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Funder: Deutsches Institut für Ernährungsforschung Potsdam-Rehbrücke (DIfE) (3440), PURPOSE: In several studies, exploratory dietary patterns (DP), derived by principal component analysis, were inversely or positively associated with incident type 2 diabetes (T2D). However, findings remained study-specific, inconsistent and rarely replicated. This study aimed to investigate the associations between DPs and T2D in multiple cohorts across the world. METHODS: This federated meta-analysis of individual participant data was based on 25 prospective cohort studies from 5 continents including a total of 390,664 participants with a follow-up for T2D (3.8-25.0 years). After data harmonization across cohorts we evaluated 15 previously identified T2D-related DPs for association with incident T2D estimating pooled incidence rate ratios (IRR) and confidence intervals (CI) by Piecewise Poisson regression and random-effects meta-analysis. RESULTS: 29,386 participants developed T2D during follow-up. Five DPs, characterized by higher intake of red meat, processed meat, French fries and refined grains, were associated with higher incidence of T2D. The strongest association was observed for a DP comprising these food groups besides others (IRRpooled per 1 SD = 1.104, 95% CI 1.059-1.151). Although heterogeneity was present (I2 = 85%), IRR exceeded 1 in 18 of the 20 meta-analyzed studies. Original DPs associated with lower T2D risk were not confirmed. Instead, a healthy DP (HDP1) was associated with higher T2D risk (IRRpooled per 1 SD = 1.057, 95% CI 1.027-1.088). CONCLUSION: Our findings from various cohorts revealed positive associations for several DPs, characterized by higher intake of red meat, processed meat, French fries and refined grains, adding to the evidence-base that links DPs to higher T2D risk. However, no inverse DP-T2D associations were confirmed.

Introduction In observational studies, venous thromboembolism (VTE) has been associated with Cushing’s syndrome and with persistent mental stress, two conditions associated with higher cortisol levels. However, it remains unknown whether high cortisol levels within the usual range are causally associated with VTE risk. We aimed to assess the association between plasma cortisol levels and VTE risk using Mendelian randomization. Methods Three genetic variants in the SERPINA1/SERPINA6 locus (rs12589136, rs11621961 and rs2749527) were used to proxy plasma cortisol. The associations of the cortisol-associated genetic variants with VTE were acquired from the INVENT (28 907 cases and 157 243 non-cases) and FinnGen (6913 cases and 169 986 non-cases) consortia. Corresponding data for VTE subtypes were available from the FinnGen consortium and UK Biobank. Two-sample Mendelian randomization analyses (inverse-variance weighted method) were performed. Results Genetic predisposition to higher plasma cortisol levels was associated with a reduced risk of VTE (odds ratio [OR] per one standard deviation increment 0.73, 95% confidence interval [CI] 0.62–0.87, p Conclusions This study provides evidence that genetically predicted plasma cortisol levels in the high end of the normal range are associated with a decreased risk of VTE and that this association may be mediated by blood pressure. This study has implications for the planning of observational studies of cortisol and VTE, suggesting that blood pressure traits should be measured and accounted for.

Supplemental material, sj-pdf-1-wes-10.1177_09500170221091886 for Predicting Child-Labour Risks by Norms in India by Jihye Kim, Wendy Olsen and Arkadiusz Wiśniowski in Work, Employment and Society

Additional file 1. Figure S1. Overall survival of four subgroups divided by first-line medication and subsequent treatment.

Supplemental material, sj-pdf-1-wes-10.1177_09500170221091886 for Predicting Child-Labour Risks by Norms in India by Jihye Kim, Wendy Olsen and Arkadiusz Wiśniowski in Work, Employment and Society

We approach the problem of improving robustness of deep learning algorithms in the presence of label noise. Building upon existing label correction and co-teaching methods, we propose a novel training procedure to mitigate the memorization of noisy labels, called CrossSplit, which uses a pair of neural networks trained on two disjoint parts of the labelled dataset. CrossSplit combines two main ingredients: (i) Cross-split label correction. The idea is that, since the model trained on one part of the data cannot memorize example-label pairs from the other part, the training labels presented to each network can be smoothly adjusted by using the predictions of its peer network; (ii) Cross-split semi-supervised training. A network trained on one part of the data also uses the unlabeled inputs of the other part. Extensive experiments on CIFAR-10, CIFAR-100, Tiny-ImageNet and mini-WebVision datasets demonstrate that our method can outperform the current state-of-the-art in a wide range of noise ratios., Comment: Accepted to ICML 2023

