Identifizierung und Charakterisierung von pathogenitätsrelevanten genomischen Bereichen in humanpathogenen enterohämorrhagischen Escherichia coli O157

Sorbit fermentierende (SF) Shiga Toxin-produzierende Escherichia coli (STEC) O157:H¯ werden in Mitteleuropa zunehmend als Erreger des hämolytisch-urämischen Syndroms (HUS) nachgewiesen. Über Virulenzfaktoren dieser Serogruppe liegen bislang nur wenige Erkenntnisse vor. Die vorliegende Arbeit ermöglicht einen weitergehenden Vergleich des Genoms von 77 SF STEC O157:H¯ -Stämmen mit dem Genom von STEC O157:H7 EDL 933. Zwei interessante genomische Inseln, die Homologien zu den Sequenzen von STEC O157:H7 EDL 933 aufweisen und möglicherweise für ein Porin und ein Protein des Eisentransportsystems kodieren wurden identifiziert. Das Vorliegen dieser genomischen Inseln konnte für alle untersuchten STEC O157:H¯ bestätigt werden. Die DNA-Sequenzanalyse für zwei dieser Stämme zeigte für beide untersuchten Fragmente eine vollständige Homologie zum Vergleichsstamm STEC O157:H7 EDL 933. Hierdurch können neue Erkenntnisse über die Evolution des Pathogenitätspotentials gewonnen werden

relationships and interdependencies

Behavioral and personality characteristics are factors that may jointly regulate body weight. This study explored the relationship between body mass index (BMI) and self-reported behavioral and personality measures. These measures included eating behavior (based on the Three-Factor Eating Questionnaire; Stunkard and Messick, 1985), sensitivity to reward and punishment (based on the Behavioral Inhibition System/Behavioral Activation System (BIS/BAS) scales) (Carver and White, 1994) and self-reported impulsivity (based on the Barratt Impulsiveness Scale-11; Patton et al., 1995). We found an inverted U-shaped relationship between restrained eating and BMI. This relationship was moderated by the level of disinhibited eating. Independent of eating behavior, BIS and BAS responsiveness were associated with BMI in a gender-specific manner with negative relationships for men and positive relationships for women. Together, eating behavior and BIS/BAS responsiveness accounted for a substantial proportion of BMI variance (men: ∼25%, women: ∼32%). A direct relationship between self-reported impulsivity and BMI was not observed. In summary, our results demonstrate a system of linear and non-linear relationships between the investigated factors and BMI. Moreover, body weight status was not only associated with eating behavior (cognitive restraint and disinhibition), but also with personality factors not inherently related to an eating context (BIS/BAS). Importantly, these relationships differ between men and women

Dissociating memory networks in early Alzheimer's disease and frontotemporal lobar degeneration - a combined study of hypometabolism and atrophy

Introduction: We aimed at dissociating the neural correlates of memory disorders in Alzheimer’s disease (AD) and frontotemporal lobar degeneration (FTLD). Methods: We included patients with AD (n = 19, 11 female, mean age 61 years) and FTLD (n = 11, 5 female, mean age 61 years) in early stages of their diseases. Memory performance was assessed by means of verbal and visual memory subtests from the Wechsler Memory Scale (WMS-R), including forgetting rates. Brain glucose utilization was measured by [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) and brain atrophy by voxel-based morphometry (VBM) of T1-weighted magnetic resonance imaging (MRI) scans. Using a whole brain approach, correlations between test performance and imaging data were computed separately in each dementia group, including a group of control subjects (n = 13, 6 female, mean age 54 years) in both analyses. The three groups did not differ with respect to education and gender. Results: Patients in both dementia groups generally performed worse than controls, but AD and FTLD patients did not differ from each other in any of the test parameters. However, memory performance was associated with different brain regions in the patient groups, with respect to both hypometabolism and atrophy: Whereas in AD patients test performance was mainly correlated with changes in the parieto-mesial cortex, performance in FTLD patients was correlated with changes in frontal cortical as well as subcortical regions. There were practically no overlapping regions associated with memory disorders in AD and FTLD as revealed by a conjunction analysis. Conclusion: Memory test performance may not distinguish between both dementia syndromes. In clinical practice, this may lead to misdiagnosis of FTLD patients with poor memory performance. Nevertheless, memory problems are associated with almost completely different neural correlates in both dementia syndromes. Obviously, memory functions are carried out by distributed networks which break down in brain degeneration

