Client processing is altered by novel myopathy-causing mutations in the HSP40 J domain

The misfolding and aggregation of proteins is often implicated in the development and progression of degenerative diseases. Heat shock proteins (HSPs), such as the ubiquitously expressed Type II Hsp40 molecular chaperone, DNAJB6, assist in protein folding and disaggregation. Historically, mutations within the DNAJB6 G/F domain have been associated with Limb-Girdle Muscular Dystrophy type 1D, now referred to as LGMDD1, a dominantly inherited degenerative disease. Recently, novel mutations within the J domain of DNAJB6 have been reported in patients with LGMDD1. Since novel myopathy-causing mutations in the Hsp40 J domain have yet to be characterized and both the function of DNAJB6 in skeletal muscle and the clients of this chaperone are unknown, we set out to assess the effect of these mutations on chaperone function using the genetically tractable yeast system. The essential yeast Type II Hsp40, Sis1, is homologous to DNAJB6 and is involved in the propagation of yeast prions. Using phenotypic, biochemical, and functional assays we found that homologous mutations in the Sis1 J domain differentially alter the processing of specific yeast prion strains, as well as a non-prion substrate. These data suggest that the newly-identified mutations in the J domain of DNAJB6 cause aberrant chaperone function that leads to the pathogenesis in LGMDD1

Accuracy of the Semi--Classical Approximation: the Pullen Edmonds Hamiltonian

A test on the numerical accuracy of the semiclassical approximation as a function of the principal quantum number has been performed for the Pullen--Edmonds model, a two--dimensional, non--integrable, scaling invariant perturbation of the resonant harmonic oscillator. A perturbative interpretation is obtained of the recently observed phenomenon of the accuracy decrease on the approximation of individual energy levels at the increase of the principal quantum number. Moreover, the accuracy provided by the semiclassical approximation formula is on the average the same as that provided by quantum perturbation theory.Comment: 12 pages, 5 figures (available upon request to the authors), LaTex, DFPD/93/TH/47, to be published in Nuovo Cimento

Chaotic advection in an archipelago

Author Posting. © American Meteorological Society, 2010. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Physical Oceanography 40 (2010): 1988–2006, doi:10.1175/2010JPO4336.1.Techniques from dynamical systems theory have been applied to study horizontal stirring of fluid in the Philippine Archipelago. The authors’ analysis is based on velocity fields produced by two high-resolution (3 and 6 km) numerical models. Particular attention is paid to identifying robust surface flow patterns and associating them with dominant Lagrangian coherent structures (LCSs). A recurrent wind-driven dipole in the lee of the coastline is considered in detail. The associated LCSs form a template for stirring, exchange, and biological transport in and around the dipole. Chaotic advection is argued to provide a relevant framework for interpreting mesoscale horizontal stirring processes in an archipelago as a whole. Implications for the formation of filaments, the production of tracer variance, and the scale at which stirring leads to mixing are discussed in connection with an observed temperature record.This work was supported by the Office of Naval Research: Grant N00014-07-1-0590 to Woods Hole Oceanographic Institution; Grant ONR- 0601153N to Stevens Institute of Technology; Grant N00014-07-1-0417 to Institute of Marine and Coastal Sciences, Rutgers University; and Grant N00014-09-1- 0582 to Lamont-Doherty Earth Observatory of Columbia University

Geo-statistical methods to analyse changes in pre-Hispanic settlement patterns in the Río Ica catchment, Peru

Within arid regions allochthonous rivers as a main source of fresh water play a significant role in the spatial organisation of human occupation.This study aims at a comprehensive view on changes in the prehistoric occupation patterns within the Río Ica catchment on the southern coast of Peru. Results of different research projects are integrated. The heterogeneous character of the catchment allows us to define three sub-sections which differ greatly in terms of vegetation, relief and water regime.Based on quantitative geo-statistical methods we analyse spatio-temporal changes in human occupation from the Early Horizon (c. 1000–200 BC) through to the Inca Late Horizon (AD 1450–1532) in the context of environmental conditions, as well as socio-economic processes. Examining known archaeological sites we are able to assess the significance of environmental location factors for pre-Hispanic settlements. In addition, areas of high human interaction are identified on the basis of a classification of archaeological sites according to their function (craft/industry, cult, cooperation and trade). We thereby transfer the concept of central place theory to the spatial distribution of archaeological remains, introducing a novel approach to identifying central functions in a spatially explicit way.Our results crystallise the changing character of occupation in the study area over more than two millennia. They contribute to the ongoing debate on the decline of the Nasca culture, endorsing a complex combination of natural and socio-economic reasons. Furthermore, the results support the concept of a more widespread exchange and cooperation during ‘Horizon’ periods in the study area and likewise indicate that the disappearance of a supra-regional administrative polity during ‘Intermediate’ periods might have led to higher human activity in smaller scale societies, as reflected in a more diverse spatial organisation in terms of geomorphometric units and central areas

