Is philosophy of education a historical mistake? Connecting philosophy and education differently

In this article, I suggest that the question whether the proper place for philosophy of education is in the domain of philosophy or the domain of education cannot be resolved as long as we think of the connection between philosophy and education in terms of the idea of 'philosophy of education'. To substantiate this point, I look into the history of the idea of 'philosophy of education', both as a general idea and with regard to the way in which it became institutionalised in universities in the English-speaking world. I contrast this with the way in which the academic study of education developed in German-speaking countries in order to highlight that 'philosophy of education' is not the only way in which philosophy and education can be connected. Being aware that the connection between philosophy and education can be made differently not only provides a way out of the discussion about the proper identity and location of philosophy of education, but also hints at forms of philosophically informed scholarship that are more firmly based with the academic field of education rather than that they remain a halfway house in between philosophy and education

Sex Differences in the Risk of Coronary Heart Disease Associated With Type 2 Diabetes: A Mendelian Randomization Analysis

OBJECTIVE: Observational studies have demonstrated that type 2 diabetes is a stronger risk factor for coronary heart disease (CHD) in women compared with men. However, it is not clear whether this reflects a sex differential in the causal effect of diabetes on CHD risk or results from sex-specific residual confounding. RESEARCH DESIGN AND METHODS: Using 270 single nucleotide polymorphisms (SNPs) for type 2 diabetes identified in a type 2 diabetes genome-wide association study, we performed a sex-stratified Mendelian randomization (MR) study of type 2 diabetes and CHD using individual participant data in UK Biobank (251,420 women and 212,049 men). Weighted median, MR-Egger, MR-pleiotropy residual sum and outlier, and radial MR from summary-level analyses were used for pleiotropy assessment. RESULTS: MR analyses showed that genetic risk of type 2 diabetes increased the odds of CHD for women (odds ratio 1.13 [95% CI 1.08–1.18] per 1-log unit increase in odds of type 2 diabetes) and men (1.21 [1.17–1.26] per 1-log unit increase in odds of type 2 diabetes). Sensitivity analyses showed some evidence of directional pleiotropy; however, results were similar after correction for outlier SNPs. CONCLUSIONS: This MR analysis supports a causal effect of genetic liability to type 2 diabetes on risk of CHD that is not stronger for women than men. Assuming a lack of bias, these findings suggest that the prevention and management of type 2 diabetes for CHD risk reduction is of equal priority in both sexes

Tobacco smoking is associated with DNA methylation of diabetes susceptibility genes.

AIMS/HYPOTHESIS: Tobacco smoking, a risk factor for diabetes, is an established modifier of DNA methylation. We hypothesised that tobacco smoking modifies DNA methylation of genes previously identified for diabetes. METHODS: We annotated CpG sites available on the Illumina Human Methylation 450K array to diabetes genes previously identified by genome-wide association studies (GWAS), and investigated them for an association with smoking by comparing current to never smokers. The discovery study consisted of 630 individuals (Bonferroni-corrected p = 1.4 × 10(-5)), and we sought replication in an independent sample of 674 individuals. The replicated sites were tested for association with nearby genetic variants and gene expression and fasting glucose and insulin levels. RESULTS: We annotated 3,620 CpG sites to the genes identified in the GWAS on type 2 diabetes. Comparing current smokers to never smokers, we found 12 differentially methylated CpG sites, of which five replicated: cg23161492 within ANPEP (p = 1.3 × 10(-12)); cg26963277 (p = 1.2 × 10(-9)), cg01744331 (p = 8.0 × 10(-6)) and cg16556677 (p = 1.2 × 10(-5)) within KCNQ1 and cg03450842 (p = 3.1 × 10(-8)) within ZMIZ1. The effect of smoking on DNA methylation at the replicated CpG sites attenuated after smoking cessation. Increased DNA methylation at cg23161492 was associated with decreased gene expression levels of ANPEP (p = 8.9 × 10(-5)). rs231356-T, which was associated with hypomethylation of cg26963277 (KCNQ1), was associated with a higher odds of diabetes (OR 1.06, p = 1.3 × 10(-5)). Additionally, hypomethylation of cg26963277 was associated with lower fasting insulin levels (p = 0.04). CONCLUSIONS/INTERPRETATION: Tobacco smoking is associated with differential DNA methylation of the diabetes risk genes ANPEP, KCNQ1 and ZMIZ1. Our study highlights potential biological mechanisms connecting tobacco smoking to excess risk of type 2 diabetes

