Hippocampal-dependent appetitive control is impaired by experimental exposure to a Western-style diet

Animals fed a Western-style diet (WS-diet) demonstrate rapid impairments in hippocampal function and poorer appetitive control. We examined if this also occurs in humans. One-hundred and ten healthy lean adults were randomised to either a 1-week WS-diet intervention or a habitual-diet control group. Measures of hippocampal dependent learning and memory (HDLM) and of appetitive control were obtained pre- and post-intervention. HDLM was retested at 3-weeks follow-up. Relative to controls, HDLM performance declined in the WS-diet group (d=0.43), but was not different at follow-up. Appetitive control also declined in the WS-diet group (d=0.47) and this was strongly correlated with HDLM decline (d=1.01). These findings demonstrate that a WS-diet can rapidly impair appetitive control in humans - an effect that could promote overeating in consumers of a WS-diet. The study also suggests a functional role for the hippocampus in appetitive control and provides new evidence for the adverse neurocognitive effects of a WS-diet

A high-fat high-sugar diet predicts poorer hippocampal-related memory and a reduced ability to suppress wanting under satiety

Animal data indicate that greater intake of fats and sugars prevalent in a Western diet impairs hippocampal memory and tests of behavioral inhibition known to be related to hippocampal function (e.g., feature negative discrimination tasks). It has been argued that such high fat high sugar diets (HFS) impair the hippocampus, which then becomes less sensitive to modulation by physiological state. Thus retrieval of motivationally salient memories (e.g., when seeing or smelling food) occurs irrespective of state. Here we examine whether evidence of similar effects can be observed in humans using a correlational design. Healthy human participants (N = 94), who varied in their habitual consumption of a HFS diet, completed the verbal paired associate (VPA) test, a known hippocampal-dependent process, as well as liking and wanting ratings of palatable snack foods, assessed both hungry and sated. Greater intake of a HFS diet was significantly associated with a slower VPA learning rate, as predicted. Importantly, for those who regularly consumed a HFS diet, while reductions in liking and wanting occurred between hungry and sated states, the reduction in wanting was far smaller relative to liking. The latter effect was strongly related to VPA learning rate, suggestive of hippocampal mediation. In agreement with the animal literature, human subjects with a greater intake of a HFS diet show deficits in hippocampal-dependent learning and memory, and their desire to consume palatable food is less affected by physiological state – a process we suggest that is also hippocampal related

Integrins Have Cell-Type-Specific Roles in the Development of Motor Neuron Connectivity

Formation of the nervous system requires a complex series of events including proper extension and guidance of neuronal axons and dendrites. Here we investigate the requirement for integrins, a class of transmembrane cell adhesion receptors, in regulating these processes across classes of C. elegans motor neurons. We show alpha integrin/ina-1 is expressed by both GABAergic and cholinergic motor neurons. Despite this, our analysis of hypomorphic ina-1(gm144) mutants indicates preferential involvement of alpha integrin/ina-1 in GABAergic commissural development, without obvious involvement in cholinergic commissural development. The defects in GABAergic commissures of ina-1(gm144) mutants included both premature termination and guidance errors and were reversed by expression of wild type ina-1 under control of the native ina-1 promoter. Our results also show that alpha integrin/ina-1 is important for proper outgrowth and guidance of commissures from both embryonic and post-embryonic born GABAergic motor neurons, indicating an ongoing requirement for integrin through two phases of GABAergic neuron development. Our findings provide insights into neuron-specific roles for integrin that would not be predicted based solely upon expression analysis

Kynurenic acid as a biochemical factor underlying the association between Western-style diet and depression : a cross-sectional study