전통사회에서는 삶과 죽음이 자연스럽게 공존했다면, 현대사회에서는 삶에서 죽음이 기피되거나 배제되는 경우가 많았다. 1960년대 이후 미국과 독일 등에서는 이러한 죽음의 배제 현상이 지닌 문제를 극복하기 위해 죽음학 연구가 시작되었으며, 죽음교육의 필요성이 대두되면서 다양한 죽음교육의 프로그램이 마련되었다. 죽음 교육은 죽음에 대한 이해 및 철학적 성찰, 타자의 죽음으로 인한 슬픔과 애도의 문제, 그리고 의학적, 과학적 생명 윤리의 문제를 통해 인간 존재에 대해 깨닫고 생명의 소중함으로 일깨우는 데 필요한 교육이다. 그러나 우리나라의 경우 죽음교육의 필요성에 대한 논의는 시작되었으나 실질적인 죽음교육에 대한 연구가 활발히 진행되고 있지 않다. 그러므로 본 연구에서는 죽음의 문제를 정면으로 다루고 있는 김애란의 소설을 분석함으로써 고등학교 『문학』 과목에 적합한 현대소설 제재 및 내용을 고찰하고, 나아가 죽음교육의 실행 가능성에 대해 생각해 보았다. 소설은 경험하지 못한 자신의 죽음뿐 아니라 주변인들의 죽음을 간접 체험하게 함으로써 죽음에 대한 공포와 슬픔을 극복하고, 죽음에 대한 태도 및 가치를 정립할 수 있게 해주기 때문이다. 김애란의 『두근두근 내 인생』은 남들보다 급격한 노화와 죽음을 겪는 조로증 환자의 서사이다. 이 소설을 통해 학습자들은 인간이 겪게 될 노화와 죽음에 대해 성찰할 수 있으며, 이를 통해 생명에 대한 소중함을 깨닫게 된다. 또한 단편소설인 「입동」과 「어디로 가고 싶으신가요」는 모두 사랑하는 가족을 잃은 후 남겨진 인물들의 이야기를 다룬 소설이다. 두 소설을 통해 학습자들은 사랑하는 이들과 사별한 이들의 슬픔과 애도의 과정을 경험하고, 나아가 죽음의 슬픔을 겪는 타자를 어떻게 위로할 것인가의 문제를 생각해 볼 수 있다. 인간은 죽음을 경험할 수밖에 없는 존재지만, 상처와 죽음이 있기에 생명을 더욱 소중히 할 수 있다. 죽음을 다루고 있는 문학작품들을 통해 학습자들은 인간 존재에 대한 성찰의 폭을 넓히고, 진정한 삶의 가치에 대해 학습할 수 있을 것이다.

광고는 근대의 일상을 소비사회로 견인한 매체였을 뿐만 아니라 인쇄매체의 발달 속에서 등장한 신흥 미술양식으로, 새로운 방식의 기록과 복제, 신속한 유통을 통해 대중이 손쉽게 접할 수 있는 시각미술이라 할 수 있다. 전시회나 전람회, 화보집을 통해서만 접할 수 있었던 미술작품들과 달리, 광고는 다양한 인쇄물에 게재되고 거리와 상점, 전차, 기차역 등 대중에게 친숙한 공간에 진열·전시된 시각문화로써 근대의 일상을 채우고 단장했다. 광고가 제공한 신문물에 대한 정보와 그것이 함의한 이상적인 근대의 도안은 다양한 매체를 통해 시간과 공간의 제약을 벗어나 대중적으로 공유되었다는 점에서 한국 근대 대중미술의 원형이 되었다고 평가할 수 있다. 본 연구는 대중매체가 출현하며 광고가 지면에 실리기 시작한 19세기 후반부터 2차 세계대전으로 대부분의 매체가 폐간된 1940년대 전반까지 신문과 잡지 등 인쇄매체에 게재된 광고 도안과 거리, 상점 등 대중에게 친숙한 공간에 전시된 광고 포스터를 중심으로 근대 광고 도안의 대중미술로서의 성격을 고찰해 보았다. 대중미술이라는 시각에서 광고를 재해석하고 미술사의 틀로 재구축함으로써 근대 시각문화의 원형을 살피고 그 이미지가 내포하는 근대와 근대성이 구축되는 과정을 시각적으로 시현시키고자 했다.

