods. However, the number of cases is vastly underreported using these methods. Seroprevalence studies estimate cumulative infection incidences and allow monitoring of transmission dynamics, and the presence of neutralizing antibodies in the population. In February 2020, the Mexican Social Security Institute began conducting anonymous unrelated sampling of residual sera from specimens across the country, excluding patients with fever within the previous two weeks and/or patients with an acute respiratory infection. Sampling was carried out weekly and began 17 days before Mexico's first officially confirmed case. The 24,273 sera obtained were analyzed by chemiluminescent-linked immunosorbent assay (CLIA) IgG S1/S2 and, later, positive cases using this technique were also analyzed to determine the rate of neutralization using the enzyme-linked immunosorbent assay (ELISA). We identified 40 CLIA IgG positive cases before the first official report of SARS-CoV-2 infection in Mexico. The national seroprevalence was 3.5% in February and 33.5% in December. Neutralizing activity among IgG positives patients during overall study period was 86.1%. The extent of the SARS-CoV-2 infection in Mexico is 21 times higher than that reported by molecular techniques. Although the general population is still far from achieving herd immunity, epidemiological indicators should be re-estimated based on serological studies of this type.

Prevalence of non-influenza respiratory viruses in acute respiratory infection cases in Mexico.

BACKGROUND: Acute respiratory infections are the leading cause of morbidity and mortality worldwide. Although a viral aetiological agent is estimated to be involved in up to 80% of cases, the majority of these agents have never been specifically identified. Since 2009, diagnostic and surveillance efforts for influenza virus have been applied worldwide. However, insufficient epidemiological information is available for the many other respiratory viruses that can cause Acute respiratory infections. METHODS: This study evaluated the presence of 14 non-influenza respiratory viruses in 872 pharyngeal exudate samples using RT-qPCR. All samples met the operational definition of a probable case of an influenza-like illness or severe acute respiratory infection and had a previous negative result for influenza by RT-qPCR. RESULTS: The presence of at least one non-influenza virus was observed in 312 samples (35.8%). The most frequent viruses were rhinovirus (RV; 33.0%), human respiratory syncytial virus (HRSV; 30.8%) and human metapneumovirus (HMPV; 10.6%). A total of 56 cases of co-infection (17.9%) caused by 2, 3, or 4 viruses were identified. Approximately 62.5% of all positive cases were in children under 9 years of age. CONCLUSION: In this study, we identified 13 non-influenza respiratory viruses that could occur in any season of the year. This study provides evidence for the prevalence and seasonality of a wide range of respiratory viruses that circulate in Mexico and constitute a risk for the population. Additionally, our data suggest that including these tests more widely in the diagnostic algorithm for influenza may reduce the use of unnecessary antibiotics, reduce the hospitalisation time, and enrich national epidemiological data with respect to the infections caused by these viruses.

The secretome of a recombinant BCG substrain reveals differences in hypothetical proteins.

Tuberculosis remains a major human health problem worldwide, and strategies for its prevention include the generation and characterization of new recombinant vaccines containing immunodominant antigens from Mycobacterium tuberculosis. By comparing the secretomes of wild-type Mycobacterium bovis and a PstS1-recombinant M. bovis BCG vaccine substrain (rBCG38), we identified six conserved hypothetical proteins (BCG2696, BCG1674, BCG0372, BCG0427, BCG2436c, and BCG3053) that are differentially expressed. Our findings will aid in the identification of highly immunogenic proteins present in rBCG.