Miracle-dz/UniFAR-FTUs huggingface dataset:
Expression of an S phase-stabilized version of the CDK inhibitor Dacapo can alter endoreplication

In developing organisms, divergence from the canonical cell division cycle is often necessary to ensure the proper growth, differentiation, and physiological function of a variety of tissues. An important example is endoreplication, in which endocycling cells alternate between G and S phase without intervening mitosis or cytokinesis, resulting in polyploidy. Although significantly different from the canonical cell cycle, endocycles use regulatory pathways that also function in diploid cells, particularly those involved in S phase entry and progression. A key S phase regulator is the Cyclin E-Cdk2 kinase, which must alternate between periods of high (S phase) and low (G phase) activity in order for endocycling cells to achieve repeated rounds of S phase and polyploidy. The mechanisms that drive these oscillations of Cyclin E-Cdk2 activity are not fully understood. Here, we show that the Drosophila Cyclin E-Cdk2 inhibitor Dacapo (Dap) is targeted for destruction during S phase via a PIP degron, contributing to oscillations of Dap protein accumulation during both mitotic cycles and endocycles. Expression of a PIP degron mutant Dap attenuates endocycle progression but does not obviously affect proliferating diploid cells. A mathematical model of the endocycle predicts that the rate of destruction of Dap during S phase modulates the endocycle by regulating the length of G phase. We propose from this model and our in vivo data that endo S phase-coupled destruction of Dap reduces the threshold of Cyclin E-Cdk2 activity necessary to trigger the subsequent G-S transition, thereby influencing endocycle oscillation frequency and the extent of polyploidy. Summary: S phase-coupled destruction of the Drosophila CDK inhibitor Dacapo mediates oscillations of Dap protein accumulation and may help to regulate endocycle frequency and polyploidization during development.
Antecedents of self-regulation in driving among older drivers

ABSTRACT Maintaining quality of life and wellbeing into advanced age is a major challenge to societies. Driving is one factor contributing to an ageing individual's independence. Understanding antecedents of driving-related self-regulation is important for designing interventions to preserve safe driving in old age. This paper reports on a study that investigated factors associated with two forms of self-regulation in driving (SRD) – avoidance of difficult driving conditions and voluntary cessation of driving – in a sample of 860 Israeli drivers aged 70 and over. We examined roles of health, vision, driving experience, driving-related self-efficacy (DRSE) and global self-esteem in SRD. Health and DRSE had direct effects on SRD, and effects of vision and driving experience were mediated by DRSE. Participants who had ceased driving were older, with poorer vision and health, and less driving confidence and experience than active drivers. Statistical analyses demonstrated that SRD is affected by a reduced sense of confidence due to an initial lower level of driving experience, compounded by deteriorating vision, and that older drivers are sensitive to factors affecting their ability to drive safely. Our results demonstrate that older drivers tend to self-regulate their driving. Programmes for older adults can be introduced for diagnosing driving capabilities, improving skills and confidence, and/or helping to develop self-regulation habits of avoiding driving in difficult conditions, and assisting drivers who must adjust to driving cessation.
Th17 Response and Inflammatory Autoimmune Diseases

The proinflammatory activity of T helper 17 (Th17) cells can be beneficial to the host during infection. However, uncontrolled or inappropriate Th17 activation has been linked to several autoimmune and autoinflammatory pathologies. Indeed, preclinical and clinical data show that Th17 cells are associated with several autoimmune diseases such as arthritis, multiple sclerosis, psoriasis, and lupus. Furthermore, targeting the interleukin-17 (IL-17) pathway has attenuated disease severity in preclinical models of autoimmune diseases. Interestingly, a recent report brings to light a potential role for Th17 cells in the autoinflammatory disorder adult-onset Still's disease (AOSD). Whether Th17 cells are the cause or are directly involved in AOSD remains to be shown. In this paper, we discuss the biology of Th17 cells, their role in autoimmune disease development, and in AOSD in particular, as well as the growing interest of the pharmaceutical industry in their use as therapeutic targets.
Predicting Health-Check Attendance Among Prior Attenders and Nonattenders: The Role of Prior Behavior in the Theory of Planned Behavior

