Individuals differ in their biological rhythms. Some persons are morning orientated, preferring morning hours for intellectual and physical activities, and others are evening orientated. Previous work on adults revealed correlations between this morningness-eveningness construct and different aspects of mental health and well-being; for example, depression and seasonal affective disorders were related to eveningness. We hypothesise that morningness-eveningness may be associated with behavioural variables as measured by Goodman's Strength and Difficulties Questionnaire (SDQ). 150 girls and 150 boys form German secondary schools participated in this study. We used the Composite Scale of Morningness (CSM) to assess chronotype and the SDQ to assess behavioural difficulties. CSM scores correlated positively with pro-social behaviour, and negatively with behavioural problems, hyperactivity, and the total problem score. These results suggest that adolescents with higher eveningness also have higher problems as measured by the SDQ.

Background The low extracellular pH (pHe) of tumors resulting from glycolytic metabolism is a stress factor for the cells independent from concomitant hypoxia. The aim of the study was to analyze the impact of acidic pHe on gene expression on mRNA and protein level in two experimental tumor lines in vitro and in vivo and were compared to hypoxic conditions as well as combined acidosis+hypoxia. Methods Gene expression was analyzed in AT1 prostate and Walker-256 mammary carcinoma of the rat by Next Generation Sequencing (NGS), qPCR and Western blot. In addition, the impact of acidosis on tumor cell migration, adhesion, proliferation, cell death and mitochondrial activity was analyzed. Results NGS analyses revealed that 147 genes were uniformly regulated in both cell lines (in vitro) and 79 genes in both experimental tumors after 24 h at low pH. A subset of 25 genes was re-evaluated by qPCR and Western blot. Low pH consistently upregulated Aox1, Gls2, Gstp1, Ikbke, Per3, Pink1, Tlr5, Txnip, Ypel3 or downregulated Acat2, Brip1, Clspn, Dnajc25, Ercc6l, Mmd, Rif1, Zmpste24 whereas hypoxia alone led to a downregulation of most of the genes. Direct incubation at low pH reduced tumor cell adhesion whereas acidic pre-incubation increased the adhesive potential. In both tumor lines acidosis induced a G1-arrest (in vivo) of the cell cycle and a strong increase in necrotic cell death (but not in apoptosis). The mitochondrial O2 consumption increased gradually with decreasing pH. Conclusions These data show that acidic pHe in tumors plays an important role for gene expression independently from hypoxia. In parallel, acidosis modulates functional properties of tumors relevant for their malignant potential and which might be the result of pH-dependent gene expression.

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