Ein stochastisches Modell für EEG-Microstates

Zeitreihen von spontan auftretenden Topograpfien elektrischer Felder an der Kopfoberfläche, die durch eine Elektroenzephalografie (EEG) gemessen werden, zeigen Zeiträume („EEG-Microstates“), während denen die Topografie quasi-stabil ist. Diese EEG-Microstates werden üblicherweise dadurch analysiert, dass die zu spezifischen Zeitpunkten beobachteten Ausprägungen des EEGs in eine kleine Anzahl von prototypischen Topografien („Karten“) eingeteilt werden. Dadurch erhält man eine diskrete Kartensequenz. Um die Struktur der Übergangswahrscheinlichkeiten in experimentellen Kartensequenzen zu beschreiben, werden diese Sequenzen durch eine reduzierte Markov-Kette modelliert mit nur einem Parameter pro Karte. Die Markov-Ketten können mithilfe von zwei bestimmten stochastischen Prozessen konstruiert werden. Durch den einen Prozess werden zufällige Intervalle definiert, die zufällig den verschiedenen Karten zugeordnet werden. Durch den anderen Prozess werden zufällige Abtastungszeitpunkte bestimmt, zu denen die Karte des jeweils aktuellen Intervalls abgelesen wird. Neben der Motivation und Vorstellung des Markov-Ketten-Modells werden in dieser Arbeit Schätzer für die Modellparameter vorgeschlagen und diskutiert sowie ihre asymptotischen Varianzen hergeleitet. Zudem wird ein Anpassungstest durchgeführt und es werden Abwandlungen des Modells untersucht.The time series of spontaneously occurring scalp electric field topographies measured by electroencephalography (EEG) shows periods (‘EEG microstates’) in which the topography is quasi-stable. These are commonly analyzed by first sampling the EEG signal at specific points in time and then classifying the EEG at these points in time into a small number of prototypical topographies (‘maps’). This results in a discrete sequence of maps. For describing the structure of the transition probabilities in experimental map sequences, these sequences are modeled by reduced Markov chains with only one parameter per map. These Markov chains can also be constructed by means of two specific stochastic processes. One of these processes defines random intervals which are randomly assigned to different maps. The other one gives random sampling points at which the map of the current interval is sampled. In this thesis, estimators for the parameters of the Markov chain model are defined and discussed, and their asymptotic variances are derived. In addition a goodness of fit test is performed and modifications of the Markov chain model are analysed

Towards Systems Biology of Heterosis: A Hypothesis about Molecular Network Structure Applied for the Arabidopsis Metabolome

We propose a network structure-based model for heterosis, and investigate it relying on metabolite profiles from Arabidopsis. A simple feed-forward two-layer network model (the Steinbuch matrix) is used in our conceptual approach. It allows for directly relating structural network properties with biological function. Interpreting heterosis as increased adaptability, our model predicts that the biological networks involved show increasing connectivity of regulatory interactions. A detailed analysis of metabolite profile data reveals that the increasing-connectivity prediction is true for graphical Gaussian models in our data from early development. This mirrors properties of observed heterotic Arabidopsis phenotypes. Furthermore, the model predicts a limit for increasing hybrid vigor with increasing heterozygosity—a known phenomenon in the literature

Contamination of surgical mask during aerosol-producing dental treatments

Objectives Surgical masks are usually contaminated during dental treatment. So far it has not been investigated whether a surgical mask itself can be a source of microbial transmission. The aim of this study was therefore to investigate the microbiological contamination of surgical masks during dental treatment and the transfer of microorganisms from the mask to the hands. Materials and methods Five dental treatment modalities were studied: carious cavity preparation (P-caries, n = 10), tooth substance preparation (P-tooth, n = 10), trepanation and root canal treatment (P-endo, n = 10), supragingival ultrasonic application (US-supra, n = 10), and subgingival periodontal ultrasonic instrumentation (US-sub, n = 10). Bacterial contamination of mask and gloves worn during treatment was tested by imprinting on agar plates. Additionally, before masks were tested, their outer surface was touched with a new sterile glove. This glove was also imprinted on agar. Bacteria were identified by MALDI TOF mass spectrometry. Colony-forming units (CFU) were scored: score 0: 0 CFU, score 1:  102 CFU, score 3: dense microbial growth. Results All masks and all gloves used during treatment displayed bacterial contamination (sample scores 0/1/2/3: masks 0/46/3/1 and gloves 0/31/10/9). After touching the masks with new sterile gloves, microorganisms were recovered with the following contamination scores: P-caries: 4/6/0/0, P-tooth: 2/8/0/0: P-endo: 7/3/0/0, US-supra: 0/9/1/0, US-sub: 2/8/0/0. No statistically significant differences were detected between the treatment modalities. Streptococci spp. and Staphylococci spp. representing the oral and cutaneous flora dominated. Conclusions Surgical masks are contaminated after aerosol-producing dental treatment procedures. Used masks have a potential to be a source of bacterial contamination of the hands. Clinical relevance Dental staff should avoid touching the outer surface of masks with their hands to prevent transmission of pathogens. It is recommendable to change the mask after each treated patient followed by hand disinfection

