The role of SQSTM1 (p62) in mitochondrial function and clearance in human cortical neurons.

Sequestosome-1 (SQSTM1/p62) is involved in cellular processes such as autophagy and metabolic reprogramming. Mutations resulting in the loss of function of SQSTM1 lead to neurodegenerative diseases including frontotemporal dementia. The pathogenic mechanism that contributes to SQSTM1-related neurodegeneration has been linked to its role as an autophagy adaptor, but this is poorly understood, and its precise role in mitochondrial function and clearance remains to be clarified. Here, we assessed the importance of SQSTM1 in human induced pluripotent stem cell (iPSC)-derived cortical neurons through the knockout of SQSTM1. We show that SQSTM1 depletion causes altered mitochondrial gene expression and functionality, as well as autophagy flux, in iPSC-derived neurons. However, SQSTM1 is not essential for mitophagy despite having a significant impact on early PINK1-dependent mitophagy processes including PINK1 recruitment and phosphorylation of ubiquitin on depolarized mitochondria. These findings suggest that SQSTM1 is important for mitochondrial function rather than clearance

The slope of the mass profile and the tilt of the fundamental plane in early-type galaxies

We present a survey, using the Chandra X-ray observatory, of the central gravitating mass profiles in a sample of 10 galaxies, groups and clusters, spanning ~2 orders of magnitude in virial mass. We find the total mass distributions from ~0.2--10Re, where Re is the optical effective radius of the central galaxy, are remarkably similar to powerlaw density profiles. The negative logarithmic slope of the mass density profiles, alpha, systematically varies with Re, from alpha=2, for systems with Re~4kpc to alpha=1.2 for systems with Re>30kpc. Departures from hydrostatic equilibrium are likely to be small and cannot easily explain this trend. We show that the conspiracy between the baryonic (Sersic) and dark matter (NFW/ Einasto) components required to maintain a powerlaw total mass distribution naturally predicts an anti-correlation between alpha and Re that is very close to what is observed. The systematic variation of alpha with Re implies a dark matter fraction within Re that varies systematically with the properties of the galaxy in such a manner as to reproduce, without fine tuning, the observed tilt of the fundamental plane. We speculate that establishing a nearly powerlaw total mass distribution is therefore a fundamental feature of galaxy formation and the primary factor which determines the tilt of the fundamental plane.Comment: 10 pages, 5 figures, 2 tables. Accepted for publication in MNRAS. Minor revisions to match accepted versio

Cine documental y periodismo : una discusión sobre ética y estética a través de obras estatales

El cinema documental, degut a la seva particular relació amb la realitat, sovint es considera com una eina periodística -i es jutjat com a tal. No obstant això, aquesta relació es complexa y dona lloc a un gran debat sobre la vocació ètica o estètica d'aquestes obres. Aquest treball pretén un apropament al debat a través de l'anàlisi d'una variada selecció de peces d'àmbit estatal. Finalment, es vol arribar a una comprensió més profunda del gènere i el seu potencial informatiu.El cine documental, por su particular relación con la realidad, a menudo es considerado como una herramienta periodística -y es juzgado como tal. Sin embargo, esta relación es compleja y da lugar a un amplio debate sobre la vocación ética o estética de estas obras. Este trabajo pretende un acercamiento a ese debate a través del análisis de una variada selección de piezas de ámbito estatal. La intención es llegar a una comprensión más profunda del género y de su potencial informativo.Due to their specific relationship with reality, documentary films are often regarded as journalistic tools -and are assessed as such. However, this relationship is complex and gives way to a large debate regarding the ethical or aesthetical purposes of these films. This paper aims to get closer to the debate with an analysis of a varied selection of Spanish works. The final intention is to reach a deeper understanding of this genre and its informational potential

The midbrain to pons ratio: a simple and specific MRI sign of progressive supranuclear palsy.

MRI-based measurements used to diagnose progressive supranuclear palsy (PSP) typically lack pathologic verification and are not easy to use routinely. We aimed to develop in histologically proven disease a simple measure of the midbrain and pons on sagittal MRI to identify PSP

The Photometric Properties of Isolated Early-Type Galaxies

Isolated galaxies are important since they probe the lowest density regimes inhabited by galaxies. We define a sample of 36 nearby isolated early-type galaxies for further study. Our isolation criteria require them to have no comparable-mass neighbours within 2 B-band magnitudes, 0.67 Mpc in the plane of the sky and 700 km/s in recession velocity. New wide-field optical imaging of 10 isolated galaxies with the Anglo-Australian Telescope confirms their early-type morphology and relative isolation. We also present imaging of 4 galaxy groups as a control sample. The isolated galaxies are shown to be more gravitationally isolated than the group galaxies. We find that the isolated early-type galaxies have a mean effective colour of (B-R)_e = 1.54 +/- 0.14, similar to their high-density counterparts. They reveal a similar colour-magnitude relation slope and small intrinsic scatter to cluster ellipticals. They also follow the Kormendy relation of surface brightness versus size for luminous cluster galaxies. Such properties suggest that the isolated galaxies formed at a similar epoch to cluster galaxies, such that the bulk of their stars are very old. However, our galaxy modelling reveals evidence for dust lanes, plumes, shells, boxy and disk isophotes in four out of nine galaxies. Thus at least some isolated galaxies have experienced a recent merger/accretion event which may have induced a small burst of star formation. We derive luminosity functions for the isolated galaxies and find a faint slope of -1.2, which is similar to the `universal' slope found in a wide variety of environments. We examine the number density distribution of galaxies in the field of the isolated galaxies.Comment: 16 pages, Latex, 17 figures, 6 tables, MNRAS in pres

Recent developments in German corporate governance.

