Fungal Virulence and Development Is Regulated by Alternative Pre-mRNA 3′End Processing in Magnaporthe oryzae

RNA-binding proteins play a central role in post-transcriptional mechanisms that control gene expression. Identification of novel RNA-binding proteins in fungi is essential to unravel post-transcriptional networks and cellular processes that confer identity to the fungal kingdom. Here, we carried out the functional characterisation of the filamentous fungus-specific RNA-binding protein RBP35 required for full virulence and development in the rice blast fungus. RBP35 contains an N-terminal RNA recognition motif (RRM) and six Arg-Gly-Gly tripeptide repeats. Immunoblots identified two RBP35 protein isoforms that show a steady-state nuclear localisation and bind RNA in vitro. RBP35 coimmunoprecipitates in vivo with Cleavage Factor I (CFI) 25 kDa, a highly conserved protein involved in polyA site recognition and cleavage of pre-mRNAs. Several targets of RBP35 have been identified using transcriptomics including 14-3-3 pre-mRNA, an important integrator of environmental signals. In Magnaporthe oryzae, RBP35 is not essential for viability but regulates the length of 3′UTRs of transcripts with developmental and virulence-associated functions. The Δrbp35 mutant is affected in the TOR (target of rapamycin) signaling pathway showing significant changes in nitrogen metabolism and protein secretion. The lack of clear RBP35 orthologues in yeast, plants and animals indicates that RBP35 is a novel auxiliary protein of the polyadenylation machinery of filamentous fungi. Our data demonstrate that RBP35 is the fungal equivalent of metazoan CFI 68 kDa and suggest the existence of 3′end processing mechanisms exclusive to the fungal kingdom

MicroRNA-377 suppresses initiation and progression of esophageal cancer by inhibiting CD133 and VEGF

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Документы архива Учреждения образования «Белорусский государственный медицинский университет» за 1976 – 2013 гг.: организация работ по комплектованию, обеспечению сохранности и использованию : реферат к дипломной работе / Ольга Викторовна Лобач; БГУ, Исторический факультет, Кафедра источниковедения; науч. рук. Яцкевич Д.Л.

Determining the underlying cause of persistent eosinophilia is important for effective clinical management but remains a diagnostic challenge in many cases. We identified STAT5B N642H, an established oncogenic mutation, in 27/1715 (1.6%) cases referred for investigation of eosinophilia. Of the 27 mutated cases, a working diagnosis of hypereosinophilic syndrome (HES; n = 7) or a myeloid neoplasm with eosinophilia (n = 20) had been made prior to the detection of STAT5B N642H. Myeloid panel analysis identified a median of 2 additional mutated genes (range 0–4) with 4 cases having STAT5B N642H as a sole abnormality. STAT5B N642H was absent in cultured T cells of 4/4 positive cases. Individuals with SF3B1 mutations (9/27; 33%) or STAT5B N642H as a sole abnormality had a markedly better overall survival compared to cases with other additional mutations (median 65 months vs. 14 months; hazard ratio = 8.1; P < 0.001). The overall survival of STAT5B-mutated HES cases was only 30 months, suggesting that these cases should be reclassified as chronic eosinophilic leukemia, not otherwise specified (CEL-NOS). The finding of STAT5B N642H as a recurrent mutation in myeloid neoplasia with eosinophilia provides a new diagnostic and prognostic marker as well as a potential target for therapy

Genetic Basis of Myocarditis: Myth or Reality?

