Molecular sensitised probe for amino acid recognition within peptide sequences.

The combination of low-temperature scanning tunnelling microscopy with a mass-selective electro-spray ion-beam deposition established the investigation of large biomolecules at nanometer and sub-nanometer scale. Due to complex architecture and conformational freedom, however, the chemical identification of building blocks of these biopolymers often relies on the presence of markers, extensive simulations, or is not possible at all. Here, we present a molecular probe-sensitisation approach addressing the identification of a specific amino acid within different peptides. A selective intermolecular interaction between the sensitiser attached at the tip-apex and the target amino acid on the surface induces an enhanced tunnelling conductance of one specific spectral feature, which can be mapped in spectroscopic imaging. Density functional theory calculations suggest a mechanism that relies on conformational changes of the sensitiser that are accompanied by local charge redistributions in the tunnelling junction, which, in turn, lower the tunnelling barrier at that specific part of the peptide.

Decoding explicit and implicit representations of health and taste attributes of foods in the human brain.

Obesity has become a significant problem word-wide and is strongly linked to poor food choices. Even in healthy individuals, taste perceptions often drive dietary decisions more strongly than healthiness. This study tested whether health and taste representations can be directly decoded from brain activity, both when explicitly considered, and when implicitly processed for decision-making. We used multivariate support vector regression for event-related potentials (as measured by the electroencephalogram) to estimate a regression model predicting ratings of tastiness and healthiness for each participant, based on their neural activity occurring in the first second of food cue processing. In Experiment 1, 37 healthy participants viewed images of various foods and explicitly rated their tastiness and healthiness. In Experiment 2, 89 healthy participants completed a similar rating task, followed by an additional experimental phase, in which they indicated their desire to consume snack foods with no explicit instruction to consider tastiness or healthiness. In Experiment 1 both attributes could be decoded, with taste information being available earlier than health. In Experiment 2, both dimensions were also decodable, and their significant decoding preceded the decoding of decisions (i.e., desire to consume the food). However, in Experiment 2, health representations were decodable earlier than taste representations. These results suggest that health information is activated in the brain during the early stages of dietary decisions, which is promising for designing obesity interventions aimed at quickly activating health awareness.

Health warnings promote healthier dietary decision making: Effects of positive versus negative message framing and graphic versus text-based warnings.

Food product health warnings have been proposed as a potential obesity prevention strategy. This study examined the effects of text-only and text-and-graphic, negatively and positively framed health warnings on dietary choice behavior. In a 2 × 5 mixed experimental design, 96 participants completed a dietary self-control task. After providing health and taste ratings of snack foods, participants completed a baseline measure of dietary self-control, operationalized as participants' frequency of choosing healthy but not tasty items and rejecting unhealthy yet tasty items to consume at the end of the experiment. Participants were then randomly assigned to one of five health warning groups and presented with 10 health warnings of a given form: text-based, negative framing; graphic, negative framing; text, positive framing; graphic, positive framing; or a no warning control. Participants then completed a second dietary decision making session to determine whether health warnings influenced dietary self-control. Linear mixed effects modeling revealed a significant interaction between health warning group and decision stage (pre- and post-health warning presentation) on dietary self-control. Negatively framed graphic health warnings promoted greater dietary self-control than other health warnings. Negatively framed text health warnings and positively framed graphic health warnings promoted greater dietary self-control than positively framed text health warnings and control images, which did not increase dietary self-control. Overall, HWs primed healthier dietary decision making behavior, with negatively framed graphic HWs being most effective. Health warnings have potential to become an important element of obesity prevention.

Food product health warnings promote dietary self-control through reductions in neural signals indexing food cue reactivity.

Modern societies are replete with palatable food cues. A growing body of evidence suggests that food cue exposure activates conditioned appetitive physiological and psychological responses that may override current metabolic needs and existing eating goals, such as the desire to maintain a healthy diet. This conditioned response results in unhealthy dietary choices and is a contributing factor in the current obesity epidemic. Prime based obesity prevention measures such as health warnings at point-of-sale or on product packaging may have the potential to counteract the influence of the obesogenic environment at the crucial moment when people make food purchasing or consumption decisions. Existing research into the efficacy of these intervention strategies has predominantly employed self-report and population level measures, and little evidence exists to support the contention that these measures counteract food cue reactivity at the time of decision making. Using a dietary self-control priming paradigm, we demonstrated that brief exposure to food product health warnings enhanced dietary self-control. Further, we analysed electroencephalographic correlates of selective attention and food cue evoked craving (N1, P3, LPP) to show that health warning exposure reduced the automatic appetitive response towards palatable food cues. These findings contribute to existing evidence that exogenous information can successfully prime latent goals, and substantiate the notion that food product health warnings may provide a new avenue through which to curb excessive energy intake and reduce rising obesity rates.

Adsorption and electronic properties of pentacene on thin dielectric decoupling layers.

