HOXA10 controls osteoblastogenesis by directly activating bone regulatory and phenotypic genes

HOXA10 is necessary for embryonic patterning of skeletal elements, but its function in bone formation beyond this early developmental stage is unknown. Here we show that HOXA10 contributes to osteogenic lineage determination through activation of Runx2 and directly regulates osteoblastic phenotypic genes. In response to bone morphogenic protein BMP2, Hoxa10 is rapidly induced and functions to activate the Runx2 transcription factor essential for bone formation. A functional element with the Hox core motif was characterized for the bone-related Runx2 P1 promoter. HOXA10 also activates other osteogenic genes, including the alkaline phosphatase, osteocalcin, and bone sialoprotein genes, and temporally associates with these target gene promoters during stages of osteoblast differentiation prior to the recruitment of RUNX2. Exogenous expression and small interfering RNA knockdown studies establish that HOXA10 mediates chromatin hyperacetylation and trimethyl histone K4 (H3K4) methylation of these genes, correlating to active transcription. HOXA10 therefore contributes to early expression of osteogenic genes through chromatin remodeling. Importantly, HOXA10 can induce osteoblast genes in Runx2 null cells, providing evidence for a direct role in mediating osteoblast differentiation independent of RUNX2. We propose that HOXA10 activates RUNX2 in mesenchymal cells, contributing to the onset of osteogenesis, and that HOXA10 subsequently supports bone formation by direct regulation of osteoblast phenotypic genes. <br/

Relationships of attitudes toward homework and time spent on homework to course outcomes: The case of foreign language learning

In previous studies of homework in core academic subjects, positive student attitudes toward homework were linked to higher achievement, whereas time spent on homework showed an inconsistent relationship with achievement. This study examined the generalizability of these findings to foreign language learning by analyzing 2,342 adult students' attitudes toward assigned homework, time spent on assigned homework, and achievement outcomes in a variety of foreign language courses. Student ratings of the relevance of homework, the usefulness of feedback provided on homework, and the fairness of homework grading were positively correlated with teacher-assigned grades and standardized proficiency test scores in listening, reading, and speaking. Reported time spent on homework, however, was negatively correlated with these measures. In hierarchical regression analyses, all homework-related variables emerged as significant predictors of outcomes after controlling for potential covariates such as language learning aptitude, demographic variables, and affective factors. Thus, these results provide evidence that language course outcomes are positively associated with attitudes toward homework but negatively associated with time spent on homework. Possible interpretations of these findings are discussed. We suggest that the negative association follows in part from the opportunity cost of time spent on assigned homework, which decreases time spent on individualized study that may be more beneficial for improving language course outcomes

Thinking Outside The Box : The Potential of Management Training for Reducing Turnover in Warehouse/Distribution Environments

Avoidable turnover is a costly issue for firms, particularly in the warehousing industry. Retaining workers is an important priority which allows firms to meet complex and demanding customer service requirements. Distribution tasks such as order processing and fulfillment are highly labor intensive and further add to the cost of turnover. Increasing order volumes also tax firms operating within a growing e-commerce economy. A sustainable solution is needed for the avoidable turnover problem in such firms. By encouraging management development programs for first line managers through coaching it is expected that the avoidable turnover rates can be reduced effectively. The theory of human resource devolution links strategic policy to employee practices by using line managers as HR implementers. Through the targeted training of line managers firms will be able to reach more of their low-level employees, increasing job embedment, job satisfaction, organizational commitment, and eventually retention rates. Several cases studies are reviewed, consisting of exploratory research on management training in warehouses as well as the barriers that improved human resource devolution currently faces. An applied case study from the Mayo Clinic is also referenced, concerning the implementation of a management training program in response to the high turnover rate of its medical staff. The literature review acknowledges the relatively new nature of its topic. Further research can be done, especially in the warehousing sector where there is both the potential for additional scholarship and a financial need to find cost effective solutions to the problem. Keywords: warehouse, first line manager, management coaching, training, development, turnover, retention, distribution, logistics, HR devolution, management training program, avoidable turnover, leader member exchange, Attraction Selection Attrition Framework, strategic human resources, leadershi

The unconventional myosin CRINKLED and its mammalian orthologue MYO7A regulate caspases in their signalling roles