Web applications that process sensitive information have become prevalent. Modern web applications rely heavily on dynamic content (i.e., page updates made by the browser using an XMLHttpRequest, and more recently the JavaScript Fetch API). Ajax technology provides fast client-server communication, which generates web traffic that updates the document object model (DOM) object in the browser interface often induced by user input. Therefore, the user’s actions are strongly correlated with timing and size of packets that carry Ajax requests. This research aims to characterize the relationship between keystroke dynamics and Ajax packets in dynamic web traffic. We investigate several dynamic web applications and the ability to measure human behavior in encrypted network traffic. Two approaches to Ajax packet detection are proposed and evaluated: longest increasing subsequence (LIS), which uses packet sizes, and dynamic time warping (DTW), which uses keystroke and packet timings. From the detected packets of recognized patterns, we examine the extent to which remote user identification in dynamic web traffic can be performed. We use a recurrent neural network (RNN) trained with triplet loss to extract deep temporal features from the detected packet timings. Leveraging recent work in keystroke dynamics, we show that user identification can be performed with modest accuracy utilizing the packet timings invoked by a user typing in a web search engine. Outstanding Thesis Captain, Republic of Korea Army Approved for public release. distribution is unlimited

BACKGROUND: The consumption of legumes is promoted as part of a healthy diet in many countries but associations of total and types of legume consumption with type 2 diabetes (T2D) are not well established. Analyses across diverse populations are lacking despite the availability of unpublished legume consumption data in prospective cohort studies. OBJECTIVE: To examine the prospective associations of total and types of legume intake with the risk of incident T2D. METHODS: Meta-analyses of associations between total legume, pulse, and soy consumption and T2D were conducted using a federated approach without physical data-pooling. Prospective cohorts were included if legume exposure and T2D outcome data were available and the cohort investigators agreed to participate. We estimated incidence rate ratios (IRRs) and CIs of associations using individual participant data including ≤42,473 incident cases among 807,785 adults without diabetes in 27 cohorts across the Americas, Eastern Mediterranean, Europe, and Western Pacific. Random-effects meta-analysis was used to combine effect estimates and estimate heterogeneity. RESULTS: Median total legume intake ranged from 0-140 g/d across cohorts. We observed a weak positive association between total legume consumption and T2D (IRR = 1.02, 95% CI: 1.01 to 1.04) per 20 g/d higher intake, with moderately high heterogeneity (I2 = 74%). Analysis by region showed no evidence of associations in the Americas, Eastern Mediterranean, and Western Pacific. The positive association in Europe (IRR = 1.05, 95% CI: 1.01 to 1.10, I2 = 82%) was mainly driven by studies from Germany, UK, and Sweden. No evidence of associations was observed for the consumption of pulses or soy. CONCLUSIONS: These findings suggest no evidence of an association of legume intakes with T2D in several world regions. The positive association observed in some European studies warrants further investigation relating to overall dietary contexts in which legumes are consumed, including accompanying foods which may be positively associated with T2D.

Additional file 1. Supplementary Table 1. Characteristics of patients.

Additional file 15 Supplementary Fig. 14. (A) Screening of synthetic lethality target of FBXW7 mutation using the DepMap dataset. (B, C) Sensitivity of the FH535 molecule in colorectal cancer cell lines with FBXW7 mutation (Wilcoxon rank sum test).

