Receipt from Holland Society of New York to Ogden Goelet

https://digitalcommons.salve.edu/goelet-personal-expenses/1035/thumbnail.jp

Титульні сторінки та зміст

Sr and Nd isotopes were determined using new thermal ionisation mass spectrometry (TIMS) techniques for a suite of 21 olivine-hosted (85-92mol% Fo) melt inclusions selected from potassic and ultra-potassic lavas from the Italian peninsula. Sr isotopes were measured using default 1

The Contact Allergen NiSO4 Triggers a Distinct Molecular Response in Primary Human Dendritic Cells Compared to Bacterial LPS

Dendritic cells (DC) play a central role in the pathogenesis of allergic contact dermatitis (ACD), the most prevalent form of immunotoxicity in humans. However, knowledge on allergy-induced DC maturation is still limited and proteomic studies, allowing to unravel molecular effects of allergens, remain scarce. Therefore, we conducted a global proteomic analysis of human monocyte-derived dendritic cells (MoDC) treated with NiSO4, the most prominent cause of ACD and compared proteomic alterations induced by NiSO4 to the bacterial trigger lipopolysaccharide (LPS). Both substances possess a similar toll-like receptor (TLR) 4 binding capacity, allowing to identify allergy-specific effects compared to bacterial activation. MoDCs treated for 24 h with 2.5 mu g/ml LPS displayed a robust immunological response, characterized by upregulation of DC activation markers, secretion of pro-inflammatory cytokines and stimulation of T cell proliferation. Similar immunological reactions were observed after treatment with 400 mu M NiSO4 but less pronounced. Both substances triggered TLR4 and triggering receptor expressed on myeloid cells (TREM) 1 signaling. However, NiSO4 also activated hypoxic and apoptotic pathways, which might have overshadowed initial signaling. Moreover, our proteomic data support the importance of nuclear factor erythroid 2-related factor 2 (Nrf2) as a key player in sensitization since many Nrf2 targets genes were strongly upregulated on protein and gene level selectively after treatment with NiSO4. Strikingly, NiSO4 stimulation induced cellular cholesterol depletion which was counteracted by the induction of genes and proteins relevant for cholesterol biosynthesis. Our proteomic study allowed for the first time to better characterize some of the fundamental differences between NiSO4 and LPS-triggered activation of MoDCs, providing an essential contribution to the molecular understanding of contact allergy

A comparative proteomics analysis of four contact allergens in THP-1 cells shows distinct alterations in key metabolic pathways

Allergic contact dermatitis (ACD) is the predominant form of immunotoxicity in humans. The sensitizing potential of chemicals can be assessed in vitro. However, a better mechanistic understanding could improve the current OECD-validated test battery. The aim of this study was to get insights into toxicity mechanisms of four contact allergens, p-benzoquinone (BQ), 2,4-dinitrochlorobenzene (DNCB), p-nitrobenzyl bromide (NBB) and NiSO4, by analyzing differential proteome alterations in THP-1 cells using two common proteomics workflows, stable isotope labeling by amino acids in cell culture (SILAC) and label-free quantification (LFQ). Here, SILAC was found to deliver more robust results. Overall, the four allergens induced similar responses in THP-1 cells, which underwent profound metabolic reprogramming, including a striking upregulation of the TCA cycle accompanied by pronounced induction of the Nrf2 oxidative stress response pathway. The magnitude of induction varied between the allergens with DNCB and NBB being most potent. A considerable overlap between transcriptome-based signatures of the GARD assay and the proteins identified in our study was found. When comparing the results of this study to a previous proteomics study in human primary monocyte-derived dendritic cells, we found a rather low share in regulated proteins. However, on pathway level, the overlap was high, indicating that affected pathways rather than single proteins are more eligible to investigate proteomic changes induced by contact allergens. Overall, this study confirms the potential of proteomics to obtain a profound mechanistic understanding, which may help improving existing in vitro assays for skin sensitization

The relationship of school performance with self-control and grit is strongly genetic and weakly causal

The non-cognitive skills self-control and grit are often considered predictors of school performance, but whether this relationship is causal remains unclear. We investigated the causality of this association using a twin design. Specifically, we evaluated the direct impact of self-control and grit on school performance, while controlling for genetic or environmental influences common to all three traits (i.e., confounding). Teachers of 4891 Dutch 12-year-old twin pairs (of which 3837 were complete pairs) completed a survey about school performance (school grades), self-control (ASEBA self-control scale), and the perseverance aspect of grit. Our analysis aimed to determine the direct impact of self-control and grit on school performance, while simultaneously controlling for genetic or environmental confounding. Establishing the regression relationship corrected for confounding supports the interpretation of the regression relationship as causal. In all analyses, we corrected for sex, rater bias of the teachers, and parental socioeconomic status. Initially, in the standard regression, self-control, and grit explained 28.4% of the school performance variance. However, allowing for genetic confounding (due to genetic pleiotropy) revealed that most of this association could be attributed to genetic influences that the three traits share. In the presence of genetic pleiotropy, the phenotypic regression of school performance on self-control and grit accounted for only 4.4% (i.e., the effect size association with the causal hypothesis). In conclusion, self-control and grit predict school performance primarily due to genetic pleiotropy, with a much smaller causal effect (R 2  = 4.4%). This suggests that interventions targeting self-control and grit alone may yield limited improvements in school performance. </p

The relationship of school performance with self-control and grit is strongly genetic and weakly causal