Using interpretative phenomenological analysis to inform physiotherapy practice: An introduction with reference to the lived experience of cerebellar ataxia

The attached file is a pre-published version of the full and final paper which can be found at the link below.This article has been made available through the Brunel Open Access Publishing Fund.Qualitative research methods that focus on the lived experience of people with health conditions are relatively underutilised in physiotherapy research. This article aims to introduce interpretative phenomenological analysis (IPA), a research methodology oriented toward exploring and understanding the experience of a particular phenomenon (e.g., living with spinal cord injury or chronic pain, or being the carer of someone with a particular health condition). Researchers using IPA try to find out how people make sense of their experiences and the meanings they attach to them. The findings from IPA research are highly nuanced and offer a fine grained understanding that can be used to contextualise existing quantitative research, to inform understanding of novel or underresearched topics or, in their own right, to provoke a reappraisal of what is considered known about a specified phenomenon. We advocate IPA as a useful and accessible approach to qualitative research that can be used in the clinical setting to inform physiotherapy practice and the development of services from the perspective of individuals with particular health conditions.This article is available through the Brunel Open Access Publishing Fund

Validated tools to identify common mental disorders in the perinatal period: A systematic review of systematic reviews.

BACKGROUND: Uncertainty remains regarding the validity of screening tools to detect common mental disorders (CMDs) during perinatal periods. This umbrella review aims to provide an up-to-date summary of psychometric properties of tools for the identification of perinatal CMDs. METHODS: Reviews were identified via Ovid MEDLINE, PsychINFO, EMBASE, Global Health and Cochrane Database of Systematic Reviews electronic databases with no date or language restriction. Pooled sensitivity and specificity estimates and ranges were extracted and summarised using forest plots. Quality assessment was conducted using Measurement Tool to Assess Systematic Reviews (AMSTAR-2). RESULTS: Of 7,891 papers identified, 31 reviews met inclusion criteria. 76 screening tools were identified; most frequently validated were Edinburgh Postnatal Depression Scale (EPDS) (n = 28 reviews), Beck's Depression Inventory (BDI) (n = 13 reviews) and Patient Health Questionnaire (PHQ) (n = 12 reviews). Forest plots demonstrated a pattern of decreasing sensitivity and increasing specificity with increasing cut-off scores. Sub-group analysis of data extracted from low quality reviews demonstrated wider 95% CIs and overall lower specificity. Validity also varied according to ethnicity, socio-economic background and age. LIMITATIONS: Despite a low Covered Corrected Area (CCA) score the primary studies included within reviews overlapped; therefore we were unable perform meta-analysis. CONCLUSIONS: The evidence suggests that the EPDS, PHQ and BDI are useful across a range of diverse settings but the context of tool application is a key factor determining validity. This review highlights that utilizing screening tools in clinical practice is complex and requires careful consideration of the population, context, and health system it will be used in

The globular cluster system of the nearest Seyfert II galaxy Circinus

Context. The globular cluster (GC) system of Circinus galaxy has not been probed previously partly because of the location of the galaxy at - 3.8$^\circ$ Galactic latitude which suffers severely from interstellar extinction, stellar crowding, and Galactic foreground contamination. However, the deep near-infrared (NIR) photometry by the VISTA Variables in the Via L\'actea Extended Survey (VVVX) in combination with the precise astrometry of Gaia EDR3 allow us to map GCs in this region. Aims. Our long-term goal is to study and characterise the distributions of GCs and Ultra-compact dwarfs of Circinus galaxy which is the nearest Seyfert II galaxy. Here we conduct the first pilot search for GCs in this galaxy. Methods. We use NIR VVVX photometry in combination with Gaia EDR3 astrometric features such as astrometric excess noise and BP/RP excess factor to build the first homogeneous catalogue of GCs in Circinus galaxy. A robust combination of selection criteria allows us to effectively clean interlopers from our sample. Results. We report the detection of$\sim$ 70 GC candidates in this galaxy at a 3 $\sigma$ confidence level. They show a bimodal colour distribution with the blue peak at (G-Ks)$_0$ = 0.985$\pm$0.127 mag with a dispersion of 0.211$\pm$0.091 mag and the red peak at (G-Ks)$_0$ = 1.625$\pm$0.177 mag with a dispersion of 0.482$\pm$0.114 mag. A GC specific frequency (S$_N$) of 1.3$\pm$0.2 was derived for the galaxy, and we estimated a total population of 120$\pm$40 GCs. Based on the projected radial distribution it appears that Circinus has a different distribution of GC candidates than MW and M31. Conclusions. We demonstrate that Circinus galaxy hosts a sizeable number of cluster candidates. This result is the first leap towards understanding the evolution of old stellar clusters in this galaxy.Comment: 15 pages, 12 figure

