Comparative profiling identifies C13orf3 as a component of the Ska complex required for mammalian cell division

Proliferation of mammalian cells requires the coordinated function of many proteins to accurately divide a cell into two daughter cells. Several RNAi screens have identified previously uncharacterised genes that are implicated in mammalian cell division. The molecular function for these genes needs to be investigated to place them into pathways. Phenotypic profiling is a useful method to assign putative functions to uncharacterised genes. Here, we show that the analysis of protein localisation is useful to refine a phenotypic profile. We show the utility of this approach by defining a function of the previously uncharacterised gene C13orf3 during cell division. C13orf3 localises to centrosomes, the mitotic spindle, kinetochores, spindle midzone, and the cleavage furrow during cell division and is specifically phosphorylated during mitosis. Furthermore, C13orf3 is required for centrosome integrity and anaphase onset. Depletion by RNAi leads to mitotic arrest in metaphase with an activation of the spindle assembly checkpoint and loss of sister chromatid cohesion. Proteomic analyses identify C13orf3 (Ska3) as a new component of the Ska complex and show a direct interaction with a regulatory subunit of the protein phosphatase PP2A. All together, these data identify C13orf3 as an important factor for metaphase to anaphase progression and highlight the potential of combined RNAi screening and protein localisation analyses

Primary care physician attitudes towards using a secure web-based portal designed to facilitate electronic communication with patients

Background Patient demand for email contact with physician practices is high. If physicians met this demand, improvements in communication, quality of care and patient satisfaction could result. However, physicians have typically been hesitant to communicate electronically with patients, largely due to concerns relating to workload, security and lack of compensation. Goal To assess physician attitudes towards electronic communication with patients six months after the implementation of an application called Patient Gateway. Patient Gateway allows patients to access an extract of their medical record and facilitates online communication with medical practices. Methods A paper-based survey was administered to the 43 primary care physicians in one integrated delivery system, with a 56% (24/43) response rate. Results Overall, physicians felt that Patient Gateway’s impact on their practices was positive, especially in the areas of refill and referral request management and appointment scheduling. However, physicians are still hesitant to increase general electronic communication with patients; none opted to use Patient Gateway’s general messaging function with patients, and those who had previously used outside systems to exchange emails with some patients continued to communicate with only a small proportion of their patient panel in this way. However, 38% of physicians already communicate with their own physicians via email, and another 19% would like to do so. Conclusions Physicians’ fears about being overwhelmed with messages were not realised. While physicians were generally enthusiastic about the application, none used it directly to communicate with patients. Over three-quarters of respondents indicated that they would be more enthusiastic about electronic communication with patients if this time were compensated

A Synthetic Interaction Screen Identifies Factors Selectively Required for Proliferation and TERT Transcription in p53-Deficient Human Cancer Cells

Numerous genetic and epigenetic alterations render cancer cells selectively dependent on specific genes and regulatory pathways, and represent potential vulnerabilities that can be therapeutically exploited. Here we describe an RNA interference (RNAi)-based synthetic interaction screen to identify genes preferentially required for proliferation of p53-deficient (p53-) human cancer cells. We find that compared to p53-competent (p53+) human cancer cell lines, diverse p53- human cancer cell lines are preferentially sensitive to loss of the transcription factor ETV1 and the DNA damage kinase ATR. In p53- cells, RNAi-mediated knockdown of ETV1 or ATR results in decreased expression of the telomerase catalytic subunit TERT leading to growth arrest, which can be reversed by ectopic TERT expression. Chromatin immunoprecipitation analysis reveals that ETV1 binds to a region downstream of the TERT transcriptional start-site in p53- but not p53+ cells. We find that the role of ATR is to phosphorylate and thereby stabilize ETV1. Our collective results identify a regulatory pathway involving ETV1, ATR, and TERT that is preferentially important for proliferation of diverse p53- cancer cells

Infants on the move: bibliometric analyses of observational vs. digital means of screening infant development

Neurodevelopmental disorders are on the rise, yet their average diagnosis is after 4.5 years old. This delay is partly due to reliance on social-communication criteria, which require longer maturation than scaffolding elements of neuromotor control. Much earlier criteria could include reflexes, monitoring of the quality of spontaneous movements from central pattern generators and maturation of intentional movements and their overall sensation. General Movement Assessment (GMA) studies these features using observational means, but the last two decades have seen a surge in digital tools that enable non-invasive, continuous tracking of infants’ spontaneous movements. Despite their importance, these tools are not yet broadly used. In this work, using CiteSpace, VOSViewer and SciMAT software, we investigate the evolution of the literature on GMA and the methods in use today, to estimate how digital techniques are being adopted. To that end, we created maps of key word co-occurrence networks, co-author networks, document co-citation analysis and strategic diagrams of 295 publications based on a search in the Web of Science, Dimensions and SCOPUS databases for: ‘general movement assessment’ OR ‘general movements assessment’. The nodes on the maps were categorized by size, cluster groups and year of publication. We found that the state-of-the-art methodology to diagnose neurodevelopmental disorders still relies heavily on observation. Several groups in classical GMA research have branched out to incorporate new techniques, but few groups have adopted digital means. We report on additional analyses of methods and biosensors usage and propose that combining traditional clinical observation criteria with digital means may allow earlier diagnoses and interventional therapies for infants

