Serum-deprivation response of ARPE-19 cells; expression patterns relevant to age-related macular degeneration.

ARPE-19 cells are derived from adult human retinal pigment epithelium (RPE). The response of these cells to the stress of serum deprivation mimics some important processes relevant to age-related macular degeneration (AMD). Here we extend the characterization of this response using RNASeq and EGSEA gene set analysis of ARPE-19 cells over nine days of serum deprivation.

Experimental NOE, Chemical Shift, and Proline Isomerization Data Provide Detailed Insights into Amelotin Oligomerization.

Amelotin is an intrinsically disordered protein (IDP) rich in Pro residues and is involved in hydroxyapatite mineralization. It rapidly oligomerizes under physiological conditions of pH and pressure but reverts to its monomeric IDP state at elevated pressure. We identified a 105-residue segment of the protein that becomes ordered upon oligomerization, and we used pressure-jump NMR spectroscopy to measure long-range NOE contacts that exist exclusively in the oligomeric NMR-invisible state.

Observations of community-based multidisciplinary team meetings in health and social care for older people with long term conditions in England.

Background: Community-based multi-disciplinary teams (MDTs) are the most common means to encourage health and social care service integration in England yet are rarely studied or directly observed. This paper reports on two rounds of non-participant observations of community-based multi-disciplinary team (MDT) meetings in two localities, as part of an evaluation of the Integrated Care and Support Pioneers Programme. We sought to understand how MDT meetings coordinate care and identify their 'added value' over bilateral discussions.

Acquired Disorder and Asymmetry in a Domain-Swapped Model for γ-Crystallin Aggregation.

Misfolding and aggregation of proteins occur in many pathological states. Because of the inherent disorder involved, these processes are difficult to study. We attempted to capture aggregation intermediates of γS-crystallin, a highly stable, internally symmetrical monomeric protein, by crystallization under mildly acidic and oxidizing conditions.

Molecular studies into cell biological role of Copine-4 in Retinal Ganglion Cells.

The molecular mechanisms underlying morphological diversity in retinal cell types are poorly understood. We have previously reported that several members of the Copine family of Ca-dependent membrane adaptors are expressed in Retinal Ganglion Cells and transcriptionally regulated by Brn3 transcription factors. Several Copines are enriched in the retina and their over-expression leads to morphological changes -formation of elongated processes-, reminiscent of neurites, in HEK293 cells.

Retbindin mediates light-damage in mouse retina while its absence leads to premature retinal aging.

Vision requires the transport and recycling of the pigment 11-cis retinaldehyde (retinal) between the retinal pigment epithelium (RPE) and photoreceptors. 11-cis retinal is also required for light-mediated photoreceptor death in dark-adapted mouse eye, probably through overstimulation of rod cells adapted for low light. Retbindin is a photoreceptor-specific protein, of unclear function, that is localized between the RPE and the tips of the photoreceptors.

Public preferences for paying for social care in later life in England: A latent class analysis.

There is ongoing debate about how the funding system for social care of older people in England should best be reformed. We investigated how public attitudes to individual and state responsibility for paying for social care in later life vary with demographic and socio-economic characteristics. Four vignettes of individuals in need of home care or residential care with varying levels of savings, income and housing wealth were presented to a sample of people aged 18-75 years (n = 3000) in December 2018.

Improving Person-Centredness in Integrated Care for Older People: Experiences from Thirteen Integrated Care Sites in Europe.

Introduction: Although person-centredness is a key principle of integrated care, successfully embedding and improving person-centred care for older people remains a challenge. In the context of a cross-European project on integrated care for older people living at home, the objective of this paper is to provide insight at an overarching level, into activities aimed at improving person-centredness within the participating integrated care sites. The paper describes experiences with these activities from the service providers' and service users' perspectives.

COVID-19: Implications for the Support of People with Social Care Needs in England.

This perspective examines the challenge posed by COVID-19 for social care services in England and describes responses to this challenge. People with social care needs experience increased risks of death and deteriorating physical and mental health with COVID-19. Social isolation introduced to reduce COVID-19 transmission may adversely affect well-being.

Amelotin is expressed in retinal pigment epithelium and localizes to hydroxyapatite deposits in dry age-related macular degeneration.

Deposition of hydroxyapatite (HAP) basal to the retinal pigment epithelium (RPE) is linked to the progression of age-related macular degeneration (AMD). Serum-deprivation of RPE cells in culture mimics some features of AMD. We now show that serum-deprivation also leads to the induction of amelotin (AMTN), a protein involved in hydroxyapatite mineralization in enamel.

Exploring improvement plans of fourteen European integrated care sites for older people with complex needs.

Integrated care programmes are increasingly being put in place to provide care to older people living at home. However, knowledge about further improving integrated care is limited. In fourteen integrated care sites in Europe, plans to improve existing ways of working were designed, implemented and evaluated to enlarge the understanding of what works and with what outcomes when improving integrated care.

Funding and planning for social care in later life: a deliberative focus group study.

