Developing a new conceptual framework of meaningful interaction for understanding social isolation and loneliness

Academic debate about social isolation and loneliness, and their adverse health and well-being implications, has resulted in many policy and programme interventions directed towards reducing both, especially among older people. However, definitions of the two concepts, their measurement, and the relationship between the two are not clearly articulated. This article redresses this and draws on theoretical constructs adapted from symbolic interactionism, together with the Good Relations Measurement Framework, developed for the Equality and Human Rights Commission in the UK, to challenge the way in which social isolation and loneliness are currently understood. It argues for a need to understand experiences of social relationships, particularly those which facilitate meaningful interaction, suggesting that opportunities and barriers to meaningful interaction are determined by wider societal issues. This is set out in a new conceptual framework which can be applied across the life course and facilitates a new discourse for understanding these challenging concepts

Genomic alterations underlie a pan-cancer metabolic shift associated with tumour hypoxia

Altered metabolism is a hallmark of cancer. However, the role of genomic changes in metabolic genes driving the tumour metabolic shift remains to be elucidated. Here, we have investigated the genomic and transcriptomic changes underlying this shift across ten different cancer types.A systematic pan-cancer analysis of 6538 tumour/normal samples covering ten major cancer types identified a core metabolic signature of 44 genes that exhibit high frequency somatic copy number gains/amplifications (>20 % cases) associated with increased mRNA expression (ρ > 0.3, q < 10(-3)). Prognostic classifiers using these genes were confirmed in independent datasets for breast and kidney cancers. Interestingly, this signature is strongly associated with hypoxia, with nine out of ten cancer types showing increased expression and five out of ten cancer types showing increased gain/amplification of these genes in hypoxic tumours (P ≤ 0.01). Further validation in breast and colorectal cancer cell lines highlighted squalene epoxidase, an oxygen-requiring enzyme in cholesterol biosynthesis, as a driver of dysregulated metabolism and a key player in maintaining cell survival under hypoxia.This study reveals somatic genomic alterations underlying a pan-cancer metabolic shift and suggests genomic adaptation of these genes as a survival mechanism in hypoxic tumours

Spatial Encoding Strategy Theory: The Relationship between Spatial Skill and STEM Achievement

Learners’ spatial skill is a reliable and significant predictor of achievement in STEM, including computing, education. Spatial skill is also malleable, meaning it can be improved through training. Most cognitive skill training improves performance on only a narrow set of similar tasks, but researchers have found ample evidence that spatial training can broadly improve STEM achievement. We do not yet know the cognitive mechanisms that make spatial skill training broadly transferable when other cognitive training is not, but understanding these mechanisms is important for developing training and instruction that consistently benefits learners, especially those starting with low spatial skill. This paper proposes the spatial encoding strategy (SpES) theory to explain the cognitive mechanisms connecting spatial skill and STEM achievement. To motivate SpES theory, the paper reviews research from STEM education, learning sciences, and psychology. SpES theory provides compelling post hoc explanations for the findings from this literature and aligns with neuroscience models about the functions of brain structures. The paper concludes with a plan for testing the theory’s validity and using it to inform future research and instruction. The paper focuses on implications for computing education, but the transferability of spatial skill to STEM performance makes the proposed theory relevant to many education communities

Who I Am: The Meaning of Early Adolescents’ Most Valued Activities and Relationships, and Implications for Self-Concept Research

Self-concept research in early adolescence typically measures young people’s self-perceptions of competence in specific, adult-defined domains. However, studies have rarely explored young people’s own views of valued self-concept factors and their meanings. For two major self domains, the active and the social self, this mixed-methods study identified factors valued most by 526 young people from socioeconomically diverse backgrounds in Ireland (10-12 years), and explored the meanings associated with these in a stratified subsample (n = 99). Findings indicate that self-concept scales for early adolescence omit active and social self factors and meanings valued by young people, raising questions about content validity of scales in these domains. Findings also suggest scales may under-represent girls’ active and social selves; focus too much on some school-based competencies; and, in omitting intrinsically salient self domains and meanings, may focus more on contingent (extrinsic) rather than true (intrinsic) self-esteem

Sub-Sets of Cancer Stem Cells Differ Intrinsically in Their Patterns of Oxygen Metabolism

PMCID: PMC3640080This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Disruption of hypoxia-inducible fatty acid binding protein 7 induces beige fat-like differentiation and thermogenesis in breast cancer cells