A prospective study applying the theory of planned behavior (TPB) to the prediction of attendance at health checks is reported. Conducted in a single general practice, 307 patients completed questionnaires based on the TPB, and were invited to attend a health check. The role of prior behavior in the TPB was assessed in 2 ways. First, it was used to assess the sufficiency of the TPB. The addition of prior attendance behavior led to a significant increase in the prediction of current behavior. Second, its role as a moderator variable was assessed. While the TPB was unsuccessful in predicting attendance behavior among prior attenders, it was able to do so among prior nonattenders. The results are discussed in relation to recent work on decision-making processes.
Hermeneutics, religious language and the Qur'an

The question, ‘Are religious propositions meaningful? ’, which dominated thought about religious language from the mid‐twentieth century, was rapidly made redundant by the understanding of language promoted by thinkers associated with hermeneutical philosophy. Instead of arguing about whether or not religious language was meaningful, philosophers and theologians explored the various ways in which religious language is rendered meaningful by the creative interaction of readers and texts. After describing the origin of modern hermeneutics in the work of F.D. E. Schleiermacher and outlining the most important developments within twentieth‐century hermeneutical philosophy, this article explores how certain key Muslim theologians deployed the ideas developed within hermeneutical philosophy as they sought to provide new understandings of the Qur'an. After highlighting the link between this new approach to religious language and the innovative understandings of the nature of revelation that have emerged from it, the article considers how the recognition that the text of the Qur'an is consistent with a number of different interpretations has led to the view that there is a plurality of equally legitimate forms of Islam. Finally, the article reviews Mohammed Arkoun's attempt to explain the unity behind this irreducible interpretive plurality by tracing its origin to what he calls the ‘Qur’ānic fact'.
Coping with Conflict within the Entrepreneurial University: Threat or Challenge for Heads of Departments in the UK Higher Education Context

This article attempts to provide an understanding of the conflict phenomenon in the UK higher education sector. A research survey was conducted in order to examine the role conflict associated with the headship position in the contemporary university context. ‘Janusian’ and ‘value’ conflict were the forms of role conflict experienced by heads of departments. On the one hand, heads' efforts to provide the critical link between the managerial requirements of the modern university and academic staffs' values of their departments, in addition to the performance of their academic core activities led to the development of ‘Janusian’ role conflict. On the other hand, the emphasis on market mechanisms in higher education and the departure from the traditional academic work values, in an era characterized by change, uncertainty and complexity contributed to the appearance of the ‘value’ conflict among heads of departments. However, both of these conflict dimensions were relative to the type of institution (new/old university category).
Ontology and the study of social reality: emergence, organisation, community, power, social relations, corporations, artefacts and money

The conception of social reality I have previously defended (and here extend), positing features such as social relations, positions and powers, is thoroughly naturalistic and even consistent with modern interpretations of quantum field theory. It also serves to ground a social science that can be scientific in the sense of natural science. This is the thesis defended here. Central to the argument is an emphasis on a 'strong' form of emergence and the category of 'organisation-in-process'. To bring out various salient features of the position defended, I take the opportunity to compare aspects of it with relevant components of the contribution of John Searle, whose ontological conception appears at once to be both very similar yet also very different. Copyright The Author 2012. Published by Oxford University Press on behalf of the Cambridge Political Economy Society. All rights reserved. , Oxford University Press.
Neuroprotective effect of mifepristone involves neuron depolarization

