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Food choices are influenced by one's current mindset, suggesting that supporting health (vs. a palatability) mindsets could improve daily food choices. The question rises, however, to what extent internal mindsets still guide choices when people are exposed to external food-context stimuli in an obesogenic environment. To examine these two competing effects we induced health vs. palatability mindsets, and investigated the robustness of the mindset effect by presenting food-context stimuli during a Pavlovian-to-Instrumental-Transfer (PIT) task in two separate cohorts of 102 (76 females) Dutch and 120 (60 females) German participants. For the mindset induction, participants rated food items on visual analogue scales (VAS), based on healthiness and palatability, respectively. In each cohort, half of the participants received a health, the other half a palatability mindset induction. Additionally, we explored whether ‘mindset triggers’ could be used to further shape behavior. Triggers were established by placing unfamiliar logos at the extreme ends of the VASs used for the mindset inductions.Independent of the mindset, food-associated stimuli influenced food choices in accordance with the previously learned association in each test phase. Health mindset induction biased food choices towards healthier, palatability mindset towards unhealthier choices in the first cohort, but not in the second. The mindset triggers had a more robust effect. These induced healthier (triggers for healthy and not-palatable) and unhealthier (triggers for unhealthy and palatable) food choices in both cohorts alike. Interestingly, these effects did not tamper with the overall effect of Pavlovian cues and were thus true in the presence and absence of food-context stimuli. Therefore, we show that, in our experimental setting, food-associated mindset triggers can be used to bias food choices towards a healthy snack even in an obesogenic environment.

OBJECTIVE Human obesity is associated with impaired central insulin signaling, and in very rare cases, severe obesity can be caused by congenital leptin deficiency. In such patients, leptin replacement results in substantial weight loss and improvement in peripheral metabolism. RESEARCH DESIGN AND METHODS In a leptin-deficient patient, we investigated the impact of leptin substitution on central insulin action, as quantified by changes in neuronal activity after intranasal insulin application. This was assessed before and during the first year of metreleptin substitution. RESULTS After only 1 year, treatment with metreleptin reestablishes brain insulin sensitivity, particularly in the hypothalamus and, to a lesser degree, in the prefrontal cortex. Results are depicted in comparison with a control group. In our patient, brain activation changes were accompanied by substantial weight loss, reduced visceral adipose tissue, reduced intrahepatic lipid content, and improved whole-body insulin sensitivity. CONCLUSIONS Leptin replacement and weight loss improved homeostatic insulin action in the patient in question.

Multiple lines of research have demonstrated that humans can perceive fat in the form of free fatty acids (FFAs). However, the dietary concentration of FFAs is generally very low and fat is mainly consumed as triacylglycerol (TAG). The aim of this study was to examine the perception of different fatty stimuli and possible associations between them. Therefore, detection thresholds for 4 fatty stimuli (oleic acid [FFA], paraffin oil [mixture of hydrocarbon molecules], canola oil [TAG-rich], and canola oil spiked with oleic acid [rich in TAGs and FFAs]) were determined in 30 healthy participants. Additionally, inter-individual differences in fat perception were examined. It was observed that oleic acid was perceivable at significantly lower concentrations than all other stimuli (P < 0.001). Similarly, canola oil with oleic acid was detectable at lower concentrations than canola oil alone (P < 0.001). Moreover, canola oil detection thresholds were significantly lower than paraffin oil detection thresholds (P = 0.017). Participants who were sensitive for low concentrations for oleic acid showed lower detection thresholds for canola oil with and without oleic acid, compared with participants that were less sensitive for oleic acid. The results of this study demonstrate that the higher the concentrations of FFAs in the stimuli, the lower the individual fat detection threshold. Moreover, participants being sensitive for lower concentrations of FFAs are also more likely to detect low concentrations of TAG-rich fats as it is found in the human diet.

Background and Objective: Hyperleptinemia is supposed to play a causal role in the development of obesity-associated hypertension, possibly via increased sympathetic tone. Hence patients with congenital leptin deficiency should be hypotensive and their low blood pressure should increase under leptin substitution. Subjects and Methods: To test this assumption, we examined ambulatory blood pressure, resting heart rate, Schellong test results, cold pressor test results, heart rate variability, catecholamine metabolites, and aldosterone levels in 6 patients with congenital leptin deficiency before as well as 2–7 days and 7–14 months after the start of leptin substitution. Ambulatory blood pressure was also examined in 3 patients with biallelic disease-causing variants in the leptin receptor gene. Results: Contrary to our expectations, even before leptin substitution, 1 patient with biallelic leptin receptor gene variants and 4 patients with leptin deficiency had been suffering from hypertension. Short-term substitution with leptin increased blood pressure further in 3 out of 4 patients (from 127.0 ± 11.7 to 133.8 ± 10.6 mm Hg), concomitant with an increase in resting heart rate as well as in heart rate during the Schellong test in all patients (from 87.6 ± 7.7 to 99.9 ± 11.0 bpm, p = 0.031, and from 102.9 ± 13.5 to 115.6 ± 11.3 bpm, p = 0.031, respectively). Furthermore, the systolic blood pressure response during the cold pressor test increased in 4 out of 6 patients. Unexpectedly, catecholamine metabolites and aldosterone levels did not increase. After long-term leptin substitution and weight loss, the resting heart rate decreased in 4 out of 6 patients compared to baseline, and in all patients below the heart rate seen immediately after the start of therapy (from 99.9 ± 11.0 to 81.7 ± 5.4 bpm; p = 0.031). Conclusions: These results show that obesity-associated hypertension does not depend on the presence of leptin. However, short-term leptin substitution can increase the blood pressure and heart rate in obese humans with leptin deficiency, indicating that leptin plays at least an additive role in obesity-associated hypertension. The mechanisms behind this are not clear but might include an increase in regional sympathetic tone.

