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

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

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

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

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

Increased Brain Reward Responsivity to Food-Related Odors in Obesity

Objective Food odors serve as powerful stimuli signaling the food quality and energy density and direct food-specific appetite and consumption. This study explored obesity-related brain activation in response to odors related to high- or low-energy-dense foods. Methods Seventeen participants with obesity (BMI > 30 kg/m2 ; 4 males and 13 females) and twenty-one with normal weight (BMI < 25 kg/m2 ; 9 males and 12 females) underwent a functional magnetic resonance imaging scan in which they received chocolate (high-energy-dense food) and cucumber (low-energy-dense food) odor stimuli. Participants' olfactory and gustatory functions were assessed by the "Sniffin' Sticks" and "Taste Strips" tests, respectively. Results Compared with normal-weight controls, participants with obesity had lower odor sensitivity (phenylethyl alcohol) and decreased odor discrimination ability. However, participants with obesity demonstrated greater brain activation in response to chocolate compared with cucumber odors in the bilateral inferior frontal operculum and cerebellar vermis, right ventral anterior insula extending to putamen, right middle temporal gyrus, and right supramarginal areas. Conclusions The present study provides preliminary evidence that obesity is associated with heightened brain activation of the reward and flavor processing areas in response to chocolate versus cucumber odors, possibly because of the higher energy density and reinforcing value of chocolate compared with cucumber.Peer reviewe

Dopamine release, diffusion and uptake : A computational model for synaptic and volume transmission

Computational modeling of dopamine transmission is challenged by complex underlying mechanisms. Here we present a new computational model that (I) simultaneously regards release, diffusion and uptake of dopamine, (II) considers multiple terminal release events and (III) comprises both synaptic and volume transmission by incorporating the geometry of the synaptic cleft. We were able to validate our model in that it simulates concentration values comparable to physiological values observed in empirical studies. Further, although synaptic dopamine diffuses into extra-synaptic space, our model reflects a very localized signal occurring on the synaptic level, i.e. synaptic dopamine release is negligibly recognized by neighboring synapses. Moreover, increasing evidence suggests that cognitive performance can be predicted by signal variability of neuroimaging data (e.g. BOLD). Signal variability in target areas of dopaminergic neurons (striatum, cortex) may arise from dopamine concentration variability. On that account we compared spatio-temporal variability in a simulation mimicking normal dopamine transmission in striatum to scenarios of enhanced dopamine release and dopamine uptake inhibition. We found different variability characteristics between the three settings, which may in part account for differences in empirical observations. From a clinical perspective, differences in striatal dopaminergic signaling contribute to differential learning and reward processing, with relevant implications for addictive- and compulsive-like behavior. Specifically, dopaminergic tone is assumed to impact on phasic dopamine and hence on the integration of reward-related signals. However, in humans DA tone is classically assessed using PET, which is an indirect measure of endogenous DA availability and suffers from temporal and spatial resolution issues. We discuss how this can lead to discrepancies with observations from other methods such as microdialysis and show how computational modeling can help to refine our understanding of DA transmission. Author summary The dopaminergic system of the brain is very complex and affects various cognitive domains like memory, learning and motor control. Alterations have been observed e.g. in Parkinson's or Huntington's Disease, ADHD, addiction and compulsive disorders, such as pathological gambling and also in obesity. We present a new computational model that allows to simulate the process of dopamine transmission from dopaminergic neurons originated in source brain regions like the VTA to target areas such as the striatum on a synaptic and on a larger, volume-spanning level. The model can further be used for simulations of dopamine related diseases or pharmacological interventions. In general, computational modeling helps to extend our understanding, gained from empirical research, to situations were in vivo measurements are not feasible.Peer reviewe

The Aetiology of Olfactory Dysfunction and Its Relationship to Diet Quality

People with olfactory loss may choose foods rich in sugar, salt and fat to compensate their loss—foods that constitute a Western-style diet (WSD). However, olfactory dysfunction has not been consistently linked to any particular type of dietary change. Here we considered whether the aetiology of olfactory dysfunction may affect consumption of a WSD. Two-hundred and twenty-two people with olfactory dysfunction of varying cause, were tested for chemosensory performance and their frequency of consumption of a WSD. There was no evidence of a link between a WSD and olfactory dysfunction at the aggregate level, but an aetiology-based approach revealed various patterns, showing both positive and negative associations between olfactory performance and consumption of a WSD. We suggest a number of reasons why, in certain cases, greater olfactory dysfunction may be linked to lower intakes of a WSD, and the role that different aetiologies may have in affecting choices for foods that may appeal following olfactory impairment

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