Conformational changes of channelrhodopsin-2.

Channelrhodopsin-2 (ChR2) is a member of the new class of light-gated ion channels which serve as phototaxis receptors in the green alga Chlamydomonas reinhardtii. The protein is employed in optogenetics where neural circuits are optically stimulated under high spatiotemporal control. Despite its rapidly growing use in physiological experiments, the reaction mechanism of ChR2 is poorly understood.

Association of apolipoproteins with symptoms of asthma and atopy among schoolchildren.

Background: There is evidence for an association between serum cholesterol concentrations and asthma, but little is known about the underlying mechanisms. We explored the associations between serum apolipoprotein concentrations and symptoms of asthma and atopy.

Methods: In a population-based cross-sectional study among 10-year-old schoolchildren (n = 462), plasma concentrations of apolipoprotein AI (apoAI) and apolipoprotein B (apoB) were measured.

Body mass index and mortality: results of a cohort of 184,697 adults in Austria.

There is still a debate about the role of body mass index (BMI) as a risk factor for all-cause mortality. Most investigations with large sample sizes focused on populations from the United States, studies from Central-European cohorts are not available. We investigated the association between BMI and all-cause mortality and cause-specific mortality within a cohort in Austria.

Effect of breastfeeding on asthma, lung function and bronchial hyperreactivity in ISAAC Phase II.

The association between breastfeeding and wheezing, lung function and atopy was evaluated in the International Study of Asthma and Allergy in Childhood (ISAAC) Phase II. Cross-sectional studies were performed in 27 centres in 20 countries. Information on disease and exposure factors was collected by parental questionnaires.

The impact of education on risk factors and the occurrence of multimorbidity in the EPIC-Heidelberg cohort.

Background: In aging populations, the prevalence of multimorbidity is high, and the role of socioeconomic status and its correlates is not well described. Thus, we investigated the association between educational attainment and multimorbidity in a prospective cohort study, taking also into account intermediate factors that could explain such associations.

Methods: We included 13,781 participants of the Heidelberg cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC), who were 50-75 years at the end of follow-up.

Asthma and allergic symptoms in relation to house dust endotoxin: Phase Two of the International Study on Asthma and Allergies in Childhood (ISAAC II).

Background: Several studies have consistently reported inverse associations between exposure to endotoxin in house dust and atopy. With regard to the association between house dust endotoxin and asthma, the results are inconsistent.

Objectives: To study the association between house dust endotoxin levels and respiratory symptoms and atopy in populations from largely different countries.

DNA repair polymorphisms and the risk of stomach adenocarcinoma and severe chronic gastritis in the EPIC-EURGAST study.

Background: The contribution of genetic variation in DNA repair genes to gastric cancer (GC) risk remains essentially unknown. The aim of this study was to explore the relative contribution of DNA repair gene polymorphisms to GC risk and severe chronic atrophic gastritis (SCAG). Method A nested case control study within the EPIC cohort was performed including 246 gastric adenocarcinomas and 1175 matched controls.

Increases in intracellular calcium triggered by channelrhodopsin-2 potentiate the response of metabotropic glutamate receptor mGluR7.

The metabotropic glutamate receptor 7a (mGluR7a), a heptahelical Galphai/o-coupled protein, has been shown to be important for presynaptic feedback inhibition at central synapses and certain forms of long term potentiation and long term depression. The intracellular C terminus of mGluR7a interacts with calmodulin in a Ca2+-dependent manner, and calmodulin antagonists have been found to abolish presynaptic inhibition of glutamate release in neurons and mGluR7a-induced activation of G-protein-activated inwardly rectifying K+ channel (GIRK) channels in HEK293 cells. Here, we characterized the Ca2+ dependence of mGluR7a signaling in Xenopus oocytes by using channelrhodopsin-2 (ChR2), a Ca2+-permeable, light-activated ion channel for triggering Ca2+ influx, and a GIRK3.

