Dickkopf-1 Overexpression in vitro Nominates Candidate Blood Biomarkers Relating to Alzheimer's Disease Pathology

BACKGROUND: Previous studies suggest that Dickkopf-1 (DKK1), an inhibitor of Wnt signaling, plays a role in amyloid-induced toxicity and hence Alzheimer's disease (AD). However, the effect of DKK1 expression on protein expression, and whether such proteins are altered in disease, is unknown. OBJECTIVE: We aim to test whether DKK1 induced protein signature obtained in vitro were associated with markers of AD pathology as used in the amyloid/tau/neurodegeneration (ATN) framework as well as with clinical outcomes. METHODS: We first overexpressed DKK1 in HEK293A cells and quantified 1,128 proteins in cell lysates using aptamer capture arrays (SomaScan) to obtain a protein signature induced by DKK1. We then used the same assay to measure the DKK1-signature proteins in human plasma in two large cohorts, EMIF (n = 785) and ANM (n = 677). RESULTS: We identified a 100-protein signature induced by DKK1 in vitro. Subsets of proteins, along with age and apolipoprotein E ɛ4 genotype distinguished amyloid pathology (A + T-N-, A+T+N-, A+T-N+, and A+T+N+) from no AD pathology (A-T-N-) with an area under the curve of 0.72, 0.81, 0.88, and 0.85, respectively. Furthermore, we found that some signature proteins (e.g., Complement C3 and albumin) were associated with cognitive score and AD diagnosis in both cohorts. CONCLUSIONS: Our results add further evidence for a role of DKK regulation of Wnt signaling in AD and suggest that DKK1 induced signature proteins obtained in vitro could reflect theATNframework as well as predict disease severity and progression in vivo

The ε3 and ε4 Alleles of Human APOE Differentially Affect Tau Phosphorylation in Hyperinsulinemic and Pioglitazone Treated Mice

Impaired insulin signalling is increasingly thought to contribute to Alzheimer's disease (AD). The ε4 isoform of the APOE gene is the greatest genetic risk factor for sporadic, late onset AD, and is also associated with risk for type 2 diabetes mellitus (T2DM). Neuropathological studies reported the highest number of AD lesions in brain tissue of ε4 diabetic patients. However other studies assessing AD pathology amongst the diabetic population have produced conflicting reports and have failed to show an increase in AD-related pathology in diabetic brain. The thiazolidinediones (TZDs), peroxisome proliferator-activated receptor gamma agonists, are peripheral insulin sensitisers used to treat T2DM. The TZD, pioglitazone, improved memory and cognitive functions in mild to moderate AD patients. Since it is not yet clear how apoE isoforms influence the development of T2DM and its progression to AD, we investigated amyloid beta and tau pathology in APOE knockout mice, carrying human APOEε3 or ε4 transgenes after diet-induced insulin resistance with and without pioglitazone treatment.Male APOE knockout, APOEε3-transgenic and APOEε4-transgenic mice, together with background strain C57BL6 mice were kept on a high fat diet (HFD) or low fat diet (LFD) for 32 weeks, or were all fed HFD for 32 weeks and during the final 3 weeks animals were treated with pioglitazone or vehicle.All HFD animals developed hyperglycaemia with elevated plasma insulin. Tau phosphorylation was reduced at 3 epitopes (Ser396, Ser202/Thr205 and Thr231) in all HFD, compared to LFD, animals independent of APOE genotype. The introduction of pioglitazone to HFD animals led to a significant reduction in tau phosphorylation at the Ser202/Thr205 epitope in APOEε3 animals only. We found no changes in APP processing however the levels of soluble amyloid beta 40 was reduced in APOE knockout animals treated with pioglitazone

Forest biodiversity, ecosystem functioning and the provision of ecosystem services

Forests are critical habitats for biodiversity and they are also essential for the provision of a wide range of ecosystem services that are important to human well-being. There is increasing evidence that biodiversity contributes to forest ecosystem functioning and the provision of ecosystem services. Here we provide a review of forest ecosystem services including biomass production, habitat provisioning services, pollination, seed dispersal, resistance to wind storms, fire regulation and mitigation, pest regulation of native and invading insects, carbon sequestration, and cultural ecosystem services, in relation to forest type, structure and diversity. We also consider relationships between forest biodiversity and multifunctionality, and trade-offs among ecosystem services. We compare the concepts of ecosystem processes, functions and services to clarify their definitions. Our review of published studies indicates a lack of empirical studies that establish quantitative and causal relationships between forest biodiversity and many important ecosystem services. The literature is highly skewed; studies on provisioning of nutrition and energy, and on cultural services, delivered by mixed-species forests are under-represented. Planted forests offer ample opportunity for optimising their composition and diversity because replanting after harvesting is a recurring process. Planting mixed-species forests should be given more consideration as they are likely to provide a wider range of ecosystem services within the forest and for adjacent land uses. This review also serves as the introduction to this special issue of Biodiversity and Conservation on various aspects of forest biodiversity and ecosystem services

