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Dendritic cells (DCs) have a role in the development and activation of self-reactive pathogenic T cells 1 , 2 . Genetic variants that are associated with the function of DCs have been linked to autoimmune disorders 3 , 4 , and DCs are therefore attractive therapeutic targets for such diseases. However, developing DC-targeted therapies for autoimmunity requires identification of the mechanisms that regulate DC function. Here, using single-cell and bulk transcriptional and metabolic analyses in combination with cell-specific gene perturbation studies, we identify a regulatory loop of negative feedback that operates in DCs to limit immunopathology. Specifically, we find that lactate, produced by activated DCs and other immune cells, boosts the expression of NDUFA4L2 through a mechanism mediated by hypoxia-inducible factor 1α (HIF-1α). NDUFA4L2 limits the production of mitochondrial reactive oxygen species that activate XBP1-driven transcriptional modules in DCs that are involved in the control of pathogenic autoimmune T cells. We also engineer a probiotic that produces lactate and suppresses T cell autoimmunity through the activation of HIF-1α–NDUFA4L2 signalling in DCs. In summary, we identify an immunometabolic pathway that regulates DC function, and develop a synthetic probiotic for its therapeutic activation. Lactate produced by dendritic cells (DCs) suppresses T-cell-mediated autoimmunity through a mechanism in which lactate activates HIF-1α–NDUFA4L2 signalling in DCs and thereby limits DC-mediated pro-inflammatory responses such as the development of encephalitogenic T cells.

Purpose This study aims to analyse the impact of company performance, company size, ownership structure, board characteristics and other company characteristics on the disclosure of managerial remuneration in 134 listed companies in India from the year 2003 to 2012. Design/methodology/approach A disclosure and compliance index is developed on the basis of 14 statements prepared regarding the disclosure of managerial remuneration in corporate governance reports of companies. The Papke and Wooldridge (2008) approach is adopted to estimate fractional response models, and fractional probit model is estimated using the generalised estimating equation approach, with an independent working correlation matrix to determine the effect of various company attributes on managerial remuneration disclosure. Findings The study shows that company size and the presence of remuneration committee are significantly related with the disclosure and compliance index of managerial remuneration. Remuneration disclosure is found to be time-dependent as time dummies for all years are found to be significant. Research limitations/implications This study highlights the importance of the formation of remuneration committees on corporate boards. The findings of the present study can be used as inputs for promoting better compliance and comprehensive executive remuneration disclosure. Originality/value Nothing concrete in the field of managerial remuneration disclosure (to the best of researcher’s knowledge) has yet been done in an emerging economy such as India. This study aims to address this gap by deriving a disclosure and compliance index for managerial remuneration disclosure and examining the impact of various corporate attributes on it.

The present study analyzes social media addiction among students in the age group of 12-20 years studying in the educational institutions of Amritsar district, Punjab. It explores the association of personal smartphone, demographics, family background with social media addiction. Convenience and snowball sampling methods were used to collect data from 88 students using a questionnaire, and their responses were analyzed using descriptive statistics, chi-square test, fisher's exact test, independent t-test, one-way ANOVA and Welch ANOVA on SPSS 20. The results revealed that 87.5% of the respondents used social media platforms irrespective of the availability of personal smartphone, and 21.6% had an average social media addiction score of more than 3, indicating their addiction to such platforms. It revealed a significant association of social media usage, time spent on social media, and purpose of using social media with personal smartphone. The study also disclosed that mean values of social media addiction were significantly different for respondents belonging to nuclear and joint families and based on qualification of the respondents' mothers. The results of the posthoc Turkey test show that social media score is significantly lower in the case of respondents whose mothers are undergraduates as compared to the respondents whose mothers are graduates (p=0.071). However, there were no differences in the social media score between the respondents who have graduate mothers and those with postgraduate mothers.

Purpose The purpose of this paper is to analyse the impact of company performance, governance structure and ownership structure in determining the managerial remuneration for 134 listed companies in India over the years 2003-2012. Design/methodology/approach Remuneration paid to the board of directors of companies is taken to represent the managerial remuneration. Exogeneity among the company performance measures is verified with the endogtest suggested in Baum et al. (2007). A fixed effects panel regression with clustered standard errors is employed after checking for the presence of heteroskedasticity, autocorrelation and cross-sectional dependence in the data. Findings The study reveals that managerial remuneration increases as the accounting performance of companies improves, whereas the market performance of companies has no significant association with managerial remuneration. The study also shows that foreign institutional shareholding is significantly and positively related with managerial remuneration in India. Research limitations/implications This study highlights the various factors which affect the determination of managerial remuneration in India. These findings can be used as inputs by regulatory authorities in framing and improving governance norms regarding managerial remuneration. This study also suggests that factors other than the number, the independence and objectivity of independent directors are more important in determining managerial remuneration. Originality/value The present study proposes more reliable results, obtained through a fixed effects panel regression model with clustered standard error estimates and also checks endogeneity of performance measures with the endogtest, which is the appropriate test to use for verifying endogeneity in panel data.

