Expression of the tudor-related gene Tdrd5 during development of the male germline in mice

Homologues of Drosophila germ cell determinant genes such as vasa, nanos and tudor have recently been implicated in development of the male germline in mice. In the present study, the mouse gene encoding Tudor domain containing protein 5 (TDRD5) was isolated from a 12.5-13.5 days post coitum (dpc) male-enriched subtracted cDNA library. Whole-mount in situ hybridization analysis of Tdrd5 expression in the mouse embryonic gonad indicated that this gene is upregulated in the developing testis from 12.5 dpc, with expression levels remaining higher in testis than ovary throughout embryogenesis. Expression of Tdrd5 was absent in testes isolated from W-e/W-e embryos, which lack germ cells. In situ hybridization (ISH) on cryosectioned 13.5 dpc testes suggests that expression of Tdrd5, like that of Oct4, is restricted to germ cells. Northern hybridization analysis of expression in adult tissues indicated that Tdrd5 is expressed in the testis only, implying that expression of this gene is restricted to the male germline throughout development to adulthood. (C) 2004 Elsevier B.V. All rights reserved.

Pax9 and Jagged1 act downstream of Gli3 in vertabrate limb development

From early in limb development the transcription factor Gli3 acts to define boundaries of gene expression along the anterior-posterior (AP) axis, establishing asymmetric patterns required to provide positional information. As limb development proceeds, posterior mesenchyme expression of Sonic hedgehog (Shh) regulates Gli3 transcription and post-translational processing to specify digit number and identity. The molecular cascades dependent on Gli3 at later stages of limb development, which link early patterning events with final digit morphogenesis, remain poorly characterised. By analysing the transcriptional consequences of loss of Gli3 in the anterior margin of the E11.5 and E12.5 limb bud in the polydactylous mouse mutant extra-toes (Gli3(Xt/Xt)), we have identified a number of known and novel transcripts dependent on Gli3 in the limb. In particular, we demonstrated that the genes encoding the paired box transcription factor Pax9, the Notch ligand Jagged1 and the cell surface receptor Cdo are dependent on Gli3 for correct expression in the anterior limb mesenchyme. Analysis of expression in compound Shh;Gli3 mutant mouse embryos and in both in vitro and in vivo Shh signaling assays, further defined the importance of Shh regulated processing of Gli3 in controlling gene expression. In particular Pax9 regulation by Shh and Gli3 was shown to be context dependent, with major differences between the limb and somite revealed by Shh bead implantation experiments in the chick. Jagged1 was shown to be induced by Shh in the chick limb and in a C3H10T1/2 cell based signaling assay, with Shh;Gli3 mutant analysis indicating that expression is dependent on Gli3 derepression. Our data have also revealed that perturbation of early patterning events within the Gli3(Xt/Xt), limb culminates in a specific delay of anterior chondrogenesis which is subsequently realised as extra digits. (c) 2005 Elsevier Ireland Ltd. All rights reserved.

Swimming behaviour and post-swimming activity in Vitamin D receptor knockout mice

Animal experiments have shown that Vitamin D plays a role in both brain development and adult brain function. The adult Vitamin D receptor null mutant mouse (VDR -/-) is reported to be less active and more anxious than wild-type litter mate controls and to have poor swimming ability. However, an anxious behavioural phenotype is inferred from differences in locomotor behaviour. This is a general problem in behavioural phenotyping where a neurological phenotype is inferred from changes in locomotion which will be affected by non-neurological factors, such as muscle fatigue. In this study of VDR -/-, we conducted a detailed examination of one form of motor behaviour, swimming, compared to wildtype littermate controls. Swimming was assessed using a forced swim test, a laneway swimming test and a watermaze test using a visible platform. Post-swimming activity was assessed by comparing grooming and rearing behaviour before, and 5 min after, the forced swimming test. We replicated previous findings in which VDR -/- mice demonstrate more sinking episodes than wildtype controls in the forced swim test but they were similar to controls in the time taken to swim a 1 m laneway, and in the time taken to reach a visible platform in the watermaze. Thus, the VDR -/- mice were able to swim but were not able to float. Grooming and rearing behaviour of the VDR -/- mice was similar to wildtype controls before the forced swim but the VDR -/- were much less active after the swim compared with wildtype mice which displayed high levels of grooming and rearing. We conclude that VDR -/- mice have muscular and motor impairments that do not affect their ability to swim but significantly alters the ability to float as well as their post-swimming activity. Differences in muscle strength may confound tests of activity that are used to infer an anxious phenotype. (c) 2005 Elsevier Inc. All rights reserved.