With the increasing use of thin dielectric decoupling layers to study the electronic properties of organic molecules on metal surfaces, comparative studies are needed in order to generalize findings and formulate practical rules. In this paper we study the adsorption and electronic properties of pentacene deposited onto h-BN/Rh(111) and compare them with those of pentacene deposited onto KCl on various metal surfaces. When deposited onto KCl, the HOMO and LUMO energies of the pentacene molecules scale with the work functions of the combined KCl/metal surface. The magnitude of the variation between the respective KCl/metal systems indicates the degree of interaction of the frontier orbitals with the underlying metal. The results confirm that the so-called IDIS model developed by Willenbockel et al. applies not only to molecular layers on bare metal surfaces, but also to individual molecules on thin electronically decoupling layers. Depositing pentacene onto h-BN/Rh(111) results in significantly different adsorption characteristics, due to the topographic corrugation of the surface as well as the lateral electric fields it presents. These properties are reflected in the divergence from the aforementioned trend for the orbital energies of pentacene deposited onto h-BN/Rh(111), as well as in the different adsorption geometry. Thus, the highly desirable capacity of h-BN to trap molecules comes at the price of enhanced metal-molecule interaction, which decreases the HOMO-LUMO gap of the molecules. In spite of the enhanced interaction, the molecular orbitals are evident in scanning tunnelling spectroscopy (STS) and their shapes can be resolved by spectroscopic mapping.

The transcriptional corepressor MTGR1 regulates intestinal secretory lineage allocation.

Notch signaling largely determines intestinal epithelial cell fate. High Notch activity drives progenitors toward absorptive enterocytes by repressing secretory differentiation programs, whereas low Notch permits secretory cell assignment. Myeloid translocation gene-related 1 (MTGR1) is a transcriptional corepressor in the myeloid translocation gene/Eight-Twenty-One family. Given that Mtgr1(-/-) mice have a dramatic reduction of intestinal epithelial secretory cells, we hypothesized that MTGR1 is a key repressor of Notch signaling. In support of this, transcriptome analysis of laser capture microdissected Mtgr1(-/-) intestinal crypts revealed Notch activation, and secretory markers Mucin2, Chromogranin A, and Growth factor-independent 1 (Gfi1) were down-regulated in Mtgr1(-/-) whole intestines and Mtgr1(-/-) enteroids. We demonstrate that MTGR1 is in a complex with Suppressor of Hairless Homolog, a key Notch effector, and represses Notch-induced Hairy/Enhancer of Split 1 activity. Moreover, pharmacologic Notch inhibition using a γ-secretase inhibitor (GSI) rescued the hyperproliferative baseline phenotype in the Mtgr1(-/-) intestine and increased production of goblet and enteroendocrine lineages in Mtgr1(-/-) mice. GSI increased Paneth cell production in wild-type mice but failed to do so in Mtgr1(-/-) mice. We determined that MTGR1 can interact with GFI1, a transcriptional corepressor required for Paneth cell differentiation, and repress GFI1 targets. Overall, the data suggest that MTGR1, a transcriptional corepressor well characterized in hematopoiesis, plays a critical role in intestinal lineage allocation.

Undetected hypoglycemia in a patient receiving TPN.

CASE REPORT: A 58-year-old female was admitted to the hospital in a severely malnourished state. She was treated for Crohn's disease with total parental nutrition (TPN). The patient's blood glucose was monitored by point of care (POC) testing every 4h, and a specimen is also drawn daily for metabolic assessment. The POC blood glucose values were consistently much higher than the lab values. Humalog insulin (5 U) was given to the patient to decrease high blood glucose levels that developed following administration of TPN. The patient then became hypoglycemic as a result of this insulin treatment. POC glucose testing, performed every 4h, did not detect the iatrogenic hypoglycemia, while lab glucose results were not given close attention. The lab sample was always drawn 1-2h after insulin was given to the patient and resulted in a lower blood glucose value. In addition, the symptoms of hypoglycemia such as shaking and dizziness were masked by the patient's poor health status, supine position, and the continuously given TPN. CONCLUSIONS: These findings highlighted the importance of the correct sampling time following insulin administration and the consideration of the lab results in addition to POC. The patient's insulin regimen was modified to prevent further hypoglycemic events.

BVES regulates EMT in human corneal and colon cancer cells and is silenced via promoter methylation in human colorectal carcinoma.

The acquisition of a mesenchymal phenotype is a critical step in the metastatic progression of epithelial carcinomas. Adherens junctions (AJs) are required for suppressing this epithelial-mesenchymal transition (EMT) but less is known about the role of tight junctions (TJs) in this process. Here, we investigated the functions of blood vessel epicardial substance (BVES, also known as POPDC1 and POP1), an integral membrane protein that regulates TJ formation. BVES was found to be underexpressed in all stages of human colorectal carcinoma (CRC) and in adenomatous polyps, indicating its suppression occurs early in transformation. Similarly, the majority of CRC cell lines tested exhibited decreased BVES expression and promoter DNA hypermethylation, a modification associated with transcriptional silencing. Treatment with a DNA-demethylating agent restored BVES expression in CRC cell lines, indicating that methylation represses BVES expression. Reexpression of BVES in CRC cell lines promoted an epithelial phenotype, featuring decreased proliferation, migration, invasion, and anchorage-independent growth; impaired growth of an orthotopic xenograft; and blocked metastasis. Conversely, interfering with BVES function by expressing a dominant-negative mutant in human corneal epithelial cells induced mesenchymal features. These biological outcomes were associated with changes in AJ and TJ composition and related signaling. Therefore, BVES prevents EMT, and its epigenetic silencing may be an important step in promoting EMT programs during colon carcinogenesis.