Caspases provide vital links in non-apoptotic regulatory networks controlling inflammation, compensatory proliferation, morphology and cell migration. How caspases are activated under non-apoptotic conditions and process a selective set of substrates without killing the cell remain enigmatic. Here we find that the Drosophila unconventional myosin CRINKLED (CK) selectively interacts with the initiator caspase DRONC and regulates some of its non-apoptotic functions. Loss of CK in the arista, border cells or proneural clusters of the wing imaginal discs affects DRONC-dependent patterning. Our data indicate that CK acts as substrate adaptor, recruiting SHAGGY46/GSK3-β to DRONC, thereby facilitating caspase-mediated cleavage and localized modulation of kinase activity. Similarly, the mammalian CK counterpart, MYO7A, binds to and impinges on CASPASE-8, revealing a new regulatory axis affecting receptor interacting protein kinase-1 (RIPK1)>CASPASE-8 signalling. Together, our results expose a conserved role for unconventional myosins in transducing caspase-dependent regulation of kinases, allowing them to take part in specific signalling events

Alcohol exposure during late gestation: Multiple developmental outcomes in sheep

Alcohol consumption during pregnancy remains common in many countries. Exposure to even low amounts of alcohol (i.e. ethanol) in pregnancy can lead to the heterogeneous fetal alcohol spectrum disorders (FASD), while heavy alcohol consumption can result in the fetal alcohol syndrome (FAS). FAS is characterized by cerebral dysfunction, growth restriction and craniofacial malformations. However, the effects of lower doses of alcohol during pregnancy, such as those that lead to FASD, are less well understood. In this article, we discuss the findings of recent studies performed in our laboratories on the effects of fetal alcohol exposure using sheep, in which we investigated the effects of late gestational alcohol exposure on the developing brain, arteries, kidneys, heart and lungs. Our studies indicate that alcohol exposure in late gestation can (1) affect cerebral white matter development and increase the risk of hemorrhage in the fetal brain, (2) cause left ventricular hypertrophy with evidence of altered cardiomyocyte maturation, (3) lead to a decrease in nephron number in the kidney, (4) cause altered arterial wall stiffness and endothelial and smooth muscle function and (5) result in altered surfactant protein mRNA expression, surfactant phospholipid composition and pro-inflammatory cytokine mRNA expression in the lung. These findings suggest that fetal alcohol exposure in late gestation can affect multiple organs, potentially increasing the risk of disease and organ dysfunction in later life

Peer interaction in text chat: Qualitative analysis of chat transcripts

Prior research has shown that intermediate-level adult learners of Russian who worked interactively with partners using text chat improved their vocabulary and oral production skills more than students who worked independently (Tare et al., 2014). Drawing on the dataset from Tare et al. (2014), the current study follows up to explore the nature of the students’ (N = 25) interactions during the text chat activities to determine potential sources of the gains. All 18 activities developed for the study encouraged interaction to complete tasks in pairs. A detailed coding of 169 text chat transcripts examined instances of peer–peer interactions. Our quantitative and qualitative analyses explored whether and to what extent real-time interactive language tasks foster the kinds of language-related moves that may support greater language learning. Results show that students spontaneously engaged in various behaviors which may support language learning, such as providing language-related assistance (self- and peer-correction, negotiation for meaning), using their partner as a resource (for clarifying information, modeling language use, or helping with unknown vocabulary), and providing encouragement (responding positively to the task and to each other, eliciting information from a partner). The most frequent instances were of positive affect, self-correction, and partner correction

Drosophila Adult Eye Model to Teach Scanning Electron Microscopy in an Undergraduate Cell Biology Laboratory

We have devised an undergraduate laboratory exercise to study tissue morphology using fruit fly, Drosophila melanogaster, as the model organism. Drosophila can be reared in a cost effective manner in a short period of time. This experiment was a part of the undergraduate curriculum of the cell biology laboratory course aimed to demonstrate the use of scanning electron microscopy (SEM) technique to study the morphology of adult eye of Drosophila. The adult eye of Drosophila is a compound eye, which comprises of 800 unit eyes, and serves as an excellent model for SEM studies. We used flies that were mutant for lobe (L), eyeless (ey), and pannier (pnr) for our studies. The mutant flies exhibit different morphologies of the adult eye. We employed a modified protocol, which reduces sample preparation steps and makes it practically feasible to complete the protocol in assigned time for the cell biology laboratory. The idea of this laboratory exercise is to: (a) familiarize students with the underlying principles of scanning electron microscopy and its application to diverse areas of research, (b) to enable students to sharpen their observation and quantitative microscopy skills, and (c) minimize the preparation time for the instructor