This study examined people's perceptions and behaviours in relation to planning for their social care needs, and their values and priorities concerning how social care should be funded. Eight deliberative focus groups were conducted in May 2018 with 53 participants, aged 25-82 years, in London, Manchester and rural locations near York and Sheffield. Multiple uncertainties created barriers to planning for social care needs including not knowing how much to save, not thinking it possible for an average person to save enough to meet significant needs, reluctance to plan for something potentially unnecessary, lack of suitable and secure ways of saving, and a perception of social care policy as unsettled.

Evaluating the design and implementation of the whole systems integrated care programme in North West London: why commissioning proved (again) to be the weakest link.

Background: Commissioning is a term used in the English National Health Service (NHS) to refer to what most health systems call health planning or strategic purchasing. Drawing on research from a recent in-depth mixed methods study of a major integrated care initiative in North West London, we examine the role of commissioning in attempts to secure large-scale change within and between health and social care services to support the delivery of integrated care for people living with complex long-term conditions.

Methods: We analysed data collected in semi-structured interviews, surveys, workshops and non-participant observations using a thematic framework derived both deductively from the literature on commissioning and integrated care, as well as inductively from our coding and analysis of interview data.

Measuring Ultra-Weak Protein Self-Association by Non-ideal Sedimentation Velocity.

Ultra-weak self-association can govern the macroscopic solution behavior of concentrated macromolecular solutions ranging from food products to pharmaceutical formulations and the cytosol. For example, it can promote dynamic assembly of multi-protein signaling complexes, lead to intracellular liquid-liquid phase transitions, and seed crystallization or pathological aggregates. Unfortunately, weak self-association is technically extremely difficult to study, as it requires very high protein concentrations where short intermolecular distances cause strongly correlated particle motion.

Correlation of phenotype with genotype and protein structure in RYR1-related disorders.

Variants in the skeletal muscle ryanodine receptor 1 gene (RYR1) result in a spectrum of RYR1-related disorders. Presentation during infancy is typical and ranges from delayed motor milestones and proximal muscle weakness to severe respiratory impairment and ophthalmoplegia. We aimed to elucidate correlations between genotype, protein structure and clinical phenotype in this rare disease population.

The SUSTAIN Project: A European Study on Improving Integrated Care for Older People Living at Home.

Introduction: Integrated care programmes are increasingly being put in place to provide care to older people who live at home. Knowledge of how to further develop integrated care and how to transfer successful initiatives to other contexts is still limited. Therefore, a cross-European research project, called Sustainable Tailored Integrated Care for Older People in Europe (SUSTAIN), has been initiated with a twofold objective: 1.

The klotho-related protein KLPH (lctl) has preferred expression in lens and is essential for expression of clic5 and normal lens suture formation.

KLPH/lctl belongs to the Klotho family of proteins. Expressed sequence tag analyses unexpectedly revealed that KLPH is highly expressed in the eye lens while northern blots showed that expression is much higher in the eye than in other tissues. In situ hybridization in mouse localized mRNA to the lens, particularly in the equatorial epithelium.

Serum starvation of ARPE-19 changes the cellular distribution of cholesterol and Fibulin3 in patterns reminiscent of age-related macular degeneration.

Retinal pigment epithelium (RPE) has been implicated as key source of cholesterol-rich deposits at Bruch's membrane (BrM) and in drusen in aging human eye. We have shown that serum-deprivation of confluent RPE cells is associated with upregulation of cholesterol synthesis and accumulation of unesterified cholesterol (UC). Here we investigate the cellular processes involved in this response.

Crystal Structure of Chicken γS-Crystallin Reveals Lattice Contacts with Implications for Function in the Lens and the Evolution of the βγ-Crystallins.

Previous attempts to crystallize mammalian γS-crystallin were unsuccessful. Native L16 chicken γS crystallized avidly while the Q16 mutant did not. The X-ray structure for chicken γS at 2.

Maturation arrest in early postnatal sensory receptors by deletion of the miR-183/96/182 cluster in mouse.

The polycistronic miR-183/96/182 cluster is preferentially and abundantly expressed in terminally differentiating sensory epithelia. To clarify its roles in the terminal differentiation of sensory receptors in vivo, we deleted the entire gene cluster in mouse germline through homologous recombination. The miR-183/96/182 null mice display impairment of the visual, auditory, vestibular, and olfactory systems, attributable to profound defects in sensory receptor terminal differentiation.

Accumulation of cholesterol and increased demand for zinc in serum-deprived RPE cells.

Purpose: Having observed that confluent ARPE-19 cells (derived from human RPE) survive well in high-glucose serum-free medium (SFM) without further feeding for several days, we investigated the expression profile of RPE cells under the same conditions.

Methods: Expression profiles were examined with microarray and quantitative PCR (qPCR) analyses, followed by western blot analysis of key regulated proteins. The effects of low-density lipoprotein (LDL) and zinc supplementation were examined with qPCR.

Costs and economic consequences of a help-at-home scheme for older people in England.

Solutions to support older people to live independently and reduce the cost of an ageing population are high on the political agenda of most developed countries. Help-at-home schemes offer a mix of community support with the aim to address a range of well-being needs. However, not much is currently known about the costs, outcomes and economic consequences of such schemes.