In several regions of the developing nervous system, neurons undergo programmed cell death. In the rat cerebellum, Purkinje cell apoptosis is exacerbated when cerebellar slices are cultured during the first postnatal week. To understand the mechanism of this developmental apoptosis, we took advantage of its inhibition by the steroid analog mifepristone. This effect did not involve the classical steroid nuclear receptors. Microarray analysis revealed that mifepristone down‐regulated mRNA levels of the Na+/K+‐ATPase α3 subunit more than three times. Consistent with the down‐regulation of the Na+/K+‐ATPase, mifepristone caused Purkinje cell membrane depolarization. Depolarizing agents like ouabain (1 µM), tetraeth‐ylammonium (2 mM), and veratridine (2 µM) protected Purkinje cells from apoptosis. These results suggest a role of excitatory inputs in Purkinje cell survival during early postnatal development. Indeed, coculturing cerebellar slices with glutamatergic inferior olivary neuron preparations allowed rescue of Purkinje cells. These findings reveal a new neuroprotective mechanism of mifepristone and support a pivotal role for excitatory inputs in the survival of Purkinje neurons. Mifepristone may be a useful lead compound in the development of novel therapeutic approaches for maintaining the resting potential of neurons at values favorable for their survival under neuropathological conditions. —Ghoumari, A. M. , Piochon, C. , Tomkiewicz, C. , Eychenne, B. , Levenes, C. , Dusart, I. , Schumacher, M. , Baulieu, E. E. Neuroprotective effect of mifepristone involves neuron depolarization. FASEB J. 20, 1377–1386 (2006)
Confirmatory factor analysis of the career decision-making self-efficacy scale among South African university students

There is a need for South African researchers to explore the potential utility of career decision-making self-efficacy in understanding the career behaviour of tertiary students. Given the lack of standardised measures for this construct, the responses of 364 South African university students to the Career Decision-Making Self-Efficacy Scale : Short Form (CDMSE-SF) were analysed using item statistics, Cronbachs alpha and confirmatory factor analysis to determine whether items supported the theorized subscales. Opsomming Dit is noodsaaklik vir Suid-Afrikaanse navorsers om die potensiele bruikbaarheid van loopbaanbesluitnemmgself-doeltreffendheid ("career decision-making self-efficacy") te ondersoek in n poging om die tersiere studente beter te begryp. Gegewe die gebrek aan gestandaardiseerde meetinstrumente vir hierdie konstruk, is response van 364 Suid-Afrikaanse universiteitstudente op die Career Decision-Making Self-Efficacy Scale: Short Form (CDMSE-SF) met behulp van itemontleding, Cronbach se alpha en bevestigende faktorontleding ontleed, om te bepaal of die vraelys-items die teoretiese subskale ondersteun.
Effect of MHC Class I Diversification on Influenza Epitope-Specific CD8+ T Cell Precursor Frequency and Subsequent Effector Function

Earlier studies of influenza-specific CD8+ T cell immunodominance hierarchies indicated that expression of the H2Kk MHC class I allele greatly diminishes responses to the H2Db-restriced DbPA224 epitope (acid polymerase, residues 224–233 complexed with H2Db). The results suggested that the presence of H2Kk during thymic differentiation led to the deletion of a prominent Vβ7+ subset of DbPA224-specific TCRs. The more recent definition of DbPA224-specific TCR CDR3β repertoires in H2b mice provides a new baseline for looking again at this possible H2Kk effect on DbPA224-specific TCR selection. We found that immune responses to several H2Db- and H2Kb-restricted influenza epitopes were indeed diminished in H2bxk F1 versus homozygous mice. In the case of DbPA224, lower numbers of naive precursors were part of the explanation, though a similar decrease in those specific for the DbNP366 epitope did not affect response magnitude. Changes in precursor frequency were not associated with any major loss of TCR diversity and could not fully account for the diminished DbPA224-specific response. Further functional and phenotypic characterization of influenza-specific CD8+ T cells suggested that the expansion and differentiation of the DbPA224-specific set is impaired in the H2bxk F1 environment. Thus, the DbPA224 response in H2bxk F1 mice is modulated by factors that affect the generation of naive epitope-specific precursors and the expansion and differentiation of these T cells during infection, rather than clonal deletion of a prominent Vβ7+ subset. Such findings illustrate the difficulties of predicting and defining the effects of MHC class I diversification on epitope-specific responses.
Developing reading achievement in primary learners of French: inferencing strategies versus exposure to ‘graded readers’