CMB constraints on noncommutative geometry during inflation

We investigate the primordial power spectrum of the density perturbations based on the assumption that spacetime is noncommutative in the early stage of inflation. Due to the spacetime noncommutativity, the primordial power spectrum can lose rotational invariance. Using the k-inflation model and slow-roll approximation, we show that the deviation from rotational invariance of the primordial power spectrum depends on the size of noncommutative length scale L_s but not on sound speed. We constrain the contributions from the spacetime noncommutativity to the covariance matrix for the harmonic coefficients of the CMB anisotropies using five-year WMAP CMB maps. We find that the upper bound for L_s depends on the product of sound speed and slow-roll parameter. Estimating this product using cosmological parameters from the five-year WMAP results, the upper bound for L_s is estimated to be less than 10^{-27} cm at 99.7% confidence level.Comment: 8 pages, 1 figure, References added, Accepted for publication in EPJC (submitted version

Re-evaluating the resource potential of lomas fog oasis environments for Preceramic hunter-gatherers under past ENSO modes on the south coast of Peru

Lomas – ephemeral seasonal oases sustained by ocean fogs – were critical to ancient human ecology on the desert Pacific coast of Peru: one of humanity’s few independent hearths of agriculture and “pristine” civilisation. The role of climate change since the Late Pleistocene in determining productivity and extent of past lomas ecosystems has been much debated. Here we reassess the resource potential of the poorly studied lomas of the south coast of Peru during the long Middle Pre-ceramic period (c. 8,000 – 4,500 BP): a period critical in the transition to agriculture, the onset of modern El Niño Southern Oscillation (‘ENSO’) conditions, and eustatic sea-level rise and stabilisation and beach progradation. Our method combines vegetation survey and herbarium collection with archaeological survey and excavation to make inferences about both Preceramic hunter-gatherer ecology and the changed palaeoenvironments in which it took place. Our analysis of newly discovered archaeological sites – and their resource context – show how lomas formations defined human ecology until the end of the Middle Preceramic Period, thereby corroborating recent reconstructions of ENSO history based on other data. Together, these suggest that a five millennia period of significantly colder seas on the south coast induced conditions of abundance and seasonal predictability in lomas and maritime ecosystems, that enabled Middle Preceramic hunter-gatherers to reduce mobility by settling in strategic locations at the confluence of multiple eco-zones at the river estuaries. Here the foundations of agriculture lay in a Broad Spectrum Revolution that unfolded, not through population pressure in deteriorating environments, but rather as an outcome of resource abundance.We thank the Ministerio de Cultural del Perú for granting permission for archaeological fieldwork (Resolución Directoral Nº 933-2012-DGPC-VMPCIC/MC, 19 December 2012 and Nº 386-2014-DGPA-VMPCIC/MC, 22 August 2014) and the export of samples for dating; Don Alberto Benavides Ganoza and the people of Samaca for facilitating fieldwork; the Leverhulme Trust (grant number RPG-117) and the late Don Alberto Benavides de la Quintana (grant number RG69428) and the McDonald Institute for Archaeological Research for funding Cambridge University’s One River Archaeological Project, and the NERC Radiocarbon facility (grant number NF/2013/2/2) for funding radiocarbon dating. We also thank the Servicio Nacional Forestal y de Fauna Silvestre (SERFOR) and the Servicio Nacional de Áreas Naturales Protegidas por el Estado (SERNANP), Peru for permits for the Proyecto Kew Perú to carry out botanical and ecological survey, and Delsy Trujillo, Eric Ramírez, Consuelo Borda and other participants of the Proyecto Kew Perú: Conservación, Restauración de Hábitats y Medios de Vida Útiles, Ica, Peru.This is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.quascirev.2015.10.02

Visie van de Boergergroep

De BoergerGroep is een netwerk van burgers die met hart en ziel mee willen denken en mee willen praten over het platteland en hoe dat er in de toekomst uit kan zien. Zij hebben daarvoor met elkaar een visie opgesteld, die we hier gepresenteerd wordt. De BoergerGroep wil meedenken over de relatie tussen stad en platteland en welke kant het met de landbouw op moet