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Characterization and regulation of expression of an antifungal peptide from hemolymph of an insect, Manduca sexta

Insects secrete antimicrobial peptides as part of the innate immune response. Most antimicrobial peptides from insects have antibacterial but not antifungal activity. We have characterized an antifungal peptide, diapausin-1 from hemolymph of a lepidopteran insect, Manduca sexta (tobacco hornworm). Diapausin-1 was isolated by size exclusion chromatography from hemolymph plasma of larvae that were previously injected with a yeast, Saccharomyces cerevisiae. Fractions containing activity against S. cerevisiae were analyzed by SDS-PAGE and MALDI-TOF MS/MS and found to contain a 45-residue peptide that was encoded by sequences identified in M. sexta transcriptome and genome databases. A cDNA for diapausin-1 was cloned from cDNA prepared from fat body RNA. Diapausin-1 is a member of the diapausin family of peptides, which includes members known to have antifungal activity. The M. sexta genome contains 14 genes with high similarity to diapausin-1, each with 6 conserved Cys residues. Diapausin-1 was produced as a recombinant protein in Escherichia coli. Purified recombinant diapausin-1 was active against S. cerevisiae, with IC50 of 12 mu M, but had no detectable activity against bacteria. Spores of some plant fungal pathogens treated with diapausin-1 had curled germination tubes or reduced and branched hyphal growth. Diapausin-1 mRNA level in fat body strongly increased after larvae were injected with yeast or with Micrococcus luteus. In addition, diapausin-1 mRNA levels increased in midgut and fat body at the wandering larval stage prior to pupation, suggesting developmental regulation of the gene. Our results indicate that synthesis of diapausin-1 is part of an antifungal innate immune response to infection in M. sexta

The Escherichia coli SRP and SecB targeting pathways converge at the translocon.

Two distinct protein targeting pathways can direct proteins to the Escherichia coli inner membrane. The Sec pathway involves the cytosolic chaperone SecB that binds to the mature region of pre-proteins. SecB targets the pre-protein to SecA that mediates pre-protein translocation through the SecYEG translocon. The SRP pathway is probably used primarily for the targeting and assembly of inner membrane proteins. It involves the signal recognition particle (SRP) that interacts with the hydrophobic targeting signal of nascent proteins. By using a protein cross-linking approach, we demonstrate here that the SRP pathway delivers nascent inner membrane proteins at the membrane. The SRP receptor FtsY, GTP and inner membranes are required for release of the nascent proteins from the SRP. Upon release of the SRP at the membrane, the targeted nascent proteins insert into a translocon that contains at least SecA, SecY and SecG. Hence, as appears to be the case for several other translocation systems, multiple targeting mechanisms deliver a variety of precursor proteins to a common membrane translocation complex of the E.coli inner membrane

Report 38: SARS-CoV-2 setting-specific transmission rates: a systematic review and meta-analysis

Since the end of 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread rapidly across the world. Understanding the drivers of SARS-CoV-2 transmission is crucial for disease control policies but evidence of transmission rates in different settings remains limited. We conducted a systematic review to estimate the secondary attack rate (SAR) and observed reproduction number (Robs) in different settings and to explore differences by age, symptom status, duration of exposure and household size. A total of 97 studies were identified, 45 of which met inclusion criteria for meta-analysis. Households showed the highest transmission rates, with pooled SAR and Robs estimates of 21.1% (95% CI: 17.4%-24.8%) and 0.96 (95% CI: 0.67-1.32), respectively. Household SAR estimates were significantly higher where the duration of household exposure exceeded 5 days compared with exposure of 5 days or less. Attack rates related to familiar and prolonged close contacts, such as social events with family and friends were higher than those related to low-risk casual contacts, such as strangers (SAR of 5.9%, 95% CI: 3.8%-8.1% vs. 1.2%, 95% CI: 0.3%-2.1%). Estimates of SAR for asymptomatic index cases were approximately two thirds of those for symptomatic index (3.5% vs. 12.8%, p<0.001). We find moderate evidence for less transmission both from and to individuals under 20 years of age in the household context, but this difference is less evident when examining all settings. Prolonged contact in households and in settings with familiar close contacts increases the potential for transmission of SARS-CoV-2. Additionally, the differences observed in transmissibility by symptom status of index cases and the potential for age-dependent effects has important implications for outbreak control strategies such as contact tracing, testing and rapid isolation of cases. There was limited data to allow exploration of transmission patterns in workplaces, schools, and care-homes, highlighting the need for further research in such settings