Assessing the psychometric and ecometric properties of neighborhood scales using adolescent survey data from urban and rural Scotland

This work was supported by NHS Health Scotland and the University of St Andrews.Background:  Despite the well-established need for specific measurement instruments to examine the relationship between neighborhood conditions and adolescent well-being outcomes, few studies have developed scales to measure features of the neighborhoods in which adolescents reside. Moreover, measures of neighborhood features may be operationalised differently by adolescents living in different levels of urban/rurality. This has not been addressed in previous studies. The objectives of this study were to: 1) establish instruments to measure adolescent neighborhood features at both the individual and neighborhood level, 2) assess their psychometric and ecometric properties, 3) test for invariance by urban/rurality, and 4) generate neighborhood level scores for use in further analysis. Methods:  Data were from the Scottish 2010 Health Behaviour in School-aged Children Survey, which included an over-sample of rural adolescents. The survey responses of interest came from questions designed to capture different facets of the local area in which each respondent resided. Intermediate data zones were used as proxies for neighborhoods. Internal consistency was evaluated by Cronbach’s alpha. Invariance was examined using confirmatory factor analysis. Multilevel models were used to estimate ecometric properties and generate neighborhood scores. Results:  Two constructs labeled neighborhood social cohesion and neighborhood disorder were identified. Adjustment was made to the originally specified model to improve model fit and measures of invariance. At the individual level, reliability was .760 for social cohesion and .765 for disorder, and between .524 and .571 for both constructs at the neighborhood level. Individuals in rural areas experienced greater neighborhood social cohesion and lower levels of neighborhood disorder compared with those in urban areas. Conclusions:  The scales are appropriate for measuring neighborhood characteristics experienced by adolescents across urban and rural Scotland, and can be used in future studies of neighborhoods and health. However, trade-offs between neighborhood sample size and reliability must be considered.Publisher PDFPeer reviewe

TRY plant trait database - enhanced coverage and open access

Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

Blockade of insulin-like growth factors increases efficacy of paclitaxel in metastatic breast cancer.

Breast cancer remains the leading cause of cancer death in women owing to metastasis and the development of resistance to established therapies. Macrophages are the most abundant immune cells in the breast tumor microenvironment and can both inhibit and support cancer progression. Thus, gaining a better understanding of how macrophages support cancer could lead to the development of more effective therapies. In this study, we find that breast cancer-associated macrophages express high levels of insulin-like growth factors 1 and 2 (IGFs) and are the main source of IGFs within both primary and metastatic tumors. In total, 75% of breast cancer patients show activation of insulin/IGF-1 receptor signaling and this correlates with increased macrophage infiltration and advanced tumor stage. In patients with invasive breast cancer, activation of Insulin/IGF-1 receptors increased to 87%. Blocking IGF in combination with paclitaxel, a chemotherapeutic agent commonly used to treat breast cancer, showed a significant reduction in tumor cell proliferation and lung metastasis in pre-clinical breast cancer models compared to paclitaxel monotherapy. Our findings provide the rationale for further developing the combination of paclitaxel with IGF blockers for the treatment of invasive breast cancer, and Insulin/IGF1R activation and IGF+ stroma cells as potential biomarker candidates for further evaluation

Regiospecific analysis of Mono and Diglycerides in Glycerolysis products by GC x GC TOF-MS.

Comprehensive bidimensional gas chromatography coupled with time-of-flight mass spectrometry (GC × GC-TOF-MS) was used for the characterization of regiospecific mono- and diglycerides (MG-DG) content in the glycerolysis products derived from five different lipids included lard (LA), sun flower seed oil (SF), corn oil (CO), butter (BU), and palm oil (PA). The combination of fast and high temperature non-orthogonal column set namely DB17ht (6 m × 0.10 mm × 0.10 μm) as the primary column and SLB-5 ms (60 cm × 0.10 mm × 0.10 μm) as the secondary column was applied in this work. System configuration involved high oven ramp temperature to obtain precise mass spectral identification and highest effluent’s resolution. 3-Monopalmitoyl-sn-glycerol (MG 3-C16) was the highest concentration in LA, BU and PA while monostearoyl-sn-glycerol (MG C18) in CO and 1,3-dilinoleol-rac-glycerol (DG C18:2c) in SF. Principal component analysis accounted 82% of variance using combination of PC1 and PC2. The presence of monostearoyl-sn-glycerol (MG C18), 3-Monopalmitoyl-sn-glycerol (MG 3-C16), 1,3-dilinoleol-rac-glycerol (DG C18:2c), 1,3-dipalmitoyl-glycerol (DG 1,3-C16), and 1,3-dielaidin (DG C18:1t) caused differentiation of the samples tested

Nitric oxide synthases in infants and children with pulmonary hypertension and congenital heart disease

Nitric oxide is an important regulator of vascular tone in the pulmonary circulation. Surgical correction of congenital heart disease limits pulmonary hypertension to a brief period. The study has measured expression of endothelial (eNOS), inducible (iNOS), and neuronal nitric oxide synthase (nNOS) in the lungs from biopsies of infants with pulmonary hypertension secondary to cardiac abnormalities (n = 26), compared to a control group who did not have pulmonary or cardiac disease (n = 8). eNOS, iNOS and nNOS were identified by immunohistochemistry and quantified in specific cell types. Significant increases of eNOS and iNOS staining were found in pulmonary vascular endothelial cells of patients with congenital heart disease compared to control infants. These changes were confined to endothelial cells and not present in other cell types. Patients who strongly expressed eNOS also had strong expression of iNOS. Upregulation of eNOS and iNOS occurs at an early stage of pulmonary hypertension, and may be a compensatory mechanism limiting the rise in pulmonary artery pressure

