<Emphasis Type="Italic">Yersinia pseudotuberculosis</Emphasis> supports Th17 differentiation and limits de novo regulatory T cell induction by directly interfering with T cell receptor signaling

Adaptive immunity critically contributes to control acute infection with enteropathogenic Yersinia pseudotuberculosis; however, the role of CD4⁺ T cell subsets in establishing infection and allowing pathogen persistence remains elusive. Here, we assessed the modulatory capacity of Y. pseudotuberculosis on CD4⁺ T cell differentiation. Using in vivo assays, we report that infection with Y. pseudotuberculosis resulted in enhanced priming of IL-17-producing T cells (Th17 cells), whereas induction of Foxp3⁺ regulatory T cells (Tregs) was severely disrupted in gut-draining mesenteric lymph nodes (mLNs), in line with altered frequencies of tolerogenic and proinflammatory dendritic cell (DC) subsets within mLNs. Additionally, by using a DC-free in vitro system, we could demonstrate that Y. pseudotuberculosis can directly modulate T cell receptor (TCR) downstream signaling within naïve CD4⁺ T cells and Tregs via injection of effector molecules through the type III secretion system, thereby affecting their functional properties. Importantly, modulation of naïve CD4⁺ T cells by Y. pseudotuberculosis resulted in an enhanced Th17 differentiation and decreased induction of Foxp3⁺ Tregs in vitro. These findings shed light to the adjustment of the Th17-Treg axis in response to acute Y. pseudotuberculosis infection and highlight the direct modulation of CD4⁺ T cell subsets by altering their TCR downstream signaling.     

Natural variation at Strubbelig Receptor Kinase 3 drives immune-triggered incompatibilities between Arabidopsis thaliana accessions

Accumulation of genetic incompatibilities within species can lead to reproductive isolation and, potentially, speciation. In this study, we show that allelic variation at SRF3 (Strubbelig Receptor Family 3), encoding a receptor-like kinase, conditions the occurrence of incompatibility between Arabidopsis thaliana accessions. The geographical distribution of SRF3 alleles reveals that allelic forms causing epistatic incompatibility with a Landsberg erecta allele at the RPP1 resistance locus are present in A. thaliana accessions in central Asia. Incompatible SRF3 alleles condition for an enhanced early immune response to pathogens as compared to the resistance-dampening effect of compatible SRF3 forms in isogenic backgrounds. Variation in disease susceptibility suggests a basis for the molecular patterns of a recent selective sweep detected at the SRF3 locus in central Asian populations.     

Common variants at TRAF3IP2 are associated with susceptibility to psoriatic arthritis and psoriasis

Psoriatic arthritis (PsA) is an inflammatory joint disease that is distinct from other chronic arthritides and which is frequently accompanied by psoriasis vulgaris (PsV) and seronegativity for rheumatoid factor. We conducted a genome-wide association study in 609 German individuals with PsA (cases) and 990 controls with replication in 6 European cohorts including a total of 5,488 individuals. We replicated PsA associations at HLA-C and IL12B and identified a new association at TRAF3IP2 (rs13190932, P = 8.56 × 10?1?). TRAF3IP2 was also associated with PsV in a German cohort including 2,040 individuals (rs13190932, P = 1.95 × 10?3). Sequencing of the exons of TRAF3IP2 identified a coding variant (p.Asp10Asn, rs33980500) as the most significantly associated SNP (P = 1.13 × 10?2?, odds ratio = 1.95). Functional assays showed reduced binding of this TRAF3IP2 variant to TRAF6, suggesting altered modulation of immunoregulatory signals through altered TRAF interactions as a new and shared pathway for PsA and PsV.     

Functional interaction between TRPC1 channel and connexin-43 protein: a novel pathway underlying S1P action on skeletal myogenesis

We recently demonstrated that skeletal muscle differentiation induced by sphingosine 1-phosphate (S1P) requires gap junctions and transient receptor potential canonical 1 (TRPC1) channels. Here, we searched for the signaling pathway linking the channel activity with Cx43 expression/function, investigating the involvement of the Ca²⁺-sensitive protease, m-calpain, and its targets in S1P-induced C2C12 myoblast differentiation. Gene silencing and pharmacological inhibition of TRPC1 significantly reduced Cx43 up-regulation and Cx43/cytoskeletal interaction elicited by S1P. TRPC1-dependent functions were also required for the transient increase of m-calpain activity/expression and the subsequent decrease of PKCα levels. Remarkably, Cx43 expression in S1P-treated myoblasts was reduced by m-calpain-siRNA and enhanced by pharmacological inhibition of classical PKCs, stressing the relevance for calpain/PKCα axis in Cx43 protein remodeling. The contribution of this pathway in myogenesis was also investigated. In conclusion, these findings provide novel mechanisms by which S1P regulates myoblast differentiation and offer interesting therapeutic options to improve skeletal muscle regeneration.     

Raspailiidae (Porifera: Demospongiae: Axinellida) from the Mexican Pacific Ocean with the description of seven new species

The taxonomy of the family Raspailiidae has always been controversial. The family was first included in the order Poecilosclerida. It was then allocated to the order Axinellida and later moved back to Poecilosclerida. Currently with the development of molecular tools it has been assigned to the order Axinellida. In this contribution we describe 10 species from the Mexican Pacific Ocean. Seven of them are new to science: Raspailia (Parasyringella) rubra sp. nov., Raspailia (Raspaxilla) hymani (Dickinson 1945 Dickinson, MG. 1945. Sponges on the Gulf of California. Allan Hancock Pac Exp, 11(1): 1–251.  [Google Scholar]), Raspailia (Raspaxilla) hyle (de Laubenfels 1930 de Laubenfels, MW. 1930. The sponges of California. (Abstracts of dissertations for the degree of doctor of philosophy). Stanford Univ Bull, 5(98): 24–29.  [Google Scholar]), Aulospongus cerebella (Dickinson 1945 Dickinson, MG. 1945. Sponges on the Gulf of California. Allan Hancock Pac Exp, 11(1): 1–251.  [Google Scholar]), Aulospongus californianus sp. nov., Aulospongus aurantiacus sp. nov., Eurypon patriciae sp. nov., Eurypon tylospinosum sp. nov., Eurypon diversicolor sp. nov. and Eurypon brunus sp. nov. We discuss the genus Eurypon and include a table for all the species described worldwide with some comments about this genus. http://www.zoobank.org/urn:lsid:zoobank.org:pub:D462084B-EE9C-4C61-884A-C9DB70003B4A     

Packaging Radium,Selling Science: Boxes,Bottles and Other Mundane Things in the World of Science

This article discusses the intersection of science and culture in the marketplace and explores the ways in which radium quack and medicinal products were packaged and labelled in the early twentieth century US. Although there is an interesting growing body of literature by art historians on package design, historians of science and medicine have paid little to no attention to the ways scientific and medical objects that were turned into commodities were packaged and commercialized. Thinking about packages not as mere containers but as multifunctional tools adds to historical accounts of science as a sociocultural enterprise and reminds us that science has always been part of consumer culture. This paper suggests that far from being receptacles that preserve their content and facilitate their transportation, bottles and boxes that contained radium products functioned as commercial and epistemic devices. It was the 1906 Pure Food and Drug Act that enforced such functions. Packages worked as commercial devices in the sense that they were used to boost sales. In addition, ‘epistemic’ points to the fact that the package is an artefact that ascribes meaning to and shapes its content while at the same time working as a device for distinguishing between patent and orthodox medicines.