Absenteeism among hospital staff during an influenza epidemic: implications for immunoprophylaxis.

The 1980-81 epidemic of influenza A/Bangkok 79 was responsible for increased absenteeism (1.7 times the rate for the corresponding period of the subsequent nonepidemic year) among selected hospital staff in Winnipeg''s Health Sciences Centre. Retrospective study of employment records for 25 of the centre''s largest departments showed excess sick-leave costs of about $24 500 during the 2-week period of peak absenteeism that included the epidemic. Although the centre was sampling prospectively for the virus the first positive results became available too late for chemoprophylactic measures to have been effective. The greater increase in absenteeism among nursing staff caring for patients with chronic respiratory disease and nurses working on general medical or pediatric acute infection/isolation wards suggested that these groups be targeted for influenza vaccination in hospitals.     

Long noncoding RNA H19 accelerates tenogenic differentiation by modulating miR-140-5p/VEGFA signaling

Rotator cuff tear (RCT) is a common tendon injury, but the mechanisms of tendon healing remain incompletely understood. Elucidating the molecular mechanisms of tenogenic differentiation is essential to develop novel therapeutic strategies in clinical treatment of RCT. The long non-coding RNA H19 plays a regulatory role in tenogenic differentiation and tendon healing, but its detailed mechanism of action remains unknown. To elucidate the role of H19 in tenogenic differentiation and tendon healing, tendon-derived stem cells were harvested from the Achilles tendons of Sprague Dawley rats and a rat model of cuff tear was established for the exploration of the function of H19 in promoting tenogenic differentiation. The results showed that H19 overexpression promoted, while H19 silencing suppressed, tenogenic differentiation of tendon-derived stem cells (TDSCs). Furthermore, bioinformatic analyses and a luciferase reporter gene assay showed that H19 directly targeted and inhibited miR-140-5p to promote tenogenic differentiation. Further, inhibiting miR-140-5p directly increased VEGFA expression, revealing a novel regulatory axis between H19, miR-140-5p, and VEGFA in modulating tenogenic differentiation. In rats with RTC, implantation of H19-overexpressing TDSCs at the lesion promoted tendon healing and functional recovery. In general, the data suggest that H19 promotes tenogenic differentiation and tendon-bone healing by targeting miR-140-5p and increasing VEGFA levels. Modulation of the H19/miR-140-5p/VEGFA axis in TDSCs is a new potential strategy for clinical treatment of tendon injury.Key words: lncRNA, miRNA, tendon stem cell, rotator cuff tear repair     

Infecting mosquitoes alters DENV-2 characteristics and enhances hemorrhage-induction potential in Stat1-/- mice

Dengue is one of the most prevalent arthropod-borne viral diseases in humans. There is still no effective vaccine or treatment to date. Previous studies showed that mosquito-derived factors present in saliva or salivary gland extract (SGE) contribute to the pathogenesis of dengue. In this study, we aimed to investigate the interplay between mosquito vector and DENV and to address the question of whether the mosquito vector alters the virus that leads to consequential disease manifestations in the mammalian host. DENV2 cultured in C6/36 cell line (culture-DENV2) was injected to Aedes aegypti intrathoracically. Saliva was collected from infected mosquitoes 7 days later. Exploiting the sensitivity of Stat1^-/- mice to low dose of DENV2 delivered intradermally, we showed that DENV2 collected in infected mosquito saliva (msq-DENV2) induced more severe hemorrhage in mice than their culture counterpart. Msq-DENV2 was characterized by smaller particle size, larger plaque size and more rapid growth in mosquito as well as mammalian cell lines compared to culture-DENV2. In addition, msq-DENV2 was more efficient than culture-DENV2 in inducing Tnf mRNA production by mouse macrophage. Together, our results point to the possibility that the mosquito vector provides an environment that alters DENV2 by changing its growth characteristics as well as its potential to cause disease.     

Gene rearrangement and sequence analysis of mitogenomes suggest polyphyly of Archaeobalanid and Balanid barnacles (Cirripedia: Balanomorpha)