Career research in a post-modern era

In recent years, career theory and practice has been challenged to revise and reinvigorate itself in order to remain relevant in the post- modern world. The most fundamental challenge is to produce an identity for career practice that is congruent with the post-modern world. Career research is facing a similar challenge as it has been dominated by methodologies that emanate out of the positivist worldview of the modern era and has been mainly quantitative in nature. In their recent research, the authors have been examining methodologies that accommodate the tenets of the post-modern world – post-modernism, constructivism and career psychology. This article overviews post- modern considerations by exploring the possibilities offered by the Systems Theory Framework of career development and the 'My System of Career Influence' reflection activity as research tools. Examples of recent research are briefly described.

Post-Fordism, the welfare state and the personal social services: A comparison of Australia and Britain

The Post-Fordist welfare state thesis locates contemporary social welfare change within a wider analysis of the transformation of capitalist accumulation regimes. Whilst this analysis is useful in directing attention to macro socio-economic change, it has for the most part contained three shortcomings. First, the Post-Fordist thesis has overemphasized the role of historical 'breaks' in the development of social welfare as it purportedly passes from Fordism to Post-Fordism. Second, the thesis has assumed a degree of convergence between welfare states as a result of global economic forces. In doing so, it has underemphasized the mediating impact of existing institutional arrangements within nations. Third, the thesis has assumed, rather than demonstrated, the specific changes which are alleged to be taking place in various fields of social welfare. As a consequence, aspects of continuity in social welfare have been neglected. These three lacunae are addressed through a comparative analysis of developments in the personal social services in Australia and Britain. Services to older people are employed as the specific context of comparison in relation to three dimensions of measuring transformation along a Post-Fordist trajectory: a shift from a unitary economy to a mixed economy of service provision; changes in the model of service delivery and consumption; and strengthening the governance function of the central state. This comparative analysis suggests the need for refinement of the Post-Fordist welfare state thesis concerning the restructuring of social welfare and its impact on the personal social services.

Is the generation of neo-antigenic determinants by free radicals central to the development of autoimmune rheumatoid disease?

Biomolecules are susceptible to many different post-translational modifications that have important effects on their function and stability, including glycosylation, glycation, phosphorylation and oxidation chemistries. Specific conversion of aspartic acid to its isoaspartyl derivative or arginine to citrulline leads to autoantibody production in models of rheumatoid disease, and ensuing autoantibodies cross-react with native antigens. Autoimmune conditions associate with increased activation of immune effector cells and production of free radical species via NADPH oxidases and nitric oxide synthases. Generation of neo-antigenic determinants by reactive oxygen and nitrogen species ROS and RNS) may contribute to epitope spreading in autoimmunity. The oxidation of amino acids by peroxynitrite, hypochlorous acid and other reactive oxygen species (ROS) increases the antigenicity of DNA, LDL and IgG, generating ligands for which autoantibodies show higher avidity. This review focuses on the evidence for ROS and RNS in promoting the autoimmune responses observed in diseases rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). It considers the evidence for ROS/RNS-induced antigenicity arising as a consequence of failure to remove or repair ROS/RNS damaged biomolecules and suggests that an associated defect, probably in T cell signal processing or/or antigen presentation, is required for the development of disease.

Causes of tension in post-observation feedback in pre-service teacher training: an alternative view

A central component in pre-service teacher training is teaching practice and feedback. In some cases, feedback results in disquiet and tension (Brandt, 2008). Many researchers attribute this tension to the incompatibility of the assessment and development roles that the trainer must perform. The research reported on here, however, suggests that tension may also be rooted in a difference in expectation amongst trainers and trainees about the purpose and performance of feedback. This can result in trainees not playing by the rules of the game (Roberts & Sarangi, 2001) either because they do not understand them or because they wish to challenge them.

Corruption in the post-Soviet workplace: the experiences of recent graduates in contemporary Ukraine

While Ukraine was bestowed market economy status by the European Union in 2005 its labour market still endures many structural problems. By exploring the experiences of young graduate employees this article highlights the difficultly in obtaining work within Ukraine's labour market and the problems they face once they have secured employment. Rather than seeing the development of a transparent labour market the collapse of the command economy has seen a relatively closed system develop. The article demonstrates how many jobs are secured through the use of connections or the demanding, and payment, of bribes.The situation does not improve once graduates obtain long-term employment. Interviewees discuss the lack of job security, the informal payment of wages and the lack of legal protection from corrupt employer practices. The article has broader resonance outside of the Ukrainian case study as the discussion of workplace corruption highlights how the issue is concerned with much more than simply cash based transactions and how those that endure it are likely to turn to the informal economy for employment.