This paper provides an overview of the German corporate governance system. We review the governance role of large shareholders, creditors, the product market and the supervisory board. We also discuss the importance of mergers and acquisitions, the market in block trades, and the lack of a hostile takeover market. Given that Germany is often referred to as a bank-based economy, we pay particular attention to the role of the universal banks (Hausbanken). We show that the German system is characterised by a market for partial corporate control, large shareholders and bank/creditor monitoring, a two-tier (management and supervisory) board with co-determination between shareholders and employees on the supervisory board, a disciplinary product-market, and corporate governance regulation largely based on EU directives but with deep roots in the German codes and legal doctrine. Another important feature of the German system is its corporate governance efficiency criterion which is focused on the maximisation of stakeholder value rather than shareholder value. However, the German corporate governance system has experienced many important changes over the last decade. First, the relationship between ownership or control concentration and profitability has changed over time. Second, the pay-for-performance relation is influenced by large shareholder control: in firms with controlling blockholders and when a universal bank is simultaneously an equity- and debtholder, the pay-for-performance relation is lower than in widely-held firms or blockholder-controlled firms. Third, since 1995 several major regulatory initiatives (including voluntary codes) have increased transparency and accountability

The differential effects of core stabilization exercise regime and conventional physiotherapy regime on postural control parameters during perturbation in patients with movement and control impairment chronic low back pain

<p>Abstract</p> <p>Background</p> <p>The purpose of the present study was to examine the differential effect of core stability exercise training and conventional physiotherapy regime on altered postural control parameters in patients with chronic low back pain (CLBP). As heterogeneity in CLBP population moderates the effect of intervention on outcomes, in this study, interventions approaches were used based on sub-groups of CLBP.</p> <p>Methods</p> <p>This was an allocation concealed, blinded, sequential and pragmatic control trial. Three groups of participants were investigated during postural perturbations: 1) CLBP patients with movement impairment (n = 15, MI group) randomized to conventional physiotherapy regime 2) fifteen CLBP patients with control impairment randomized to core stability group (CI group) and 3) fifteen healthy controls (HC).</p> <p>Results</p> <p>The MI group did not show any significant changes in postural control parameters after the intervention period however they improved significantly in disability scores and fear avoidance belief questionnaire work score (P < 0.05). The CI group showed significant improvements in Fx, Fz, and My variables (p < 0.013, p < 0.006, and p < 0.002 respectively with larger effect sizes: Hedges's g > 0.8) after 8 weeks of core stability exercises for the adjusted p values. Postural control parameters of HC group were analyzed independently with pre and post postural control parameters of CI and MI group. This revealed the significant improvements in postural control parameters in CI group compared to MI group indicating the specific adaptation to the core stability exercises in CI group. Though the disability scores were reduced significantly in CI and MI groups (p < 0.001), the post intervention scores between groups were not found significant (p < 0.288). Twenty percentage absolute risk reduction in flare-up rates during intervention was found in CI group (95% CI: 0.69-0.98).</p> <p>Conclusions</p> <p>In this study core stability exercise group demonstrated significant improvements after intervention in ground reaction forces (Fz, Mz; g > 0.8) indicating changes in load transfer patterns during perturbation similar to HC group.</p> <p>Trial registration</p> <p>UTRN095032158-06012009423714</p

Movement control tests of the low back; evaluation of the difference between patients with low back pain and healthy controls

<p>Abstract</p> <p>Background</p> <p>To determine whether there is a difference between patients with low back pain and healthy controls in a test battery score for movement control of the lumbar spine.</p> <p>Methods</p> <p>This was a case control study, carried out in five outpatient physiotherapy practices in the German-speaking part of Switzerland. Twelve physiotherapists tested the ability of 210 subjects (108 patients with non-specific low back pain and 102 control subjects without back pain) to control their movements in the lumbar spine using a set of six tests. We observed the number of positive tests out of six (mean, standard deviation and 95% confidence interval of the mean). The significance of the differences between the groups was calculated with Mann-Whitney U test and <it>p </it>was set on <0.05. The effect size (d) between the groups was calculated and d>0.8 was considered a large difference.</p> <p>Results</p> <p>On average, patients with low back pain had 2.21(95%CI 1.94–2.48) positive tests and the healthy controls 0.75 (95%CI 0.55–0.95). The effect size was d = 1.18 (p < 0.001). There was a significant difference between acute and chronic (p < 0.01), as well as between subacute and chronic patient groups (p < 0.03), but not between acute and subacute patient groups (p > 0.7).</p> <p>Conclusion</p> <p>This is the first study demonstrating a significant difference between patients with low back pain and subjects without back pain regarding their ability to actively control the movements of the low back. The effect size between patients with low back pain and healthy controls in movement control is large.</p