OPERA-LG: efficient and exact scaffolding of large, repeat-rich eukaryotic genomes with performance guarantees

10.1186/s13059-016-0951-yGenome Biology17110

MicroRNA miR-378 Regulates Nephronectin Expression Modulating Osteoblast Differentiation by Targeting GalNT-7

MicroRNAs (miRNAs) are small fragments of single-stranded RNA containing 18-24 nucleotides, and are generated from endogenous transcripts. MicroRNAs function in post-transcriptional gene silencing by targeting the 3′-untranslated region (UTR) of mRNAs, resulting in translational repression. We have developed a system to study the role of miRNAs in cell differentiation. We have found that one of the miRNAs tested in our system (miR-378, also called miR-378*) plays a role in modulating nephronectin-mediated differentiation in the osteoblastic cell line, MC3T3-E1. Nephronectin is an extracellular matrix protein, and we have demonstrated that its over-expression enhanced osteoblast differentiation and bone nodule formation. Furthermore, we found that the nephronectin 3′-untranslated region (3′UTR) contains a binding site for miR-378. Stable transfection of MC3T3-E1 cells with miR-378 inhibited cell differentiation. MC3T3-E1 cells stably transfected with nephronectin exhibited higher rates of differentiation and nodule formation as compared with cells transfected with nephronectin containing the 3′UTR in the early stages of development, suggesting that endogenous miR-378 is present and active. However, in the later stages of MC3T3-E1 development, the differentiation rates were opposite, with higher rates of differentiation and nodule formation in the cells over-expressing the 3′UTR of nephronectin. This appeared to be the consequence of competition between nephronectin and UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase 7 (GalNAc-T7 or GalNT7) for miR-378 binding, resulting in increased GalNT7 activity, which in turn lead to increased nephronectin glycosylation and product secretion, thereby resulting in a higher rate of osteoblast differentiation

Differential co-expression framework to quantify goodness of biclusters and compare biclustering algorithms

<p>Abstract</p> <p>Background</p> <p>Biclustering is an important analysis procedure to understand the biological mechanisms from microarray gene expression data. Several algorithms have been proposed to identify biclusters, but very little effort was made to compare the performance of different algorithms on real datasets and combine the resultant biclusters into one unified ranking.</p> <p>Results</p> <p>In this paper we propose differential co-expression framework and a differential co-expression scoring function to objectively quantify quality or goodness of a bicluster of genes based on the observation that genes in a bicluster are co-expressed in the conditions belonged to the bicluster and not co-expressed in the other conditions. Furthermore, we propose a scoring function to stratify biclusters into three types of co-expression. We used the proposed scoring functions to understand the performance and behavior of the four well established biclustering algorithms on six real datasets from different domains by combining their output into one unified ranking.</p> <p>Conclusions</p> <p>Differential co-expression framework is useful to provide quantitative and objective assessment of the goodness of biclusters of co-expressed genes and performance of biclustering algorithms in identifying co-expression biclusters. It also helps to combine the biclusters output by different algorithms into one unified ranking i.e. meta-biclustering.</p

Holding Teacher Preparation Accountable: A Review of Claims and Evidence

Teacher preparation has emerged as an acutely politicized and publicized issue in U.S. education policy and practice, and there have been fierce debates about the methods and reasoning behind it. Because of the importance of teachers and teacher education, policy should be driven by the best evidence based on high-quality research. In Holding Teacher Preparation Accountable: A Review of Claims and Evidence, four major national initiatives intended to improve teacher quality by “holding teacher education accountable” for arrangements and outcomes are explored. This policy brief scrutinizes each initiative in light of the research evidence

Predicted contribution of folic acid fortification of corn masa flour to the usual folic acid intake for the US population: National Health and Nutrition Examination Survey 2001–2004

Background: Folic acid can prevent up to 70% of neural tube defects (NTDs) if taken before pregnancy. Compared with other race-ethnicities, Hispanic women have higher rates of NTDs, lower rates of folic acid supplement use, and lower total folic acid intakes. Objective: The objective was to assess potential effects of fortifying corn masa flour with folic acid on Mexican American women and other segments of the US population. Design: A model was developed by using data from the National Health and Nutrition Examination Survey 2001-2004 to estimate the folic acid content in foods containing corn masa flour if fortified at a level of 140 ug folic acid/100 g corn masa flour. Results: Had corn masa flour fortification occurred, we estimated that Mexican American women aged 15-44 y could have increased their total usual daily folic acid intake by 19.9% and non-Hispanic white women by 4.2%. Among the US population, estimated relative percentage increases in total usual daily folic acid intake with corn masa flour fortification were greatest among Mexican Americans (16.8%) and lowest among children aged 1-3 y (2%) and adults aged \u3e51 y (0-0.5%). Conclusion: Analyses suggest that corn masa flour fortification would have effectively targeted Mexican Americans, specifically, Mexican American women, without substantially increasing folic acid intake among other segments of the population. Such increases could reduce the disparity in total folic acid intake between Mexican American and non-Hispanic white women of childbearing age and implies that an additional NTD preventive benefit would be observed for Mexican American women

