A Combination of CD28 (rs1980422) and IRF5 (rs10488631) Polymorphisms Is Associated with Seropositivity in Rheumatoid Arthritis: A Case Control Study

IntroductionThe aim of the study was to analyse genetic architecture of RA by utilizing multiparametric statistical methods such as linear discriminant analysis (LDA) and redundancy analysis (RDA).MethodsA total of 1393 volunteers, 499 patients with RA and 894 healthy controls were included in the study. The presence of shared epitope (SE) in HLA-DRB1 and 11 SNPs (PTPN22 C/T (rs2476601), STAT4 G/T (rs7574865), CTLA4 A/G (rs3087243), TRAF1/C5 A/G (rs3761847), IRF5 T/C (rs10488631), TNFAIP3 C/T (rs5029937), AFF3 A/T (rs11676922), PADI4 C/T (rs2240340), CD28 T/C (rs1980422), CSK G/A (rs34933034) and FCGR3A A/C (rs396991), rheumatoid factor (RF), anti–citrullinated protein antibodies (ACPA) and clinical status was analysed using the LDA and RDA.ResultsHLA-DRB1, PTPN22, STAT4, IRF5 and PADI4 significantly discriminated between RA patients and healthy controls in LDA. The correlation between RA diagnosis and the explanatory variables in the model was 0.328 (Trace = 0.107; F = 13.715; P = 0.0002). The risk variants of IRF5 and CD28 genes were found to be common determinants for seropositivity in RDA, while positivity of RF alone was associated with the CTLA4 risk variant in heterozygous form. The correlation between serologic status and genetic determinants on the 1st ordinal axis was 0.468, and 0.145 on the 2nd one (Trace = 0.179; F = 6.135; P = 0.001). The risk alleles in AFF3 gene together with the presence of ACPA were associated with higher clinical severity of RA.ConclusionsThe association among multiple risk variants related to T cell receptor signalling with seropositivity may play an important role in distinct clinical phenotypes of RA. Our study demonstrates that multiparametric analyses represent a powerful tool for investigation of mutual relationships of potential risk factors in complex diseases such as RA.     

Anti-cancer activities of cytokinin ribosides

Phytochemistry Reviews - Cytokinins are plant hormones and play essential roles in regulating plant growth and development. They also have diverse pharmacological effects in animals and humans....     

Comparison of five different scoring methods in the evaluation of inflammatory infiltration (tumor‐infiltrating lymphocytes) in superficial spreading and nodular melanoma

The objective of our study was to compare the five different scoring methods of tumor‐infiltrating lymphocytes (TILs) assessment in a group of 213 cases of superficial spreading and nodular melanoma. The scoring methods include (a) Clark scoring; (b) Melanoma Institute Australia system; (c) scoring system used in the study of Saldanha et al.; (d) scoring system used in the TCGA study and modified by Park et al.; and (e) the system recently proposed by the “International Immuno‐Oncology Biomarker Working Group” for TILs scoring in all solid tumors. Prediction of survival with three main outcomes—disease‐specific‐free survival, local recurrence‐free survival, and distant metastasis‐free survival—was evaluated. The prognostic value of TILs showed statistical significance in univariate analysis regarding all three of the outcomes only for three of the five evaluated methods; the Clark scoring, the Melanoma Institute Australia system, and the system proposed by the “International Immuno‐Oncology Biomarker Working Group”. However, in multivariate analysis with covariants including Breslow thickness, type of melanoma, location, sex, and age, we did not find TILs to be an independent prognostic factor.     

New players in the field: Ecology and biocontrol potential of three species of mollusc-parasitic nematodes of the genus Phasmarhabditis

BioControl - Nematodes of the genus Phasmarhabditis are facultative parasites of molluscs with a world-wide distribution but, so far, only one species P. hermaphrodita has been thoroughly studied...     

Reintroduction of large herbivores restored plant species richness in abandoned dry temperate grassland

Naturalistic grazing by large herbivores is an increasingly practiced way of managing habitats with conservational value. It has the potential to restore and enhance biodiversity, creating self-sustainable environments vital for organisms requiring regular disturbances to moderate and/or reverse successional changes. European bison, Exmoor pony, and Tauros cattle were introduced in 2015 to a former military training area in Milovice, Czech Republic. The prevailing vegetation type is a forest-steppe savanna with Bromus erectus-dominated xeric grasslands mixed with deciduous shrubs and trees. After the cessation of military use, the area was abandoned which led to successional changes, including the dominance of tall grasses, litter accumulation, and bush encroachment. In 2017–2021, we monitored grassland vegetation in 30 grazed permanent plots (2?×?2 m) and 5 control plots representative of ungrazed, abandoned vegetation adjacent to the grazed areas. Naturalistic grazing increased species richness and the cover of forbs, while the cover of grasses and legumes was minimally affected. Grazing increased functional diversity of plant community, promoted a compositional change to small statured species and an increased incidence of red-list species. Seven years of continuous grazing increased the conservation value of this forest-steppe vegetation, a habitat type rapidly declining in Europe.