Association of single nucleotide polymorphisms in the endothelial differentiation sphingolipid G-protein-coupled receptor 1 gene with marbling in Japanese Black beef cattle

Marbling defined by the amount and distribution of intramuscular fat, so-called Shimofuri , is an economically important trait of beef cattle in Japan. The endothelial differentiation sphingolipid G-protein-coupled receptor 1 ( EDG1 ) gene, involved in blood vessel formation, has been previously shown to be expressed at different levels in musculus longissimus muscle between low-marbled and high-marbled steer groups. It is located within the genomic region of a quantitative trait locus for marbling, and thus was considered as a positionally functional candidate for the gene responsible for marbling. In this study, two single nucleotide polymorphisms (SNPs) in the 5' untranslated region (UTR) and the 3' UTR of EDG1 , referred to as c. - 312A>G and c.*446G>A , respectively, were detected between the two steer groups. The two SNPs were associated with the predicted breeding value for beef marbling standard number by analyses using a population of Japanese Black beef cattle. The effect of genotypes at each of the SNPs on the predicted breeding value for subcutaneous fat thickness was not statistically significant ( P  >   0.05). Reporter gene assays revealed no significant differences in gene expression between alleles at each of the SNPs. These findings suggest that EDG1 SNPs, although they may not be regarded as a causal mutation, may be useful for effective marker-assisted selection to increase the levels of marbling in Japanese Black beef cattle.     

Mitochondrial Profiling of Acute Myeloid Leukemia in the Assessment of Response to Apoptosis Modulating Drugs

BH3 profiling measures the propensity of transformed cells to undergo intrinsic apoptosis and is determined by exposing cells to BH3-mimicking peptides. We hypothesized that basal levels of prosurvival BCL-2 family proteins may modulate the predictive power of BH3 profiling and termed it mitochondrial profiling. We investigated the correlation between cell sensitivity to apoptogenic agents and mitochondrial profiling, using a panel of acute myeloid leukemias induced to undergo apoptosis by exposure to cytarabine, the BH3 mimetic ABT-199, the MDM2 inhibitor Nutlin-3a, or the CRM1 inhibitor KPT-330. We found that the apoptogenic efficacies of ABT-199 and cytarabine correlated well with BH3 profiling reflecting BCL2, but not BCL-XL or MCL-1 dependence. Baseline BCL-2 protein expression analysis increased the ability of BH3 profiling to predict resistance mediated by MCL-1. By utilizing engineered cells with overexpression or knockdown of BCL-2 family proteins, Ara-C was found to be independent, while ABT-199 was dependent on BCL-XL. BCL-2 and BCL-XL overexpression mediated resistance to KPT-330 which was not reflected in the BH3 profiling assay, or in baseline BCL-2 protein levels. In conclusion, mitochondrial profiling, the combination of BH3 profiling and prosurvival BCL-2 family protein analysis, represents an improved approach to predict efficacy of diverse agents in AML and may have utility in the design of more effective drug combinations.     

Distribution of Posterior Corneal Astigmatism According to Axis Orientation of Anterior Corneal Astigmatism

Purpose

To investigate the distribution of posterior corneal astigmatism in eyes with with-the-rule (WTR) and against-the-rule (ATR) anterior corneal astigmatism.

Methods

We retrospectively examined six hundred eight eyes of 608 healthy subjects (275 men and 333 women; mean age ± standard deviation, 55.3 ± 20.2 years). The magnitude and axis orientation of anterior and posterior corneal astigmatism were determined with a rotating Scheimpflug system (Pentacam HR, Oculus) when we divided the subjects into WTR and ATR anterior corneal astigmatism groups.

Results

The mean magnitudes of anterior and posterior corneal astigmatism were 1.14 ± 0.76 diopters (D), and 0.37 ± 0.19 D, respectively. We found a significant correlation between the magnitudes of anterior and posterior corneal astigmatism (Pearson correlation coefficient r = 0.4739, P<0.001). In the WTR anterior astigmatism group, we found ATR astigmatism of the posterior corneal surface in 402 eyes (96.6%). In the ATR anterior astigmatism group, we found ATR posterior corneal astigmatism in 82 eyes (73.9%). Especially in eyes with ATR anterior corneal astigmatism of 1 D or more and 1.5 D or more, ATR posterior corneal astigmatism was found in 28 eyes (59.6%) and 9 eyes (42.9%), respectively.

Conclusions

WTR anterior astigmatism and ATR posterior astigmatism were found in approximately 68% and 91% of eyes, respectively. The magnitude and the axis orientation of posterior corneal astigmatism were not constant, especially in eyes having high ATR anterior corneal astigmatism, as is often the case in patients who have undergone toric IOL implantation.     