Increased Expression of Cell-Cell Signaling Genes by Stimulated Mononuclear Leukocytes in Patients with Previous Atherothrombotic Stroke A Whole Genome Expression Profile Study

Background/Aims: Inflammation plays an important role in atherosclerosis and stroke. Acute infections are recognized as trigger factors for ischemic stroke. Methods: In this whole genome expression profile study of 15 patients and 15 control subjects, we tested the hypothesis that patients with a history of atherothrombotic stroke show enhanced transcription of inflammatory genes in circulating leukocytes. RNA from unstimulated or lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells (PBMCs) was analyzed with Affymetrix U133A GeneChips using a pooling design. Expression of single genes and functional groups of genes was analyzed by global statistical tests. Results: A total of 10,197 probe sets showed positive calls. After correction for multiple testing no single probe set revealed significant differences either without or with LPS stimulation. However, significant global expression differences were found upon LPS stimulation for the group of genes that are involved in cell-cell signaling. Conclusion: LPS stimulation of PBMCs, a condition mimicking bacterial infection, induces differential expression of a group of cell-cell signaling genes in patients with previous atherothrombotic stroke. This finding can be caused by genetic differences between both groups, but acquired risk factors, medication and technical factors may also have contributed to the result. Copyright (C) 2009 S. Karger AG, Base

Flexible Adaptive Paradigms for fMRI Using a Novel Software Package ‘Brain Analysis in Real-Time’ (BART)

In this work we present a new open source software package offering a unified framework for the real-time adaptation of fMRI stimulation procedures. The software provides a straightforward setup and highly flexible approach to adapt fMRI paradigms while the experiment is running. The general framework comprises the inclusion of parameters from subject’s compliance, such as directing gaze to visually presented stimuli and physiological fluctuations, like blood pressure or pulse. Additionally, this approach yields possibilities to investigate complex scientific questions, for example the influence of EEG rhythms or fMRI signals results themselves. To prove the concept of this approach, we used our software in a usability example for an fMRI experiment where the presentation of emotional pictures was dependent on the subject’s gaze position. This can have a significant impact on the results. So far, if this is taken into account during fMRI data analysis, it is commonly done by the post-hoc removal of erroneous trials. Here, we propose an a priori adaptation of the paradigm during the experiment’s runtime. Our fMRI findings clearly show the benefits of an adapted paradigm in terms of statistical power and higher effect sizes in emotion-related brain regions. This can be of special interest for all experiments with low statistical power due to a limited number of subjects, a limited amount of time, costs or available data to analyze, as is the case with real-time fMRI

Molecular Imaging of Central Dopamine in Obesity : A Qualitative Review across Substrates and Radiotracers

Dopamine is a neurotransmitter that plays a crucial role in adaptive behavior. A wealth of studies suggests obesity-related alterations in the central dopamine system. The most direct evidence for such differences in humans comes from molecular neuroimaging studies using positron emission tomography (PET) and single-photon emission computed tomography (SPECT). The aim of the current review is to give a comprehensive overview of molecular neuroimaging studies that investigated the relation between BMI or weight status and any dopamine target in the striatal and midbrain regions of the human brain. A structured literature search was performed and a summary of the extracted findings are presented for each of the four available domains: (1) D2/D3 receptors, (2) dopamine release, (3) dopamine synthesis, and (4) dopamine transporters. Recent proposals of a nonlinear relationship between severity of obesity and dopamine imbalances are described while integrating findings within and across domains, after which limitations of the review are discussed. We conclude that despite many observed associations between obesity and substrates of the dopamine system in humans, it is unlikely that obesity can be traced back to a single dopaminergic cause or consequence. For effective personalized prevention and treatment of obesity, it will be crucial to identify possible dopamine (and non-dopamine) profiles and their functional characteristics.Peer reviewe

Psychometric Evaluation of the German Version of the Dietary Fat and Free Sugar-Short Questionnaire

