Fine-Scale Mapping of the 4q24 Locus Identifies Two Independent Loci Associated with Breast Cancer Risk

Background: A recent association study identified a common variant (rs9790517) at 4q24 to be associated with breast cancer risk. Independent association signals and potential functional variants in this locus have not been explored. Methods: We conducted a fine-mapping analysis in 55,540 breast cancer cases and 51,168 controls from the Breast Cancer Association Consortium. Results: Conditional analyses identified two independent association signals among women of European ancestry, represented by rs9790517 [conditional P = 2.51 × 10−4; OR, 1.04; 95% confidence interval (CI), 1.02–1.07] and rs77928427 (P = 1.86 × 10−4; OR, 1.04; 95% CI, 1.02–1.07). Functional annotation using data from the Encyclopedia of DNA Elements (ENCODE) project revealed two putative functional variants, rs62331150 and rs73838678 in linkage disequilibrium (LD) with rs9790517 (r2 ≥ 0.90) residing in the active promoter or enhancer, respectively, of the nearest gene, TET2. Both variants are located in DNase I hypersensitivity and transcription factor–binding sites. Using data from both The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC), we showed that rs62331150 was associated with level of expression of TET2 in breast normal and tumor tissue. Conclusion: Our study identified two independent association signals at 4q24 in relation to breast cancer risk and suggested that observed association in this locus may be mediated through the regulation of TET2. Impact: Fine-mapping study with large sample size warranted for identification of independent loci for breast cancer risk

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Parenting and Children's Socioemotional and Academic Development among White, Latino, Asian, and Black families

ABSTRACT OF THE DISSERTATIONParenting and Children's Socioemotional and Academic Development among White, Latino, Asian, and Black familiesByHannah S. KangDoctor of Philosophy in Psychology and Social BehaviorUniversity of California, Irvine 2014Professor Chuansheng Chen, ChairA large body of research has demonstrated the crucial role of parenting in children's socioemotional and academic development (Maccoby &amp; Martin, 1983). This literature, however, has major limitations in the following three aspects: sample representativeness, consideration of cultural differences, and bidirectional effects of parenting and child behaviors. Using a nationally representative sample (N = 20,203) from the Early Childhood Longitudinal Study, Kindergarten Class of 1998-1999 (ECLS-K), the current study explored associations between three aspects parenting (i.e., parental warmth, parental expectations, and corporal punishment) and child outcomes among White, Asian, Latino, and Black families. The study also examined bidirectional relationships between parenting dimensions and child outcomes across Kindergarten, 1st, 3rd, and 5th grades. The sample consisted of 58% White (N = 11,788), 16% Black (N = 3,224), 19% Latino (N = 3,826), and 7% Asian (N = 1,365) children. The mean age of the participants when they were in Kindergarten was 5.44 years, and gender was approximately evenly split (female = 49%, male = 51%). Cross-lagged analyses were conducted to examine bidirectional (longitudinal) associations between parenting dimensions and child academic and socioemotional outcomes. Multiple group comparisons were used to test hypotheses about ethnic and developmental differences in those associations. Results indicated that, for the total sample, positive parenting (parent warmth, positive parent evaluation, and not using corporal punishment) was associated with higher academic achievement and better socioemotional development both cross-sectionally and longitudinally. There were significant ethnic differences in child outcomes and parenting measures. Asians and Whites showed better academic outcomes than Latinos, who in turn showed better academic outcomes than did Blacks. Asians also showed better socioemotional outcomes (i.e., fewer internalizing and externalizing problems) than Whites and Latinos, who in turn showed better socioemotional outcomes than did Blacks. In terms of parenting, White parents showed the highest level of warmth, Asian parents the highest level of expectations/evaluations, and Blacks the most frequent corporal punishment. In terms of the associations between parenting and child outcomes, parental warmth was more important for the socioemotional outcomes of White and Black children than it was case for Asian and Latino children. Parental evaluation was generally more important for White students' outcomes than for those of Blacks, Latinos, and Asians. One possible explanation for this result lies in cultural differences in parent-child communication patterns. For example, White parents have been found to be more likely than minority parents such as Asian Americans to communicate their expectations directly and verbally. Finally, corporal punishment was associated with negative outcomes to a greater extent for White students than for others. In fact, with one exception, the association between spanking and negative academic child outcomes was nonsignificant for Asians, suggesting that spanking may be culturally accepted among Asians by both the parents and the child. Taken together, the findings indicated that it is important to consider the role of culture in parenting and children's academic and socioemotional development

Locus of control and peer relationships among Caucasian, Hispanic, Asian, and African American adolescents.