Dendritic cells (DCs) control the generation of self-reactive pathogenic T cells. Thus, DCs are considered attractive therapeutic targets for autoimmune diseases. Using single-cell and bulk transcriptional and metabolic analyses in combination with cell-specific gene perturbation studies we identified a negative feedback regulatory pathway that operates in DCs to limit immunopathology. Specifically, we found that lactate, produced by activated DCs and other immune cells, boosts NDUFA4L2 expression through a mechanism mediated by HIF-1α. NDUFA4L2 limits the production of mitochondrial reactive oxygen species that activate XBP1-driven transcriptional modules in DCs involved in the control of pathogenic autoimmune T cells. Moreover, we engineered a probiotic that produces lactate and suppresses T-cell autoimmunity in the central nervous system via the activation of HIF-1α/NDUFA4L2 signaling in DCs. In summary, we identified an immunometabolic pathway that regulates DC function, and developed a synthetic probiotic for its therapeutic activation.

Objectives The current systematic review and meta‐analysis aims to assess the safety and immunogenicity of the anticaries vaccines currently available. Materials and Methods Electronic searches of PubMed, Scopus, Web of Science and Science Direct were performed. Studies assessing the safety and effectiveness of the anticaries vaccination, including the dose, plasmids, serum IgG and IgA levels after immunization, were included. Studies in which animals were used for anticaries vaccine were also included. Combining more than one trial was done to estimate the pooled intervention effect using the meta‐analysis when studies examined the same intervention and outcomes with comparable methods in similar populations. The continuous data was pooled using the inverse variance method, and dichotomous data using the Mantel‐Haenszel method. Results Out of 4701 records, only 17 publications met the eligibility criteria. Although all studies were assessed as having an overall low risk of bias, certain domains (D3, D5, and D7) exhibited a high risk across most studies. The pooled RR, derived using a random‐effects model, was 0.53 (95% CI: 0.46–0.62), indicating a statistically significant 47% reduction in risk across studies. Conclusions There is excellent potential for dental caries vaccines to transform oral health in the future. Various vaccines, such as Killed Formalin‐treated Donor strain 2 ‐ recombinant Protein Antigen c and anti‐CAT‐SYIIgY antibodies, have demonstrated prophylactic effects against Streptococcus mutans colonization on teeth. These interventions exhibit a sustained reduction in S. mutans colonization, which may contribute to the prevention of dental caries. A vaccination of this kind would significantly lower tooth decay prevalence and the financial and health costs that go along with it. Although there isn't currently a vaccination that is widely used, advances in the field and further study indicate that one could be developed in the near future to prevent dental caries. •A vaccination of this kind would significantly lower tooth decay prevalence and the financial and health costs that go along with it.•Additional study, clinical studies, and regulatory permissions are necessary for the development and successful deployment. The search for dental caries vaccines is an appealing path for future developments in healthcare because of the possible influence on oral health around the world.

In the current semiconductor scenario, multiple gate FETs like tri-gate (TG) FinFETs have been a boon to continue the scaling of devices below 32 nm technology. The application of strained silicon has further enhanced drive currents. Leakage currents have been reduced by employing high-k materials, which has led to enhanced device switching characteristics. The development and characterization of a 10 nm channel TG n-FinFET device incorporating a tri-layered strained silicon channel and stacked high-k dielectric materials as the gate oxide are the motivation of this paper. The electrical characteristics and short channel effects (SCEs) of all the devices have been determined by replacing the SiO2 gate oxide with a stacked gate oxide of 0.5 nm of SiO2 and 0.5 nm EOT of various high-k dielectric materials like ZrO2, Al2O3, Si3N4, and HfO2. It is observed that SCEs and leakage characteristics are significantly improved by the use of stacked high-k dielectric materials like HfO2, and the strain in the channel region significantly improves the drive current without hampering SCEs. Thus, the combination of strained silicon and HfO2 dielectrics showed improved performance of the developed device with a reduced chip area.

Although acute encephalopathy is quite commonly seen in patients of SARS-CoV-2 infection, encephalitis characterised by brain inflammation is relatively rare. Encephalitis caused by Herpes simplex type 1 is the most common cause of identified sporadic encephalitis, and early diagnosis and prompt treatment can prevent the devastating outcome. In this brief communication, we report a case of SARS-CoV-2 associated haemorrhagic encephalitis mimicking herpes encephalitis. In today’s pandemic era, it is especially important to distinguish herpes encephalitis from SARS-CoV-2-associated encephalitis as treatment and prognosis of both the conditions differ greatly. This case highlights the importance of suspecting SARS-CoV-2 infection in a patient presenting with clinical symptoms and brain imaging suggestive of Herpes encephalitis.