Dendritic Spine Shape Analysis: A Clustering Perspective

Functional properties of neurons are strongly coupled with their morphology. Changes in neuronal activity alter morphological characteristics of dendritic spines. First step towards understanding the structure-function relationship is to group spines into main spine classes reported in the literature. Shape analysis of dendritic spines can help neuroscientists understand the underlying relationships. Due to unavailability of reliable automated tools, this analysis is currently performed manually which is a time-intensive and subjective task. Several studies on spine shape classification have been reported in the literature, however, there is an on-going debate on whether distinct spine shape classes exist or whether spines should be modeled through a continuum of shape variations. Another challenge is the subjectivity and bias that is introduced due to the supervised nature of classification approaches. In this paper, we aim to address these issues by presenting a clustering perspective. In this context, clustering may serve both confirmation of known patterns and discovery of new ones. We perform cluster analysis on two-photon microscopic images of spines using morphological, shape, and appearance based features and gain insights into the spine shape analysis problem. We use histogram of oriented gradients (HOG), disjunctive normal shape models (DNSM), morphological features, and intensity profile based features for cluster analysis. We use x-means to perform cluster analysis that selects the number of clusters automatically using the Bayesian information criterion (BIC). For all features, this analysis produces 4 clusters and we observe the formation of at least one cluster consisting of spines which are difficult to be assigned to a known class. This observation supports the argument of intermediate shape types.Comment: Accepted for BioImageComputing workshop at ECCV 201

Targeting of Chimeric G-Alpha(I) Proteins to Specific Membrane Domains

Heterotrimeric guanine nucleotide-regulatory (G) proteins are associated with a variety of intracellular membranes and specific plasma membrane domains. In polarized epithelial LLC-PK1 cells we have shown previously that endogenous Galpha(i-2) is localized on the basolateral plasma membrane, whereas Galpha(i-3) is localized on Golgi membranes. The targeting of these highly homologous Galpha(i) proteins to distinct membrane domains was studied by the transfection and expression of chimeric Galpha(i) proteins in LLC-PK1 cells. Chimeric cDNAs were constructed from the cDNAs for Galpha(i-3) and Galpha(i-2) and introduced into a pMXX eukaryotic expression vector containing a mouse metaltothionein-I promotor. Stably transfected cell lines were produced that expressed either Galpha(i-2/3) or Galpha(i-3/2) chimeric proteins. Chimeric and endogenous Galpha(i) proteins were detected in cells using specific carboxy-terminal peptide antibodies. Immunofluorescence staining was used to localize endogenous and chimeric Galpha(i) proteins in LLC-PK1 cells. The staining of chimeric proteins was detected as an increased intensity of staining on membranes containing endogenous Galpha(i) proteins. Using confocal microscopy and image analysis we localized Galpha(i-2) to a specific sub-domain of the lateral membrane of polarized cells, the chimeric Galpha(i-3/2) protein was then shown to colocalize with endognenous Galpha(i-2) in the same lateral plasma membrane domain. The chimeric Galpha(i-2/3) protein colocalized with endogenous Galpha(i-3) on Golgi membranes in LLC-PK1 cells. These results show that chimeric Galpha(i) proteins were targeted to the same membrane domains as endogenous Galpha(i) proteins and the specificity of their membrane targeting was conferred by the carboxy-terminal end of the proteins. These data provide the first evidence for specific targeting information contained in the carboxy termini of Galpha(i) proteins, which appears to be independent of amino-terminal membrane attachment sites in these proteins

Gene set of nuclear-encoded mitochondrial regulators is enriched for common inherited variation in obesity

There are hints of an altered mitochondrial function in obesity. Nuclear-encoded genes are relevant for mitochondrial function (3 gene sets of known relevant pathways: (1) 16 nuclear regulators of mitochondrial genes, (2) 91 genes for oxidative phosphorylation and (3) 966 nuclear-encoded mitochondrial genes). Gene set enrichment analysis (GSEA) showed no association with type 2 diabetes mellitus in these gene sets. Here we performed a GSEA for the same gene sets for obesity. Genome wide association study (GWAS) data from a case-control approach on 453 extremely obese children and adolescents and 435 lean adult controls were used for GSEA. For independent confirmation, we analyzed 705 obesity GWAS trios (extremely obese child and both biological parents) and a population-based GWAS sample (KORA F4, n = 1,743). A meta-analysis was performed on all three samples. In each sample, the distribution of significance levels between the respective gene set and those of all genes was compared using the leading-edge-fraction-comparison test (cut-offs between the 50(th) and 95(th) percentile of the set of all gene-wise corrected p-values) as implemented in the MAGENTA software. In the case-control sample, significant enrichment of associations with obesity was observed above the 50(th) percentile for the set of the 16 nuclear regulators of mitochondrial genes (p(GSEA,50) = 0.0103). This finding was not confirmed in the trios (p(GSEA,50) = 0.5991), but in KORA (p(GSEA,50) = 0.0398). The meta-analysis again indicated a trend for enrichment (p(MAGENTA,50) = 0.1052, p(MAGENTA,75) = 0.0251). The GSEA revealed that weak association signals for obesity might be enriched in the gene set of 16 nuclear regulators of mitochondrial genes

Predictive factors of developing diabetes mellitus in women with gestational diabetes.

