Implication of coronin 7 in body weight regulation in humans, mice and flies

Background: Obesity is a growing global concern with strong associations with cardiovascular disease, cancer and type-2 diabetes. Although various genome-wide association studies have identified more than 40 genes associated with obesity, these genes cannot fully explain the heritability of obesity, suggesting there may be other contributing factors, including epigenetic effects. Results: We performed genome wide DNA methylation profiling comparing normal-weight and obese 9-13 year old children to investigate possible epigenetic changes correlated with obesity. Of note, obese children had significantly lower methylation levels at a CpG site located near coronin 7 (CORO7), which encodes a tryptophan-aspartic acid dipeptide (WD)-repeat containing protein most likely involved in Golgi complex morphology and function. Anatomical profiling of coronin 7 (Coro7) mRNA expression in mice revealed that it is highly expressed in appetite and energy balance regulating regions, including the hypothalamus, striatum and locus coeruleus, the main noradrenergic brain site. Interestingly, we found that food deprivation in mice downregulates hypothalamic Coro7 mRNA levels, and injecting ethanol, an appetite stimulant, increased the number of Coro7 expressing cells in the locus coeruleus. Finally, by employing the genetically-tractable Drosophila melanogaster model we were able to demonstrate an evolutionarily conserved metabolic function for the CORO7 homologue pod1. Knocking down the pod1 in the Drosophila adult nervous system increased their resistance to starvation. Furthermore, feeding flies a high-calorie diet significantly increased pod1 expression. Conclusion: We conclude that coronin 7 is involved in the regulation of energy homeostasis and this role stems, to some degree, from the effect on feeding for calories and reward

Assessment of low-dose cisplatin as a model of nausea and emesis in beagle dogs, potential for repeated administration

Cisplatin is a highly emetogenic cancer chemotherapy agent, which is often used to induce nausea and emesis in animal models. The cytotoxic properties of cisplatin also cause adverse events that negatively impact on animal welfare preventing repeated administration of cisplatin. In this study, we assessed whether a low (subclinical) dose of cisplatin could be utilized as a model of nausea and emesis in the dog while decreasing the severity of adverse events to allow repeated administration. The emetic, nausea-like behavior and potential biomarker response to both the clinical dose (70 mg/m2) and low dose (15 mg/m2) of cisplatin was assessed. Plasma creatinine concentrations and granulocyte counts were used to assess adverse effects on the kidneys and bone marrow, respectively. Nausea-like behavior and emesis was induced by both doses of cisplatin, but the latency to onset was greater in the low-dose group. No significant change in plasma creatinine was detected for either dose groups. Granulocytes were significantly reduced compared with baseline (P = 0.000) following the clinical, but not the low-dose cisplatin group. Tolerability of repeated administration was assessed with 4 administrations of an 18 mg/m2 dose cisplatin. Plasma creatinine did not change significantly. Cumulative effects on the granulocytes occurred, they were significantly decreased (P = 0.03) from baseline at 3 weeks following cisplatin for the 4th administration only. Our results suggest that subclinical doses (15 and 18 mg/m2) of cisplatin induce nausea-like behavior and emesis but have reduced adverse effects compared with the clinical dose allowing for repeated administration in crossover studies

Childhood experiences of parenting and cancer risk at older ages: findings from the English Longitudinal Study of Ageing (ELSA)

Objectives: Despite the importance of childhood experiences for adult health and psychosocial factors for cancer development, parenting, a key childhood psychosocial exposure, has yet to be studied in relation to cancer risk at older ages. We examined whether childhood experiences of poor-quality parenting are associated with an increased risk of cancer at older ages. Methods: We used a sample of 4471 community dwellers aged ≥ 55 years in 2007. Poor-quality parenting was defined as low levels of parental care and high levels of parental overprotection. Results: Overall poorer experiences of parenting, decreasing parental care and increasing parental overprotection were associated with increased risk of incident all-site and skin cancer in men, but not in women. Increasing paternal overprotection was also associated with increased risk of incident colorectal cancer in men. Overall poorer experiences of parenting and increasing paternal overprotection were associated with increased risk of prevalent all-site and colorectal cancer in women. Adjustment for covariates explained a small part of these associations. Conclusions: Older adults who reported childhood experiences of poorer quality parenting appear to have an increased risk of cancer. These findings improve our understanding of the role of psychosocial factors in cancer over the life course

Environmental Factors in the Relapse and Recurrence of Inflammatory Bowel Disease:A Review of the Literature

