Src family kinases are required for limb trajectory selection by spinal motor axons

Signal relay by guidance receptors at the axonal growth cone is a process essential for the assembly of a functional nervous system. We investigated the in vivo function of Src family kinases (SFKs) as growth cone guidance signaling intermediates in the context of spinal lateral motor column (LMC) motor axon projection toward the ventral or dorsal limb mesenchyme. Using in situ mRNA detection we determined that Src and Fyn are expressed in LMC motor neurons of chick and mouse embryos at the time of limb trajectory selection. Inhibition of SFK activity by C-terminal Src kinase (Csk) overexpression in chickLMCaxons using in ovo electroporation resulted inLMC axons selecting the inappropriate dorsoventral trajectory within the limb mesenchyme, with medial LMC axon projecting into the dorsal and ventral limb nerve with apparently random incidence. We also detected LMC axon trajectory choice errors in Src mutant mice demonstrating a nonredundant role for Src in motor axon guidance in agreement with gain and loss of Src function in chickLMCneurons which led to the redirection ofLMCaxons. Finally, Csk-mediated SFK inhibition attenuated the retargeting ofLMCaxons caused by EphA or EphB over-expression, implying the participation of SFKs in Eph-mediated LMC motor axon guidance. In summary, our findings demonstrate that SFKs are essential for motor axon guidance and suggest that they play an important role in relaying ephrin:Eph signals that mediate the selection of motor axon trajectory in the limb.

The BTB/POZ Transcription Factor Miz-1 Is Required To Regulate The Commitment, Survival And Differentiation Of Early B And T Cell Lineages

Les lymphocytes B et T sont issus de cellules progénitrices lymphoïdes de la moelle osseuse qui se différencient grâce à l’action de facteurs de transcription, cytokines et voies de signalisation, dont l’interleukine-7 (IL-7)/IL-7 récepteur (IL-7R). Le facteur de transcription c-Myc est exprimé par les cellules lymphoïdes et contrôle leur croissance et leur différenciation. Cette régulation transcriptionnelle peut être coordonnée par le complexe c-Myc/Myc-Interacting Zinc finger protein-1 (Miz-1). Le but de ce projet était de comprendre les mécanismes qui impliquent Miz-1 et le complexe c-Myc/Miz-1 dans le développement des lymphocytes B et T. Pour réaliser ce projet, des souris déficientes pour le domaine de transactivation de Miz-1 (Miz-1POZ) et des souris à allèles mutantes pour c-MycV394D, mutation qui empêche l’interaction avec Miz-1, ont été générées. La caractérisation des souris Miz 1POZ a démontré que l’inactivation de Miz-1 perturbe le développement des lymphocytes B et T aux stades précoces de leur différenciation qui dépend de l’IL-7. L’analyse de la cascade de signalisation IL-7/IL-7R a montré que ces cellules surexpriment la protéine inhibitrice SOCS1 qui empêche la phosphorylation de STAT5 et perturbe la régulation à la hausse de la protéine de survie Bcl-2. De plus, Miz-1 se lie directement au promoteur de SOCS1 et contrôle son activité. En plus de contrôler l’axe IL-7/IL-7R/STAT5/Bcl-2 spécifiquement aux stades précoces du développement afin d’assurer la survie des progéniteurs B et T, Miz-1 régule l’axe EBF/Pax-5/Rag-1/2 dans les cellules B afin de coordonner les signaux nécessaires pour la différenciation des cellules immatures. La caractérisation des souris c-MycV394D a montré, quant à elle, que les fonctions de Miz-1 dans les cellules B et T semblent indépendantes de c-Myc. Les cellules T des souris Miz-1POZ ont un défaut de différenciation additionnel au niveau de la -sélection, étape où les signaux initiés par le TCR remplacent ceux induits par IL-7 pour assurer la prolifération et la différenciation des thymocytes en stades plus matures. À cette étape du développement, une forme fonctionnelle de Miz-1 semble être requise pour contrôler le niveau d’activation de la voie p53, induite lors du processus de réarrangement V(D)J du TCR. L’expression de gènes pro-apoptotiques PUMA, NOXA, Bax et du régulateur de cycle cellulaire p21CIP1 est régulée à la hausse dans les cellules des souris Miz-1POZ. Ceci provoque un débalancement pro-apoptotique qui empêche la progression du cycle cellulaire des cellules TCR-positives. La survie des cellules peut être rétablie à ce stade de différenciation en assurant une coordination adéquate entre les signaux initiés par l’introduction d’un TCR transgénique et d’un transgène codant pour la protéine Bcl-2. En conclusion, ces études ont montré que Miz-1 intervient à deux niveaux du développement lymphoïde: l’un précoce en contrôlant la signalisation induite par l’IL-7 dans les cellules B et T, en plus de l’axe EBF/Pax-5/Rag-1/2 dans les cellules B; et l’autre tardif, en coordonnant les signaux de survie issus par le TCR et p53 dans les cellules T. Étant donné que les thymocytes et lymphocytes B immatures sont sujets à plusieurs rondes de prolifération, ces études serviront à mieux comprendre l’implication des régulateurs du cycle cellulaire comme c-Myc et Miz-1 dans la génération des signaux nécessaires à la différenciation non aberrante et à la survie des ces cellules. Enfin, les modèles expérimentaux, souris déficientes ou à allèles mutantes, utilisés pour ce travail permettront de mieux définir les bases moléculaires de la transformation maligne des lymphocytes B et T et de révéler les mécanismes conduisant au lymphome.