BACKGROUND: To investigate which factors during gestational diabetes pregnancies correlate with the risk of developing impaired glucose tolerance or diabetes 1 year postpartum and to compare this risk in women with gestational diabetes and women with a normal oral glucose tolerance test during pregnancy. METHODS: Of 315 women with gestational diabetes, defined as a 2-hr blood glucose value of at least 9.0 mmol/l at a 75-g oral glucose tolerance test, who delivered in Lund 1991-99, 229 (73%) performed a new test 1 year postpartum. We compared maternal and fetal factors during pregnancy with the test value at follow up. A control group of 153 women with a 2-hr test value below 7.8 mmol/l during pregnancy were invited to a new test 1 year postpartum and 60 (39%) accepted. RESULTS: At 1 year follow up, 31% of the women with gestational diabetes but only one of the 60 controls showed pathologic glucose tolerance and one had developed diabetes. The following factors in women with gestational diabetes were identified as predicting impaired glucose tolerance or diabetes at 1 year follow up: maternal age over 40 and--in a multiple regression analysis, independent of each other--a high 2-hr value at oral glucose tolerance test during pregnancy and insulin treatment during pregnancy. CONCLUSION: The risk of developing manifest diabetes after gestational diabetes may be high enough to justify a general screening or diagnostic procedure in all pregnant women to identify women with gestational diabetes and a postpartum follow up program for them. This study did not identify any particular factor during pregnancy with enough precision to predict a later progression to diabetes

A [4Fe-4S]-Fe(CO)(CN)-L-cysteine intermediate is the first organometallic precursor in [FeFe] hydrogenase H-cluster bioassembly.

Biosynthesis of the [FeFe] hydrogenase active site (the 'H-cluster') requires the interplay of multiple proteins and small molecules. Among them, the radical S-adenosylmethionine enzyme HydG, a tyrosine lyase, has been proposed to generate a complex that contains an Fe(CO)2(CN) moiety that is eventually incorporated into the H-cluster. Here we describe the characterization of an intermediate in the HydG reaction: a [4Fe-4S][(Cys)Fe(CO)(CN)] species, 'Complex A', in which a CO, a CN- and a cysteine (Cys) molecule bind to the unique 'dangler' Fe site of the auxiliary [5Fe-4S] cluster of HydG. The identification of this intermediate-the first organometallic precursor to the H-cluster-validates the previously hypothesized HydG reaction cycle and provides a basis for elucidating the biosynthetic origin of other moieties of the H-cluster

The effectiveness of a nurse-led intervention with the distress thermometer for patients treated with curative intent for breast cancer: design of a randomized controlled trial.

Background Distress in patients with cancer influences their quality of life. Worldwide, screening on distress with the Distress Thermometer (DT) in patients with cancer is recommended. However, the effects of the use of the DT on the psychosocial wellbeing of the patient are unknown. A study to assess the psychosocial consequences of the systematic use of the DT and its discussion by a nurse as compared to the usual care provided to outpatients who are treated for primary breast cancer is needed.Methods/design The effectiveness of a nurse-led intervention with the DT will be tested in a non-blinded randomized controlled trial. Patients treated with curative intent for breast cancer will be recruited from the Radboud University Medical Center. The intervention consists of the DT together with discussion of the results with the patient by a trained oncology nurse added to the usual care. Patients will be randomly allocated (1:1) to either receive usual care or the usual care plus the intervention. Primary outcome measure is global quality of life measured with the EORTC QLQ-C30. The functional and symptom scales of the EORTC QLQ-C30 and BR23, Hospital Anxiety and Depression Scale, Impact of Event Scale, Illness Cognition Questionnaire and DT (baseline and final measurement only) will be used to measure secondary outcomes. Questionnaires are obtained in both arms at baseline, after completion of each type of cancer treatment modality and during follow up, with a three and six months' interval during the first and second year respectively.Discussion This study will be the first randomized controlled longitudinal study about the effectiveness of the DT as nurse led-intervention. In case of proven effectiveness, future implementation and standardization of use of the DT as part of routine care will be recommended.Trial registration This study is registered at clinicaltrial.gov march 17, 2010 ( NCT01091584 )