Do gluten peptides stimulate weight gain in humans?

Observations from animal and in vitro laboratory research, and anecdotal evidence, have led to the suggestion that gluten consumption stimulates weight gain by the presence of peptides expressing opioid activity. Another proposed mechanism is that gluten peptides decrease resting energy expenditure resulting in a positive energy balance. In order to induce such effects in vivo, intact food peptides must be absorbed in sufficient quantities, remain intact in the blood for sufficient time to have long-lasting biological activity and bind to receptors involved in appetite, satiety and energy regulation. However, although peptides from food may pass from the intestine into the blood in extremely low quantities, they are generally rapidly degraded by plasma and vasculum-bound aminopeptidases, resulting in very short half-lives and loss of bioactivity. At present, gluten peptide sequences that influence regulators of energy metabolism have not been identified. Furthermore, data on the quantitative absorption of gluten peptides in the blood stream, their stability and lasting bioactivity are also lacking. Therefore, there is no evidence for proposed effects on driving appetite by the brain, nor on energy expenditure and weight gain. Furthermore, the level of overweight observed in various countries appears to be independent of the level of wheat consumption, and abundant observational evidence in humans shows that the levels of gluten consumption are neither related to daily calorie intake nor to BMI. This narrative review therefore discusses the proposed effects of gluten on bodyweight (BW) and putative biological mechanisms in the light of the current evidence

High-throughput AFM analysis reveals unwrapping pathways of H3 and CENP-A nucleosomes

Nucleosomes, the fundamental units of chromatin, regulate readout and expression of eukaryotic genomes. Single-molecule experiments have revealed force-induced nucleosome accessibility, but a high-resolution unwrapping landscape in the absence of external forces is currently lacking. Here, we introduce a high-throughput pipeline for the analysis of nucleosome conformations based on atomic force microscopy and automated, multi-parameter image analysis. Our data set of ∼10 000 nucleosomes reveals multiple unwrapping states corresponding to steps of 5 bp DNA. For canonical H3 nucleosomes, we observe that dissociation from one side impedes unwrapping from the other side, but in contrast to force-induced unwrapping, we find only a weak sequence-dependent asymmetry. Notably, centromeric CENP-A nucleosomes do not unwrap anti-cooperatively, in stark contrast to H3 nucleosomes. Finally, our results reconcile previous conflicting findings about the differences in height between H3 and CENP-A nucleosomes. We expect our approach to enable critical insights into epigenetic regulation of nucleosome structure and stability and to facilitate future high-throughput AFM studies that involve heterogeneous nucleoprotein complexes

The free energy landscape of retroviral integration

Retroviral integration, the process of covalently inserting viral DNA into the host genome, is a point of no return in the replication cycle. Yet, strand transfer is intrinsically iso-energetic and it is not clear how efficient integration can be achieved. Here we investigate the dynamics of strand transfer and demonstrate that consecutive nucleoprotein intermediates interacting with a supercoiled target are increasingly stable, resulting in a net forward rate. Multivalent target interactions at discrete auxiliary interfaces render target capture irreversible, while allowing dynamic site selection. Active site binding is transient but rapidly results in strand transfer, which in turn rearranges and stabilizes the intasome in an allosteric manner. We find the resulting strand transfer complex to be mechanically stable and extremely long-lived, suggesting that a resolving agent is required in vivo

Design approaches in technology enhanced learning

Design is a critical to the successful development of any interactive learning environment (ILE). Moreover, in technology enhanced learning (TEL), the design process requires input from many diverse areas of expertise. As such, anyone undertaking tool development is required to directly address the design challenge from multiple perspectives. We provide a motivation and rationale for design approaches for learning technologies that draws upon Simon's seminal proposition of Design Science (Simon, 1969). We then review the application of Design Experiments (Brown, 1992) and Design Patterns (Alexander et al., 1977) and argue that a patterns approach has the potential to address many of the critical challenges faced by learning technologists

Does wheat make us fat and sick?

After earlier debates on the role of fat, high fructose corn syrup, and added sugar in the aetiology of obesity, it has recently been suggested that wheat consumption is involved. Suggestions have been made that wheat consumption has adverse effects on health by mechanisms related to addiction and overeating. We discuss these arguments and conclude that they cannot be substantiated. Moreover, we conclude that assigning the cause of obesity to one specific type of food or food component, rather than overconsumption and inactive lifestyle in general, is not correct. In fact, foods containing whole-wheat, which have been prepared in customary ways (such as baked or extruded), and eaten in recommended amounts, have been associated with significant reductions in risks for type 2 diabetes, heart disease, and a more favourable long term weight management. Nevertheless, individuals that have a genetic predisposition for developing celiac disease, or who are sensitive or allergic to wheat proteins, will benefit from avoiding wheat and other cereals that contain proteins related to gluten, including primitive wheat species (einkorn, emmer, spelt) and varieties, rye and barley. It is therefore important for these individuals that the food industry should develop a much wider spectrum of foods, based on crops that do not contain proteins related to gluten, such as teff, amaranth, oat, quinoa, and chia. Based on the available evidence, we conclude that wholewheat consumption cannot be linked to increased prevalence of obesity in the general population