Non-University Higher Education and the Relationship of Its Graduates and the World of Work: Colombia

The non-university sector has been part of the Colombian higher education system for more than 50-years. Despite its long years of existence, it has never occupied such an important role within the education system as the one it is having today. Therefore, the aim of this work is to analyze the development of the non-university sector in the framework of the country’s social, educational and economic demands. Likewise, its actual situation and certain aspects of the relationship between its graduates and the world of work, i.e., graduates’ employment characteristics, the relationship of higher education studies and their work, as well as their early career success, are examined. In order to generate the required information, a graduate survey was carried out in Atlántico (Colombia). The target population was graduates from higher education institutions registered in Atlántico who were awarded a technical, technological or professional degree in 2008 from any of the following knowledge areas: Fine Arts, Health Science, Economy-Administration-Accountancy and similar, and Engineering-Architecture-Urban planning and similar. Besides, interviews with academic and administrative staff from non-university institutions were carried out, and higher education related documents were analyzed. As a whole, the findings suggest that the non-university sector is expanding and may help to achieve some of the goals, for which it is widely promoted i.e., access expansion for under-represented groups, enhancement of the higher education system, and the provision of programs pertinent to the needs of the market. Nevertheless, some aspects require further consideration, e.g., the sector’s consolidation within the system and its quality. As for the relationship between non-university higher education and the world of work, it was found to be close; particularly in those aspects related to the use of knowledge and skills in the work, and the relationship between graduates’ studies and their work. Additionally, the analysis of the graduates’ in their early career stages exposes the significant role that the socioeconomic stratum plays in their working life, particularly in their wages. This indicates that apart from education, other factors like the graduates’ economic or social capital may have an impact on their future work perspectives

System Design: Introduction to Group Work

In this course you will learn a number of different ways in which to describe a system, at both a high level (using SSM) and a low level (using UML). The main coursework for the course is to work in groups and use these techniques on a case study of your collective choosing. In this session we put the students into groups, run a brainstorming activity on potential businesses, and outline some of the group activities that will be required over the course.

Assisted remote viewing of a teleoperation work cell

Intelligent viewing systems are required if efficient and productive teleoperation is to be applied to dynamic manufacturing environments. These systems must automatically provide remote views to an operator which assist in the completion of the task. This assistance increases the productivity of the teleoperation task if the robot controller is responsive to the unpredictable dynamic evolution of the workcell. Behavioral controllers can be utilized to give reactive 'intelligence.' The inherent complex structure of current systems, however, places considerable time overheads on any redesign of the emergent behavior. In industry, where the remote environment and task frequently change, this continual redesign process becomes inefficient. We introduce a novel behavioral controller, based on an 'ego-behavior' architecture, to command an active camera (a camera mounted on a robot) within a remote workcell. Using this ego-behavioral architecture the responses from individual behaviors are rapidly combined to produce an 'intelligent' responsive viewing system. The architecture is single-layered, each behavior being autonomous with no explicit knowledge of the number, description or activity of other behaviors present (if any). This lack of imposed structure decreases the development time as it allows each behavior to be designed and tested independently before insertion into the architecture. The fusion mechanism for the behaviors provides the ability for each behavior to compete and/or co-operate with other behaviors for full or partial control of the viewing active camera. Each behavior continually reassesses this degree of competition or co-operation by measuring its own success in controlling the active camera against pre-defined constraints. The ego-behavioral architecture is demonstrated through simulation and experimentation.