The non-cognitive skills self-control and grit are often considered predictors of school performance, but whether this relationship is causal remains unclear. We investigated the causality of this association using a twin design. Specifically, we evaluated the direct impact of self-control and grit on school performance, while controlling for genetic or environmental influences common to all three traits (i.e., confounding). Teachers of 4891 Dutch 12-year-old twin pairs (of which 3837 were complete pairs) completed a survey about school performance (school grades), self-control (ASEBA self-control scale), and the perseverance aspect of grit. Our analysis aimed to determine the direct impact of self-control and grit on school performance, while simultaneously controlling for genetic or environmental confounding. Establishing the regression relationship corrected for confounding supports the interpretation of the regression relationship as causal. In all analyses, we corrected for sex, rater bias of the teachers, and parental socioeconomic status. Initially, in the standard regression, self-control, and grit explained 28.4% of the school performance variance. However, allowing for genetic confounding (due to genetic pleiotropy) revealed that most of this association could be attributed to genetic influences that the three traits share. In the presence of genetic pleiotropy, the phenotypic regression of school performance on self-control and grit accounted for only 4.4% (i.e., the effect size association with the causal hypothesis). In conclusion, self-control and grit predict school performance primarily due to genetic pleiotropy, with a much smaller causal effect (R 2  = 4.4%). This suggests that interventions targeting self-control and grit alone may yield limited improvements in school performance. </p

The relationship of school performance with self-control and grit is strongly genetic and weakly causal

The non-cognitive skills self-control and grit are often considered predictors of school performance, but whether this relationship is causal remains unclear. We investigated the causality of this association using a twin design. Specifically, we evaluated the direct impact of self-control and grit on school performance, while controlling for genetic or environmental influences common to all three traits (i.e., confounding). Teachers of 4891 Dutch 12-year-old twin pairs (of which 3837 were complete pairs) completed a survey about school performance (school grades), self-control (ASEBA self-control scale), and the perseverance aspect of grit. Our analysis aimed to determine the direct impact of self-control and grit on school performance, while simultaneously controlling for genetic or environmental confounding. Establishing the regression relationship corrected for confounding supports the interpretation of the regression relationship as causal. In all analyses, we corrected for sex, rater bias of the teachers, and parental socioeconomic status. Initially, in the standard regression, self-control, and grit explained 28.4% of the school performance variance. However, allowing for genetic confounding (due to genetic pleiotropy) revealed that most of this association could be attributed to genetic influences that the three traits share. In the presence of genetic pleiotropy, the phenotypic regression of school performance on self-control and grit accounted for only 4.4% (i.e., the effect size association with the causal hypothesis). In conclusion, self-control and grit predict school performance primarily due to genetic pleiotropy, with a much smaller causal effect (R 2  = 4.4%). This suggests that interventions targeting self-control and grit alone may yield limited improvements in school performance. </p

The relationship of school performance with self-control and grit is strongly genetic and weakly causal

The non-cognitive skills self-control and grit are often considered predictors of school performance, but whether this relationship is causal remains unclear. We investigated the causality of this association using a twin design. Specifically, we evaluated the direct impact of self-control and grit on school performance, while controlling for genetic or environmental influences common to all three traits (i.e., confounding). Teachers of 4891 Dutch 12-year-old twin pairs (of which 3837 were complete pairs) completed a survey about school performance (school grades), self-control (ASEBA self-control scale), and the perseverance aspect of grit. Our analysis aimed to determine the direct impact of self-control and grit on school performance, while simultaneously controlling for genetic or environmental confounding. Establishing the regression relationship corrected for confounding supports the interpretation of the regression relationship as causal. In all analyses, we corrected for sex, rater bias of the teachers, and parental socioeconomic status. Initially, in the standard regression, self-control, and grit explained 28.4% of the school performance variance. However, allowing for genetic confounding (due to genetic pleiotropy) revealed that most of this association could be attributed to genetic influences that the three traits share. In the presence of genetic pleiotropy, the phenotypic regression of school performance on self-control and grit accounted for only 4.4% (i.e., the effect size association with the causal hypothesis). In conclusion, self-control and grit predict school performance primarily due to genetic pleiotropy, with a much smaller causal effect (R 2  = 4.4%). This suggests that interventions targeting self-control and grit alone may yield limited improvements in school performance. </p

The relationship of school performance with self-control and grit is strongly genetic and weakly causal

The non-cognitive skills self-control and grit are often considered predictors of school performance, but whether this relationship is causal remains unclear. We investigated the causality of this association using a twin design. Specifically, we evaluated the direct impact of self-control and grit on school performance, while controlling for genetic or environmental influences common to all three traits (i.e., confounding). Teachers of 4891 Dutch 12-year-old twin pairs (of which 3837 were complete pairs) completed a survey about school performance (school grades), self-control (ASEBA self-control scale), and the perseverance aspect of grit. Our analysis aimed to determine the direct impact of self-control and grit on school performance, while simultaneously controlling for genetic or environmental confounding. Establishing the regression relationship corrected for confounding supports the interpretation of the regression relationship as causal. In all analyses, we corrected for sex, rater bias of the teachers, and parental socioeconomic status. Initially, in the standard regression, self-control, and grit explained 28.4% of the school performance variance. However, allowing for genetic confounding (due to genetic pleiotropy) revealed that most of this association could be attributed to genetic influences that the three traits share. In the presence of genetic pleiotropy, the phenotypic regression of school performance on self-control and grit accounted for only 4.4% (i.e., the effect size association with the causal hypothesis). In conclusion, self-control and grit predict school performance primarily due to genetic pleiotropy, with a much smaller causal effect (R 2  = 4.4%). This suggests that interventions targeting self-control and grit alone may yield limited improvements in school performance. </p