Consumption of a Western-style diet (WS-diet), high in saturated fat and added sugar, is associated with increased depression risk. However, the physiological mechanisms underlying the relationship requires elucidation. Diet can alter tryptophan metabolism along the kynurenine pathway (KP), potentially linking inflammation and depression. This study aimed to examine whether urinary inflammatory markers and KP metabolites differed according to WS-diet consumption and depression severity. Depression symptoms and habitual WS-diet consumption were assessed in 169 healthy adults aged 17–35 recruited from two experimental studies. Targeted metabolomics profiling of seven KP metabolites, ELISA-based assays of interleukin-6 (IL-6) and C-reactive protein (CRP) were performed using urine samples collected from the participants. Parametric tests were performed for group comparison and associations analysis. Multilevel mixed-effect modelling was applied to control for biases. Higher intake of WS-diet was associated with lower levels of neuroprotective kynurenic acid (KA; R = −0.17, p = 0.0236). There were no differences in IL-6 or CRP across diet groups (p > 0.05). Physical activity had negative associations with most KP metabolites. Mixed-effects regression analysis showed the glutamatergic inhibitor, KA, was the only biomarker to have a significant association with depression symptoms in a model adjusted for demographic and lifestyle variables: a unit increase in KA was associated with 0.21 unit decrease in Depression Anxiety and Stress Scale-21 depression score (p = 0.009). These findings suggest that urinary KA is associated with both habitual WS-diet intake, and levels of depression symptoms, independent of inflammation. Findings support the role of neuroprotection and glutamatergic modulation in depression. We propose that KA may act as endogenous glutamatergic inhibition in regulating depression severity in the absence of inflammation. Further comparison with blood-based markers will assist in validating the utility of non-invasive urine samples for measuring KP metabolites

Chemosensory abilities in consumers of a western-style diet

People vary in their habitual diet and also in their chemosensory abilities. In this study we examined whether consumption of a Western-style diet, rich in saturated fat and added sugar, is associated with either poorer or different patterns of chemosensory perception, relative to people who consume a healthier diet. Participants were selected based on a food frequency questionnaire, which established whether they were likely to consume a diet either higher or lower in saturated fat and added sugar. Eighty-seven participants were tested for olfactory ability (threshold, discrimination, identification), gustatory ability (PROP sensitivity, taste intensity, quality and hedonics), and flavour processing (using dairy fat-sugar-odour mixtures). A Western-style diet was associated with poorer odour identification ability, greater PROP sensitivity, poorer fat discrimination, different patterns of sweetness taste enhancement, and hedonic differences in taste and flavour perception. No differences were evident for odour discrimination or threshold, in perception of taste intensity/quality (excluding PROP) or the ability of fats to affect flavour perception. The significant relationships were of small to moderate effect size, and would be expected to work against consuming a healthier diet. The discussion focuses on whether these diet-related differences precede adoption of a Western-style diet and/or are a consequence of it

Loss of N-WASP drives early progression in an Apc model of intestinal tumourigenesis

N‐WASP (WASL) is a widely expressed cytoskeletal signalling and scaffold protein also implicated in regulation of Wnt signalling and homeostatic maintenance of skin epithelial architecture. N‐WASP mediates invasion of cancer cells in vitro and its depletion reduces invasion and metastatic dissemination of breast cancer. Given this role in cancer invasion and universal expression in the gastrointestinal tract, we explored a role for N‐WASP in the initiation and progression of colorectal cancer. While deletion of N‐wasp is not detectably harmful in the murine intestinal tract, numbers of Paneth cells increased, indicating potential changes in the stem cell niche and migration up the crypt‐villus axis was enhanced. Loss of N‐wasp promoted adenoma formation in an adenomatous polyposis coli (Apc) deletion model of intestinal tumourigenesis. Thus, we establish a tumour suppressive role of N‐WASP in early intestinal carcinogenesis despite its later pro‐invasive role in other cancers. Our study highlights that while the actin cytoskeletal machinery promotes invasion of cancer cells, it also maintains normal epithelial tissue function and thus may have tumour suppressive roles in pre‐neoplastic tissues

Classification of TP53 mutations and HPV predict survival in advanced larynx cancer

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134126/1/lary25915-sup-0001-suppinfo.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134126/2/lary25915_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134126/3/lary25915.pd

Cluster randomised controlled trial of a theory-based multiple behaviour change intervention aimed at healthcare professionals to improve their management of type 2 diabetes in primary care