Past research has shown that locus of control plays an important role in a wide range of behaviors, such as academic achievement and positive social behaviors. However, little is known about whether locus of control plays the same role in minority adolescents' peer relationships. The current study examined ethnic differences in the associations between locus of control and peer relationships in early adolescence using samples from the Early Childhood Longitudinal Study (ECLS-K: 5,612 Caucasian, 1,562 Hispanic, 507 Asian, and 908 African-American adolescents) and the National Education Longitudinal Study (NELS: 8,484 Caucasian, 1,604 Hispanic, and 860 Asian, and 1,228 African American adolescents). Gender was approximately evenly split in both samples. The results from the two datasets were highly consistent. Significant interactions between ethnicity and locus of control indicated that having a more internal locus of control was particularly important for Caucasian students' peer relationships (ECLS-K) and social status (NELS), but less so for Asian, Hispanic, and African American students. Our findings suggest that the role of locus of control in peer relationship is contingent upon culture

1,5-Anhydroglucitol as a Useful Marker for Assessing Short-Term Glycemic Excursions in Type 1 Diabetes

BackgroundType 1 diabetes is associated with more severe glycemic variability and more frequent hypoglycemia than type 2 diabetes. Glycemic variability is associated with poor glycemic control and diabetic complications. In this study, we demonstrate the clinical usefulness of serum 1,5-anhydroglucitol (1,5-AG) for assessing changes in glycemic excursion in type 1 diabetes.MethodsSeventeen patients with type 1 diabetes were enrolled in this study. A continuous glucose monitoring system (CGMS) was applied twice at a 2-week interval to evaluate changes in glycemic variability. The changes in serum glycemic assays, including 1,5-AG, glycated albumin and hemoglobin A1c (HbA1c), were also evaluated.ResultsMost subjects showed severe glycemic excursions, including hypoglycemia and hyperglycemia. The change in 1,5-AG level was significantly correlated with changes in the glycemic excursion indices of the standard deviation (SD), mean amplitude of glucose excursion (MAGE), lability index, mean postmeal maximum glucose, and area under the curve for glucose above 180 mg/dL (r=-0.576, -0.613, -0.600, -0.630, and -0.500, respectively; all P<0.05). Changes in glycated albumin were correlated with changes in SD and MAGE (r=0.495 and 0.517, respectively; all P<0.05). However, changes in HbA1c were not correlated with any changes in the CGMS variables.Conclusion1,5-AG may be a useful marker for the assessment of short-term changes in glycemic variability. Furthermore, 1,5-AG may have clinical implications for the evaluation and treatment of glycemic excursions in type 1 diabetes

Site-Specific Transition Metal Occupation in Multicomponent Pyrophosphate for Improved Electrochemical and Thermal Properties in Lithium Battery Cathodes: A Combined Experimental and Theoretical Study

As an attempt to develop lithium ion batteries with excellent performance, which is desirable for a variety of applications including mobile electronics, electrical vehicles, and utility grids, the battery community has continuously pursued cathode materials that function at higher potentials with efficient kinetics for lithium insertion and extraction. By employing both experimental and theoretical tools, herein we report multicomponent pyrophosphate (Li2MP2O7, M = Fe1/3Mn1/3Co1/3) cathode materials with novel and advantageous properties as compared to the single-component analogues and other multicomponent polyanions. Li(2)Fei(1/3)Mn(1/3)Co(1/3)P(2)O(7) is formed on the basis of a solid solution among the three individual transition-metal-based pyrophosphates. The unique crystal structure of pyrophosphate and the first principles calculations show that different transition metals have a tendency to preferentially occupy either octahedral or pyramidal sites, and this site-specific transition metal occupation leads to significant improvements in various battery properties: a single-phase mode for Li insertion/extraction, improved cell potentials for Fe2+/Fe3+ (raised by 0.18 eV) and Co2+/Co3+ (lowered by 0.26 eV), and increased activity for Mn2+/Mn3+ with significantly reduced overpotential. We reveal that the favorable energy of transition metal mixing and the sequential redox reaction for each TM element with a sufficient redox gap is the underlying physical reason for the preferential single-phase mode of Li intercalation/deintercalation reaction in pyrophosphate, a general concept that can be applied to other multicomponent systems. Furthermore, an extremely small volume change of similar to 0.7% between the fully charged and discharged states and the significantly enhanced thermal stability are observed for the present material, the effects unseen in previous multicomponent battery materials.

Balsamic Vinegar Improves High Fat-Induced Beta Cell Dysfunction via Beta Cell ABCA1

BackgroundThe aim of this study was to investigate the effects of balsamic vinegar on β-cell dysfunction.MethodsIn this study, 28-week-old Otsuka Long-Evans Tokushima Fatty (OLETF) rats were fed a normal chow diet or a high-fat diet (HFD) and were provided with tap water or dilute balsamic vinegar for 4 weeks. Oral glucose tolerance tests and histopathological analyses were performed thereafter.ResultsIn rats fed both the both chow diet and the HFD, the rats given balsamic vinegar showed increased insulin staining in islets compared with tap water administered rats. Balsamic vinegar administration also increased β-cell ATP-binding cassette transporter subfamily A member 1 (ABCA1) expression in islets and decreased cholesterol levels.ConclusionThese findings provide the first evidence for an anti-diabetic effect of balsamic vinegar through improvement of β-cell function via increasing β-cell ABCA1 expression