How screening criteria change during brand development

Purpose - Despite the increasing sophistication of new product development (NPD) research, the reliance on traditional approaches to studying NPD has left several areas in need of further research. The authors propose addressing some of these gaps, especially the limited focus on consumer brands, evaluation criteria used across different project-review points in the NPD process, and the distinction between "kills", "successes", and "failures". Moreover, they propose investigating how screening criteria change across project-review points, using real-time NPD projects. Design/methodology/approach - A postal survey generated 172 usable questionnaires from a sample of European, North American, Far Eastern and Australian consumer packaged-goods firms, providing data on 314 new product projects covering different development and post-commercialization review points. Findings - The results confirm that acceptance-rejection criteria vary through the NPD process. However, financial criteria dominate across all the project-review points. Initial screening is coarse, focusing predominantly on financial criteria. Fit with organizational, product, brand, promotional, and market requirements dominate in the detailed screen and pre-development evaluation points. At pre-launch, decision-makers focus on product, brand, and promotional criteria. Commercial fit, production synergies, and reliability of the firm's market intelligence are significant discriminators in the post-launch review. Moreover, the importance of marketing and channel issues makes the criteria for screening brands different from those of industrial markets. Originality/value - The study, although largely descriptive and involves a relatively small sample of consumer goods firms, offers new insights into NPD project evaluation behavior. Future, larger-scale investigations covering a broader spectrum of consumer product sectors are needed to validate our results and to explain the reasons behind managers' decisions. © Emerald Group Publishing Limited.

Everyday tactics and spaces of power: the role of informal economies in post-Soviet Ukraine

Utilising de Certeau's concepts of daily life and his delineation between strategies and tactics as everyday practices this paper examines the role of informal economies in post-Ukraine. Based on 700 household surveys and seventy-five in-depth interviews, conducted in three Ukrainian cities, the paper argues that individuals/households have developed a wide range of tactics in response to the economic marginalisation the country has endured since the collapse of the Soviet Union. Firstly, the paper details the importance of informal economies in contemporary Ukraine while highlighting that many such practices are operated out of necessity due to low wage and pension rates and high levels of corruption. This challenges state-produced statistics on the scale of economic marginalisation currently experienced in the country. By exploring a variety of these tactics the paper then examines how unequal power relations shape the spaces in which these practices operate in and how they can be simultaneously sites of exploitation and resistance to economic marginalisation. The paper concludes pessimistically by suggesting that the way in which these economic spaces are shaped precludes the development of state policies which might benefit the economically marginalised.

Development of a near activity visual questionnaire to assess accommodating intraocular lenses

Purpose: To develop a questionnaire that subjectively assesses near visual function in patients with 'accommodating' intraocular lenses (IOLs). Methods: A literature search of existing vision-related quality-of-life instruments identified all questions relating to near visual tasks. Questions were combined if repeated in multiple instruments. Further relevant questions were added and item interpretation confirmed through multidisciplinary consultation and focus groups. A preliminary 19-item questionnaire was presented to 22 subjects at their 4-week visit post first eye phacoemulsification with 'accommodative' IOL implantation, and again 6 and 12 weeks post-operatively. Rasch Analysis, Frequency of Endorsement, and tests of normality (skew and kurtosis) were used to reduce the instrument. Cronbach's alpha and test-retest reliability (intraclass correlation coefficient, ICC) were determined for the final questionnaire. Construct validity was obtained by Pearson's product moment correlation (PPMC) of questionnaire scores to reading acuity (RA) and to Critical Print Size (CPS) reading speed. Criterion validity was obtained by receiver operating characteristic (ROC) curve analysis and dimensionality of the questionnaire was assessed by factor analysis. Results: Rasch Analysis eliminated nine items due to poor fit statistics. The final items have good separation (2.55), internal consistency (Cronbach's α = 0.97) and test-retest reliability (ICC = 0.66). PPMC of questionnaire scores with RA was 0.33, and with CPS reading speed was 0.08. Area under the ROC curve was 0.88 and Factor Analysis revealed one principal factor. Conclusion: The pilot data indicates the questionnaire to be internally consistent, reliable and a valid instrument that could be useful for assessing near visual function in patients with 'accommodating' IOLS. The questionnaire will now be expanded to include other types of presbyopic correction. © 2007 British Contact Lens Association.

Size frequency distribution of senile plaques in post-mortem brains of five patients with senile dementia of the Alzheimer type (SDAT)

Numerous senile plaques are one of the most characteristic histological findings in SDAT brains. Large classical plaques may develop from smaller uncored forms. There is no strong evidence that, once formed, plaques disappear from the tissue. We have examined cresyl-violet stained sections of the parahippocampal gyrus (PHG), hippocampus, frontal lobe and temporal lobe of five SDAT patients. The frequency of various sizes of plaques were determined in each of these brain regions. Statistical analysis showed that the ratio of large plaques to small plaques was greater in the hippocampal formation (especially the PHG) than in the neocortex. One explanation of these results is that plaques grow more rapidly in the hippocampal formation than elsewhere. Alternatively, if the rate of plaque growth is much the same in different brain regions, the data suggest that plaques develop first in the hippocampal formation (especially the PHG) and only later spread to the neocortex. This interpretation is also consistent with the theory that the neuropathology of SDAT spreads from the olfactory cortex via the hippocampal formation to the neocortex. Further development of this technique may help identify the site of the primary lesion in SDAT.