Mammographic density and ageing:A collaborative pooled analysis of cross-sectional data from 22 countries worldwide

BACKGROUND: Mammographic density (MD) is one of the strongest breast cancer risk factors. Its age-related characteristics have been studied in women in western countries, but whether these associations apply to women worldwide is not known. METHODS AND FINDINGS: We examined cross-sectional differences in MD by age and menopausal status in over 11,000 breast-cancer-free women aged 35-85 years, from 40 ethnicity- and location-specific population groups across 22 countries in the International Consortium on Mammographic Density (ICMD). MD was read centrally using a quantitative method (Cumulus) and its square-root metrics were analysed using meta-analysis of group-level estimates and linear regression models of pooled data, adjusted for body mass index, reproductive factors, mammogram view, image type, and reader. In all, 4,534 women were premenopausal, and 6,481 postmenopausal, at the time of mammography. A large age-adjusted difference in percent MD (PD) between post- and premenopausal women was apparent (-0.46 cm [95% CI: -0.53, -0.39]) and appeared greater in women with lower breast cancer risk profiles; variation across population groups due to heterogeneity (I2) was 16.5%. Among premenopausal women, the √PD difference per 10-year increase in age was -0.24 cm (95% CI: -0.34, -0.14; I2 = 30%), reflecting a compositional change (lower dense area and higher non-dense area, with no difference in breast area). In postmenopausal women, the corresponding difference in √PD (-0.38 cm [95% CI: -0.44, -0.33]; I2 = 30%) was additionally driven by increasing breast area. The study is limited by different mammography systems and its cross-sectional rather than longitudinal nature. CONCLUSIONS: Declines in MD with increasing age are present premenopausally, continue postmenopausally, and are most pronounced over the menopausal transition. These effects were highly consistent across diverse groups of women worldwide, suggesting that they result from an intrinsic biological, likely hormonal, mechanism common to women. If cumulative breast density is a key determinant of breast cancer risk, younger ages may be the more critical periods for lifestyle modifications aimed at breast density and breast cancer risk reduction

Assessment of motor functioning in the preschool period

The assessment of motor functioning in young children has become increasingly important in recent years with the acknowledgement that motor impairment is linked with cognitive, language, social and emotional difficulties. However, there is no one gold standard assessment tool to investigate motor ability in children. The aim of the current paper was to discuss the issues related to the assessment of motor ability in young pre-school children and to provide guidelines on the best approach for motor assessment. The paper discusses the maturational changes in brain development at the preschool level in relation to motor ability. Other issues include sex differences in motor ability at this young age, and evidence for this in relation to sociological versus biological influences. From the previous literature it is unclear what needs to be assessed in relation to motor functioning. Should the focus be underlying motor processes or movement skill assessment? Several key assessment tools are discussed that produce a general measure of motor performance followed by a description of tools that assess specific skills, such as fine and gross motor, ball and graphomotor skills. The paper concludes with recommendations on the best approach in assessing motor function in pre-school children

Thymic stromal lymphopoietin fosters human breast tumor growth by promoting type 2 inflammation

TSLP released from human breast cancer cells promotes OX40L expression on DCs, and these OX40L-expressing DCs drive development of inflammatory Th2 cells which promote breast tumor development

MicroRNA miR-328 Regulates Zonation Morphogenesis by Targeting CD44 Expression

Morphogenesis is crucial to initiate physiological development and tumor invasion. Here we show that a microRNA controls zonation morphogenesis by targeting hyaluronan receptor CD44. We have developed a novel system to study microRNA functions by generating constructs expressing pre-miRNAs and mature miRNAs. Using this system, we have demonstrated that expression of miR-328 reduced cell adhesion, aggregation, and migration, and regulated formation of capillary structure. Protein analysis indicated that miR-328 repressed CD44 expression. Activities of luciferase constructs harboring the target site in CD44, but not the one containing mutation, were repressed by miR-328. Zonation morphogenesis appeared in cells transfected by miR-328: miR-328-transfected cells were present on the surface of zonating structures while the control cells stayed in the middle. MiR-328-mediated CD44 actions was validated by anti-CD44 antibody, hyaluronidase, CD44 siRNA, and CD44 expression constructs. In vivo experiments showed that CD44-silencing cells appeared as layers on the surfaces of nodules or zonating structures. Immuno-histochemistry also exhibited CD44-negative cells on the surface layers of normal rat livers and the internal zones of Portal veins. Our results demonstrate that miR-328 targets CD44, which is essential in regulating zonation morphogenesis: silencing of CD44 expression is essential in sealing the zonation structures to facilitate their extension and to inhibit complex expansion