Infrequent promoter methylation of the MGMT gene in liver metastases from uveal melanoma.

Uveal melanoma is associated with a high mortality rate once metastases occur, with over >90% of metastatic patients dying within less than 1 year from metastases to the liver. The intraarterial hepatic (iah) administration of the alkylating agent fotemustine holds some promise with response rates of 36% and median survival of 15 months. Here, we investigated whether the DNA-repair-protein MGMT may be involved in the variability of response to fotemustine and temozolomide in uveal melanoma.

Diet in the aetiology of ulcerative colitis: a European prospective cohort study.

Background/aims: The causes of ulcerative colitis are unknown, although it is plausible that dietary factors are involved. Case-control studies of diet and ulcerative colitis are subject to recall biases. The aim of this study was to examine the prospective relationship between the intake of nutrients and the development of ulcerative colitis in a cohort study.

Associations of adipokines with asthma, rhinoconjunctivitis, and eczema in German schoolchildren.

There is growing evidence for an association between obesity and asthma, but little is known about the underlying mechanisms. We hypothesized that high plasma leptin and low plasma adiponectin concentrations might be related to asthma and allergies in children. Plasma leptin and adiponectin concentrations were measured in a cross-sectional study involving 462 children aged 10 years.

Prevalence and cluster of cardiometabolic biomarkers in overweight and obese schoolchildren: results from a large survey in southwest Germany.

Background: Obesity is associated with substantial metabolic changes and subclinical inflammation. We explored associations between body mass index (BMI) and cardiometabolic biomarkers and their clustering in overweight and obese schoolchildren.

Methods: In this population-based, cross-sectional study among 450 children 10 years old, we measured adiponectin, leptin, inflammatory markers, apolipoprotein (apo) AI and B, and lipoprotein-associated phospholipase A(2) (Lp-PLA(2)).

Spectral characteristics of the photocycle of channelrhodopsin-2 and its implication for channel function.

In 2003, channelrhodopsin-2 (ChR2) from Chlamydomonas reinhardtii was discovered to be a light-gated cation channel, and since that time the channel became an excellent tool to control by light neuronal cells in culture as well as in living animals with high temporal and spatial resolution in a noninvasive manner. However, little is known about the spectral properties and their relation to the channel function. We have expressed ChR2 in the yeast Pichia pastoris and purified the protein.

MGMT in primary and recurrent human glioblastomas after radiation and chemotherapy and comparison with p53 status and clinical outcome.

The DNA repair protein O(6)-methylguanine-DNA methyltransferase (MGMT) plays a pivotal role in alkylating drug resistance. Here, we determined MGMT activity in primary and recurrent glioblastomas (GBM, WHO grade IV) of patients who received radiation therapy (RT) or RT plus chemotherapy with alkylating agents (temozolomide, chloroethylnitrosoureas). The mean MGMT activity of untreated GBM was 37 +/- 45 (range 0-205) fmol/mg proteins.

Negative charged threonine 95 of c-Jun is essential for c-Jun N-terminal kinase-dependent phosphorylation of threonine 91/93 and stress-induced c-Jun biological activity.

Activation of c-Jun, a major component of the AP-1 transcription factor, represents a paradigm for transcriptional response to stress. Transactivation of c-Jun is regulated by Jun-N-terminal kinases (JNKs) through phosphorylation at serine 63 and 73 (S63/S73), as well as at threonine 91 and 93 (T91/T93). How these two groups of phosphoacceptor sites respond to different grades of genotoxic stress and whether DNA-damage pathways influence the extent of their JNK-dependent phosphorylations remain to be elucidated.

Multimodal fast optical interrogation of neural circuitry.

Our understanding of the cellular implementation of systems-level neural processes like action, thought and emotion has been limited by the availability of tools to interrogate specific classes of neural cells within intact, living brain tissue. Here we identify and develop an archaeal light-driven chloride pump (NpHR) from Natronomonas pharaonis for temporally precise optical inhibition of neural activity. NpHR allows either knockout of single action potentials, or sustained blockade of spiking.