Background: The amount of fat in ingested food dictates specific activation patterns in the brain, particularly in homeostatic and reward-related areas. Taste-specific brain activation changes have also been shown and the sensitivity to the oral perception of fat is associated with differential eating behavior and physiological parameters. The association between oral fat sensitivity and neuronal network functions has, however, not yet been defined. Objective: We aimed to investigate the association between fat-dependent neuronal functional connectivity patterns and oral fat sensitivity. Design: To investigate the underlying changes in network dynamics caused by fat intake, we measured resting-state functional connectivity in 11 normal-weight male participants before and after a high- vs. a low-fat meal on two separate study days. Oral fat sensitivity was also measured on both days. We used a high-resolution functional magnetic resonance imaging (MRI) sequence to measure any connectivity changes in networks with the seed in the brainstem (nucleus tractus solitarii, NTS), in homeostatic (hypothalamus) and in reward regions (ventral and dorsal striatum). Seed-based functional connectivity (FC) maps were analyzed using factorial analyses and correlation analyses with oral fat sensitivity were also performed. Results: Regardless of fat content, FC between NTS and reward and gustatory areas was lower after ingestion. Oral fat sensitivity was positively correlated with FC between homeostatic regions and limbic areas in the high-fat condition, but negatively correlated with FC between the dorsal striatum and somatosensory regions in the low-fat condition. Conclusion: Our results show the interaction of oral fat sensitivity with the network based neuronal processing of high- vs. low-fat meals. Variations in neuronal connectivity network patterns might therefore be a possible moderator of the association of oral fat sensitivity and eating behavior.

The International Dark-Sky Places (IDSP) program of the International Dark-Sky Association is a voluntary certification in which communities commit via legislative changes to move towards more sustainable lighting that reduces light pollution. As over 115 IDSP have now been certified, it is interesting to ask the extent to which this certification results in reduced light emissions. In this paper, we compared trends in upward light emission of 98 communities located in or near IDSP to those of 98 similarly sized communities further away from the IDSP, using a night lights observing satellite (the Visible Infrared Imaging Radiometer Suite Day-Night Band). The current dataset is not sufficient to distinguish the hypothesis that IDSP certification results in a lower rate of change in upward light emissions from the null hypothesis that IDSP certification has no impact. This result is with regard to upward light emissions only: it is possible that certification has resulted in decreases in night sky brightness that the satellite is not able to observe.

ZusammenfassungMenschen unterscheiden sich aus gustatori-schen und verhaltensassoziierten Gründen in ihrer Fett-Präferenz, welche die Nahrungsaus-wahl und die Energieaufnahme beeinflusst und sich dadurch auch auf das Körpergewicht auswirken kann. In dieser Studie wurde eine deutschsprachige Version des Fett-Präferenz-Fragebogens (Fat Preference Questionnaire, FPQ©) und dessen externe Validität anhand von Ernährungstagebüchern sowie Fragebögen zum Essverhalten evaluiert. Der FPQ© besteht aus drei Skalen und erhebt bei 19 fettreichen bzw. fettreduzierten Lebensmitteln, wie viel Prozent der fettreichen Variante geschmacklich bevorzugt (GESCHMACK) und häufiger verzehrt werden (HÄUFIGKEIT). Die Differenz der beiden Skalen ist ein Maß für gezügeltes Essverhalten (DIFFERENZ). Die externe Validität belegen positive Korrelationen von GESCHMACK bzw. HÄUFIGKEIT sowie eine negative Korrelation der DIFFERENZ mit dem tatsächlichen Fettgehalt der aufgenommenen Nahrung. Die Parameter „kognitive Kontrolle” und „gezügeltes Essverhalten” korrelieren positiv mit der DIFFERENZ. Der FPQ© ist eine schnelle, zuverlässige Methode zur Erfassung der Fett-Präferenz, der Rückschlüsse auf gezügeltes Essverhalten ermöglicht.

