Self and Microbiota-Derived Epitopes Induce CD4⁺ T Cell Anergy and Conversion into CD4⁺Foxp3⁺ Regulatory Cells

The physiological role of T cell anergy induction as a key mechanism supporting self-tolerance remains undefined, and natural antigens that induce anergy are largely unknown. In this report, we used TCR sequencing to show that the recruitment of CD4+CD44+Foxp3−CD73+FR4+ anergic (Tan) cells expands the CD4+Foxp3+ (Tregs) repertoire. Next, we report that blockade in peripherally-induced Tregs (pTregs) formation due to mutation in CNS1 region of Foxp3 or chronic exposure to a selecting self-peptide result in an accumulation of Tan cells. Finally, we show that microbial antigens from Akkermansia muciniphila commensal bacteria can induce anergy and drive conversion of naive CD4+CD44-Foxp3− T (Tn) cells to the Treg lineage. Overall, data presented here suggest that Tan induction helps the Treg repertoire to become optimally balanced to provide tolerance toward ubiquitous and microbiome-derived epitopes, improving host ability to avert systemic autoimmunity and intestinal inflammation

Trust, Salience and Deterrence: Evidence from an Antitrust Experiment

We present results from a laboratory experiment identifying the main channels through which different law enforcement strategies deter organized economic crime. The absolute level of a fine has a strong deterrence effect, even when the exogenous probability of apprehension is zero. This effect appears to be driven by distrust or fear of betrayal, as it increases significantly when the incentives to betray partners are strengthened by policies offering amnesty to “turncoat whistleblowers”. We also document a strong deterrence effect of the sum of fines paid in the past, which suggests a significant role for salience or availability heuristic in law enforcement

Expression of the Inherently Autoreactive Idiotope 9G4 on Autoantibodies to Citrullinated Peptides and on Rheumatoid Factors in Patients with Early and Established Rheumatoid Arthritis.

The pre-symptomatic stage of Rheumatoid arthritis (RA) is associated with pro-inflammatory cytokines and autoantibodies. High levels and epitope spread by Rheumatoid factors (RhF) and autoantibodies to citrullinated proteins signify progression towards disease expression. In established RA, the persistence of high autoantibody levels reflects production by both long-lived plasma cells and short-lived plasmablasts. Neither the relative contributions to pathogenesis by autoantibodies from either source, nor the factors responsible for deciding the fate of autoantigen specific 'parent' B-cells, is understood. Phenotypic markers identifying subsets of autoreactive B-cells are therefore of interest in understanding the origin and perpetuation of the autoimmune response in RA. One such phenotypic marker is the rat monoclonal antibody, 9G4, which recognises an idiotope on immunoglobuins derived from the inherently autoreactive VH-gene, VH4-34. We therefore investigated whether the 9G4 idiotope was expressed on autoantibodies in patients with RA

Inwazja obcych taksonów (Solidago sp.) na siedliska miejskie na przykładzie wybranych miast w południowej Polsce

In Poland there are three invasive species of the genus Solidago native to North America. In the years 2010-2015 field survey in five tows in Oswiecim Basin and its vicinity was performed which aimed to examine frequency, habitat preferences and basic parameters of populations of these species. Amongst invasive goldenrods S. canadensis (79 localities) and S. gigantea (74) prevailed in the study area and are much more frequent than S. graminifolia (8). Populations of goldenrods were not very abundant and did not occupy large area, however, there were populations exceeding 500 m2 and that had more than 500 ramets except for S. graminifolia which occur at low densities. The Canadian goldenrod S. canadensis tended to occur more frequently in ruderal and segetal habitats than S. gigantea whereas S. graminifolia was encountered only at fallows. Both S. gigantea and S. canadensis were reported to occur in wetland habitats and sometimes formed monospecific stands what prove negative influence on biodiversity.W Polsce występują trzy inwazyjne gatunki z rodzaju nawłoć Solidago rodzime dla Ameryki Północnej. W latach 2010-2015 przeprowadzono badania pilotażowe w pięciu miastach Kotliny Oświęcimskiej i w jej sąsiedztwie. Badania miały na celu określenie częstości występowania, preferencji siedliskowych i podstawowych parametrów populacji tych taksonów. Wśród inwazyjnych nawłoci przeważały: nawłoć kanadyjska S. canadensis (79 stanowisk) oraz nawłoć późna (n. olbrzymia) S. gigantea (74) nad nawłocią trawolistną S. graminifolia (zaledwie 8 stanowisk). Populacje nawłoci nie były liczebne i zajmowały niewielką powierzchnię, aczkolwiek występowały populacje przekraczające 500 m2 i mające więcej niż 500 pędów (ramet) z wyjątkiem S. graminifolia, która pojawiała się tylko w małej liczbie okazów. Nawłoć kanadyjska miała tendencję do występowania na bardziej ruderalnych i segetalnych siedliskach niż S. gigantea, podczas gdy S. gramifolia została odnotowana wyłącznie na ugorach. Zarówno S. gigantea, jak i S. canadensis zostały stwierdzone na siedliskach mokradłowych i czasami tworzyły jednogatunkowe płaty, co jest przejawem negatywnego wpływu na rodzimą różnorodność biologiczną

On-Line Electrochemical Reduction of Disulfide Bonds: Improved FTICR-CID and -ETD Coverage of Oxytocin and Hepcidin

Proteomic