Dietary patterns and survival of older Europeans: the EPIC-Elderly Study (European Prospective Investigation into Cancer and Nutrition).

Objective: To investigate the association of a posteriori dietary patterns with overall survival of older Europeans.

Design And Setting: This is a multi-centre cohort study. Cox regression analysis was used to investigate the association of the prevailing, a posteriori-derived, plant-based dietary pattern with all-cause mortality in a population of subjects who were 60 years or older at recruitment to the European Prospective Investigation into Cancer and Nutrition (EPIC-Elderly cohort).

Long-term reproducibility of a food-frequency questionnaire and dietary changes in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Heidelberg cohort.

Within a prospective cohort study, we explored the long-term reproducibility of the food-frequency questionnaire (FFQ) and dietary changes in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Heidelberg cohort. After a mean follow-up time of 68.8 (sd 4.

Alcohol intake and breast cancer risk: the European Prospective Investigation into Cancer and Nutrition (EPIC).

Objective: Most epidemiologic studies have suggested an increased risk of breast cancer with increasing alcohol intake. Using data from 274,688 women participating in the European Prospective Investigation into Cancer and Nutrition study (EPIC), we investigated the relation between alcohol intake and the risk of breast cancer.

Methods: Incidence rate ratios (IRRs) based on Cox proportional hazard models were calculated using reported intake of alcohol, recent (at baseline) and lifetime exposure.

Socioeconomic position and the risk of gastric and oesophageal cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC-EURGAST).

Objectives: To evaluate the association of socioeconomic position with adenocarcinoma of the oesophagus and stomach.

Methods: The European Prospective Investigation into Cancer and Nutrition (EPIC) cohort comprises about 520 000 participants mostly aged 35-70 years. Information on diet and lifestyle was collected at recruitment.

[The expert patient: medical consequences].

The expression expert patient appeared about ten years ago. It defines the role of patients who are actively involved in their disease management. Most clinical oncologists are challenged by expert patients.

Use of hormone replacement therapy (HRT) among women aged 45-64 years in the German EPIC-cohorts.

Objective: To describe the prevalence and to assess type and indicators of hormone replacement therapy (HRT) use in the two German EPIC-cohorts.

Methods: Approximately 30,000 women predominantly aged 35-65 years were recruited in EPIC-Heidelberg and EPIC-Potsdam between 1994 and 1998. Information on diet and lifestyle, medical history and use of hormone therapy was collected at recruitment.

Polymorphisms in metabolic genes related to tobacco smoke and the risk of gastric cancer in the European prospective investigation into cancer and nutrition.

Metabolizing enzymes, which often display genetic polymorphisms, are involved in the activation of compounds present in tobacco smoke that may be relevant to gastric carcinogenesis. We report the results of a study looking at the association between risk of gastric adenocarcinoma and polymorphisms in genes CYP1A1, CYP1A2, EPHX1, and GSTT1. A nested case-control study was carried out within the European Prospective Investigation into Cancer and Nutrition, developed in 10 European countries.

Salmonella typhimurium meningitis in an adult patient with AIDS.

Salmonella meningitis is an unusual complication of Salmonella sepsis and occurs mainly in children. A rare case of Salmonella typhimurium meningitis occurring in an adult HIV positive man who presented with a history of fever and diarrhoea is reported. On examination he was dehydrated, and had oral thrush, weakness of lower limbs and neck stiffness.

CagA+ Helicobacter pylori infection and gastric cancer risk in the EPIC-EURGAST study.

Helicobacter pylori (H. pylori), atrophic gastritis, dietary and life-style factors have been associated with gastric cancer (GC). These factors have been evaluated in a large case-control study nested in the European Prospective Investigation into Cancer and Nutrition carried out in 9 countries, including the Mediterranean area.