Factors associated with regular physical activity participation among people with severe mental ill health

Purpose People with severe mental ill health (SMI) are less physically active and more sedentary than the general population. There is limited research investigating the correlates of physical activity (PA) in people with SMI impeding development of successful interventions. This study aimed to assess the factors associated with regular participation of PA among a large sample of people with SMI. Methods The data for this study were collected from the ‘Lifestyle Health and Wellbeing’ (HWB) cohort that collected data through self-administered questionnaire from participants with SMI. Self-reported participation in regular PA was the main outcome variable. Potential predictors of PA were grouped as demographic, biological, psychological and behavioural variables. Multivariable logistic regressions were conducted considering PA participation as the dependent variable adjusted for possible correlated predictors. Results In total, 3,287 people with SMI (mean (SD) age 47.7 (14.58) years, 59% male) were included; 38% reported undertaking regular PA and 61% wanted to undertake more physical activity. Multivariable logistic regressions showed that the following factors were associated with undertaking more regular PA: being male, aged 18-65 years, having a body mass index between 18.5 and 30 kg/m2, having better self-perceived general health condition, not having a health problem that limits activity, giving higher importance to maintain a healthy lifestyle, and eating more fruit and vegetables. Conclusions Having a better self-perceived general health and placing importance on maintaining a healthy lifestyle were important predictors of regular PA. Lifestyle interventions targeting increased PA among people with SMI should be shaped by their health perception and informed by their needs

Trends in the prevalence of grandparents living with grandchild(ren) in selected European countries and the United States

Research from the United States has shown significant increases in the prevalence of three-generation households and in households consisting solely of grandparents and grandchildren. Such shifts in household composition, which are associated with socio-economic disadvantage, may reflect the activation of grandparents as a latent network of support in response to social and demographic changes such as rising partnership disruption. However, to date, little is known in Europe about trends in grandparent households or whether these households are also likely to be disadvantaged. Moreover, we know little about how the familistic and defamilised policy environments in Europe may affect the activation of such latent kin networks. Employing the Integrated Public Use Microdata Series—International and the Office for National Statistics’ Longitudinal Study for England and Wales, we used multivariate techniques to investigate changes in prevalence over time in co-residence with a grandchild across Austria, England and Wales, France, Greece, Portugal, Romania, and the United States. We expected increases in grandparent households in Portugal and Greece, familistic societies with few public alternatives to family support. However, only Romania (like the US) showed an increase in the percentage of people aged 40 and over co-residing with their grandchildren in three-generation households between the late 1970s and 2002. Given rises in poverty and limited support for low-income families in Romania, rises in grandparent coresidence may reflect a coping strategy among poorer families to increasing financial hardship. Regardless of the trends, grandparent households in all the countries studied remained associated with socio-economic disadvantag

Perceptions of wood in rivers and challenges for stream restoration in the United States

This article reports a study of the public perception of large wood in rivers and streams in the United States. Large wood is an element of freshwater aquatic ecosystems that has attracted much scientific interest in recent years because of its value in biological and geomorphological processes. At the heart of the issue is the nature of the relationship between scientific recognition of the ecological and geomorphological benefits of wood in rivers, management practices utilizing wood for river remediation progress, and public perceptions of in-channel wood. Surveys of students' perceptions of riverscapes with and without large wood in the states of Colorado, Connecticut, Georgia, Illinois, Iowa, Missouri, Oregon, and Texas suggest that many individuals in the United States adhere to traditionally negative views of wood. Except for students in Oregon, most respondents considered photographs of riverscapes with wood to be less aesthetically pleasing and needing more improvement than rivers without wood. Analysis of reasons given for improvement needs suggest that Oregon students are concerned with improving channels without wood for fauna habitat, whereas respondents elsewhere focused on the need for cleaning wood-rich channels for flood risk management. These results underscore the importance of public education to increase awareness of the geomorphological and ecological significance of wood in stream systems. This awareness should foster more positive attitudes toward wood. An integrated program of research, education, and policy is advocated to bridge the gap between scientific knowledge and public perception for effective management and restoration of river systems with wood