Early predictors of impaired social functioning in male rhesus macaques (Macaca mulatta)

Autism spectrum disorder (ASD) is characterized by social cognition impairments but its basic disease mechanisms remain poorly understood. Progress has been impeded by the absence of animal models that manifest behavioral phenotypes relevant to ASD. Rhesus monkeys are an ideal model organism to address this barrier to progress. Like humans, rhesus monkeys are highly social, possess complex social cognition abilities, and exhibit pronounced individual differences in social functioning. Moreover, we have previously shown that Low-Social (LS) vs. High-Social (HS) adult male monkeys exhibit lower social motivation and poorer social skills. It is not known, however, when these social deficits first emerge. The goals of this study were to test whether juvenile LS and HS monkeys differed as infants in their ability to process social information, and whether infant social abilities predicted later social classification (i.e., LS vs. HS), in order to facilitate earlier identification of monkeys at risk for poor social outcomes. Social classification was determined for N = 25 LS and N = 25 HS male monkeys that were 1–4 years of age. As part of a colony-wide assessment, these monkeys had previously undergone, as infants, tests of face recognition memory and the ability to respond appropriately to conspecific social signals. Monkeys later identified as LS vs. HS showed impairments in recognizing familiar vs. novel faces and in the species-typical adaptive ability to gaze avert to scenes of conspecific aggression. Additionally, multivariate logistic regression using infant social ability measures perfectly predicted later social classification of all N = 50 monkeys. These findings suggest that an early capacity to process important social information may account for differences in rhesus monkeys’ motivation and competence to establish and maintain social relationships later in life. Further development of this model will facilitate identification of novel biological targets for intervention to improve social outcomes in at-risk young monkeys

STIM2 regulates PKA-dependent phosphorylation and trafficking of AMPARs

STIMs (STIM1 and STIM2 in mammals) are transmembrane proteins that reside in the endoplasmic reticulum (ER) and regulate store-operated Ca2+ entry (SOCE). The function of STIMs in the brain is only beginning to be explored, and the relevance of SOCE in nerve cells is being debated. Here we identify STIM2 as a central organizer of excitatory synapses. STIM2, but not its paralogue STIM1, influences the formation of dendritic spines and shapes basal synaptic transmission in excitatory neurons. We further demonstrate that STIM2 is essential for cAMP/PKA-dependent phosphorylation of the AMPA receptor (AMPAR) subunit GluA1. cAMP triggers rapid migration of STIM2 to ER–plasma membrane (PM) contact sites, enhances recruitment of GluA1 to these ER-PM junctions, and promotes localization of STIM2 in dendritic spines. Both biochemical and imaging data suggest that STIM2 regulates GluA1 phosphorylation by coupling PKA to the AMPAR in a SOCE-independent manner. Consistent with a central role of STIM2 in regulating AMPAR phosphorylation, STIM2 promotes cAMP-dependent surface delivery of GluA1 through combined effects on exocytosis and endocytosis. Collectively our results point to a unique mechanism of synaptic plasticity driven by dynamic assembly of a STIM2 signaling complex at ER-PM contact sites

CD33 Alzheimer’s disease locus: Altered monocyte function and amyloid biology

In our functional dissection of the CD33 Alzheimer’s disease susceptibility locus, we find that the rs3865444C risk allele is associated with greater cell surface expression of CD33 in monocytes (t50 = 10.06, pjoint=1.3×10–13) of young and older individuals. It is also associated with (1) diminished internalization of Aβ42) (2) accumulation of neuritic amyloid pathology and fibrillar amyloid on in vivo imaging and (3), increased numbers of activated human microglia

Molecular Mechanisms Associated with Nicotine Pharmacology and Dependence.

Tobacco dependence is a leading cause of preventable disease and death worldwide. Nicotine, the main psychoactive component in tobacco cigarettes, has also been garnering increased popularity in its vaporized form, as derived from e-cigarette devices. Thus, an understanding of the molecular mechanisms underlying nicotine pharmacology and dependence is required to ascertain novel approaches to treat drug dependence. In this chapter, we review the field's current understanding of nicotine's actions in the brain, the neurocircuitry underlying drug dependence, factors that modulate the function of nicotinic acetylcholine receptors, and the role of specific genes in mitigating the vulnerability to develop nicotine dependence. In addition to nicotine's direct actions in the brain, other constituents in nicotine and tobacco products have also been found to alter drug use, and thus, evidence is provided to highlight this issue. Finally, currently available pharmacotherapeutic strategies are discussed, along with an outlook for future therapeutic directions to achieve to the goal of long-term nicotine cessation

Linking formal child care characteristics to children's socioemotional well-being: A comparative perspective

Most research on formal child care and children’s outcomes has focused on single countries. We, however, contend that policy context may moderate the association between formal child care characteristics and children’s socioemotional well-being. We examined this by comparing the Netherlands, Finland and the UK; three countries that differ regarding family policies. Of these three countries, Finland was recently ranked highest (ranked 1st) with regards to quality of child care in a recent analysis by the Economist ,followed by the UK (ranked 3rd) and then the Netherlands (ranked 7th) .We hypothesized that children who attend child - care settings in countries with higher- uality formal child- are provision would generally show better socioemotional outcomes. Data from the comparative ‘F amilies 24/7’ survey were used, including 990 parents with children aged 0–12. We distinguished between two age groups in our analysis. Results indicated that, compared to the UK, longer hours in formal care were less beneficial in the Netherlands. Furthermore, spen ding time in formal care during nonstandard hours was more harmful for children in Finland compared to the UK. Lastly, receiving care from multiple caregivers was more disruptive for British children than for Dutch children. No differences were found between Finland and the Netherlands