Nutritional fat is one of the most controversial topics in nutritional research, particularly against the background of obesity. Studies investigating fat taste perception have revealed several associations with sensory, genetic, and personal factors (e.g. BMI). However, neuronal activation patterns, which are known to be highly sensitive to different tastes as well as to BMI differences, have not yet been included in the scheme of fat taste perception. We will therefore provide a comprehensive survey of the sensory, genetic, and personal factors associated with fat taste perception and highlight the benefits of applying neuroimaging research. We will also give a critical overview of studies investigating sensory fat perception and the challenges resulting from multifaceted methodological approaches. In conclusion, we will discuss a multifactorial approach to fat perception to gain a better understanding of the underlying mechanisms that cause varying fat sensitivity which could be responsible for overeating. Such knowledge might be beneficial in new treatment strategies for obesity and overweight.

Reward sensitivity and possible alterations in the dopaminergic-reward system are associated with obesity. We therefore aimed to investigate the influence of dopamine depletion on food-reward processing. We investigated 34 female subjects in a randomized placebo controlled, within-subject design (body mass index (BMI) = 27.0 kg/m(2) +/- 4.79 SD; age = 28 years +/- 4.97 SD) using an acute phenylalanine/tyrosine depletion drink representing dopamine depletion and a balanced amino acid drink as the control condition. Brain activity was measured with functional magnetic resonance imaging during a 'wanting' and 'liking' rating of food items. Eating behavior-related traits and states were assessed on the basis of questionnaires. Dopamine depletion resulted in reduced activation in the striatum and higher activation in the superior frontal gyms independent of BMI. Brain activity during the wanting task activated a more distributed network than during the liking task This network included gustatory, memory, visual, reward, and frontal regions. An interaction effect of dopamine depletion and the wanting/liking task was observed in the hippocampus. The interaction with the covariate BMI was significant in motor and control regions but not in the striatum. Our results support the notion of altered brain activity in the reward and prefrontal network with blunted dopaminergic action during food-reward processing. This effect is, however, independent of BMI, which contradicts the reward-deficiency hypothesis. This hints to the hypothesis suggesting a different or more complex mechanism underlying the dopaminergic reward function in obesity.

An increasing number of studies using real-time fMRI neurofeedback have demonstrated that successful regulation of neural activity is possible in various brain regions. Since these studies focused on the regulated region(s), little is known about the target-independent mechanisms associated with neurofeedback-guided control of brain activation, i.e. the regulating network. While the specificity of the activation during self-regulation is an important factor, no study has effectively determined the network involved in self-regulation in general. In an effort to detect regions that are responsible for the act of brain regulation, we performed a post-hoc analysis of data involving different target regions based on studies from different research groups. We included twelve suitable studies that examined nine different target regions amounting to a total of 175 subjects and 899 neurofeedback runs. Data analysis included a standard first-(single subject, extracting main paradigm) and second-level (single subject, all runs) general linear model (GLM) analysis of all participants taking into account the individual timing. Subsequently, at the third level, a random effects model GLM included all subjects of all studies, resulting in an overall mixed effects model. Since four of the twelve studies had a reduced field of view (FoV), we repeated the same analysis in a subsample of eight studies that had a well-overlapping FoV to obtain a more global picture of self-regulation. The GLM analysis revealed that the anterior insula as well as the basal ganglia, notably the striatum, were consistently active during the regulation of brain activation across the studies. The anterior insula has been implicated in interoceptive awareness of the body and cognitive control. Basal ganglia are involved in procedural learning, visuomotor integration and other higher cognitive processes including motivation. The larger FoV analysis yielded additional activations in the anterior cingulate cortex, the dorsolateral and ventrolateral prefrontal cortex, the temporo-parietal area and the visual association areas including the temporo-occipital junction. In conclusion, we demonstrate that several key regions, such as the anterior insula and the basal ganglia, are consistently activated during self-regulation in real-time fMRI neurofeedback independent of the targeted region-ofinterest. Our results imply that if the real-time fMRI neurofeedback studies target regions of this regulation network, such as the anterior insula, care should be given whether activation changes are related to successful regulation, or related to the regulation process per se. Furthermore, future research is needed to determine how activation within this regulation network is related to neurofeedback success. (C) 2015 Elsevier Inc. All rights reserved.

Variation in FTO is the strongest genetic determinant of body weight and has recently been linked with impaired neural processing of food stimuli. However, whether this brain-expressed gene affects neuronal processing of food-related stimuli after ingestion is still poorly understood. In this study, twenty-four participants were examined before, 30 and 120min after ingesting 75g of glucose solution or water on two separate days. Functional magnetic resonance imaging (fMRI) during visual food presentation was performed. All participants were genotyped for FTO SNP rs8050136. We detected significant differences between FTO genotypes in the prefrontal cortex 30min post-glucose load in BOLD-response to food pictures (p=0.0017), while no differences were detected in response to water ingestion or 120min post-glucose load. Since the prefrontal cortex plays a major role in the inhibitory control of eating, we propose that reduced postprandial activity in FTO risk allele carriers contributes to overeating and obesity.