All primary school children in England are to be entitled to learn a foreign language by 2010, based on the belief that an early start is beneficial for language learning in the long run. However, the evidence of the benefits of an early start is inconclusive, and it is also unclear what type of curriculum and pedagogy would be most appropriate for these young-beginner learners. This pilot study of Year 6 (ages 10–11) children learning French aimed to provide some initial evidence that a literacy-based component has a place in a primary language learning curriculum. A group of learners were given an intervention comprising some special materials designed to develop their ‘inferencing strategies’ when confronted with new or unfamiliar French words in short texts. This group was compared with a group of learners who were simply exposed to a diet of ‘graded French readers’ without any strategy instruction. Both groups were, in turn, compared with a control group which continued with their normal learning experience. Both the inferencing strategies group and the graded readers group made significant advances in their reading comprehension, but, further, the inferencing strategies group outperformed the graded readers group in inferencing ability and in the learning of function words. The findings suggest a need to pursue this area of enquiry further with a larger and more controlled study.
Restorative Justice Conference as an Early Response to Young Offenders

Those seeking to deter young offenders from further delinquency will benefit from the information provided in these pages. Recently reported findings of the Office of Juvenile Justice and Delinquency Prevention’s (OJJDP’s) Study Group on Very Young Offenders confirm the seriousness of early offending behavior. Study Group researchers report, for example, that the risk of becoming a more serious offender is two to three times higher for child delinquents (those ages 7–12) than for later onset offenders (Loeber, Farrington, and Petechuk, in press). 2 Child delinquents also account for a relatively high proportion of some types of offenses. They represent 1 in 3 juvenile arrests for arson, 1 in 5 juvenile arrests for vandalism, and 1 in 12 juvenile arrests for violent crime (Loeber and Farrington, 2000). For some young offenders, early involvement in status offenses and delinquency is a stepping stone in a pathway to serious, violent, and chronic offending. Communities should not ignore the delinquent acts and problem behaviors of young offenders in the hope that they will “grow out of it” (Loeber, Farrington, and Petechuk, in press). Because such young offenders have a high likelihood of reoffending, communities should develop and implement effective early interventions for very young offenders.
Similar Processes but Different Environmental Filters for Soil Bacterial and Fungal Community Composition Turnover on a Broad Spatial Scale

Spatial scaling of microorganisms has been demonstrated over the last decade. However, the processes and environmental filters shaping soil microbial community structure on a broad spatial scale still need to be refined and ranked. Here, we compared bacterial and fungal community composition turnovers through a biogeographical approach on the same soil sampling design at a broad spatial scale (area range: 13300 to 31000 km2): i) to examine their spatial structuring; ii) to investigate the relative importance of environmental selection and spatial autocorrelation in determining their community composition turnover; and iii) to identify and rank the relevant environmental filters and scales involved in their spatial variations. Molecular fingerprinting of soil bacterial and fungal communities was performed on 413 soils from four French regions of contrasting environmental heterogeneity (Landes<Burgundy≤Brittany<<South-East) using the systematic grid of French Soil Quality Monitoring Network to evaluate the communities’ composition turnovers. The relative importance of processes and filters was assessed by distance-based redundancy analysis. This study demonstrates significant community composition turnover rates for soil bacteria and fungi, which were dependent on the region. Bacterial and fungal community composition turnovers were mainly driven by environmental selection explaining from 10% to 20% of community composition variations, but spatial variables also explained 3% to 9% of total variance. These variables highlighted significant spatial autocorrelation of both communities unexplained by the environmental variables measured and could partly be explained by dispersal limitations. Although the identified filters and their hierarchy were dependent on the region and organism, selection was systematically based on a common group of environmental variables: pH, trophic resources, texture and land use. Spatial autocorrelation was also important at coarse (80 to 120 km radius) and/or medium (40 to 65 km radius) spatial scales, suggesting dispersal limitations at these scales.
Psychometric Properties of a Spanish Version of the Beck Anxiety Inventory (BAI) in General Population

