Highlights d Longitudinal scRNA-seq of tumor-specific TCF-1 + CD8 + T cells in KP lung adenocarcinoma d Identified a proliferative Slamf6 + TCF-1 + T cell subset and a non-cycling SlamF6 À subset d The lymph node contains a recruitable reservoir of functional TCF-1 + CD8 + T cells d Flt3L+CD40 boosts cDC1, increases TCF-1 + CD8 + T cell frequencies, decreases tumor burden

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Objective: To analyse the association of alcohol consumption and blood lipids, haemostatic factors, and homocysteine in German adults by gender and age groups. Design: Cross-sectional population-based survey. Setting: Data from the German National Health Interview and Examination Survey 1998, representative for age, gender, community size, and federal state. Subjects: From a sample of 7124 Germans between 18 and 79 y old, 2420 women and 2365 men were selected. Only individuals who were not currently receiving medical treatment or did not have disorders related to cardiovascular disease were selected for this study. Results: Using analyses of variance, mean blood levels of total cholesterol, HDL cholesterol, HDL/total cholesterol ratio, total glycerides, fibrinogen, antithrombin III, and homocysteine adjusted for age, socioeconomic status, East/West Germany residence, body mass index, tobacco use, sports activity, and coffee consumption, if appropriate are presented by alcohol consumption groups (0, 40-10, 410-20, 420-30 and 430 g/day). The HDL/total cholesterol ratio increased with higher alcohol groups up to 10-20 g/day ( þ 15%) for women and 430 g/day ( þ 18%) for men, showing the strongest rise among men aged 55-79 y. Fibrinogen decreased with higher alcohol groups up to 10-20 g/day for women and 20-30 g/day for men. Among women, homocysteine levels showed a U-shaped curve with a minimum of 8.49 mmol/l at 10-20 g alcohol/day (À8%, reference: nondrinking), whereas an inverse association was observed for men. Conclusions: Moderate alcohol consumption is associated with favourable levels of several cardiovascular risk factors. The most favourable cardiovascular risk factor profile among women was observed among those drinking 10-20 g alcohol/day. Beneficial effects seem to be more pronounced among older men.

Nur77 orphan steroid receptor and its family member Nor-1 are required for apoptosis of developing T cells. In thymocytes, signals from the TCR complex induce Nur77 and Nor-1 expression followed by translocation from the nucleus to mitochondria. Nur77 and Nor-1 associate with Bcl-2 in the mitochondria, resulting in a conformation change that exposes the Bcl-2 BH3 domain, a presumed pro-apoptotic molecule of Bcl-2. As Nur77 and Nor-1 are heavily phosphorylated, we examined the requirement of Nur77 and Nor-1 phosphorylation in mitochondria translocation and Bcl-2 BH3 exposure. We found that HK434, a PKC agonist, in combination with calcium ionophore, can induce Nur77 and Nor-1 phosphorylation, translocation, Bcl-2 BH3 exposure and thymocyte apoptosis. Inhibitors of both classical and novel forms of PKC were able to block this process. In contrast, only the general but not classical PKC-specific inhibitors were able to block the same process initiated by PMA, a commonly used PKC agonist. These data demonstrate a differential activation of PKC isoforms by PMA and HK434 in thymocytes, and show the importance of PKC in mitochondria translocation of Nur77/Nor-1 and Bcl-2 conformation change during TCR-induced thymocyte apoptosis.

Objective: To analyse the alcohol consumption behaviour of the German adult population, with a focus on the characteristics of persons drinking more than the tolerable upper alcohol intake level (TUAL) of 10-12 g day 21 for healthy adult women and 20 -24 g day 21 for healthy adult men. Design and setting: For the German National Health Interview and Examination Survey 1998, a representative sample of free-living adults was drawn. A total of 7124 participants were interviewed comprehensively about their sociodemographic background, lifestyle and eating habits including alcohol consumption. Subjects: A sub-sample of 4030 women and men, 18 -79 years old, who were involved in the integrated German Nutrition Survey. Results: About 16% of women and 31% of men had mean alcohol consumption above the TUAL. Among other factors, the inclination to exceed the TUAL was related to middle-age, high socio-economic status, smoking and use of soft drugs. Among both women and men, a high proportion of persons drinking above the TUAL was observed among those consuming low amounts of soft drinks, fruit, poultry, milk products, bread and cake/biscuits. Women preferred to drink wine, whereas men preferred to drink beer. Conclusions: Many Germans have an alcohol consumption level above the TUAL and thus are supposed to be at increased risk for alcohol-associated diseases.

Tobacco consumption increases the risk of many chronic degenerative diseases and causes considerable social follow-up costs. The ongoing high tobacco consumption in the population, therefore, highlights an area in which health policy action is urgently required. According to the Telephone Health Survey 2003, about 37% of men aged 18 years and older and 28% of women of the same age are smokers. Almost half of the male daily smokers and a third of the female daily smokers consume 20 or more cigarettes a day, thus exposing themselves to a serious health risk. Among persons of socially disadvantaged groups, smoking prevalence is particularly high; they are also more likely to be heavy smokers and less likely to stop smoking. In the last 20 years, tobacco consumption has only declined slightly among men, while it has increased among women. These results underline the necessity for comprehensive tobacco prevention and tobacco control, and this means not only general measures but also initiatives focusing on specific target groups.

Key Points miR-146a and miR-146b are upregulated during premalignancy in the thymus of T cell–specific PTEN-deficient mice. Transgenic expression of mir-146a/b delays PTEN-deficient lymphomagenesis through repression of TCR signals critical for c-myc activation.