ZusammenfassungNeurowissenschaftliche Studien zeigen, dass die Wahl sowie die Wahrnehmung unserer Speisen ein Ergebnis komplexer neuronaler Prozesse darstellt. Während hirngeschichtlich ältere Areale wie der Hypothalamus vorwiegend bei der Steuerung des Energiehaushalts eine zentrale Rolle spielen, sind auch gustatorisch/hedonische Areale bei der Wahl und Verarbeitung von Speisen von großer Bedeutung. In diesem Übersichtsartikel fassen wir Studien zusammen, die akute und langfristige Verarbeitung von Fett in der Nahrung mittels funktioneller Bildgebung untersuchten. Während sofort nach Aufnahme eines fetthaltigen Lebensmittels vor allem das Aroma, die Textur und der Fetteindruck zu unterschiedlichen neuronalen Antworten in zahlreichen Hirnarealen führen, ist die metabolische Reaktion auf eine tatsächlich fetthaltige Mahlzeit vor allem im homöostatischen System repräsentiert. Gleichzeitig scheint der Fettgehalt in der Nahrung die Interaktion zwischen dem homöostatischen und dem gustatorischen System zu mediieren. Fettassoziierte Aromastoffe scheinen sich dagegen primär in gustatorischen Arealen auszuwirken. Dies ist vermutlich auf unbewusste Lernprozesse zurückzuführen, über die die Wahrnehmung der Aromastoffe mit der tatsächlichen Aufnahme fetthaltiger Lebensmittel assoziiert ist.

OBJECTIVE Obesity and type 2 diabetes mellitus (T2DM) are associated with altered food-related neuronal functions. Besides weight loss, substantial improvement of glucose metabolism in patients with T2DM can be achieved by bariatric surgery. We aimed to target the neuronal and behavioral correlates of improved glycemic control after bariatric surgery. RESEARCH DESIGN AND METHODS Two patient groups with T2DM were recruited. The treatment group (n = 12) consisted of patients who had undergone Roux-en-Y gastric bypass (RYGB) surgery, and a control group consisted of patients who did not undergo surgery (n = 12). The groups were matched for age and current BMI. HbA1c was matched by using the presurgical HbA1c of the RYGB group and the current HbA1c of the nonsurgical group. Neuronal activation during a food reward task was measured using functional MRI (fMRI). Behavioral data were assessed through questionnaires. RESULTS RYGB improved HbA1c from 7.07 ± 0.50 to 5.70 ± 0.16% (P < 0.05) and BMI from 52.21 ± 1.90 to 35.71 ± 0.84 kg/m2 (P < 0.001). Behavioral results showed lower wanting and liking scores as well as lower eating behavior–related pathologies for the patients after RYGB than for similar obese subjects without surgery but with impaired glycemic control. The fMRI analysis showed higher activation for the nonsurgical group in areas associated with inhibition and reward as well as in the precuneus, a major connectivity hub in the brain. By contrast, patients after RYGB showed higher activation in the visual, motor, cognitive control, memory, and gustatory regions. CONCLUSIONS In obese patients with diabetes, RYGB normalizes glycemic control and leads to food reward–related brain activation patterns that are different from those of obese patients with less-well-controlled T2DM and without bariatric surgery. The differences in food reward processing might be one factor in determining the outcome of bariatric surgery in patients with T2DM.

Aim: There is accumulating evidence that food consumption is controlled by a wide range of brain circuits outside of the homeostatic system. Activation in these brain circuits may override the homeostatic system and also contribute to the enormous increase of obesity. However, little is known about the influence of hormonal signals on the brain's non-homeostatic system. Thus, selective insulin action in the brain was investigated by using intranasal application. Methods: We performed ‘resting-state' functional magnetic resonance imaging in 17 healthy lean female subjects to assess intrinsic brain activity by fractional amplitude of low-frequency fluctuations (fALFF) before, 30 and 90 min after application of intranasal insulin. Results: Here, we showed that insulin modulates intrinsic brain activity in the hypothalamus and orbitofrontal cortex. Furthermore, we could show that the prefrontal and anterior cingulate cortex response to insulin is associated with body mass index. Conclusion: This demonstrates that hormonal signals as insulin may reduce food intake by modifying the reward and prefrontal circuitry of the human brain, thereby potentially decreasing the rewarding properties of food. Due to the alarming increase in obesity worldwide, it is of great importance to identify neural mechanisms of interaction between the homeostatic and non-homeostatic system to generate new targets for obesity therapy.

Context: Mutations that lead to congenital leptin deficiency cause severe obesity, hyperphagia, and impaired satiety due to malfunctions of peripheral and brain-related mechanisms. Design and Patient: In a leptin-deficient adolescent girl, we investigated brain-related changes before and at two time points after leptin therapy (3 d and 6 months). Functional magnetic resonance imaging was performed during visual stimulation with food (high and low caloric) and nonfood pictures. Results: Results show acute and long-term effects in the amygdala, the orbitofrontal cortex, and the substantia nigra/ventral tegmental area for the comparison of food and nonfood pictures. For the comparison of high and low caloric pictures, pure acute effects in the ventral striatum and the orbitofrontal cortex could be observed as well as acute and long-term effects in the hypothalamus. Conclusion: This study gives additional insight in the influence of leptin therapy on brain functions in leptin deficiency.

