C-terminal citrullinated peptide alters antigen-specific APC:T cell interactions leading to breach of immune tolerance.

In rheumatoid arthritis, the emergence of anti-citrullinated autoimmunity is associated with HLA-antigen-T cell receptor complexes. The precise mechanisms underpinning this breach of tolerance are not well understood. Porphyromonas gingivalis expresses an enzyme capable of non-endogenous C-terminal citrullination with potential to generate citrullinated autoantigens. Here we document how C-terminal citrullination of ovalbumin peptide323-339 alters the interaction between antigen-presenting cells and OTII T cells to induce functional changes in responding T cells. These data reveal that C-terminal citrullination is sufficient to breach T cell peripheral tolerance in vivo and reveal the potential of C-terminal citrullination to lower the threshold for T cell activation. Finally, we demonstrate a role for the IL-2/STAT5/CD25 signalling axis in breach of tolerance. Together, our data identify a tractable mechanism and targetable pathways underpinning breach of tolerance in rheumatoid arthritis and provide new conceptual insight into the origins of anti-citrullinated autoimmunity.

Mechanical biofilm disruption causes microbial and immunological shifts in periodontitis patients.

Periodontitis is characterized by subgingival biofilm dysbiosis, inflammation and tissue destruction. Current treatment involves mechanical biofilm disruption known as non-surgical periodontal therapy (NSPT). This study sought to characterise the impact of treatment on microbial diversity and overall community, and the parallel impact on host inflammation in the oral cavity. Fourty-two periodontitis patients were included in this study, with periodontal clinical parameters, subgingival plaque and saliva samples collected at baseline and 90 days after treatment. Salivary cytokines were quantified, and subgingival plaque was analysed using 16S rRNA sequencing. After treatment, there were marked health-associated alterations in microbial composition and diversity, including differential abundance of 42 genera and 61 species. These changes were accompanied by substantial clinical improvement (pockets ≥ 5 mm, 27.50% to 9.00%, p < 0.001) and a decrease in salivary IL-1ß (p < 0.001)-a putative marker of periodontal inflammation. Despite significant reductions in disease associated anaerobes, several genera (Fusobacterium, Prevotella, Tanenerella, Treponema) remained present and formed a distinct subnetwork associated with residual disease. Collectively, this study shows that current periodontal treatment results in partial restoration of a healthy microbial ecosystem, but features of biofilm dysbiosis and host inflammation remain in some patients, which were surprisingly independent of clinical response.

How strong is the link between periodontitis and stroke?

Data sources PubMed, Scopus, Web of Science, The Cochrane Library, LILACS, OpenGrey and Google Scholar. No language restriction applied; studies conducted until September 2018.Study selection Observational studies in humans exposed and not exposed to periodontitis, in which the primary outcome was the risk of cerebrovascular accident, including haemorrhagic and ischaemic attacks (transient ischaemic attack and ischaemic stroke).Data extraction and synthesis Three examiners conducted a literature search. Duplicates, opinion articles, technical articles, guides and animal studies were excluded. Quality assessment was carried out followed by assessment of risk of bias. The extracted data were analysed using RevMan software. The meta-analysis looked for odds ratio (OR) in case-control studies and risk ratio (RR) in cohort studies as well as their 95% confidence intervals.Results Ten studies were included, all showing low risk of bias. The number of patients ranged from 80 to 15,792 with follow-up duration from 0 to 15 years. The studies showed variable heterogeneity. For stroke in case-control studies (seven studies), the overall heterogeneity was considerable (I2 = 77%). For ischaemic stroke in case-control studies (five studies), the overall heterogeneity was considerable (I2 = 72%), but after an outlying study was removed (I2 = 78%), it reduced significantly (I2 = 4%). For stroke in cohort studies (three studies), null heterogeneity was observed (I2 = 0%). The meta-analysis informed the three main outcomes: 1) individuals with periodontitis were twice as likely to suffer stroke (OR 2.31 [1.39, 3.84], p = 0.001, I2 = 77%); 2) individuals with periodontitis were twice as likely to suffer ischaemic stroke (OR 2.72 [2.00, 3.71], p <0.00001, I2 = 4%); and 3) individuals with periodontitis had a higher risk of experiencing stroke (RR 1.88 [1.55, 2.28], p <0.00001). Overall, the authors found that stroke events were associated with periodontitis.Conclusions The meta-analysis suggests an association between risk of stroke and periodontal disease. However, there is a need for prospective studies to ascertain the relationship between periodontal disease severity and stroke severity; whether there is an impact of periodontal treatment and to review whether periodontal disease impacts on stroke survival.

Gold nanoparticle-decorated graphene as a nonlinear optical material in the visible and near-infrared spectral range.

There have been numerous reports of boosting nonlinear optical phenomena in plasmonic nanostructures through local-field enhancement as well as through intrinsic metal nonlinearities. Here, we study the possibility of plasmonic enhancement of graphene's nonlinear absorption by creating a composite material: gold nanoparticle-decorated graphene dispersed in water. To evaluate the additive effect of combining the two materials on the saturable absorption efficiency we performed a series of f-scan (modified Z-scan) measurements using femtosecond laser pulses in the broad spectral range from 530 to 1600 nm. These studies are supplemented by TEM, UV-vis, ATR and Raman spectroscopy, revealing the mechanisms behind the formation of the composite material.

End-to-end self-assembly of gold nanorods in isopropanol solution: experimental and theoretical studies.

ABSTRACT: We describe here a modification of properties of colloidal gold nanorods (NRs) resulting from the chemical treatment used to carry out their transfer into isopropanol (IPA) solution. The NRs acquire a tendency to attach one to another by their ends (end-to-end assembly). We focus on the investigation of the change in position and shape of the longitudinal surface plasmon (l-SPR) band after self-assembly. The experimental results are supported by a theoretical calculation, which rationalizes the dramatic change in optical properties when the NRs are positioned end-to-end at short distances. The detailed spectroscopic characterization performed at the consecutive stages of transfer of the NRs from water into IPA solution revealed the features of the interaction between the polymers used as ligands and their contribution to the final stage, when the NRs were dispersed in IPA solution. The efficient method of aligning the NRs detailed here may facilitate applications of the self-assembled NRs as building blocks for optical materials and biological sensing.

Phenomenological description of phase inversion.

We propose an extended Ginzburg-Landau model for a description of the ambivalence region associated with the phenomenon of phase inversion observed in dispersed water-oil flow through a pipe. In analogy to the classical mean-field theory of phase transitions, it is shown that a good quantitative representation of the ambivalence region is obtained by using the injected phase volume fraction and a friction factor as the appropriate physical parameters.