Explore the vast range of titles available.

Canine circovirus (CanineCV) has been detected in some dogs with severe haemorrhagic diarrhoea, but its pathogenic role is unclear. This study evaluated a suspected association between the presence of CanineCV and acute haemorrhagic diarrhoea syndrome (AHDS) in dogs. The prevalence of CanineCV in dogs with AHDS was compared with that in healthy dogs and those infected with canine parvovirus (CPV). Additionally, time to recovery and mortality rate were compared between CanineCV-positive and CanineCV-negative dogs. Faecal samples of dogs with AHDS (n=55), healthy dogs (n=66) and dogs infected with CPV (n=54) were examined by two real-time TaqMan PCR assays targeting the replicase and capsid genes of CanineCV. CanineCV was detected in faecal samples of two dogs with AHDS, three healthy controls and seven dogs infected with CPV. Among the three groups, there was no significant difference in prevalence of CanineCV. CPV-infected animals that were coinfected with CanineCV had a significantly higher mortality rate compared with those negative for CanineCV. CanineCV does not appear to be the primary causative agent of AHDS in dogs, but might play a role as a negative co-factor in disease outcome in dogs with CPV infection.

The RNA genome of orthoflaviviruses encodes a methyltransferase within the non-structural protein NS5, which is involved in 2’-O-methylation of the 5’-terminal nucleotide of the viral genome resulting in a cap1 structure. While a 2’-O-unmethylated cap0 structure is recognized in vertebrates by the RNA sensor RIG-I, the cap1 structure allows orthoflaviviruses to evade the vertebrate innate immune system. Here, we analyzed whether the cap0 structure is also recognized in mosquitoes. Replication analyses of 2’-O-methyltransferase deficient yellow fever virus mutants (YFV NS5-E218A) of the vaccine 17D and the wild-type Asibi strain in mosquito cells revealed a distinct downregulation of the cap0 viruses. Interestingly, the level of inhibition differed for various mosquito cells. The most striking difference was found in Aedes albopictus -derived C6/36 cells with YFV-17D cap0 replication being completely blocked. Replication of YFV-Asibi cap0 was also suppressed in mosquito cells but to a lower extent. Analyses using chimeras between YFV-17D and YFV-Asibi suggest that a synergistic effect of several mutations across the viral genome accompanied by a faster initial growth rate of YFV-Asibi cap1 correlates with the lower level of YFV-Asibi cap0 attenuation. Viral growth analyses in Dicer-2 knockout cells demonstrated that Dicer-2 is entirely dispensable for attenuating the YFV cap0 viruses. Translation of a replication-incompetent cap0 reporter YFV-17D genome was reduced in mosquito cells, indicating a cap0 sensing translation regulation mechanism. Further, oral infection of Aedes aegypti mosquitoes resulted in lower infection rates for YFV-Asibi cap0. The latter is related to lower viral loads found in the midguts, which largely diminished dissemination to secondary tissues. After intrathoracic infection, YFV-Asibi cap0 replicated slower and to decreased amounts in secondary tissues compared to YFV-Asibi cap1. These results suggest the existence of an ubiquitously expressed innate antiviral protein recognizing 5’-terminal RNA cap-modifications in mosquitoes, both in the midgut as well as in secondary tissues.

Parties in advanced democracies take ideological positions as part of electoral competition, but some parties communicate their position more clearly than others. Existing research on democratic party competition has paid much attention to assessing partisan position taking in electoral manifestos, but it has largely overlooked how manifestos reflect the clarity of these positions. This article presents a scaling procedure that better reflects the data-generating process of party manifestos. This new estimator allows us to recover not only positional estimates, but also estimates for the ideological clarity or ambiguity of parties. The study validates its results using Monte Carlo tests, a manifesto-drafting simulation and a human coding exercise. Finally, the article applies the estimator to party manifestos in four multiparty democracies and demonstrates that ambiguity can enhance the appeal of parties with platforms that become more moderate, and lessen the appeal of parties with platforms that become more extreme.

Nine new compounds, namely sinularones A–I (1–9), characterized as cyclopentenone and butenolide-type analogues, were isolated from a soft coral Sinularia sp., together with a known butenolide (10). Their structures were elucidated by means of spectroscopic (IR, MS, 1D and 2D NMR, CD) analysis. The absolute configurations were determined on the basis of CD and specific rotation data in association with the computed electronic circular dichroism (ECD) by time dependent density functional theory (TD DFT) at 6-31+G(d,p)//DFT B3LYP/6-31+G(d,p) level. Compounds 1–2 and 7–10 showed potent antifouling activities against the barnacle Balanus amphitrite.