Additional file 3 Supplementary Fig. 2. (A) Spearman’s correlation of variant allele fractions (VAFs) between organoid RNA and organoid DNA. (B) Characteristics of variants detected in organoid DNA and not in tissue RNA; the variants detected in organoids only were associated with low read depth in primary tissue sequences or subclonal events based on organoid sequencing (Wilcoxon rank-sum test). (C) Spearman’s correlation of VAFs between organoid DNA and tissue RNA. (D) Spearman’s correlation of VAF in each gene between organoid DNA and tissue RNA.

Additional file 10 Supplementary Fig. 9. (A) Classification of the TIM using primary cancer tissue. (B) Immune cell types from CIBERSORT based on the TIM class (Wilcoxon rank-sum test). (C) Immune cell types using MCP score based on the TIM class (Kruskal Wallis test). (D) Validation of the exhausted TIM class based on CD8+ T cell exhaustion score using GSVA analysis (Wilcoxon rank-sum test). (E) Significant correlation of HLA-I expression in CCOs versus primary tumor tissues (Spearman correlation test). (F) Fraction of copy number variation (CNV) based on the TIM class (Kruskal Wallis test). (G) Fusion number based on the TIM class (Kruskal Wallis test). TIM, tumor immune microenvironment; CCO, colorectal cancer organoid.

Additional file 13 Supplementary Fig. 12. (A) Enrichment of KRAS (biallelic) mutations in tumors with decreased CD8+ T cells (10,000 randomly permutated p values and one-sided Wilcoxon rank sum test). (B) Increased frequency of KRAS biallelic mutation in non-immunogenic (immuno-desert TIM) tumors (Fisher’s exact test). (C, D) KRAS mutation status and TIM. (E) Characteristics of gene expression and infiltrating immune cell types based on the KRAS mutation status (Spearman’s correlation test). TIM, tumor immune microenvironment.

Additional file 6 Supplementary Fig. 5. (A) Ki-67 immunohistochemistry in the primary tumor tissues and its interpretation by a pathologist and by image analysis. (B) Significant correlation of the Ki-67 proliferation index between the pathologist’s result and image analysis. (C) No correlations in Ki-67 mRNA expression between bulk primary tissues including tumor microenvironment and cancer cells and CCOs. (D) Comparison of our molecular subgrouping and CMS classification in CCOs (Chi-squared test). CCO, colorectal cancer organoid.

Additional file 11 Supplementary Fig. 10. No significant differential gene expression in organoids based on the tumor immune microenvironment (TIM) class of primary tissues (FDR q > 0.25 by one-way ANOVA test).

Additional file 12 Supplementary Fig. 11. (A) Pathway analysis using tissue RNA sequence data based on the tumor immune microenvironment (TIM) class. (B, C) Significance of Wnt/β-catenin signaling pathway in the non-immunogenic group using GSVA analysis (Wilcoxon rank-sum test). (D) APC mutation status based on the TIM class. (E) Significance of biallelic APC mutation and TIM class (Fisher’s exact test). (F) Expression of target genes belonging to the Wnt/beta-catenin pathway (Wilcoxon rank-sum test).

Additional file 2 Supplementary Fig. 1. (A) Histology and immunohistochemistry of the established CCOs and the corresponding primary tumors. (B) Distribution of variant allele fraction (VAF) of detected variants in the MSI-high group and the MSI-low/MSS group. CCO, colorectal cancer organoid; MSI, microsatellite instability; MSS, microsatellite stable; H&E, hematoxylin and eosin.

Additional file 16 Supplementary Fig. 15. (A) FH535 induced cell death and destroyed the organoid structure in the two CCOs with FBXW7 mutation (AMC-17CT-019 and AMC-17CT-048). (B) Sensitivity of the FH535 molecule in CCOs with FBXW7 mutation (Wilcoxon-rank sum test). (C) Sensitivities of various WNT signaling drugs targets showing non-significant responses to drugs targeting WNT pathways in colorectal cancer cells with FBXW7 mutation. (D) CCOs with FBXW7 mutation also showed non-significant responses to ICG-001, which also targets the WNT/β-catenin pathway, suggesting that FH535 has a different mechanism action in colorectal cancers harboring the FBXW7 mutation. CCO, colorectal cancer organoid.