Coiled coils have attracted considerable interest as design templates in a wide range of applications. Successful coiled-coil design strategies therefore require a detailed understanding of coiled-coil folding. One common feature shared by coiled coils is the presence of a short autonomous helical folding unit, termed “trigger sequence,” that is indispensable for folding. Detailed knowledge of trigger sequences at the molecular level is thus key to a general understanding of coiled-coil formation. Using a multidisciplinary approach, we identify and characterize here the molecular determinants that specify the helical conformation of the monomeric early folding intermediate of the GCN4 coiled coil. We demonstrate that a network of hydrogen-bonding and electrostatic interactions stabilize the trigger-sequence helix. This network is rearranged in the final dimeric coiled-coil structure, and its destabilization significantly slows down GCN4 leucine zipper folding. Our findings provide a general explanation for the molecular mechanism of coiled-coil formation.

Remorins form a superfamily of plant-specific plasma membrane/lipid-raft-associated proteins of unknown structure and function. Using specific antibodies, we localized tomato remorin 1 to apical tissues, leaf primordia and vascular traces. The deduced remorin protein sequence contains a predicted coiled coil-domain, suggesting its participation in protein-protein interactions. Circular dichroism revealed that recombinant potato remorin contains an alpha-helical region that forms a functional coiled-coil domain. Electron microscopy of purified preparations of four different recombinant remorins, one from potato, two divergent isologs from tomato, and one from Arabidopsis thaliana , demonstrated that the proteins form highly similar filamentous structures. The diameters of the negatively-stained filaments ranged from 4.6-7.4 nm for potato remorin 1, 4.3-6.2 nm for tomato remorin 1, 5.7-7.5 nm for tomato remorin 2, and 5.7-8.0 nm for Arabidopsis Dbp. Highly polymerized remorin 1 was detected in glutaraldehyde-crosslinked tomato plasma membrane preparations and a population of the protein was immunolocalized in tomato root tips to structures associated with discrete regions of the plasma membrane.

The aggregation of acetylcholine receptors on postsynaptic membranes is a key step in neuromuscular junction development. This process depends on alternatively spliced forms of the proteoglycan agrin with “B-inserts” of 8, 11, or 19 residues in the protein's globular C-terminal domain, G3. Structures of the neural B8 and B11 forms of agrin-G3 were determined by X-ray crystallography. The structure of G3-B0, which lacks inserts, was determined by NMR. The agrin-G3 domain adopts a β jellyroll fold. The B insert site is flanked by four loops on one edge of the β sandwich. The loops form a surface that corresponds to a versatile interaction interface in the family of structurally related LNS proteins. NMR and X-ray data indicate that this interaction interface is flexible in agrin-G3 and that flexibility is reduced by Ca2+ binding. The plasticity of the interaction interface could enable different splice forms of agrin to select between multiple binding partners.

In mature collagen type III the homotrimer is C-terminally cross-linked by an interchain cystine knot consisting of three disulfide bridges of unknown connectivity. This cystine knot with two adjacent cysteine residues on each of the three alpha chains has recently been used for the synthesis and expression of model homotrimers. To investigate the origin of correct interchain cysteine pairings, (Pro-Hyp-Gly)(n) peptides of increasing triplet number and containing the biscysteinyl sequence C- and N-terminally were synthesised. The possibilities were that this origin may be thermodynamically coupled to the formation of the collagen triple helix as happens in the oxidative folding of proteins, or it could represent a post-folding event. Only with five triplets, which is known to represent the minimum number for self-association of collagenous peptides into a triple helix, air-oxidation produces the homotrimer in good yields (70 %), the rest being intrachain oxidised monomers. Increasing the number of triplets has no effect on yield suggesting the formation of kinetically trapped intermediates, which are not reshuffled by the glutathione redox buffer. N-terminal incorporation of the cystine knot is significantly less efficient in the homotrimerisation step and also in terms of triple-helix stabilisation. Compared to an artificial C-terminal cystine knot consisting of two interchain disulfide bridges, the collagen type III cystine knot produces collagenous homotrimers of remarkably high thermostability, although the concentration-independent refolding rates are not affected by the type of disulfide bridging. Since the natural cystine knot allows ready access to homotrimeric collagenous peptides of significantly enhanced triple-helix thermostability it may well represent a promising approach for the preparation of collagen-like innovative biomaterials. Conversely, the more laborious regioselectively formed artificial cystine knot still represents the only synthetic strategy for heterotrimeric collagenous peptides.