ADCY5 gene expression in adipose tissue is related to obesity in men and mice

Genome wide association studies revealed an association of the single nucleotide polymorphism rs11708067 within the ADCY5 gene—encoding adenylate cyclase 5—with increased type 2 diabetes (T2D) risk and higher fasting glucose. However, it remains unclear whether the association between ADCY5 variants and glycemic traits may involve adipose tissue (AT) related mechanisms. We therefore tested the hypothesis that ADCY5 mRNA expression in human and mouse AT is related to obesity, fat distribution, T2D in humans and high fat diet (HFD) in mice. We measured ADCY5 mRNA expression in paired samples of visceral and subcutaneous adipose tissue from 244 individuals with a wide range of body weight and parameters of hyperglycemia, which have been genotyped for rs11708067. In addition, AT ADCY5 mRNA was assessed in C57BL/6NTac which underwent a 10 weeks standard chow (n = 6) or high fat diet (HFD, n = 6). In humans, visceral ADCY5 expression is significantly higher in obese compared to lean individuals. ADCY5 expression correlates with BMI, body fat mass, circulating leptin, fat distribution, waist and hip circumference, but not with fasting plasma glucose and HbA1c. Adcy5 expression in mouse AT is significantly higher after a HFD compared to chow (p<0.05). Importantly, rs11708067 is not associated with ADCY5 mRNA expression levels in either fat depot in any of the genetic models tested. Our results suggest that changes in AT ADCY5 expression are related to obesity and fat distribution, but not with impaired glucose metabolism and T2D. However, altered ADCY5 expression in AT does not seem to be the mechanism underlying the association between rs11708067 and increased T2D risk

Extensive weight loss reveals distinct gene expression changes in human subcutaneous and visceral adipose tissue

Weight loss has been shown to significantly improve Adipose tissue (AT) function, however changes in AT gene expression profiles particularly in visceral AT (VAT) have not been systematically studied. Here, we tested the hypothesis that extensive weight loss in response to bariatric surgery (BS) causes AT gene expression changes, which may affect energy and lipid metabolism, inflammation and secretory function of AT. We assessed gene expression changes by whole genome expression chips in AT samples obtained from six morbidly obese individuals, who underwent a two step BS strategy with sleeve gastrectomy as initial and a Roux-en-Y gastric bypass as second step surgery after 12 ± 2 months. Global gene expression differences in VAT and subcutaneous (S)AT were analyzed through the use of genome-scale metabolic model (GEM) for adipocytes. Significantly altered gene expressions were PCR-validated in 16 individuals, which also underwent a two-step surgery intervention. We found increased expression of cell death-inducing DFFA-like effector a (CIDEA), involved in formation of lipid droplets in both fat depots in response to significant weight loss. We observed that expression of the genes associated with metabolic reactions involved in NAD+, glutathione and branched chain amino acid metabolism are significantly increased in AT depots after surgery-induced weight loss

Environmental Risk Factors for Chronic Pancreatitis and Pancreatic Cancer

Chronic pancreatitis has long been thought to be mainly associated with immoderate alcohol consumption. The observation that only ∼10% of heavy drinkers develop chronic pancreatitis not only suggests that other environmental factors, such as tobacco smoke, are potent additional risk factors, but also that the genetic component of pancreatitis is more common than previously presumed. Either disease-causing or protective traits have been indentified for mutations in different trypsinogen genes, the gene for the trypsin inhibitor SPINK1, chymotrypsinogen C, and the cystic fibrosis transmembane conductance regulator (CFTR). Other factors that have been proposed to contribute to pancreatitis are obesity, diets high in animal protein and fat, as well as antioxidant deficiencies. For the development of pancreatic cancer, preexisting chronic pancreatitis, more prominently hereditary pancreatitis, is a risk factor. The data on environmental risk factors for pancreatic cancer are, with the notable exception of tobacco smoke, either sparse, unconfirmed or controversial. Obesity appears to increase the risk of pancreatic cancer in the West but not in Japan. Diets high in processed or red meat, diets low in fruits and vegetables, phytochemicals such as lycopene and flavonols, have been proposed and refuted as risk or protective factors in different trials. The best established and single most important risk factor for cancer as well as pancreatitis and the one to clearly avoid is tobacco smoke

Extensive weight loss reveals distinct gene expression changes in human subcutaneous and visceral adipose tissue

Weight loss has been shown to significantly improve Adipose tissue (AT) function, however changes in AT gene expression profiles particularly in visceral AT (VAT) have not been systematically studied. Here, we tested the hypothesis that extensive weight loss in response to bariatric surgery (BS) causes AT gene expression changes, which may affect energy and lipid metabolism, inflammation and secretory function of AT. We assessed gene expression changes by whole genome expression chips in AT samples obtained from six morbidly obese individuals, who underwent a two step BS strategy with sleeve gastrectomy as initial and a Roux-en-Y gastric bypass as second step surgery after 12 ± 2 months. Global gene expression differences in VAT and subcutaneous (S)AT were analyzed through the use of genome-scale metabolic model (GEM) for adipocytes. Significantly altered gene expressions were PCR-validated in 16 individuals, which also underwent a two-step surgery intervention. We found increased expression of cell death-inducing DFFA-like effector a (CIDEA), involved in formation of lipid droplets in both fat depots in response to significant weight loss. We observed that expression of the genes associated with metabolic reactions involved in NAD+, glutathione and branched chain amino acid metabolism are significantly increased in AT depots after surgery-induced weight loss