The causes of relapse in patients with Crohn's disease (CD) and ulcerative colitis (UC) are largely unknown. This paper reviews the epidemiological and clinical data on how medications (non-steroidal anti-inflammatory drugs, estrogens and antibiotics), lifestyle factors (smoking, psychological stress, diet and air pollution) may precipitate clinical relapses and recurrence. Potential biological mechanisms include: increasing thrombotic tendency, imbalances in prostaglandin synthesis, alterations in the composition of gut microbiota, and mucosal damage causing increased permeability

Effect of religiosity/spirituality and sense of coherence on depression within a rural population in Greece: the Spili III project

Background: Recent research has addressed the hypothesis that religiosity/spirituality and sense of coherence buffer the negative effects of stress on numerous health issues. The aim of the current study was to further this work by exploring potential links between psycho-social factors such as religiosity/ spirituality and sense of coherence with depression. Methods: A total of 220 subjects of the SPILI III cohort (1988-2012) attending a primary care setting in the town of Spili on rural Crete represented the target group. All participants underwent a standardized procedure. Validated questionnaires were used to evaluate sense of coherence, depression levels and religious and spiritual beliefs. A multiple linear regression analysis of the Beck Depression Inventory Scale (BDI) in relation to demographic characteristics, scores on the Royal Free Interview for Spiritual and Religious Beliefs scale (RFI-SRB) and Sense of Coherence scale (SOC) was used. Results: A significant inverse association was found between BDI and RFI-SRB scale (B-coef=-0.6999, p<0.001), as well as among BDI and SOC scale (B-coef=-0.556, p<0.001). Conclusions: The findings of the current observational study indicate that highly religious participants are less likely to score high in the depression scale. Furthermore, participants with high SOC scored significantly low in the BDI scale. Further research is required in order to explore the potential effect of SOC and religiosity/spirituality in mental health

Identification of lifestyle patterns associated with obesity and fat mass in children: the Healthy Growth Study

Objective: To investigate possible associations of lifestyle patterns with obesity and fat mass in children. Design: Cross-sectional epidemiological study. Principal component analysis was used to identify lifestyle patterns. Setting: Primary schools from four regions in Greece. Subjects: A total of 2073 schoolchildren (aged 9–13 years). Results: Children in the fourth quartile of the lifestyle pattern combining higher dairy foods with more adequate breakfast consumption were 39·4 %, 45·2 % and 32·2 % less likely to be overweight/obese and in the highest quartile of sum of skinfold thicknesses and fat mass, respectively, than children in the first quartile of this pattern. Similarly, children in the fourth quartile of a lifestyle pattern comprising consumption of high-fibre foods, such as fruits, vegetables and wholegrain products, were 27·4 % less likely to be in the highest quartile of sum of skinfold thicknesses than children in the first lifestyle pattern quartile. Finally, children in the fourth quartile of a lifestyle pattern characterized by more time spent on moderate-to-vigorous physical activity and more frequent meals were 38·0 %, 26·3 % and 29·5 % less likely to be overweight, centrally obese and in the highest quartile of fat mass, respectively, than their peers in the first quartile of this lifestyle pattern (all P < 0·05). Conclusions: The current study identified three lifestyle patterns (i.e. one pattern comprising higher dairy consumption with a more adequate breakfast; a second pattern characterized by increased consumption of high-fibre foods; and a third pattern combining higher physical activity levels with more frequent meals), which were all related with lower odds of obesity and/or increased fat mass levels. From a public health perspective, promotion of these patterns among children and their families should be considered as one of the components of any childhood obesity preventive initiative

An Epigenetic Blockade of Cognitive Functions in the Neurodegenerating Brain

Cognitive decline is a debilitating feature of most neurodegenerative diseases of the central nervous system, including Alzheimer’s disease. The causes leading to such impairment are only poorly understood and effective treatments are slow to emerge. Here we show that cognitive capacities in the neurodegenerating brain are constrained by an epigenetic blockade of gene transcription that is potentially reversible. This blockade is mediated by histone deacetylase 2, which is increased by Alzheimer’s-disease-related neurotoxic insults in vitro, in two mouse models of neurodegeneration and in patients with Alzheimer’s disease. Histone deacetylase 2 associates with and reduces the histone acetylation of genes important for learning and memory, which show a concomitant decrease in expression. Importantly, reversing the build-up of histone deacetylase 2 by short-hairpin-RNA-mediated knockdown unlocks the repression of these genes, reinstates structural and synaptic plasticity, and abolishes neurodegeneration-associated memory impairments. These findings advocate for the development of selective inhibitors of histone deacetylase 2 and suggest that cognitive capacities following neurodegeneration are not entirely lost, but merely impaired by this epigenetic blockade

Epigenetic and Genetic Factors Predict Women's Salivary Cortisol following a Threat to the Social Self

10.1371/journal.pone.0048597PLoS ONE711