Developmental Trajectories of Social Skills during Early Childhood and Links to Parenting Practices in a Japanese Sample

This study used data from a nationwide survey in Japan to model the developmental course of social skills during early childhood. The goals of this study were to identify longitudinal profiles of social skills between 2 and 5 years of age using a group-based trajectory approach, and to investigate whether and to what extent parenting practices at 2 years of age predicted developmental trajectories of social skills during the preschool period. A relatively large sample of boys and girls (N > 1,000) was assessed on three social skill dimensions (Cooperation, Self-control, and Assertion) at four time points (ages 2, 3, 4, and 5), and on four parenting practices (cognitive and emotional involvement, avoidance of restriction and punishment, social stimulation, and social support for parenting) at age 2. The results indicated that for each social skill dimension, group-based trajectory models identified three distinct trajectories: low, moderate, and high. Multinomial regression analysis revealed that parenting practice variables showed differential contributions to development of child social skills. Specifically, Cooperation and Assertion were promoted by cognitive and emotional involvement, Self-control by social stimulation, and Assertion by avoidance of restriction and punishment. Abundant social support for parenting was not associated with higher child social skills trajectories. We found heterogeneity in developmental profiles of social skills during the preschool ages, and we identified parenting practices that contributed to different patterns of social skills development. We discussed the implications of higher-quality parenting practices on the improvement of child social skills across early childhood.     

IL-38: A new factor in rheumatoid arthritis

The newly characterized cytokine IL-38 (IL-1F10) belongs to the IL-1 family of cytokines. Previous work has demonstrated that IL-38 inhibited Candida albicans-induced IL-17 production from peripheral blood mononuclear cells. However, it is still unclear whether IL-38 is an inflammatory or an anti-inflammatory cytokine. We generated anti-human IL-38 monoclonal antibodies in order to perform immunohistochemical staining and an enzyme-linked immunosorbent assay. While human recombinant IL-38 protein was not cleaved by recombinant caspase-1, chymase, or PR3 in vitro, overexpression of IL-38 cDNA produced a soluble form of IL-38 protein. Furthermore, immunohistochemical analysis showed that synovial tissues obtained from RA patients strongly expressed IL-38 protein. To investigate the biological role of IL-38, C57BL/6 IL-38 gene-deficient (^?/?) mice were used in an autoantibody-induced rheumatoid arthritis (RA) mouse model. As compared with control mice, IL-38 ^(?/?) mice showed greater disease severity, accompanied by higher IL-1β and IL-6 gene expression in the joints. Therefore, IL-38 acts as an inhibitor of the pathogenesis of autoantibody-induced arthritis in mice and may have a role in the development or progression of RA in humans.     

Phase II enzyme induction by a carotenoid,lutein, in a PC12D neuronal cell line

The mechanism by which lutein, a carotenoid, acts as an antioxidant in retinal cells is still not fully understood. Here, lutein treatment of a neuronal cell line (PC12D) immediately resulted in reduced intracellular ROS levels, implying that it has a direct role in ROS scavenging. Significantly, lutein treatment also induced phase II antioxidative enzyme expression, probably via a nuclear factor-like 2 (Nrf2) independent pathway. This latter mechanism could explain why lutein acts diversely to protect against oxidative/cytotoxic stress, and why it is physiologically involved in the human neural tissue, such as the retina.     

Polyphenol‐solubility alters amyloid fibril formation of α‐synuclein

Amyloid fibril formation is associated with various amyloidoses, including neurodegenerative diseases such as Alzheimer''s and Parkinson''s diseases. Amyloid fibrils form above the solubility of amyloidogenic proteins or peptides upon breaking supersaturation, followed by a nucleation and elongation mechanism, which is similar to the crystallization of solutes. Many additives, including salts, detergents, and natural compounds, promote or inhibit amyloid formation. However, the underlying mechanisms of the opposing effects are unclear. We examined the effects of two polyphenols, that is, epigallocatechin gallate (EGCG) and kaempferol‐7─O─glycoside (KG), with high and low solubilities, respectively, on the amyloid formation of α‐synuclein (αSN). EGCG and KG inhibited and promoted amyloid formation of αSN, respectively, when monitored by thioflavin T (ThT) fluorescence or transmission electron microscopy (TEM). Nuclear magnetic resonance (NMR) analysis revealed that, although interactions of αSN with soluble EGCG increased the solubility of αSN, thus inhibiting amyloid formation, interactions of αSN with insoluble KG reduced the solubility of αSN, thereby promoting amyloid formation. Our study suggests that opposing effects of polyphenols on amyloid formation of proteins and peptides can be interpreted based on the solubility of polyphenols.