Background: The Dietary Fat and free Sugar – Short Questionnaire (DFS) is a cost- and time-efficient self-report screening instrument to estimate dietary intake of saturated fat and free sugar. To date, only the English version has been psychometrically evaluated. We assessed the psychometric characteristics of the German version of the DFS in normal weight, overweight and obese individuals. Method: 65 adult participants completed a German translation of the DFS and a validated food frequency questionnaire (FFQ). We correlated participants’ percentage of energy intake from saturated fat and free sugar from the FFQ with the DFS scores. To establish test-retest reliability, participants completed the DFS a second time. To investigate convergent validity, we correlated participants DFS scores with self-reported eating behaviour and sensitivity to reward. Results: DFS scores correlated with percentage of energy from free sugar (rs = .443) and saturated fatty acids (rs = .258) but not with non-target nutrients. The correlation between DFS scores and percentage energy from free sugar was not moderated by BMI, whereas the correlation with percentage energy from saturated fat slightly decreased with BMI. Intra-class correlation was .801, suggesting excellent test-retest reliability. DFS scores correlated significantly with restraint of eating behaviour (rs = -.380) and feelings of hunger (rs =.275). Correlations of the DFS score with disinhibited eating and sensitivity to reward failed to be significant. Conclusion: Our results suggest that the German version of the DFS provides a reliable and valid estimation for the dietary saturated fat and free sugar intake of normal weight, overweight, and obese individuals.Peer reviewe

Loss of control over eating : A systematic review of task based research into impulsive and compulsive processes in binge eating

Recurring episodes of excessive food intake in binge eating disorder can be understood through the lens of behavioral control systems: patients repeat maladaptive behaviors against their explicit intent. Self-report measures show enhanced impulsivity and compulsivity in binge eating (BE) but are agnostic as to the processes that might lead to impulsive and compulsive behavior in the moment. Task-based neurocognitive investigations can tap into those processes. In this systematic review, we synthesize neurocognitive research on behavioral impulsivity and compulsivity in BE in humans and animals, published between 2010-2020. Findings on impulsivity are heterogeneous. Findings on compulsivity are sparse but comparatively consistent, indicating an imbalance of goal-directed and habitual control as well as deficits in reversal learning. We urge researchers to address heterogeneity related to mood states and the temporal dynamics of symptoms, to systematically differentiate contributions of body weight and BE, and to ascertain the validity and reliability of tasks. Moreover, we propose to further scrutinize the compulsivity findings to unravel the computational mechanisms of a potential reinforcement learning deficit.Peer reviewe

Unhealthy yet Avoidable-How Cognitive Bias Modification Alters Behavioral and Brain Responses to Food Cues in Individuals with Obesity

Obesity is associated with automatically approaching problematic stimuli, such as unhealthy food. Cognitive bias modification (CBM) could beneficially impact problematic approach behavior. However, it is unclear which mechanisms are targeted by CBM in obesity. Candidate mechanisms include: (1) altering reward value of food stimuli; and (2) strengthening inhibitory abilities. Thirty-three obese adults completed either CBM or sham training during functional magnetic resonance imaging (fMRI) scanning. CBM consisted of implicit training to approach healthy and avoid unhealthy foods. At baseline, approach tendencies towards food were present in all participants. Avoiding vs. approaching food was associated with higher activity in the right angular gyrus (rAG). CBM resulted in a diminished approach bias towards unhealthy food, decreased activation in the rAG, and increased activation in the anterior cingulate cortex. Relatedly, functional connectivity between the rAG and right superior frontal gyrus increased. Analysis of brain connectivity during rest revealed training-related connectivity changes of the inferior frontal gyrus and bilateral middle frontal gyri. Taken together, CBM strengthens avoidance tendencies when faced with unhealthy foods and alters activity in brain regions underpinning behavioral inhibition.Peer reviewe

Insulin Resistance Is Associated with Reduced Food Odor Sensitivity across a Wide Range of Body Weights

The worldwide obesity epidemic is a major health problem driven by the modern food environment. Recently, it has been shown that smell perception plays a key role in eating behavior and is altered in obesity. However, the underlying mechanisms of this phenomenon are not well understood yet. Since the olfactory system is closely linked to the endocrine system, we hypothesized that hormonal shifts in obesity might explain this relationship. In a within-subject, repeated-measures design, we investigated sensitivity to a food and a non-food odor in the hungry and sated state in 75 young healthy (26 normal weight, 25 overweight, and 24 obese) participants (37 women). To determine metabolic health status and hormonal reactivity in response to food intake, we assessed pre- and postprandial levels of insulin, leptin, glucose, and ghrelin. Odor sensitivity did not directly depend on body weight status/body mass index (BMI) or hunger state. However, we could establish a strong negative mediating effect of insulin resistance on the relationship between BMI/waist-hip ratio and olfactory sensitivity for the food odor. These findings indicate an impact of metabolic health status on sensitivity to food odors. Our results contribute to a better understanding of the mechanisms behind altered smell perception in obesity.Peer reviewe