An in vitro stem cell model of human epiblast and yolk sac interaction.

Human embryogenesis entails complex signalling interactions between embryonic and extra-embryonic cells. However, how extra-embryonic cells direct morphogenesis within the human embryo remains largely unknown due to a lack of relevant stem cell models. Here, we have established conditions to differentiate human pluripotent stem cells (hPSCs) into yolk sac-like cells (YSLCs) that resemble the post-implantation human hypoblast molecularly and functionally. YSLCs induce the expression of pluripotency and anterior ectoderm markers in human embryonic stem cells (hESCs) at the expense of mesoderm and endoderm markers. This activity is mediated by the release of BMP and WNT signalling pathway inhibitors, and, therefore, resembles the functioning of the anterior visceral endoderm signalling centre of the mouse embryo, which establishes the anterior-posterior axis. Our results implicate the yolk sac in epiblast cell fate specification in the human embryo and propose YSLCs as a tool for studying post-implantation human embryo development in vitro.</i

Keeping an eye on noisy movements: On different approaches to perceptual-motor skill research and training

Contemporary theorising on the complementary nature of perception and action in expert performance has led to the emergence of different emphases in studying movement coordination and gaze behaviour. On the one hand, coordination research has examined the role that variability plays in movement control, evidencing that variability facilitates individualised adaptations during both learning and performance. On the other hand, and at odds with this principle, the majority of gaze behaviour studies have tended to average data over participants and trials, proposing the importance of universal 'optimal' gaze patterns in a given task, for all performers, irrespective of stage of learning. In this article, new lines of inquiry are considered with the aim of reconciling these two distinct approaches. The role that inter- and intra-individual variability may play in gaze behaviours is considered, before suggesting directions for future research

The C-Terminal Domain of the Novel Essential Protein Gcp Is Critical for Interaction with Another Essential Protein YeaZ of Staphylococcus aureus

Previous studies have demonstrated that the novel protein Gcp is essential for the viability of various bacterial species including Staphylococcus aureus; however, the reason why it is required for bacterial growth remains unclear. In order to explore the potential mechanisms of this essentiality, we performed RT-PCR analysis and revealed that the gcp gene (sa1854) was co-transcribed with sa1855, yeaZ (sa1856) and sa1857 genes, indicating these genes are located in the same operon. Furthermore, we demonstrated that Gcp interacts with YeaZ using a yeast two-hybrid (Y2H) system and in vitro pull down assays. To characterize the Gcp-YeaZ interaction, we performed alanine scanning mutagenesis on the residues of C-terminal segment of Gcp. We found that the mutations of the C-terminal Y317-F322 region abolished the interaction of Gcp and YeaZ, and the mutations of the D324-N329 and S332-Y336 regions alleviated Gcp binding to YeaZ. More importantly, we demonstrated that these key regions of Gcp are also necessary for the bacterial survival since these mutated Gcp could not complement the depletion of endogenous Gcp. Taken together, our data suggest that the interaction of Gcp and YeaZ may contribute to the essentiality of Gcp for S. aureus survival. Our findings provide new insights into the potential mechanisms and biological functions of this novel essential protein

Research Methodologies and Business Discourse Teaching

This chapter will:; ; ; Define English for specific purposes and indicate the specific ways in which it has been influential on business discourse teaching;; ; ; Discuss the most relevant approaches to genre analysis that have been used in business discourse teaching;; ; ; Explore the most relevant approaches to critical discourse analysis and organizational rhetoric for business discourse teaching;; ; ; Identify the most relevant aspects of multimodal discourse analysis for business discourse teaching;; ; ; Provide a case study that illustrates the use of one approach to business discourse teaching, showing how practitioners can incorporate it into their classroom- or consultancy-based ideas

Increased classical endoplasmic reticulum stress is sufficient to reduce chondrocyte proliferation rate in the growth plate and decrease bone growth

Copyright: © 2015 Kung et al. Mutations in genes encoding cartilage oligomeric matrix protein and matrilin-3 cause a spectrum of chondrodysplasias called multiple epiphyseal dysplasia (MED) and pseudoachondroplasia (PSACH). The majority of these diseases feature classical endoplasmic reticulum (ER) stress and activation of the unfolded protein response (UPR) as a result of misfolding of the mutant protein. However, the importance and the pathological contribution of ER stress in the disease pathogenesis are unknown. The aim of this study was to investigate the generic role of ER stress and the UPR in the pathogenesis of these diseases. A transgenic mouse line (ColIITgcog) was generated using the collagen II promoter to drive expression of an ER stress-inducing protein (Tgcog) in chondrocytes. The skeletal and histological phenotypes of these ColIITgcog mice were characterised. The expression and intracellular retention of Tgcog induced ER stress and activated the UPR as characterised by increased BiP expression, phosphorylation of eIF2á and spliced Xbp1. ColIITgcog mice exhibited decreased long bone growth and decreased chondrocyte proliferation rate. However, there was no disruption of chondrocyte morphology or growth plate architecture and perturbations in apoptosis were not apparent. Our data demonstrate that the targeted induction of ER stress in chondrocytes was sufficient to reduce the rate of bone growth, a key clinical feature associated with MED and PSACH, in the absence of any growth plate dysplasia. This study establishes that classical ER stress is a pathogenic factor that contributes to the disease mechanism of MED and PSACH. However, not all the pathological features of MED and PSACH were recapitulated, suggesting that a combination of intra- and extra-cellular factors are likely to be responsible for the disease pathology as a whole

The unfolded protein response and its relevance to connective tissue diseases

The unfolded protein response (UPR) has evolved to counter the stresses that occur in the endoplasmic reticulum (ER) as a result of misfolded proteins. This sophisticated quality control system attempts to restore homeostasis through the action of a number of different pathways that are coordinated in the first instance by the ER stress-senor proteins IRE1, ATF6 and PERK. However, prolonged ER-stress-related UPR can have detrimental effects on cell function and, in the longer term, may induce apoptosis. Connective tissue cells such as fibroblasts, osteoblasts and chondrocytes synthesise and secrete large quantities of proteins and mutations in many of these gene products give rise to heritable disorders of connective tissues. Until recently, these mutant gene products were thought to exert their effect through the assembly of a defective extracellular matrix that ultimately disrupted tissue structure and function. However, it is now becoming clear that ER stress and UPR, because of the expression of a mutant gene product, is not only a feature of, but may be a key mediator in the initiation and progression of a whole range of different connective tissue diseases. This review focuses on ER stress and the UPR that characterises an increasing number of connective tissue diseases and highlights novel therapeutic opportunities that may arise

Leveraging student-led interviews in the multilingual workplace

Descriptive and Comparative Linguistic

The role of CO2 capture and utilization in mitigating climate change

To offset the cost associated with CO2 capture and storage (CCS), there is growing interest in finding commercially viable end-use opportunities for the captured CO2. In this Perspective, we discuss the potential contribution of carbon capture and utilization (CCU). Owing to the scale and rate of CO2 production compared to that of utilization allowing long-term sequestration, it is highly improbable the chemical conversion of CO2 will account for more than 1% of the mitigation challenge, and even a scaled-up enhanced oil recovery (EOR)-CCS industry will likely only account for 4–8%. Therefore, whilst CO2-EOR may be an important economic incentive for some early CCS projects, CCU may prove to be a costly distraction, financially and politically, from the real task of mitigation