Background Humans produce heat through non-shivering thermogenesis, a metabolic process that occurs in inducible beige adipocytes expressing uncoupling protein 1 (UCP1). UCP1 dissipates the proton gradient of the mitochondrial inner membrane and converts that energy into heat. It is unclear whether cancer cells can exhibit autonomous thermogenesis. Previously, we found that the knockdown of hypoxia-inducible fatty acid binding protein 7 (FABP7) increased reactive oxygen species (ROS) in breast cancer cells. ROS are known to induce beige adipocyte differentiation. Methods We investigated the association of tumor hypoxia, FABP7, and UCP1 across breast cancer patients using METABRIC and TCGA data sets. Furthermore, using a breast cancer cell line, HCC1806, we tested the effect of FABP7 knockdown on cellular physiology including thermogenesis. Results We found a strong mutual exclusivity of FABP7 and UCP1 expression both in METABRIC and in TCGA, indicating major metabolic phenotypic differences. FABP7 was preferentially distributed in poorly differentiated-, estrogen receptor (ER) negative tumors. In contrast, UCP1 was highly expressed in normal ducts and well-differentiated-, ER positive-, less hypoxic tumors. In the cell line-based experiments, UCP1 and its transcriptional regulators were upregulated upon FABP7 knockdown. UCP1 was induced in about 20% of cancer cells, and the effect was increased further in hypoxia. UCP1 depolarized mitochondrial membranes at the site of expression. UCP1 induction was associated with the increase in proton leak, glycolysis, and maximal respiration, mimicking the typical energy profile of beige adipocytes. Most importantly, UCP1 induction elevated cancer cell temperature associated with increased vulnerability to hypoxia and gamma-irradiation. Conclusions We demonstrated that breast cancer cells can undergo thermogenesis through UCP1 induction. Disrupting FABP7-mediated fatty acid metabolism can unlock UCP1-mediated thermogenesis, potentially making it possible to develop therapies to target thermogenesis. Further study would be warranted to investigate the effect of rise in temperature of cancer cells on patients' outcomes and the relationship to other metabolic pathways

The TSC1-2 tumor suppressor controls insulin–PI3K signaling via regulation of IRS proteins

Insulin-like growth factors elicit many responses through activation of phosphoinositide 3-OH kinase (PI3K). The tuberous sclerosis complex (TSC1-2) suppresses cell growth by negatively regulating a protein kinase, p70S6K (S6K1), which generally requires PI3K signals for its activation. Here, we show that TSC1-2 is required for insulin signaling to PI3K. TSC1-2 maintains insulin signaling to PI3K by restraining the activity of S6K, which when activated inactivates insulin receptor substrate (IRS) function, via repression of IRS-1 gene expression and via direct phosphorylation of IRS-1. Our results argue that the low malignant potential of tumors arising from TSC1-2 dysfunction may be explained by the failure of TSC mutant cells to activate PI3K and its downstream effectors

Fatty acid uptake and lipid storage induced by HIF-1α contribute to cell growth and survival after hypoxia-reoxygenation.

An in vivo model of antiangiogenic therapy allowed us to identify genes upregulated by bevacizumab treatment, including Fatty Acid Binding Protein 3 (FABP3) and FABP7, both of which are involved in fatty acid uptake. In vitro, both were induced by hypoxia in a hypoxia-inducible factor-1α (HIF-1α)-dependent manner. There was a significant lipid droplet (LD) accumulation in hypoxia that was time and O2 concentration dependent. Knockdown of endogenous expression of FABP3, FABP7, or Adipophilin (an essential LD structural component) significantly impaired LD formation under hypoxia. We showed that LD accumulation is due to FABP3/7-dependent fatty acid uptake while de novo fatty acid synthesis is repressed in hypoxia. We also showed that ATP production occurs via β-oxidation or glycogen degradation in a cell-type-dependent manner in hypoxia-reoxygenation. Finally, inhibition of lipid storage reduced protection against reactive oxygen species toxicity, decreased the survival of cells subjected to hypoxia-reoxygenation in vitro, and strongly impaired tumorigenesis in vivo

"Of course I will ..." : The combined effect of certainty and level of expectancies on persistence and performance

The importance of performance expectancies for the prediction of regulation of behavior and actual performance has long been established. Building on theories from the field of social cognition, we suggest that the level of performance expectancies, as well as the certainty of the expectancy, have a joint influence on an individual’s beliefs and behavior. In two studies (one cross sectional using a sample of secondary school students and one longitudinal using a sample of university students) we found that expectancies more strongly predicted persistence, and subsequent performance, the more certain the expectancy was. This pattern was found even if prior performance was controlled, as in Study 2. The data give an indication that it may be useful to include certainty as an additional variable in expectancy models