Irreversible compressible work and APE dissipation in turbulent stratified fluid

Although it plays a key role in the theory of stratified turbulence, the concept of available potential energy (APE) dissipation has remained until now a rather mysterious quantity, owing to the lack of rigorous result about its irreversible character or energy conversion type. Here, we show by using rigorous energetics considerations rooted in the analysis of the Navier-Stokes for a fully compressible fluid with a nonlinear equation of state that the APE dissipation is an irreversible energy conversion that dissipates kinetic energy into internal energy, exactly as viscous dissipation. These results are established by showing that APE dissipation contributes to the irreversible production of entropy, and by showing that it is a part of the work of expansion/contraction. Our results provide a new interpretation of the entropy budget, that leads to a new exact definition of turbulent effective diffusivity, which generalizes the Osborn-Cox model, as well as a rigorous decomposition of the work of expansion/contraction into reversible and irreversible components. In the context of turbulent mixing associated with parallel shear flow instability, our results suggests that there is no irreversible transfer of horizontal momentum into vertical momentum, as seems to be required when compressible effects are neglected, with potential consequences for the parameterisations of momentum dissipation in the coarse-grained Navier-Stokes equations.

Time for review: supporting the work of an advisory group

This paper raises methodological issues about the challenges and dilemmas of inclusive research practices reflecting on the work of an advisory group carrying out research on using Information and Communication Technology (ICT) to enhance community participation. The interests of three parties can be identified – the commissioning agent, the researchers and the researched – and these interplayed throughout the course of the research determining the outcomes. Given the relationship between inclusive research and advocacy, there were particular gains in enabling the voice of the advisory group to shape the way in which the research was conducted and to disseminate the findings both within the organisation and beyond. However, the fragility of these new structures required organisational changes for the research to be truly empowering. The experience of the group suggests the need for their involvement at all stages of the research process

Only subtle protein conformational adaptations are required for ligand binding to thyroid hormone receptors: Simulations using a novel multipoint steered molecular dynamics approach

Thyroid hormone receptors (TR) are hormone-dependent transcription regulators that play a major role in human health, development, and metabolic functions. The thyroid hormone resistance syndrome, diabetes, obesity, and some types of cancer are just a few examples of important diseases that are related to TR malfunctioning, particularly impaired hormone binding. Ligand binding to and dissociation from the receptor ultimately control gene transcription and, thus, detailed knowledge of binding and release mechanisms are fundamental for the comprehension of the receptor`s biological function and development of pharmaceuticals. In this work, we present the first computational study of ligand entry into the ligand binding domain (LBD) of a nuclear receptor. We report molecular dynamics simulations of ligand binding to TRs using a generalization of the steered molecular dynamics technique designed to perform single-molecule pulling simulations along arbitrarily nonlinear driving pathways. We show that only gentle protein movements and conformational adaptations are required for ligand entry into the LBDs and that the magnitude of the forces applied to assist ligand binding are of the order of the forces involved in ligand dissociation. Our simulations suggest an alternative view for the mechanisms ligand binding and dissociation of ligands from nuclear receptors in which ligands can simply diffuse through the protein surface to reach proper positioning within the binding pocket. The proposed picture indicates that the large-amplitude protein motions suggested by the apo- and holo-RXR alpha crystallographic structures are not required, reconciling conformational changes of LBDs required for ligand entry with other nuclear receptors apo-structures that resemble the ligand-bound LBDs.

Distance learning for laboratory practical work in microcontrollers

This paper presents a simple and relatively straightforward solution to the problems of equity in laboratory practical exposure between distance-education students and their traditional, on-campus, fellow cohort. This system has been implemented for the past five years in a university that is amongst the leaders in distance education delivery and has proved to be extremely successful and very well accepted by all students. While the intention was to allow distance education students easy access to the required laboratory practical content of the course, the solution found has proved to have many advantages for the on-campus students. Although this specific implementation is based upon microcontroller technology units in an engineering degree course, the methodology is easily transferable to other disciplines and courses.

On the edge: how well do fire mitigation strategies work on the urban fringe?

The reduction of loss of lives and assets during bushfire is one of the primary aims or lire management agencies. Traditional fire mitigation strategies include strategic fire hreaks, static water points, management of ignition sources, rapid detection and local response, air attack, and fuel reduction burning. There have been few quantitative studies that assess the success or these strategies. We need to promote 'new' strategies more focused on human hehaviour and community preparedness.
DeJcndable space provides our best strategy for reducing losses during major bushfires. The size or the defendable space depends on the type of house to be defended, who is defending it, and the spatial context of the property. In the urban fi'inge, remnant vegetation on private property often has
high conservation values, and application of traditional mitigation strategies, as well as the vegetation modification required to achieve defendable space, may have significant impacts on conservation and biodiversity values.