Additional file 5 Supplementary Fig. 4. (A) Spearman’s correlation coefficient matrix of CCOs versus primary tumor tissues. (B) Total immune score and stromal score of CCOs versus primary tumor tissues. (C) Genes that are differentially expressed between CCOs and primary tumor tissues. (D) Spearman correlation of the expression of differentiation or stem cell markers in CCOs versus primary tumor tissues. CCO, colorectal cancer organoid; TIM, tumor immune microenvironment.

Additional file 4 Supplementary Fig. 3. (A) Profiles of copy number variations with microsatellite instability (MSI) information in the 87 CCOs. (B) Circos plot of the detected fusions in the 87 CCOs. (C) HLA class I molecular typing and its frequency in 87 CCOs. (D) Frequency of the HLA supertype in 87 CCOs. CCO, colorectal cancer organoid.

Additional file 14 Supplementary Fig. 13. (A) Frequency of TP53 gain-of-function (GOF) mutation based on the tumor immune microenvironment (TIM) class, showing a high frequency of TP53 GOF mutations in the Desert group (p = 0.033, Fisher’s exact test). (B) Association between TP53 GOF mutations and decreased CD8+ T cell (10,000 random permutation test and Spearman’s correlation test). (C) Tendency for the exclusive occurrence of TP53 and KRAS mutation. (D) Enriched unfolded protein response pathway (GSVA score) in the immune-exhausted group (Wilcoxon rank-sum test).

Additional file 8 Supplementary Fig. 7. (A) Prognostic impact of gene expression in HLA class II in CCOs. (B) Patient survival based on HLA class II expression level using immunohistochemistry (IHC) in cancer cells from primary tissue (log-rank test).

Additional file 1 Appendices.

Recent studies have revealed the importance of long noncoding RNAs (lncRNAs) as tissue-specific regulators of gene expression. There is ample evidence that distinct types of vasculature undergo tight transcriptional control to preserve their structure, identity, and functions. We determine a comprehensive map of lineage-specific lncRNAs in human dermal lymphatic and blood vascular endothelial cells (LECs and BECs), combining RNA-Seq and CAGE-Seq. Subsequent antisense oligonucleotide-knockdown transcriptomic profiling of two LEC- and two BEC-specific lncRNAs identifies LETR1 as a critical gatekeeper of the global LEC transcriptome. Deep RNA-DNA, RNA-protein interaction studies, and phenotype rescue analyses reveal that LETR1 is a nuclear trans-acting lncRNA modulating, via key epigenetic factors, the expression of essential target genes, including KLF4 and SEMA3C, governing the growth and migratory ability of LECs. Together, our study provides several lines of evidence supporting the intriguing concept that every cell type expresses precise lncRNA signatures to control lineage-specific regulatory programs., Nature Communications, 12 (1), ISSN:2041-1723

Background Atopic dermatitis (AD) represents the most common inflammatory skin disorder in children showing massive infiltration of immune cells. The colonization of AD-afflicted skin by Staphylococcus aureus and S. aureus-derived extracellular vesicles (SEVs) has been associated with AD pathogenesis; however, the molecular mechanism underlying SEV-mediated inflammatory responses remains unclear. Objective We investigated how SEVs can mediate inflammatory responses in AD pathogenesis by examining the effect of SEVs on human dermal microvascular endothelia cells (HDMECs). Methods HDMECs were treated with SEVs, and the expression of cell adhesion molecules or cytokines was assessed using RT-qPCR, Western blot or cytokine array analyses. The receptor for SEVs and related signalling molecules in HDMECs were addressed and verified via gene knockdown or inhibitor experiments. The recruitment assay of human THP-1 monocytic cells on HDMECs was performed after SEV treatment in the presence or absence of the verified receptor or signalling molecule. Results SEVs, but not other gram-positive bacteria-derived extracellular vesicles, directly activated HDMECs by increasing the expression of cell adhesion molecules (E-selectin, VCAM1 and ICAM1) and that of IL-6, the inflammatory cytokine; consequently, they enhanced the recruitment of THP-1 monocytic cells to HDMECs. The SEV-induced HDMEC activation was dependent on Toll-like receptor 4 and the NF-κB signalling pathway, which was rapidly activated within 1 hour post-treatment and followed by an upregulation of cell adhesion molecules and IL-6 at later time-points. Moreover, SEV-mediated HDMEC responses were more rapid and intense than those induced by the same protein concentrations of S. aureus extracts. Conclusions & clinical relevance SEVs as proinflammatory factors could mediate immune cell infiltration in AD by efficiently inducing endothelial cell activation and monocyte recruitment, which may provide insights into alleviating the S. aureus-mediated onset or progression of AD and its phenotypes.