A cartilage tissue engineering approach combining starch-polycaprolactone fibre mesh scaffolds with bovine articular chondrocytes

In the present work we originally tested the suitability of corn starch-polycaprolactone (SPCL) scaffolds for pursuing a cartilage tissue engineering approach. Bovine articular chondrocytes were seeded on SPCL scaffolds under dynamic conditions using spinner flasks (total of 4 scaffolds per spinner flask using cell suspensions of 0.5×106 cells/ml) and cultured under orbital agitation for a total of 6 weeks. Poly(glycolic acid) (PGA) non-woven scaffolds and bovine native articular cartilage were used as standard controls for the conducted experiments. PGA is a kind of standard in tissue engineering approaches and it was used as a control in that sense. The tissue engineered constructs were characterized at different time periods by scanning electron microscopy (SEM), hematoxylin-eosin (H&E) and toluidine blue stainings, immunolocalisation of collagen types I and II, and dimethylmethylene blue (DMB) assay for glycosaminoglycans (GAG) quantification assay. SEM results for SPCL constructs showed that the chondrocytes presented normal morphological features, with extensive cells presence at the surface of the support structures, and penetrating the scaffolds pores. These observations were further corroborated by H&E staining. Toluidine blue and immunohistochemistry exhibited extracellular matrix deposition throughout the 3D structure. Glycosaminoglycans, and collagen types I and II were detected. However, stronger staining for collagen type II was observed when compared to collagen type I. The PGA constructs presented similar features toSPCLat the end of the 6 weeks. PGA constructs exhibited higher amounts of matrix glycosaminoglycans when compared to the SPCL scaffolds. However, we also observed a lack of tissue in the central area of the PGA scaffolds. Reasons for these occurrences may include inefficient cells penetration, necrosis due to high cell densities, or necrosis related with acidic by-products degradation. Such situation was not detected in the SPCL scaffolds, indicating the much better biocompatibility of the starch based scaffolds

Vitamin D prevents endothelial progenitor cell dysfunction induced by sera from women with preeclampsia or conditioned media from hypoxic placenta

Context: Placenta-derived circulating factors contribute to the maternal endothelial dysfunction underlying preeclampsia. Endothelial colony forming cells (ECFC), a sub-population of endothelial progenitor cells (EPCs), are thought to be involved in vasculogenesis and endothelial repair. Low vitamin D concentrations are associated with an increased risk for preeclampsia. Objective: We hypothesized that the function of human fetal ECFCs in culture would be suppressed by exposure to preeclampsia-related factors-preeclampsia serum or hypoxic placental conditioned medium- in a fashion reversed by vitamin D. Design, Setting, Patients: ECFCs were isolated from cord blood of uncomplicated pregnancies and expanded in culture. Uncomplicated pregnancy villous placenta in explant culture were exposed to either 2% (hypoxic), 8% (normoxic) or 21% (hyperoxic) O2 for 48 h, after which the conditioned media (CM) was collected. Outcome Measures: ECFC tubule formation (Matrigel assay) and migration were examined in the presence of either maternal serum from preeclampsia cases or uncomplicated pregnancy controls, or pooled CM, in the presence or absence of 1,25(OH)2 vitamin D3. Results: 1,25(OH)2 vitamin D3 reversed the adverse effects of preeclampsia serum or CM from hypoxic placenta on ECFCs capillary-tube formation and migration. Silencing of VDR expression by VDR siRNA, VDR blockade, or VEGF pathway blockade reduced ECFC functional abilities. Effects of VDR or VEGF blockade were partially prevented by vitamin D. Conclusion: Vitamin D promotes the capillary-like tubule formation and migration of ECFCs in culture, minimizing the negative effects of exposure to preeclampsia-related factors. Further evaluation of the role of vitamin D in ECFC regulation and preeclampsia is warranted. © 2014 Brodowski et al