Revisiting caveolin trafficking: the end of the caveosome

In this issue, a study by Hayer et al. (2010. J. Cell Biol. doi: 10.1083/jcb.201003086) provides insights into the trafficking of caveolins, the major membrane proteins of caveolae. As well as providing evidence for ubiquitin-mediated endosomal sorting and degradation of caveolin in multivesicular bodies (MVBs), the new findings question the existence of a unique organelle proposed nine years ago, the caveosome

Boundary Crossing in School Governing Bodies: Perspectives from the Business Community

Policy changes to school governance have led to Governing Bodies (GBs) increasingly appointing skilled professionals from the business community. Research into these GBs views governors from business as a threat to lay governors and the stakeholder model (Young, 2017). Whilst there has been exploration of the contributions of business governors, the ways in which business volunteers develop into their new roles as business governors have not been captured. This paper is drawn from an evaluation of Lloyds Banking Group’s (LBG) school governance programme where 18 LBG employees were interviewed throughout the first year in their governor roles. Adapting Young’s (2017) categorisation of knowledge as ‘managerial’, ‘educational’ and ‘lay’, this paper articulates how LBG governors acquired ‘educational’ and ‘lay’ knowledge to transform their practices and how this was underpinned by ‘authenticity’ associated with the stakeholder model (Connolly, 2017). The paper presents perspectives from other GB stakeholders which suggest that the transformation of the LBG governors’ practice impacted upon GBs, with them crossing boundaries between landscapes of practice (Wenger-Trayner and Wenger-Trayner, 2014). The implications are that, within the context of performativity, the wider business sector has a role to play in school governance and understanding governor professional development is key to this

On the cohomology of some exceptional symmetric spaces

This is a survey on the construction of a canonical or "octonionic K\"ahler" 8-form, representing one of the generators of the cohomology of the four Cayley-Rosenfeld projective planes. The construction, in terms of the associated even Clifford structures, draws a parallel with that of the quaternion K\"ahler 4-form. We point out how these notions allow to describe the primitive Betti numbers with respect to different even Clifford structures, on most of the exceptional symmetric spaces of compact type.Comment: 12 pages. Proc. INdAM Workshop "New Perspectives in Differential Geometry" held in Rome, Nov. 2015, to appear in Springer-INdAM Serie

Subcellular mRNA localisation at a glance.

mRNA localisation coupled to translational regulation provides an important means of dictating when and where proteins function in a variety of model systems. This mechanism is particularly relevant in polarised or migrating cells. Although many of the models for how this is achieved were first proposed over 20 years ago, some of the molecular details are still poorly understood. Nevertheless, advanced imaging, biochemical and computational approaches have started to shed light on the cis-acting localisation signals and trans-acting factors that dictate the final destination of localised transcripts. In this Cell Science at a Glance article and accompanying poster, we provide an overview of mRNA localisation, from transcription to degradation, focusing on the microtubule-dependent active transport and anchoring mechanism, which we will use to explain the general paradigm. However, it is clear that there are diverse ways in which mRNAs become localised and target protein expression, and we highlight some of the similarities and differences between these mechanisms.This work was supported by a Wellcome Trust Senior Research Fellowship to I.D. supporting R.M.P. [grant number: 096144], a studentship from the Wellcome Trust to A.D. [grant number: 097304], the University of Cambridge, ISSF to T.T.W. [grant number 097814].This is the final version of the article. It first appeared from the Company of Biologists via http://dx.doi.org/10.1242/jcs.11427

Localized Translation of gurken/TGF-α mRNA during Axis Specification Is Controlled by Access to Orb/CPEB on Processing Bodies.

In Drosophila oocytes, gurken/TGF-α mRNA is essential for establishing the future embryonic axes. gurken remains translationally silent during transport from its point of synthesis in nurse cells to its final destination in the oocyte, where it associates with the edge of processing bodies. Here we show that, in nurse cells, gurken is kept translationally silent by the lack of sufficient Orb/CPEB, its translational activator. Processing bodies in nurse cells have a similar protein complement and ultrastructure to those in the oocyte, but they markedly less Orb and do not associate with gurken mRNA. Ectopic expression of Orb in nurse cells at levels similar to the wild-type oocyte dorso-anterior corner at mid-oogenesis is sufficient to cause gurken mRNA to associate with processing bodies and translate prematurely. We propose that controlling the spatial distribution of translational activators is a fundamental mechanism for regulating localized translation.This work was supported by a studentship from the Wellcome Trust (grant 097304 to A.D.), a Wellcome Trust Senior Research Fellowship (grant 096144 to I.D and supporting R.M.P), the University of Cambridge, ISSF (grant 097814 to T.T.W), and Wellcome Trust Strategic Awards 091911 and 107457 supporting advanced microscopy at Micron Oxford (http://micronoxford.com).This is the author accepted manuscript. The final version is available from Cell Press via http://dx.doi.org/10.1016/j.celrep.2016.02.03

A mechanistic modelling approach for the determination of the mechanisms of inhibition by cyclosporine on the uptake and metabolism of atorvastatin in rat hepatocytes using a high throughput uptake method