In a designed fusion protein the trimeric domain foldon from bacteriophage T4 fibritin was connected to the C terminus of the collagen model peptide (GlyProPro)(10) by a short Gly-Ser linker to facilitate formation of the three-stranded collagen triple helix. Crystal structure analysis at 2.6 A resolution revealed conformational changes within the interface of both domains compared with the structure of the isolated molecules. A striking feature is an angle of 62.5 degrees between the symmetry axis of the foldon trimer and the axis of the triple helix. The melting temperature of (GlyProPro)(10) in the designed fusion protein (GlyProPro)(10)foldon is higher than that of isolated (GlyProPro)(10,) which suggests an entropic stabilization compensating for the destabilization at the interface.

Agrin is the key organizer of postsynaptic differentiation at the neuromuscular junction. This organization activity requires the binding of agrin to the synaptic basal lamina. Binding is conferred by the N-terminal agrin (NtA) domain, which mediates a high-affinity interaction with the coiled coil domain of laminins. Here, we report the crystal structure of chicken NtA at 1.6 A resolution. The structure reveals that NtA harbors an oligosaccharide/oligonucleotide-binding fold with several possible sites for the interaction with different ligands. A high structural similarity of NtA with the protease inhibition domain in tissue inhibitor of metalloproteinases-1 (TIMP-1) supports the idea of additional functions of agrin besides synaptogenic activity.

The RNA fingerprint method was used to identify mRNAs that were differentially expressed during the development of human mesothelial cell cancer. We report the isolation of two differentially expressed clones. One clone was expressed in the metastatic mesothelioma cell line M1A and in the malignant mesothelioma cell line M1 and downregulated in normal mesothelial cells. M1 and M1A were derived from a primary and metastatic tumor of the same patient. The other clone was only expressed in normal mesothelial cells. The different expression pattern was confirmed by Northern blot analysis. One clone had a striking sequence homology to the soares pregnant uterus NbHPU homo sapiens cDNA clone. The other clone contained a high sequence homology to the human mRNA for ORF. The biological function of the corresponding genes is unknown. The specificity of expression of the two sequence tags was further examined on different cancer cell lines and normal tissues.

A modified differential display method called RNA fingerprinting was used to identify mRNAs that were differentially expressed during human mesothelial cancer progression. We report the isolation of five different clones. Two clones were expressed in the metastatic mesothelioma cell line M1A and the malignant mesothelioma cell line M1, one clone was expressed uniquely in the metastatic cell line M1A and one clone was solely expressed in the normal mesothelial cells. The other clone was downregulated in the metastatic cell line M1A. The different expression patterns were confirmed by Northern blot analysis. Three clones had no homology to known genes, whereas the other two clones had a striking sequence homology to the M130 antigen and rab 12 mRNA, respectively. The clone that contained a high sequence homology to the M130 antigen mRNA was expressed in the mesothelioma cell lines M1 and M1A and not in any further investigated cancer cell line. This sequence tag may be of interest as a specific mesothelioma tumor marker.

Background: Low- and high-fat meals affect homeostatic and gustatory brain areas differentially. In a previous study, we showed that a high-fat meal decreased cerebral blood flow (CBF) in homeostatic brain areas (hypothalamus), whereas a low-fat meal increased CBF in gustatory regions (anterior insula). Objective: The aim of this study was to investigate the long-lasting effect of fat-free flavor-active compounds of olive oil on the brain and whether those aroma components can trigger fat-associated brain responses in homeostatic and gustatory regions. Design: Eleven healthy male subjects participated in a functional magnetic resonance imaging study. On 2 measurement days, subjects consumed single-blinded a plain low-fat yogurt or low-fat yogurt mixed with a fat-free aroma extract of olive oil. Resting CBF was measured pre and 30 and 120 min post yogurt intake. Hunger was rated before each measurement. Blood samples were collected at 6 time points. Results: The extract-containing yogurt elicited higher CBF in the frontal operculum 30 and 120 min post meal. Furthermore, the activity change in the anterior insula after 30 min correlated positively with the glucose change in the extract condition only. No effects were observed in the hypothalamus. Conclusions: The anterior insula and the frontal operculum are regarded as the primary taste cortex. Modulation of the frontal operculum by the yogurt containing the olive oil extract suggests that it might be possible to simulate fat-triggered sensations in the brain on the gustatory level, possibly by ingredients the body implicitly associates with fat. This trial was registered at clinicaltrials.gov as NCT01716286. Am J Clin Nutr doi: 10.3945/ajcn.113.062679.

The way we think about ourselves impacts greatly on our behaviour. This paper describes a behavioural study and a computational model that sheds new light on this important area. Participants were primed 'clever' and 'stupid' using a scrambled sentence task, and we measured the effect on response time and error-rate on a rule-association task. First, we observed a confirmation bias effect in that associations to being 'stupid' led to a gradual decrease in performance, whereas associations to being 'clever' did not. Second, we observed that the activated self-concepts selectively modified attention towards one's performance. There was an early to late double dissociation in RTs in that primed 'clever' resulted in RT increase following error responses, whereas primed 'stupid' resulted in RT increase following correct responses. We propose a computational model of subjects' behaviour based on the logic of the experimental task that involves two processes; memory for rules and the integration of rules with subsequent visual cues. The model also incorporates an adaptive decision threshold based on Bayes rule, whereby decision thresholds are increased if integration was inferred to be faulty. Fitting the computational model to experimental data confirmed our hypothesis that priming affects the memory process. This model explains both the confirmation bias and double dissociation effects and demonstrates that Bayesian inferential principles can be used to study the effect of self-concepts on behaviour.