To identify genetic variants associated with diabetic retinopathy (DR), we performed a large multiethnic genome-wide association study. Discovery included eight European cohorts (n = 3,246) and seven African American cohorts (n = 2,611). We meta-analyzed across cohorts using inverse-variance weighting, with and without liability threshold modeling of glycemic control and duration of diabetes. Variants with a P value

Cellular metabolic rate is a good indicator of the physiological state of cells and its changes, which can be measured by total heat flux accompanying metabolism. Chip calorimeters can provide label-free and high throughput measurements of cellular metabolic rate, however, lack of high power resolution and microfluidic sample handling capability has been preventing their wide applications. We report high-resolution chip calorimeters integrated with thin-film parylene microfluidics, which can reliably measure metabolic heat from mammalian cells with controlled stimuli. The molding and bonding technique allowed fast and reliable parylene microfluidic channel fabrications and highly sensitive vanadium oxide thermistor enabled temperature resolution as small as ~ 15 {\mu}K, which led to a three-orders-of-magnitude improvement in volume specific power resolutions. Measurements of metabolic heat were successfully demonstrated with adherent and nonadherent cells. We expect the chip calorimeter will provide a universal platform for fundamental cell-biology studies and biomedical applications including cell-based assay for drug discovery.

The present study was carried out to explore the potential effects of novel lactic acid bacteria Pediococcus penticeous KCC-23 (KCC-23) and Lactobacillus plantarum KCC-24 (KCC-24) on rye haylage fermentation at National Institute of Animal Science, Cheonan province in Korea. The experiment contains three different groups such as control without lactic acid bacteria, rye haylage with KCC-23 and rye haylage KCC-24. After experimental periods, the content of crude protein, acid detergent fiber (ADF), neutral detergent fiber (NDF), the activity of total digestible nutrient (TDN) and In-vitro digestibility (IVD) was similar in control and LAB treated haylage (p

Korean Abstract: 본 연구는 최근의 인구구조 및 사회경제적 변화를 반영한 생애주기를 바탕으로 2017년 가계금융복지조사 자료를 활용하여 가계의 재무상태를 평가해보고 재무적으로 취약한 가계를 살펴보고자 하였다. 연구결과 첫째, 1인 가구의 증가, 이혼율 증가, 자녀의 늦은 독립, 저출산 등으로 인해 나타난 다양한 가계 형태를 반영할 수 있는 확장된 생애주기가 15가지 유형으로 분류되었다. 확장된 생애주기는 전통적인 가족생애주기에서 나타나지 않았던 가계들을 포괄하여 가계의 재무상태를 실효성 있게 분석할 수 있었다. 둘째, 확장된 생애주기를 바탕으로 구체적으로 각 가계의 재무상태가 어떠한지 살펴본 결과 동일한 연령대에서도 생애주기적 사건의 유무에 따라 가계의 재무상태가 차이 있는 것으로 나타났다. 이는 재무상태를 평가함에 있어 생애주기적 요소를 반드시 고려해야 하며 연령뿐만 아니라 다양한 생애주기 특성에 따라 재무상태를 평가할 수 있는 가이드라인에 대한 연구가 필요함을 시사한다. 또한 소비자에게 재무정보를 제공할 때 생애주기 특성을 바탕으로 차별화된 재무 정보를 제공할 필요가 있음을 보여준다. 마지막으로 전통적인 생애주기 단계에 있는 가계에 비해 확장된 생애주기에서 도출된 가계들의 경우 재무 건전성과 성장성에 있어 대체로 열악한 가계로 분석되었다. 기존의 가계 정책들은 다수의 전통적인 가계에 초점을 두고 있으나 본 연구결과와 같이 최근에는 다양한 형태의 가계들이 존재하고 있으며 이러한 소수의 가계에 대해서도 생애주기 내에서 지속적인 연구가 이루어져야 할 필요가 있음을 시사한다. English Abstract: This study analyzes the financial status of households based on the life-cycle that reflects recent demographic and socio-economic changes. Using the 2017 Survey of Household Finances, this study compared the financial status of households in terms of financial stability and growth analyzed the financially weak households. The results of this study are as follows: First, there are 15 types of extended(revised) life-cycle that can reflect various types of households such as an increase in single-person households, an increase in divorce rates, late independence of children, and low birthrates. The extended life-cycle was able to effectively analyse the financial status of households by encompassing the types of households that did not appear in the traditional family life-cycle. Second, based on the extended life-cycle, the financial status of each household was examined. As a result, there were significant differences in the financial structure and financial status of households according to the existence of life-cycle events in the same age group. This shows that life-cycle factors must be taken into account in assessing the financial status. There is also a need for ongoing research into guidelines for assessing financial status in terms of age as well as life-cycle. It also shows that it is necessary to provide differentiated financial information based on life-cycle characteristics when providing financial information to consumers. Finally, households derived from the extended life-cycle as compared to households in the traditional life-cycle stage were analyzed as generally vulnerable households in terms of financial stability and growth. Most household policies focus on traditional households. However, as in the present study, there are various types of households in recent years, and these non-traditional households are more likely to be financially weak. Therefore it is necessary to continue research on these few households within the life-cycle.