(1) Determine the inhibition mechanism through which cyclosporine inhibits the uptake and metabolism of atorvastatin in fresh rat hepatocytes using mechanistic models applied to data generated using a high throughput oil spin method. (2) Atorvastatin was incubated in fresh rat hepatocytes (0.05–150 nmol/ml) with or without 20 min pre-incubation with 10 nmol/ml cyclosporine and sampled over 0.25–60 min using a high throughput oil spin method. Micro-rate constant and macro-rate constant mechanistic models were ranked based on goodness of fit values. (3) The best fitting model to the data was a micro-rate constant mechanistic model including non-competitive inhibition of uptake and competitive inhibition of metabolism by cyclosporine (Model 2). The association rate constant for atorvastatin was 150-fold greater than the dissociation rate constant and 10-fold greater than the translocation into the cell. The association and dissociation rate constants for cyclosporine were 7-fold smaller and 10-fold greater, respectively, than atorvastatin. The simulated atorvastatin-transporter-cyclosporine complex derived using the micro-rate constant parameter estimates increased in line with the incubation concentration of atorvastatin. (4) The increased amount of data generated with the high throughput oil spin method, combined with a micro-rate constant mechanistic model helps to explain the inhibition of uptake by cyclosporine following pre-incubation

Children, family and the state : revisiting public and private realms

The state is often viewed as part of the impersonal public sphere in opposition to the private family as a locus of warmth and intimacy. In recent years this modernist dichotomy has been challenged by theoretical and institutional trends which have altered the relationship between state and family. This paper explores changes to both elements of the dichotomy that challenge this relationship: a more fragmented family structure and more individualised and networked support for children. It will also examine two new elements that further disrupt any clear mapping between state/family and public/private dichotomies: the third party role of the child in family/state affairs and children's application of virtual technology that locates the private within new cultural and social spaces. The paper concludes by examining the rise of the 'individual child' hitherto hidden within the family/state dichotomy and the implications this has for intergenerational relations at personal and institutional levels

Investigating the Period of Practice Needed to Acquire Expertise in Great Britain 2012 Track and Field Olympic Athletes

Deliberate practice theory argues that expertise can be acquired only after 10 years of domain-specific deliberate practice. To assess this prediction, we examined data from track (n = 57) and field (n = 15) athletes representing Great Britain Track and Field team (Team GB) at the 2012 Olympics. We defined the period to excellence as the difference in age between achieving expertise (the first selection for an international senior outdoor athletic championship) and starting age (joining a club, being coached, or engaging in competition). Results indicated that elite track (75.4%) and field (93.3%) athletes acquired expertise in significantly less than 10 years (M = 7.20, SD = 3.20, p < .001). Expertise mostly relying on the anaerobic pathway (n = 51) was acquired significantly faster than expertise mostly utilizing the aerobic pathway (n = 21), 6.15 ± 2.84 years vs. 9.78 ± 2.52 years (p < .001). Those who did not specialize early (n = 40) were faster in acquiring expertise in a new sport than those who specialized early (n = 32), 6.27 ± 2.78 vs. 8.38 ± 3.34 years (p = .005), contrary to deliberate-practice contention that early specialization is critical

Early specialization and critical periods in acquiring expertise: A comparison of Traditional vs. Detection Talent Identification in Team GB Cycling at London 2012

The aim of this study was to compare two methodologies employed by the British Cycling talent identification program. Specifically, the authors investigated cyclists selected to represent GB cycling team at the London 2012 Olympics using (a) a traditional talent identification methodology (British Cycling Olympic Development Program), where selection is based upon race results and (b) a detection talent identification methodology (U.K. Sport Talent Team Program), which is a multi-Olympic event initiative that identifies athletic potential from physical and skill-based tests. To facilitate this comparison, the authors calculated the speed with which expertise was acquired. A Mann–Whitney U test (U = 16.0, p = .031) indicated that the speed of acquiring expertise was quicker in detection talent identification (Mdn = 5.4) than traditional talent identification (Mdn = 7.2). Practice started later with detection talent identification than with traditional talent identification (14.12 years vs. 11.23 years, respectively), which affected the period to excellence. Thus, detection talent identification resulted in an absence of early specialization, which suggests a critical period for attaining cycling expertise. The authors hypothesize a genetic basis of talent and propose that critical periods are important in detection talent identification programs

VIP21, a 21-kD membrane protein is an integral component of trans-Golgi-network-derived transport vesicles

In simple epithelial cells, apical and basolateral proteins are sorted into separate vesicular carriers before delivery to the appropriate plasma membrane domains. To dissect the putative sorting machinery, we have solubilized Golgi-derived transport vesicles with the detergent CHAPS and shown that an apical marker, influenza haemagglutinin (HA), formed a large complex together with several integral membrane proteins. Remarkably, a similar set of CHAPS-insoluble proteins was found after solubilization of a total cellular membrane fraction. This allowed the cloning of a cDNA encoding one protein of this complex, VIP21 (Vesicular Integral-membrane Protein of 21 kD). The transiently expressed protein appeared on the Golgi-apparatus, the plasma membrane and vesicular structures. We propose that VIP21 is a component of the molecular machinery of vesicular transport