OBJECTIVE: Neuroimaging studies have demonstrated alterations in brain activity in obese (OB) subjects that might be causally linked to their disorder. Roux-en Y gastric bypass (RYGB) surgery induces a marked and sustained weight loss and may affect brain activity. The aim of this study was to compare brain activity pattern between severely OB women (n = 11), normal-weight women (NW, n = 11) and previously severely OB women who had undergone RYGB surgery (RYGB, n = 9) on average 3.4 +/- 0.8 years (all > 1 year) before the experiment. DESIGN: Brain activity was assessed by functional magnetic resonance imaging during a one-back task containing food- and non-food-related pictures and during resting state. Hunger and satiety were repeatedly rated on a visual analog scale during the experiment. RESULTS: As compared with NW and also with RYGB women, OB women showed (1) a higher cerebellar and a lower fusiform gyrus activity during the visual stimulation independently of the picture category, (2) a higher hypothalamic activation during the presentation of low-vs high-caloric food pictures, (3) a higher hippocampal and cerebellar activity during the working memory task and (4) a stronger functional connectivity in frontal regions of the default mode network during resting state. There were no differences in brain activity between the NW and RYGB women, both during picture presentation and during resting state. RYGB women generally rated lower on hunger and higher on satiety, whereas there were no differences in these ratings between the OB and NW women. CONCLUSION: Data provide evidence for an altered brain activity pattern in severely OB women and suggest that RYGB surgery and/or the surgically induced weight loss reverses the obesity-associated alterations.

Background: The hypothalamus is the central homeostatic control region of the brain and, therefore, highly influenced by nutrients such as glucose and fat. Immediate and prolonged homeostatic effects of glucose ingestion have been well characterized. However, studies that used stimulation with fat have mainly investigated immediate perceptional processes. Besides homeostatic processes, the gustatory cortex, including parts of the insular cortex, is crucial for the processing of food items. Objective: The aim of this study was to investigate the effect of high- compared with low-fat meals on the hypothalamus and the insular cortex. Design: Eleven healthy men participated in a single-blinded, functional MRI study of high- and low-fat meals on 2 measurement days. Cerebral blood flow (CBF) was measured before and 30 and 120 min after intake of high- and low-fat yogurts. Hunger was rated and blood samples were taken before each CBF measurement. Results: High-fat yogurt induced a pronounced decrease in CBF in the hypothalamus, and the corresponding CBF change correlated positively with the insulin change. Furthermore, insular activity was increased after 120 min in the low-fat condition only. The CBF change in both regions correlated positively in the high-fat condition. Conclusions: The decrease in hypothalamic activity and the interaction with the insular cortex elicited by fat may contribute to an efficient energy homeostasis. Therefore, fat might be a modulator of homeostatic and gustatory brain regions and their interaction. This trial was registered at clinicaltrials.gov as NCT01516021. Am J Clin Nutr doi: 10.3945/ajcn.111.031492.

The anterior insular cortex (AIC) is involved in emotional processes and gustatory functions which can be examined by imaging techniques. Such imaging studies showed increased activation in the insula in response to food stimuli as well as a differential activation in lean and obese people. Additionally, studies investigating lean subjects established the voluntary regulation of the insula by a real-time functional magnetic resonance imaging-brain computer interface (rtfMRI-BCI) approach. In this exploratory study, 11 lean and 10 obese healthy, male participants were investigated in a rtfMRI-BCI protocol. During the training sessions, all obese participants were able to regulate the activity of the AIC voluntarily, while four lean participants were not able to regulate at all. In successful regulators, functional connectivity during regulation vs. relaxation between the AIC and all other regions of the brain was determined by a seed voxel approach. Lean in comparison to obese regulators showed stronger connectivity in cingular and temporal cortices during regulation. We conclude, that obese people possess an improved capacity to self-regulate the anterior insula, a brain system tightly related to bodily awareness and gustatory functions.

