Meiotic Recombination Hotspots of Fission Yeast Are Directed to Loci that Express Non-Coding RNA

Polyadenylated, mRNA-like transcripts with no coding potential are abundant in eukaryotes, but the functions of these long non-coding RNAs (ncRNAs) are enigmatic. In meiosis, Rec12 (Spo11) catalyzes the formation of dsDNA breaks (DSBs) that initiate homologous recombination. Most meiotic recombination is positioned at hotspots, but knowledge of the mechanisms is nebulous. In the fission yeast genome DSBs are located within 194 prominent peaks separated on average by 65-kbp intervals of DNA that are largely free of DSBs.). Furthermore, we tested and rejected the hypothesis that the ncRNA loci and DSB peaks localize preferentially, but independently, to a third entity on the chromosomes.Meiotic DSB hotspots are directed to loci that express polyadenylated ncRNAs. This reveals an unexpected, possibly unitary mechanism for what directs meiotic recombination to hotspots. It also reveals a likely biological function for enigmatic ncRNAs. We propose specific mechanisms by which ncRNA molecules, or some aspect of RNA metabolism associated with ncRNA loci, help to position recombination protein complexes at DSB hotspots within chromosomes

The global distribution of lymphatic filariasis, 2000–18: a geospatial analysis

Background Lymphatic filariasis is a neglected tropical disease that can cause permanent disability through disruption of the lymphatic system. This disease is caused by parasitic filarial worms that are transmitted by mosquitos. Mass drug administration (MDA) of antihelmintics is recommended by WHO to eliminate lymphatic filariasis as a public health problem. This study aims to produce the first geospatial estimates of the global prevalence of lymphatic filariasis infection over time, to quantify progress towards elimination, and to identify geographical variation in distribution of infection. Methods A global dataset of georeferenced surveyed locations was used to model annual 2000–18 lymphatic filariasis prevalence for 73 current or previously endemic countries. We applied Bayesian model-based geostatistics and time series methods to generate spatially continuous estimates of global all-age 2000–18 prevalence of lymphatic filariasis infection mapped at a resolution of 5 km2 and aggregated to estimate total number of individuals infected. Findings We used 14 927 datapoints to fit the geospatial models. An estimated 199 million total individuals (95% uncertainty interval 174–234 million) worldwide were infected with lymphatic filariasis in 2000, with totals for WHO regions ranging from 3·1 million (1·6–5·7 million) in the region of the Americas to 107 million (91–134 million) in the South-East Asia region. By 2018, an estimated 51 million individuals (43–63 million) were infected. Broad declines in prevalence are observed globally, but focal areas in Africa and southeast Asia remain less likely to have attained infection prevalence thresholds proposed to achieve local elimination. Interpretation Although the prevalence of lymphatic filariasis infection has declined since 2000, MDA is still necessary across large populations in Africa and Asia. Our mapped estimates can be used to identify areas where the probability of meeting infection thresholds is low, and when coupled with large uncertainty in the predictions, indicate additional data collection or intervention might be warranted before MDA programmes cease

SARS-CoV-2 Nsp13 encodes for an HLA-E-stabilizing peptide that abrogates inhibition of NKG2A-expressing NK cells

26sinoneNatural killer (NK) cells are innate immune cells that contribute to host defense against virus infections. NK cells respond to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro and are activated in patients with acute coronavirus disease 2019 (COVID-19). However, by which mechanisms NK cells detect SARS-CoV-2-infected cells remains largely unknown. Here, we show that the Non-structural protein 13 of SARS-CoV-2 encodes for a peptide that is presented by human leukocyte antigen E (HLA-E). In contrast with self-peptides, the viral peptide prevents binding of HLA-E to the inhibitory receptor NKG2A, thereby rendering target cells susceptible to NK cell attack. In line with these observations, NKG2A-expressing NK cells are particularly activated in patients with COVID-19 and proficiently limit SARS-CoV-2 replication in infected lung epithelial cells in vitro. Thus, these data suggest that a viral peptide presented by HLA-E abrogates inhibition of NKG2A+ NK cells, resulting in missing self-recognition.noneHammer Q.; Dunst J.; Christ W.; Picarazzi F.; Wendorff M.; Momayyezi P.; Huhn O.; Netskar H.K.; Maleki K.T.; Garcia M.; Sekine T.; Sohlberg E.; Azzimato V.; Aouadi M.; Degenhardt F.; Franke A.; Spallotta F.; Mori M.; Michaelsson J.; Bjorkstrom N.K.; Ruckert T.; Romagnani C.; Horowitz A.; Klingstrom J.; Ljunggren H.-G.; Malmberg K.-J.Hammer, Q.; Dunst, J.; Christ, W.; Picarazzi, F.; Wendorff, M.; Momayyezi, P.; Huhn, O.; Netskar, H. K.; Maleki, K. T.; Garcia, M.; Sekine, T.; Sohlberg, E.; Azzimato, V.; Aouadi, M.; Degenhardt, F.; Franke, A.; Spallotta, F.; Mori, M.; Michaelsson, J.; Bjorkstrom, N. K.; Ruckert, T.; Romagnani, C.; Horowitz, A.; Klingstrom, J.; Ljunggren, H. -G.; Malmberg, K. -J

Midgut Bacterial Diversity Of Wild Populations Of Phlebotomus (P.) Papatasi, The Vector Of Zoonotic Cutaneous Leishmaniasis (Zcl) In Turkey

Phlebotomine sand flies are hematophagous insects that harbor bacterial, viral and parasitic agents like Bartonella sp., Phleboviruses and Leishmania spp., respectively. There are few reports on bacterial microbiota of Phlebotomus (P.) papatasi but no data available for natural populations of Turkey, where leishmaniasis is endemic. Therefore, we aimed to investigate the midgut bacterial flora of different populations of P. papatasi. Sand flies were collected from different towns (Karaburun, Urla, Ayvacik and Başçayır) located in the western part of Turkey. Laboratory reared P. papatasi were included in the study as an insectarium population. After sterile washing steps, sand flies were dissected and guts were separated. Three pools, (males, unfed females and blood-fed females) were generated for each population. Prokaryotic 16 S rRNA gene was amplified and DGGE was performed. Fourteen different organisms belonging to two Phylum (Proteobactericea and Furmicutes) were identified according to sequence results in the studied pools. The presence of Wolbachia sp. was shown for the first time in the wild-caught sand fly populations of Turkey. This is the first report of gut bacterial flora of wild-caught P. papatasi collected in an endemic area for leishmaniasis in Turkey. Microbiome profiling of wild-caught sand flies will be of great help in the investigating of possible vector control candidates for paratransgenic control approach.PubMedWoSScopu