Results from observational studies examining dyslipidemia as a risk factor for diabetic retinopathy (DR) have been inconsistent. We evaluated the causal relationship between plasma lipids and DR using a Mendelian randomization approach. We pooled genome-wide association studies summary statistics from 18 studies for two DR phenotypes: any DR (N = 2,969 case and 4,096 control subjects) and severe DR (N = 1,277 case and 3,980 control subjects). Previously identified lipid-associated single nucleotide polymorphisms served as instrumental variables. Meta-analysis to combine the Mendelian randomization estimates from different cohorts was conducted. There was no statistically significant change in odds ratios of having any DR or severe DR for any of the lipid fractions in the primary analysis that used single nucleotide polymorphisms that did not have a pleiotropic effect on another lipid fraction. Similarly, there was no significant association in the Caucasian and Chinese subgroup analyses. This study did not show evidence of a causal role of the four lipid fractions on DR. However, the study had limited power to detect odds ratios less than 1.23 per SD in genetically induced increase in plasma lipid levels, thus we cannot exclude that causal relationships with more modest effect sizes exist.

SummaryRecent studies in humans and in genetic mouse models have identified Slit- and NTRK-like family (Slitrks) as candidate genes for neuropsychiatric disorders. All Slitrk isotypes are highly expressed in the CNS, where they mediate neurite outgrowth, synaptogenesis, and neuronal survival. However, the molecular mechanisms underlying these functions are not known. Here, we report that Slitrk5 modulates brain-derived neurotrophic factor (BDNF)-dependent biological responses through direct interaction with TrkB receptors. Under basal conditions, Slitrk5 interacts primarily with a transsynaptic binding partner, protein tyrosine phosphatase δ (PTPδ); however, upon BDNF stimulation, Slitrk5 shifts to cis-interactions with TrkB. In the absence of Slitrk5, TrkB has a reduced rate of ligand-dependent recycling and altered responsiveness to BDNF treatment. Structured illumination microscopy revealed that Slitrk5 mediates optimal targeting of TrkB receptors to Rab11-positive recycling endosomes through recruitment of a Rab11 effector protein, Rab11-FIP3. Thus, Slitrk5 acts as a TrkB co-receptor that mediates its BDNF-dependent trafficking and signaling.