The acorn barnacles (Cirripedia, Thoracica, Balanomorpha) are a diverse group of crustaceans found in virtually all marine and estuarine habitats. Barnacles are important model species in various biological researches, including evolution, intertidal ecology, larval biology and antifouling. However, there remains a lack of a thorough understanding of the phylogeny for this group of animals, particularly at higher taxonomic levels. In this study, we attempt to determine the phylogenetic relationships among balanomorphan families based on analysis of complete mitochondrial genome from various barnacle families and investigate the evolution of mitogenome in barnacles. Whole mitogenomes of six barnacles were newly sequenced, including Acasta sulcata (Archaeobalanidae), Armatobalanus allium (Archaeobalanidae), Chelonibia testudinaria (Chelonibiidae), Octomeris sp. (Chthamalidae), Savignium biporata (Pyrgomatidae) and Tetraclitella divisa (Tetraclitidae), which exhibit five different gene arrangements. Phylogenetic analysis on 15 complete mitochondrial genome sequences from major barnacle families supported Chthamalidae, Pyrgomatidae and Tetraclitidae formed monophyletic units, but suggested polyphyly of both Archaeobalanidae and Balanidae. Chthamalidae was the earliest diverged lineage in Balanomorpha. Chelonibiidae + Tetraclitidae formed the sister taxon to the monophyletic superfamily Balanoidea (Archaeobalanidae + Balanidae + Pyrgomatidae). The members of Archaeobalanidae and Balanidae intermingled in the inferred topology with the monophyletic Pyrgomatidae deeply nested within. Two Megabalanus species from the family Balanidae and A. sulcata from the family Archaeobalanidae share the same six‐gene‐cluster inversion as compared to the other ten balanomorphan barnacles, providing further evidence for the non‐monophyly for the two families. We showed here that the informativeness of the complete mitogenome sequence and rare genomic events in resolving various questions concerning Balanomorpha relationships. The non‐monophyletic status of Archaeobalanidae and Balanidae falsified many previous hypotheses concerning the complex evolution of Balanomorpha and call for further investigations and careful revision on the taxonomy of the group. Future study focusing on the enigmatic and tentatively basal lineages, for example, Chionelasmatoidea Pachylasmatoidea and Catophragmidae, would be most helpful in fully resolving the phylogeny and mitogenome evolutionary history of acorn barnacles.     

Poly (AT) deletion/insertion polymorphism of the XPC gene contributes to urinary system cancer susceptibility: A meta-analysis

Numerous studies have investigated the association between xeroderma pigmentosum complementation group C (XPC) poly (AT) deletion/insertion (PAT −/+) polymorphism and cancer susceptibility; however, the findings are inconsistent. Therefore, we performed a meta-analysis based on 32 publications including 10,214 cases and 11,302 controls to acquire a more robust estimation of the relationship. We searched publications from MEDLINE, EMBASE and CBM which assessed the associations between XPC PAT −/+ polymorphism and cancer risk. We calculated pooled odds ratio (OR) and 95% confidence interval (CI) by using either fixed-effects or random-effects model. We found that individuals carrying the PAT +/+ genotype have significantly increased cancer risk (PAT +/+ vs. PAT −/−: OR = 1.18, 95% CI = 1.03–1.35 and recessive model: OR = 1.19, 95% CI = 1.06–1.33). Further stratification analysis showed a significantly increased risk for prostate cancer (PAT +/+ vs. PAT −/−: OR = 2.20, 95% CI = 1.39–3.48, recessive model: OR = 2.07, 95% CI = 1.33–3.23 and PAT + vs. PAT −: OR = 1.39, 95% CI = 1.12–1.71), bladder cancer (recessive model: OR = 1.33, 95% CI = 1.03–1.72), Caucasian ethnicity (recessive model: OR = 1.21, 95% CI = 1.02–1.43), population-based studies (recessive model: OR = 1.23, 95% CI = 1.05–1.43) and studies with relatively large sample size (PAT +/+ vs. PAT −/−: OR = 1.18, 95% CI = 1.04–1.35 and recessive model: OR = 1.20, 95% CI = 1.08–1.33). Despite some limitations, this meta-analysis established solid statistical evidence for the association between the XPC PAT +/+ genotype and cancer risk, especially for urinary system cancer, but this association warrants further validation in single large studies.     

Rsp5 WW domains interact directly with the carboxyl-terminal domain of RNA polymerase II

RSP5 is an essential gene in Saccharomyces cerevisiae and was recently shown to form a physical and functional complex with RNA polymerase II (RNA pol II). The amino-terminal half of Rsp5 consists of four domains: a C2 domain, which binds membrane phospholipids; and three WW domains, which are protein interaction modules that bind proline-rich ligands. The carboxyl-terminal half of Rsp5 contains a HECT (homologous to E6-AP carboxyl terminus) domain that catalytically ligates ubiquitin to proteins and functionally classifies Rsp5 as an E3 ubiquitin-protein ligase. The C2 and WW domains are presumed to act as membrane localization and substrate recognition modules, respectively. We report that the second (and possibly third) Rsp5 WW domain mediates binding to the carboxyl-terminal domain (CTD) of the RNA pol II large subunit. The CTD comprises a heptamer (YSPTSPS) repeated 26 times and a PXY core that is critical for interaction with a specific group of WW domains. An analysis of synthetic peptides revealed a minimal CTD sequence that is sufficient to bind to the second Rsp5 WW domain (Rsp5 WW2) in vitro and in yeast two-hybrid assays. Furthermore, we found that specific "imperfect" CTD repeats can form a complex with Rsp5 WW2. In addition, we have shown that phosphorylation of this minimal CTD sequence on serine, threonine and tyrosine residues acts as a negative regulator of the Rsp5 WW2-CTD interaction. In view of the recent data pertaining to phosphorylation-driven interactions between the RNA pol II CTD and the WW domain of Ess1/Pin1, we suggest that CTD dephosphorylation may be a prerequisite for targeted RNA pol II degradation.