A multi-center study of their physicochemical characteristics, cell culture and in vivo experiments

PVP-capped silver nanoparticles with a diameter of the metallic core of 70 nm, a hydrodynamic diameter of 120 nm and a zeta potential of −20 mV were prepared and investigated with regard to their biological activity. This review summarizes the physicochemical properties (dissolution, protein adsorption, dispersability) of these nanoparticles and the cellular consequences of the exposure of a broad range of biological test systems to this defined type of silver nanoparticles. Silver nanoparticles dissolve in water in the presence of oxygen. In addition, in biological media (i.e., in the presence of proteins) the surface of silver nanoparticles is rapidly coated by a protein corona that influences their physicochemical and biological properties including cellular uptake. Silver nanoparticles are taken up by cell-type specific endocytosis pathways as demonstrated for hMSC, primary T-cells, primary monocytes, and astrocytes. A visualization of particles inside cells is possible by X-ray microscopy, fluorescence microscopy, and combined FIB/SEM analysis. By staining organelles, their localization inside the cell can be additionally determined. While primary brain astrocytes are shown to be fairly tolerant toward silver nanoparticles, silver nanoparticles induce the formation of DNA double-strand-breaks (DSB) and lead to chromosomal aberrations and sister-chromatid exchanges in Chinese hamster fibroblast cell lines (CHO9, K1, V79B). An exposure of rats to silver nanoparticles in vivo induced a moderate pulmonary toxicity, however, only at rather high concentrations. The same was found in precision-cut lung slices of rats in which silver nanoparticles remained mainly at the tissue surface. In a human 3D triple-cell culture model consisting of three cell types (alveolar epithelial cells, macrophages, and dendritic cells), adverse effects were also only found at high silver concentrations. The silver ions that are released from silver nanoparticles may be harmful to skin with disrupted barrier (e.g., wounds) and induce oxidative stress in skin cells (HaCaT). In conclusion, the data obtained on the effects of this well-defined type of silver nanoparticles on various biological systems clearly demonstrate that cell-type specific properties as well as experimental conditions determine the biocompatibility of and the cellular responses to an exposure with silver nanoparticles

A Genome-Scale DNA Repair RNAi Screen Identifies SPG48 as a Novel Gene Associated with Hereditary Spastic Paraplegia

We have identified a novel gene in a genome-wide, double-strand break DNA repair RNAi screen and show that is involved in the neurological disease hereditary spastic paraplegia

They've Come Loose: Brazilian and Bolivian Microsolutions as Viable Options for Aiding Street Children

There is a street child phenomenon that can be observed in various large urban centers throughout Latin America. A product of increasing poverty and other complex factors, street children are ultimately extremely poor children who have “come loose” from traditional family structures. In developing countries, such as Brazil and Bolivia, where street children are common, factors such as the rise of global capitalism, the economic policies of institutions such as the IMF and World Bank, increased rural to urban migration, unemployment, the extreme polarization of income, and political corruption make the issues of urban poverty and poor street children virtually impossible to isolate and examine on their own. Methodology includes a literature review, and examination of the problems that lead to urban poverty and the problems street children face in Bolivia and Brazil

Person-centred Healthcare in CMHTs: Developing the delivery of person-centred healthcare in CMHTs taking a collaborative perspective

This report presents the results of a study on how Community Mental Health Teams (CMHTs) within the NHS Highland understand and deliver person-centred healthcare (PCH). PCH is a dominant principle and an explicit standard in current policy initiatives. Based on a mixedmethod research design, the study summarizes facets attributed to PCH by mental healthcare practitioners. Furthermore, it identifies factors which are argued to support or inhibit the effectiveness and efficiency of PCH-delivery. Collaborative team work and integrated systems are considered as pivotal elements. Within the context of community services in the Scottish Highlands, region-specific constraints to teamwork and collaboration are discussed. The study identifies possible relationship and communication issues within and beyond CMHT-boundaries resulting from differences across professions and agencies, different notions of responsibility and different models of care. It is these differences and similarities that can get in the way of or help facilitate collaborative and integrated teamwork. Semi-structured interviews and a questionnaire survey are used to explore these issues with CMHT-members