We previously reported that Eriobotrya japonica (EJ) improves the cognitive dysfunction caused by amyloid-β (Aβ) peptide injection. Here, we further examined the possible neuroprotective effects and the combined ameliorating effects of EJ and Salvia miltiorrhiza Bunge (SM) in various in vitro and in vivo models. We confirmed the combined effects of a mixture of 5% ethanol extract from EJ leaves (EJE) and water extract from SM roots (SMW) on Aβ1–42-induced toxicity in an in vitro model. Treatment with the mixture (1:1) of EJ and SM (Mix) produced significantly better protection of cells from Aβ-induced toxicity and more strongly suppressed caspase-3 activity compared to treatment with EJE or SMW alone. Additionally, EJE, SMW, and Mix attenuated CoCl2-induced hypoxic damage and corticosterone-induced impairment in SH-SY5Y cells. To examine the combined effects of EJE and SMW in in vivo models, behavioral performance in the Morris water maze was tested two days after injection of Aβ1–42. Administration of Mi...

【This study was carried out to investigate nutritional and physiologically active characterizations of sikhae and the seasoned products from the sea squirt Halocynthia roretzi. The total taste values of sikhae fermented for 4 and 5 days were 10.9 and 15.4, respectively, which was lower than for commercially seasoned sea squirts. The sikhaes contained mostly glutamic and aspartic acids. The total amino acid contents of sikhaes fermented for 4 and 5 days were 5.5 and 6.0 g/100 g, respectively, which were lower than those of commercial seasoned-sea squirts or similar. An amount of 100 g of sikhae and its seasoned products contained P, K, Mg and Fe, and these minerals, which are deemed good for our health, were at 10% above the recommended daily requirements. The functional properties of sikhae fermented for 4 and 5 days were as follows: for ACE inhibiting activity, 69 and 69.5%, respectively; for antioxidative activity, 28.9 and 29.3%, respectively; for xanthine oxidase inhibitory activity, 52.8 and 53.1%, respectively; and for ${\alpha}$ -glucosidase inhibitory activity, 2.4 and 1.4%, respectively. Antimicrobial activity of the 5 day fermented sikhae against Vibrio parahaemolyticus and Staphyloccus aureus was detected in 8 mm and in 7 mm against Escherichia coli.】

Although reading is part and parcel for the development of L2 literacy skills, such as in reading and writing, the skill has been practiced more often...

This study examined the taste, nutritional and functional characterizations of commercial seasoned sea squirt Halocynthia roretzi (CSS). Total taste values of CSS ranged from 7.6 to 69.5 and the major free amino acids were glutamic acid and aspartic acid. Total contents of amino acids in CSS ranged from 5.91 to 7.59 g/100 g and the major amino acids were also glutamic acid and aspartic acid. When taking 100 g of CSS, the minerals that could be expected to have functional health effects (minerals whose levels were above 10% of the recommended daily requirements) were P, Mg and Fe. Other minerals were also present in non-negligible quantities. In terms of the functional properties of CSS, ACE inhibitory activity was 21.2-37.1%, antioxidative activity was 55.4-90.4%, xanthine oxidase inhibitory activity was 52.9-76.6% and -glucosidase inhibitory activity was 0-32%. Antimicrobial activity against Vibrio parahaemolyticus was not detected, but activity against Staphylococcus aureus, groups such as KB, GG, CY, DN, HC and KH, and against Escherichia coli groups such as SF, WD, KB and GG, was detected.

This study investigated the food biochemical characterization of commercial seasoned sea squirt Halocynthia roretzi (CSS). The proximate composition of CSS was 77.2-82.7% moisture, 7.1-9.1% crude protein, 0.3-2.6% crude lipid and 3.5-6.3% ash. Taste compound contents of CSS were 2.3-5.4% salinity (saltiness), 0.42-1.12 g/100 g total acidity (sourness) and 114.9-330.2 mg/100 g amino nitrogen (taste intensity). The Hunter color values of CSS were 23.79-32.50 for lightness, 9.97-20.45 for redness, 14.01-20.96 for yellowness and 64.50-76.63 for color difference. The odor intensity of CSS was 35.0-62.0. According to these results, there were large differences in proximate composition, taste compounds, Hunter color values and odor intensity of CSS. Viable cell counts ranged from 6.20 to 7.69 log (CFU/g), and most of the viable cells comprised of lactic acid-forming bacteria. CSS was not detected in the coliform group.