"Join together, work together, for the common good - solidarity": village formation processes in the rural south of Laos

This article explores the concept of the solidary village in contemporary Laos. It argues that the "village" today is not a fixed, primordial entity, but a continually emergent formation resulting from numerous processes, including but not limited to modern state processes. The notion of "village" circulates in the ambiguous "common sense" pertaining to rural Laos, in the attitudes, expectations, representations, and regulated requirements of the rural, in what I term village formation projects. Case studies of "village formation projects" in one village in southern Laos illustrate not only the importance of the village concept, but also its indeterminacy and fluidity, and the ensuing difficulty of achieving the "solidarity" and cooperative donation required by poverty reduction policies.

What can we learn about social work assessment from the textbooks?

Summary: Although often criticized for inadequacies, textbooks are both highly influential and a readily available source of information about contemporary thinking in social work theory and practice. As part of a series of studies about facilitating learning and teaching about assessment in social work, the authors have been conducting a review of how this professional task is presented in textbooks which are currently known to be used in programmes of social work education in the UK. Relevant chapters of each of the selected textbooks were subjected to an in-depth analysis in order to determine how assessment was understood, assessment processes, relevance to the UK practice context and evidence bases.

Findings: What are considered the key issues in, and skills required for, social work assessment are contested, with considerable variety between textbooks as to the extent of detail and topics covered in relation to assessment. Some issues which are prominent in the policy context, such as the need to ensure the involvement of service user and carer perspectives, and multidisciplinary assessment, were hardly mentioned. Changes in emphasis over time and differences in emphasis between textbooks published in the UK and North America were found.

Applications: Given the many differences in emphasis and depth of content between textbooks ostensibly outlining the same aspects of practice, it is essential that educators have a clear rationale for recommending particular textbooks.

Assessment methods in social work education: a review of the literature

Student assessment is an important component of social work education, and consumes considerable effort on behalf of both students and staff members. Social work educators in higher education face the challenge of constructing assessment methods, which encourage the development of reflective and critical learning, as well as enabling students to demonstrate acquisition of required knowledge and/or skills. While there is now a substantial literature on field education, the assessment of classroom-based units has warranted less attention. This paper examines the range of assessment methods reported in the social work education literature, the evidence which supports the use of these methods and issues associated with the identified assessment methods.

Returning to work: exploring the experiences of women with acute coronary syndromes

Aims: The aim of this study was to explore the transition experiences of Australian women in resuming paid employment after an acute coronary syndrome (ACS) event. Background: Until recently cardiovascular research has focused predominantly on men but this is changing and research exploring women’s experiences of ACS has increased. Despite knowing that many women do not resume paid employment following an ACS event, little is known about the experience of those women who do, even though it is understood that returning to the previous level of employment after an ACS event is a positive outcome. Design: An exploratory qualitative approach underpinned by naturalistic inquiry was undertaken. Methods: A purposive sample of seven women who had experienced their first ACS event 12 months ago was selected. Each woman was interviewed using a semi–structured format and their interviews were transcribed verbatim. Thematic analysis of the transcript set and conceptual mapping were employed to formulate key themes. Findings: All women (mean age 52.6 years) resumed paid employment at various stages during their recovery, but reported similar transition processes. Three key themes representing this process were identified: primary motivation; influence through guidance and support; and resuming paid employment. Conclusions: Study findings revealed that these women required substantial support from family, friends and employers, with ongoing guidance from health professionals to return to paid work. The time frames for their return varied and some modified their roles within the workforce to enable them to return to paid work. However, formal cardiac rehabilitation did not appear to have a significant impact on these participants' decisions to return to work. They felt that more information about this decision may have been helpful if given at the time of cardiac rehabilitation.

Designing, implementing and evaluating a social work practice skills course: a case example

Practice skills, such as communication and interviewing skills, are an integral part of every undergraduate course that aims to provide professional qualification for social workers. While there is substantial literature about the skills required to be a proficient social work practitioner, there is a dearth of literature about how to teach such skills and particularly how students experience such a course. By critically reflecting on the design, implementation and evaluation of a social work practice skills course, this article is offered as a contribution toward filling an identified gap in social work education literature. The course evaluation particularly highlights the importance of face to face interaction between students and teachers to the process of learning.