Background: National diabetes audits in the UK show room for improvement in the quality of care delivered to people with type 2 diabetes in primary care. Systematic reviews of quality improvement interventions show that such approaches can be effective but there is wide variability between trials and little understanding concerning what explains this variability. A national cohort study of primary care across 99 UK practices identified modifiable predictors of healthcare professionals' prescribing, advising and foot examination. Our objective was to evaluate the effectiveness of an implementation intervention to improve six guideline-recommended health professional behaviours in managing type 2 diabetes in primary care: prescribing for blood pressure and glycaemic control, providing physical activity and nutrition advice and providing updated diabetes education and foot examination. Methods: Two-armed cluster randomised trial involving 44 general practices. Primary outcomes (at 12 months follow-up): from electronic medical records, the proportion of patients receiving additional prescriptions for blood pressure and insulin initiation for glycaemic control and having a foot examination; and from a patient survey of a random sample of 100 patients per practice, reported receipt of updated diabetes education and physical activity and nutrition advice. Results: The implementation intervention did not lead to statistically significant improvement on any of the six clinical behaviours. 1,138,105 prescriptions were assessed. Intervention (29% to 37% patients) and control arms (31% to 35%) increased insulin initiation relative to baseline but were not statistically significantly different at follow-up (IRR 1.18, 95% CI 0.95-1.48). Intervention (45% to 53%) and control practices (45% to 50%) increased blood pressure prescription from baseline to follow-up but were not statistically significantly different at follow-up (IRR 1.05, 95% CI 0.96 to 1.16). Intervention (75 to 78%) and control practices (74 to 79%) increased foot examination relative to baseline; control practices increased statistically significantly more (OR 0.84, 95% CI 0.75-0.94). Fewer patients in intervention (33%) than control practices (40%) reported receiving updated diabetes education (OR = 0.74, 95% CI 0.57-0.97). No statistically significant differences were observed in patient reports of having had a discussion about nutrition (intervention = 73%; control = 72%; OR = 0.98, 95% CI 0.59-1.64) or physical activity (intervention = 57%; control = 62%; OR = 0.79, 95% CI 0. 56-1.11). Development and delivery of the intervention cost 1191 pound per practice. Conclusions: There was no measurable benefit to practices' participation in this intervention. Despite widespread use of outreach interventions worldwide, there is a need to better understand which techniques at which intensity are optimally suited to address the multiple clinical behaviours involved in improving care for type 2 diabetes.Peer reviewe

PerR controls oxidative stress defence and aerotolerance but not motility-associated phenotypes of Campylobacter jejuni

The foodborne bacterial pathogen Campylobacter jejuni is an obligate microaerophile, which is exposed to atmospheric oxygen during transmission through the food chain. Survival under aerobic conditions requires the concerted control of oxidative stress systems, which in C. jejuni are intimately connected with iron metabolism via the PerR and Fur regulatory proteins. Here we have characterised the roles of C. jejuni PerR in oxidative stress- and motility phenotypes, and its regulon at the level of transcription, protein expression and promoter interactions. Insertional inactivation of perR in the C. jejuni reference strains NCTC 11168, 81-176 and 81116 did not result in any growth deficiencies, but strongly increased survival in atmospheric oxygen conditions, and allowed growth around filter discs infused with up to 30% H2O2 (8.8 M). Expression of catalase, alkyl hydroperoxide reductase, thioredoxin reductase and the Rrc desulforubrerythrin were increased in the perR mutant, and this was mediated at the transcriptional level as shown by electrophoretic mobility shift assays of the katA, ahpC and trxB promoters using purified PerR. Differential RNA-seq analysis of a fur perR mutant allowed the identification of eight previously unknown transcription start sites of genes controlled by either Fur and/or PerR. Finally, inactivation of perR in C. jejuni did not result in reduced motility, and did not reduce killing of Galleria melonella wax moth larvae. In conclusion, PerR plays an important role in controlling oxidative stress resistance and aerobic survival of C. jejuni, but this role does not extend into control of motility and associated phenotypes