This is the first study that provides normative, reliability, factor validity and discriminant validity data of the Beck Anxiety Inventory (BAI; Beck, Epstein, Brown, & Steer, 1988) in the Spanish general population. Sanz and Navarro's (2003) Spanish version of the BAI was administered to 249 adults. Factor analyses suggested that the BAI taps a general anxiety dimension comprising two related factors (somatic and affective-cognitive symptoms), but these factors hardly explained any additional variance and, therefore, little information is lost in considering only full-scale scores. Internal consistency estimate for the BAI was high (α = .93). The BAI was correlated . 63 with the BDI-II and . 32 with the Trait-Anger scale of the STAXI 2, but a factor analysis of their items revealed three factors, suggesting that the correlations between the instruments may be better accounted for by relationships between anxiety, depression, and anger, than by problems of discriminant validity. The mean BAI total score and the distribution of BAI scores were similar to those found in other countries. BAI norm scores for the community sample were provided from the total sample and from the male and female subsamples, as females scored higher than males. The utility of these scores for assessing clinical significance of treatment outcomes for anxiety is discussed. Se presentan por primera vez datos normativos, de fiabilidad, validez factorial y validez discriminante del Inventario de Ansiedad de Beck (BAI; Beck, Epstein, Brown y Steer, 1988) en la población general española. La versión española del BAI de Sanz y Navarro (2003) fue administrada a 249 adultos. Los análisis factoriales indicaron que el BAI mide una dimensión general de ansiedad compuesta de dos factores relacionados (somático y afectivo cognitivo), pero estos factores apenas explicaban varianza adicional por lo que no se pierde mucha información al considerar únicamente la puntuación global. La fiabilidad de consistencia interna del BAI fue elevada (alfa = 0,93). El BAI correlacionó 0,63 con el BDI-II y 0,32 con la escala de Ira Rasgo del STAXI 2, pero el análisis factorial de los tres instrumentos reveló que sus ítems formaban tres factores, sugiriendo que las correlaciones entre instrumentos se deben más a la relación entre ansiedad, depresión e ira que a un problema de validez discriminante. La puntuación media en el BAI y la distribución de sus puntuaciones fueron similares a las encontradas en otros países. Se ofrecen baremos para la muestra total y dividida por el sexo, ya que las mujeres puntuaron más alto que los varones, y se discute su utilidad para evaluar la significación clínica de los resultados de los tratamientos para la ansiedad.
It all used to be better? Different generations on continuity and change in urban children's daily use of space

Abstract There is much speculation about children's changing space–time behaviour, yet little is actually known about it. The study reported on here, which was based on oral histories, statistical and archive research, and observations in Amsterdam, compared children's use of space during the 1950s and early 1960s with that of today. The public space of the street used to be a child space, but in two of the three streets studied it has been transformed into an adult space. Conversely, private home space—traditionally the domain of adults—has become a child space. Over time, children's geographies have become more diverse. In addition to the traditional childhood of outdoor children, we distinguish indoor children and children of the backseat generation. These two new types are characterized by a decrease in playing outdoors and an increase in adult supervision. Although this may be regarded as a loss, new children's activities have emerged, outdoors as well as indoors. Contemporary cities can be exciting places for children, but it is clear that inequality by class has become more manifest. Both new geographical childhoods have resulted in a decrease in children's agency, which may have a negative impact on segregation patterns.