Julkaisuarkisto

The RNA-dependent RNA polymerase (RdRP) is the only homologous gene shared among current members of the kingdom Orthornavirae in the realm Riboviria. It is therefore used as a hallmark gene to infer their evolutionary relationships, and to guide their taxonomic classification. While sequence similarity between RNA viruses is often limited and sequences problematic to align, the conservation between the three-dimensional tertiary structures of viral RdRPs is notable, supporting analysis of deep evolutionary relationships. Nevertheless, the limited availability of experimental RdRP structures restricts structure-based phylogenetic analyses. We used protein structure prediction algorithm AlphaFold to alleviate this restriction and predicted structure models for 989 viral RdRPs. Through structural alignment with Homologous Structure Finder, we identified 211 structurally equivalent residues for RdRPs, representing 96 virus genera recognized by the International Committee on Taxonomy of Viruses. These equivalent residues were used to deduce a comprehensive structure-based phylogenetic tree for viral RdRPs, which was validated using a jackknifing approach developed in this study. For comparison, structural phylogenies were inferred using alignments produced with FoldTree and FoldMason software. The resulting trees mostly support the current taxonomic assignments of RNA viruses at the class rank. However, they do not support the monophyly of phyla Pisuviricota and Duplornaviricota. Furthermore, flaviviruses frequently group apart from other members of Kitrinoviricota. The conservation of protein structures over long periods of evolutionary time, when detectable sequence homology may be lost and sequence alignment problematic, supports the use of protein structure comparison methods for demonstrating the deeper evolutionary histories of RNA viruses.

Artikkelissa tarkastellaan Marius Raichin ja Charlie Bauerin ammatillisia uria keskittymällä heidän vaikutukseensa suomalaisessa elokuvateollisuudessa. Analyysi perustuu arkistoaineistoihin, jotka tarjoavat vihjeitä heidän koulutustaustastaan ja työelämästään. Artikkeli keskittyy Raichin ja Bauerin työtehtäviin ja työehtoihin suomalaisessa elokuvateollisuudessa sekä erityisesti heidän vaikutukseensa Suomi-Filmin ja Suomen Filmiteollisuuden tuotannoissa.

Raichin ja Bauerin ura alkoi Ranskan kansainvälisessä elokuvateollisuudessa, jossa he saivat koulutuksensa. Vuosina 1937 ja 1938 he muuttivat Suomeen, missä he työskentelivät Suomi-Filmin ja Suomen Filmiteollisuuden studioilla. Raichin ja Bauerin työtä tarkastellaan osana laajempaa kontekstia, jossa he vaikuttivat elokuvailmaisun kehittymiseen Suomessa.

Tämä tulkinta avaa uusia näkökulmia siihen, miten ulkomaalaiset ammattilaiset ovat vaikuttaneet suomalaiseen elokuvaan ja sen kehitykseen, ja korostaa kansainvälisten tekijöiden merkitystä kansallisen elokuvan muotoutumisessa.

The reliability of adhesive bonding to CAD/CAM resin composites is influenced not only by material composition and surface treatment but also by the testing methodology used to assess bond strength. However, the impact of different shear bond strength (SBS) test configurations remains insufficiently clarified. This study evaluated the influence of different surface pretreatment protocols and SBS test methods on the bonding performance of a self-adhesive resin cement to two CAD/CAM materials: a conventional particulate-filled composite (Cerasmart 270) and an experimental short glass fiber-reinforced composite (SFRC CAD). Specimens (14 × 12 × 3 mm; n = 80 per material) were ground with 320-grit silicon carbide paper and divided according to surface pretreatment: airborne-particle abrasion (APA) or APA followed by hydrofluoric acid application for 60 s (APA + HF). Each group was further subdivided based on the SBS test method using either resin cement cylinders fabricated with a custom transparent mold (diameter: 3.6 mm; height: 3 mm) or metallic cylinders cemented to the treated surface. Half of the specimens were tested after 48 h of water storage, while the remainder underwent hydrothermal aging by boiling in water for 16 h prior to testing. Material type, SBS test method, surface pretreatment, and aging significantly affected bond strength (p < 0.05). The metallic cylinder method produced higher SBS values than the transparent mold technique, particularly for SFRC CAD. APA + HF tended to reduce SBS in Cerasmart 270, particularly after aging, whereas SFRC CAD showed comparable or higher bond strength values with APA alone. Aging decreased SBS in most groups. Overall, bond strength was influenced by both material type and test methodology. Within the limitations of this study, airborne-particle abrasion alone may be sufficient for SFRC CAD materials, while additional HF treatment may not provide further benefit. These findings highlight the importance of considering both material characteristics and test configuration when interpreting laboratory bond strength data.

Background & aims: Proton pump inhibitor (PPI) use has been associated with metabolic dysfunction associated with steatotic liver disease (MASLD) in multiple studies. While the association is confounded by various risk factors, such as BMI and age, a potential mediating factor of the microbiome has been suggested. In this study, we aimed to identify bacterial clades with the highest mediating potential and evaluate the serially mediated path through microbially derived endogenous ethanol.

Methods: Microbiome mediation analysis of PPI use and MASLD was conducted in two cohorts. In a bariatric surgery cohort (n = 122), liver biopsy-proven steatosis grade and postprandial ethanol concentrations were used as outcomes. In the HELIUS cohort (n = 2440), a general population cohort study, mediation was performed using the Fatty Liver Index (FLI) score. The strongest associations were validated in the FINRISK cohort (n = 7066).

Results: Several bacterial taxa, which are predominantly found in the small intestine, showed a potential role in mediating the effects of PPIs on MASLD, postprandial ethanol levels, and FLI score. The Lactobacillales order showed the strongest mediating potential across the outcomes tested in both discovery cohorts. A notable serial mediation pathway was identified, linking PPI use to MASLD via Lactobacillales abundance and postprandial plasma ethanol concentrations. The mediating role of Lactobacillales in the association between PPI use and FLI scores was confirmed in the final study cohort.

Conclusions: Data from multiple cross-sectional cohort studies support a mediating potential of the microbiome in the association between PPI use and hepatic steatosis, independent of alcohol consumption. The effect of PPIs on MASLD appears to be mediated mainly by increased lactic acid bacteria abundance, and is potentially, in part, serially mediated by endogenous ethanol production.

Keywords: MASLD; ethanol; fermentation; gastrointestinal microbiome; lactobacillales; mediation analysis; obesity; proton pump inhibitors; small intestine.