Adverse Reactions to Wheat or Wheat Components

Wheat is an important staple food globally, providing a significant contribution to daily energy, fiber, and micronutrient intake. Observational evidence for health impacts of consuming more whole grains, among which wheat is a major contributor, points to significant risk reduction for diabetes, cardiovascular disease, and colon cancer. However, specific wheat components may also elicit adverse physical reactions in susceptible individuals such as celiac disease (CD) and wheat allergy (WA). Recently, broad coverage in the popular and social media has suggested that wheat consumption leads to a wide range of adverse health effects. This has motivated many consumers to avoid or reduce their consumption of foods that contain wheat/gluten, despite the absence of diagnosed CD or WA, raising questions about underlying mechanisms and possible nocebo effects. However, recent studies did show that some individuals may suffer from adverse reactions in absence of CD and WA. This condition is called non-celiac gluten sensitivity (NCGS) or non-celiac wheat sensitivity (NCWS). In addition to gluten, wheat and derived products contain many other components which may trigger symptoms, including inhibitors of α-amylase and trypsin (ATIs), lectins, and rapidly fermentable carbohydrates (FODMAPs). Furthermore, the way in which foods are being processed, such as the use of yeast or sourdough fermentation, fermentation time and baking conditions, may also affect the presence and bioactivity of these components. The present review systematically describes the characteristics of wheat-related intolerances, including their etiology, prevalence, the components responsible, diagnosis, and strategies to reduce adverse reactions

Embolic strokes of undetermined source: prevalence and patient features in the ESUS Global Registry

Background: Recent evidence supports that most non-lacunar cryptogenic strokes are embolic. Accordingly, these strokes have been designated as embolic strokes of undetermined source (ESUS). Aims: We undertook an international survey to characterize the frequency and clinical features of ESUS patients across global regions. Methods: Consecutive patients hospitalized for ischemic stroke were retrospectively surveyed from 19 stroke research centers in 19 different countries to collect patients meeting criteria for ESUS. Results: Of 2144 patients with recent ischemic stroke, 351 (16%, 95% CI 15% to 18%) met ESUS criteria, similar across global regions (range 16% to 21%), and an additional 308 (14%) patients had incomplete evaluation required for ESUS diagnosis. The mean age of ESUS patients (62 years; SD = 15) was significantly lower than the 1793 non-ESUS ischemic stroke patients (68 years, p ≤ 0.001). Excluding patients with atrial fibrillation (n = 590, mean age = 75 years), the mean age of the remaining 1203 non-ESUS ischemic stroke patients was 64 years (p = 0.02 vs. ESUS patients). Among ESUS patients, hypertension, diabetes, and prior stroke were present in 64%, 25%, and 17%, respectively. Median NIHSS score was 4 (interquartile range 2–8). At discharge, 90% of ESUS patients received antiplatelet therapy and 7% received anticoagulation. Conclusions: This cross-sectional global sample of patients with recent ischemic stroke shows that one-sixth met criteria for ESUS, with additional ESUS patients likely among those with incomplete diagnostic investigation. ESUS patients were relatively young with mild strokes. Antiplatelet therapy was the standard antithrombotic therapy for secondary stroke prevention in all global regions

A rare missense mutation in <i>GJB3</i> (Cx31G45E) is associated with a unique cellular phenotype resulting in necrotic cell death

Erythrokeratodermia variabilis et progressiva (EKV-P) is caused by mutations in either the GJB3 (Cx31) or GJB4 genes (Cx30.3). We identified a rare GJB3 missense mutation, c.134G>A (p.G45E), in two unrelated patients and investigated its cellular characteristics. Expression of Cx31G45E-GFP caused previously undescribed changes within HeLa cells and HaCaT cells, a model human keratinocyte cell line. Cx31WT-GFP localised to the plasma membrane, but expression of Cx31G45E-GFP caused vacuolar expansion of the endoplasmic reticulum (ER), the mutant protein accumulated within the ER membrane and disassembly of the microtubular network occurred. No ER stress responses were evoked. Cx31WT-myc-myc-6xHis and Cx31G45E-GFP co-immunoprecipitated, indicative of heteromeric interaction, but co-expression with Cx31WT-mCherry, Cx26 or Cx30.3 did not mitigate the phenotype. Cx31 and Cx31G45E both co-immunoprecipitated with Cx43, indicating the ability to form heteromeric connexons. WT-Cx31 and Cx43 assembled into large gap junction plaques at points of cell-to-cell contact; Cx31G45E restricted the ability of Cx43 to reach the plasma membrane in both HaCaT cells and HeLa cells stably expressing Cx43 where the proteins strongly co-localised with the vacolourised ER. Cell viability assays identified an increase in cell death in cells expressing Cx31G45E-GFP, which FACS analysis determined was necrotic. Blocking connexin channel function with 18α-glycyrrhetinic acid did not completely rescue necrosis or prevent propidium iodide uptake, suggesting that expression of Cx31G45E-GFP damages the cellular membrane independent of its channel function. Our data suggest that entrapment of Cx43 and necrotic cell death in the epidermis could underlie the EKV skin phenotype