Prior studies have shown an increase in mortality in elderly patients when compared to their younger cohort. Level 1 trauma patients ≥50 years old were recruited upon admission to the ICU and prospectively followed. After an initial survey, inpatient data were collected and phone surveys were completed at 3 and 6 months. 100 patients were included. There was an 18% inpatient mortality. At 6 months, the mortality rate was 24%; 73% of surviving patients reported good health. 6-month nonsurvivors had a higher percentage requiring preinjury assistance with ambulation. Severe trauma in patients ≥50 years of age carries a significant rate of mortality however survivors have good outcomes. Need for assistance with ambulation prior to injury is associated with 6 month mortality and could be used as a screening tool for interventions. •Older trauma patients experience high mortality.•Older trauma survivors have good health at 6 months.•Need for assistance with ambulation associated with higher mortality.

Background Topical application of the synthetic triterpenoid RTA 408 to rodents elicits a potent dermal cytoprotective phenotype through activation of the transcription factor Nrf2. Therefore, studies were conducted to investigate if such cytoprotective properties translate to human dermal cells, and a topical lotion formulation was developed and evaluated clinically. Methods In vitro , RTA 408 (3–1000 nM) was incubated with primary human keratinocytes for 16 h. Ex vivo , RTA 408 (0.03, 0.3, or 3 %) was applied to healthy human skin explants twice daily for 3 days. A Phase 1 healthy volunteer clinical study with RTA 408 Lotion (NCT02029716) consisted of 3 sequential parts. In Part A, RTA 408 Lotion (0.5 %, 1 %, and 3 %) and lotion vehicle were applied to individual 4-cm 2 sites twice daily for 14 days. In Parts B and C, separate groups of subjects had 3 % RTA 408 Lotion applied twice daily to a 100-cm 2 site for 14 days or a 500-cm 2 site for 28 days. Results RTA 408 was well-tolerated in both in vitro and ex vivo settings up to the highest concentrations tested. Further, RTA 408 significantly and dose-dependently induced a variety of Nrf2 target genes. Clinically, RTA 408 Lotion was also well-tolerated up to the highest concentration, largest surface area, and longest duration tested. Moreover, significant increases in expression of the prototypical Nrf2 target gene NQO1 were observed in skin biopsies, suggesting robust activation of the pharmacological target. Conclusions Overall, these data suggest RTA 408 Lotion is well-tolerated, activates Nrf2 in human skin, and appears suitable for continued clinical development.

Beta defensins (BDs) are cationic peptides with antimicrobial activity that defend epithelial surfaces including the skin, gastrointestinal, and respiratory tracts. However, BD expression and function in the urinary tract are incompletely characterized. The purpose of this study was to describe Beta Defensin-1 (BD-1) expression in the lower urinary tract, regulation by cystitis, and antimicrobial activity toward uropathogenic Escherichia coli (UPEC) in vivo. Human DEFB1 and orthologous mouse Defb1 mRNA are detectable in bladder and ureter homogenates, and human BD-1 protein localizes to the urothelium. To determine the relevance of BD-1 to lower urinary tract defense in vivo, we evaluated clearance of UPEC by Defb1 knockout (Defb1(-/-)) mice. At 6, 18, and 48 hours following transurethral UPEC inoculation, no significant differences were observed in bacterial burden in bladders or kidneys of Defb1(-/-) and wild type C57BL/6 mice. In wild type mice, bladder Defb1 mRNA levels decreased as early as two hours post-infection and reached a nadir by six hours. RT-PCR profiling of BDs identified expression of Defb3 and Defb14 mRNA in murine bladder and ureter, which encode for mBD-3 and mBD-14 protein, respectively. MBD-14 protein expression was observed in bladder urothelium following UPEC infection, and both mBD-3 and mBD-14 displayed dose-dependent bactericidal activity toward UPEC in vitro. Thus, whereas mBD-1 deficiency does not alter bladder UPEC burden in vivo, we have identified mBD-3 and mBD-14 as potential mediators of mucosal immunity in the lower urinary tract.

Chemical examination of a Chinese soft coral Lobophytum pauciflorum resulted in the isolation of five new biscembranoids named lobophytones O–S (1–5) and a new “monomeric” cembrane lobophytone T (6). The structures of the new compounds were elucidated by interpretation of 1D and 2D NMR (COSY, HSQC, HMBC, and NOESY) spectroscopic data in association with MS and IR data. Lobophytone Q showed significant inhibition against lipopolysaccharide (LPS)-induced nitric oxide (NO) release in mouse peritoneal macrophages, while lobophytones Q and T showed inhibitory activities against the bacteria S. aureus and S. pneumoniae.

Genomic mining revealed one major nonribosomal peptide synthetase (NRPS) phylogenetic cluster in 12 marine sponge species, one ascidian, an actinobacterial isolate and seawater. Phylogenetic analysis predicts its taxonomic affiliation to the actinomycetes and hydroxy-phenyl-glycine as a likely substrate. Additionally, a phylogenetically distinct NRPS gene cluster was discovered in the microbial metagenome of the sponge Aplysina aerophoba, which shows highest similarities to NRPS genes that were previously assigned, by ways of single cell genomics, to a Chloroflexi sponge symbiont. Genomic mining studies such as the one presented here for NRPS genes, contribute to on-going efforts to characterize the genomic potential of sponge-associated microbiota for secondary metabolite biosynthesis.