In most cases obesity, a major risk factor for diabetes mellitus type 2 and other associated chronic diseases, is generated by excessive eating. For a better understanding of eating behavior, it is necessary to determine how it is modulated by factors such as the calorie content of food, satiety and gender. Twelve healthy normal weighted participants (six female) were investigated in a functional magnetic resonance imaging (fMRI) study. In order to prevent the influence of social acceptability, an implicit one-back task was chosen for stimulus presentation. We presented food (high- and low-caloric) and non-food pictures in a block design and subjects had to indicate by button press whether two consecutive pictures were the same or not. Each subject performed the task in a hungry and satiated state on two different days. High-caloric pictures compared to low-caloric pictures led to increased activity in food processing and reward related areas, like the orbitofrontal and the insular cortex. In addition, we found activation differences in visual areas (occipital lobe), despite the fact that the stimuli were matched for their physical features. Detailed investigation also revealed gender specific effects in the fusiform gyrus. Women showed higher activation in the fusiform gyrus while viewing high-caloric pictures in the hungry state. This study shows that the calorie content of food pictures modulates the activation of brain areas related to reward processing and even early visual areas. In addition, satiation seems to influence the processing of food pictures differently in men and women. Even though an implicit task was used, activation differences could also be observed in the orbitofrontal cortex, known to be activated during explicit stimulation with food related stimuli.

Die regelmasige Nutzung von Mobilfunkgeraten durch Kinder und Jugendliche ist bereits eine Tatsache. Laut der jungsten KIM-Studie steht 44 Prozent der 6- bis 13-Jahrigen ein Handy zur Verfugung, wobei Funktionalitaten wie SMS, MMS, Bluetooth, aber auch eingebaute Digital-Kameras und Handy-Spiele von ihnen genutzt werden.1 Man muss also kein Prophet sein, um zu erkennen, dass die Zukunft eine verstarkte Nutzung der mobilen Medien mit sich bringen wird. Bereits heute gehort der Gebrauch von Handys, Palms und Smartphones zum Alltag.

Phospholamban (PLB), a 52-membered integral membrane protein, is a major regulator of the kinetics of cardiac contractility. It is located in the sarcoplasmatic reticulum and it inhibits the activity of the resident -ATPase (SERCA2) [for recent reviews, see 1,2]. The trans-membrane domain of PLB associates to a five-stranded coiled coil which partly dissociates upon dephosphorylation of the cytoplasmatic domain. Recently, the sequence of another transmembrane peptide, located in the sarcoplasmatic reticulum, was determined and named sarcolipin (SLN) [3,4]. It shows high sequence homology with the C-terminal region of PLB, with numerous hydrophobic amino acid residues. The function of this 31-membered “proteolipid” is associated with a fast-twitch skeletal muscle ATPase (SERCA1). In an attempt to determine the biophysical properties of SLN and to compare them with PLB, we have synthesized the whole SLN peptide and the C-terminal sequence of phospholamban PLB(24-52) (Fig. 1).

Die Freiwillige Selbstkontrolle Multimedia e.V. (fortan: FSM) ist ein gemeinnutziger Verein, der von zahlreichen Verbanden und Unternehmen als „Einrichtung der freiwilligen Selbstkontrolle“ gegrundet wurde.

The directional dependence of folding rates for rod-like macromolecules such as parallel alpha-helical coiled-coils, DNA double-helices, and collagen triple helices is largely unexplored. This is mainly due to technical difficulties in measuring rates in different directions. Folding of collagens is nucleated by trimeric non-collagenous domains. These are usually located at the COOH terminus, suggesting that triple helix folding proceeds from the COOH to the NH(2) terminus. Evidence is presented here that effective nucleation is possible at both ends of the collagen-like peptide (Gly-Pro-Pro)(10), using designed proteins in which this peptide is fused either NH(2)- or COOH-terminal to a nucleation domain, either T4-phage foldon or the disulfide knot of type III collagen. The location of the nucleation domain influences triple-helical stability, which might be explained by differences in the linker sequences and the presence or absence of repulsive charges at the carboxyl-terminal end of the triple helix. Triple helical folding rates are found to be independent of the site of nucleation and consistent with cis-trans isomerization being the rate-limiting step.

Matrilins constitute a family of four oligomeric extracellular proteins that are involved in the development and homeostasis of cartilage and bone. To reveal their homo- and heterotypic oligomerization propensities, we analyzed the four human matrilin coiled-coil domains by biochemical and biophysical methods. These studies not only confirmed the homo- and heterotypic oligomerization states reported for the full-length proteins but revealed seven novel matrilin isoforms. Specific heterotrimeric interactions of variable chain stoichiometries were observed between matrilin-1 and matrilin-2, matrilin-1 and matrilin-4, and matrilin-2 and matrilin-4. In addition, matrilin-1 formed two different specific heterotetramers with matrilin-3. Interestingly, a distinct heterotrimer consisting of three different chains was formed between matrilin-1, matrilin-2, and matrilin-4. No interactions, however, were observed between matrilin-2 and matrilin-3 or between matrilin-3 and matrilin-4. Both homo- and heterotypic oligomers folded into parallel disulfide-linked structures, although coiled-coil formation was not dependent on disulfide bridge formation. Our results indicate that the heterotypic preferences seen for the matrilin coiled-coil domains are the result of the packing of the hydrophobic core rather than ionic interactions. Mass spectrometry revealed that the concentrations of the individual chains statistically determined the stoichiometry of the heteromers, suggesting that formation of the different matrillin chain combinations is controlled by expression levels.