Mass spectrometric analysis of PTM dynamics using stable isotope labeled metabolic precursors in cell culture

Biological organisms represent highly dynamic systems, which are continually exposed to environmental factors and always strive to restore steady-state homeostasis. Posttranslational modifications are key regulators with which biological systems respond to external stimuli. To understand how homeostasis is restored, it is important to study the kinetics of posttranslational modifications. In this review we discuss proteomic approaches using stable isotope labeled metabolic precursors to study dynamics of posttranslational modifications in cell culture

‘The night is for sleeping’:how nurses care for conflicting temporal orders in older person care

This paper examines the conflicting temporal orders of the regional nurse, a role which has been introduced to deal with the increasing demands of aged care and workforce shortages in regional settings. We build on ethnographic research in the Netherlands, in which we examine regional district nurses as a new professional role that attends to (sub)acute care needs, connecting and coordinating different places of care during out of office hours. We use the concept of ‘temporal regional order’ to reflect on the different ways caring practices are temporally structured by management and care practitioners, in close interaction with patients and informal care givers. In the results three types of disruptions of the regional temporal order are distinguished: interfering bodily rhythms and needs; (un)expected workings of technologies; and disrupting acts of patient and relatives. It was region nurses’ prime responsibility to stabilise these interferences and prevent or soften a disruption of the regional order. In accomplishing this, we show how nurses craft their professional role in between various care settings, without getting involved too much in patient care, to be mobile as ‘temporal caregivers’.</p

‘The night is for sleeping’:how nurses care for conflicting temporal orders in older person care

This paper examines the conflicting temporal orders of the regional nurse, a role which has been introduced to deal with the increasing demands of aged care and workforce shortages in regional settings. We build on ethnographic research in the Netherlands, in which we examine regional district nurses as a new professional role that attends to (sub)acute care needs, connecting and coordinating different places of care during out of office hours. We use the concept of ‘temporal regional order’ to reflect on the different ways caring practices are temporally structured by management and care practitioners, in close interaction with patients and informal care givers. In the results three types of disruptions of the regional temporal order are distinguished: interfering bodily rhythms and needs; (un)expected workings of technologies; and disrupting acts of patient and relatives. It was region nurses’ prime responsibility to stabilise these interferences and prevent or soften a disruption of the regional order. In accomplishing this, we show how nurses craft their professional role in between various care settings, without getting involved too much in patient care, to be mobile as ‘temporal caregivers’.</p

Caring Peripheries:How care practitioners respond to processes of peripheralization

The centralisation of acute health care is a key policy concern in many countries. Less attention has been given to the side effects of centralisation: peripheralisation, occurring mainly in rural areas and post-industrial towns. In this research, we start filling this gap by exploring how this trend of concentration of health care can contribute to a phenomenon referred to as ‘discursive peripheralisation’. This article contributes to the literature on discursive peripheralisation by focusing on how actors, in our case acute care practitioners, cope with or oppose such processes. We draw on empirical data from two healthcare regions in different geographical contexts in Norway and The Netherlands. In these regions, we zoom in on the work of care practitioners and how they, in relation to care organisations and local authorities, aim to organise care for patients in ‘the periphery’ and how this contributes to more diverse and alternative narratives and practices of health care in these areas. Our findings offer important insights for both rural and regional policy. We conclude that other narratives, for instance, about perceptions of quality of care should be considered to avoid too much emphasis on the disadvantages faced by peripheral areas, compared to their urban counterparts

Bedside Politics and Precarious Care:New Directions of Inquiry in Critical Nursing Studies

Health care systems are facing soaring workforce shortages, challenging their ability to secure timely access to good-quality care. In this context, nurses make difficult decisions about which patients to deliver care to, transfer to other providers, or strategically ignore. Yet, we still know little about how nurses engage in situated practices of bedside rationing. Building on the work of Giorgio Agamben and Judith Butler, we have developed a research agenda that homes in on a politics of bedside rationing. We argue that this agenda is essential to better understand the implications of scarcity for nursing and to explore new ways to cope with challenges faced

Natural isotope correction improves analysis of protein modification dynamics

Stable isotope labelling in combination with high-resolution mass spectrometry approaches are increasingly used to analyze both metabolite and protein modification dynamics. To enable correct estimation of the resulting dynamics, it is critical to correct the measured values for naturally occurring stable isotopes, a process commonly called isotopologue correction or deconvolution. While the importance of isotopologue correction is well recognized in metabolomics, it has received far less attention in proteomics approaches. Although several tools exist that enable isotopologue correction of mass spectrometry data, the majority is tailored for the analysis of low molecular weight metabolites. We here present PICor which has been developed for isotopologue correction of complex isotope labelling experiments in proteomics or metabolomics and demonstrate the importance of appropriate correction for accurate determination of protein modifications dynamics, using histone acetylation as an example

Creativity at the margins: A cross-country case study on how Dutch and Norwegian peripheries address challenges to quality work in care for older persons

Background Peripheral areas are often overlooked in health-care research but they in fact deserve specific attention. Such areas struggle to maintain access to good quality health-care services due to their geographical context. At the same time, new interventions or promising innovations often emerge in places where creativity is urgently needed. In this paper, we explore this creativity at the margins in older persons care organizations in peripheral areas, which other healthcare providers and policymakers can learn from. Methods This exploratory study is based on two large research projects on the quality of care for older persons in Norway and the Netherlands. We performed secondary analysis of interviews with quality managers and other quality workers and used additional document analysis and expert interviews to deepen our analysis. Results The results show that older persons care organizations working in peripheral areas must deal with a number of challenges caused by their geographical context, e.g. geographical distances (between services and to the geographical center), workforce shortages, and landscape characteristics. We found that organizations use different strategies to tackle these challenges, such as scaling up, brightening up and opening up. These strategies, conceptualized as creativity at the margins, impact quality work in different ways, for example by enabling more person-centered care. Conclusion We conclude that both policymakers and research should overcome their peripheral blindness by learning from and supporting creativity at the margins in future policies and research.publishedVersio

Anti-metastatic effects of viral and non-viral mediated Nk4 delivery to tumours

The most common cause of death of cancer sufferers is through the occurrence of metastases. The metastatic behaviour of tumour cells is regulated by extracellular growth factors such as hepatocyte growth factor (HGF), a ligand for the c-Met receptor tyrosine kinase, and aberrant expression/activation of the c-Met receptor is closely associated with metastatic progression. Nk4 (also known as Interleukin (IL)32b) is a competitive antagonist of the HGF c-Met system and inhibits c-Met signalling and tumour metastasis. Nk4 has an additional anti-angiogenic activity independent of its HGF-antagonist function. Angiogenesis-inhibitory as well as cancer-specific apoptosis inducing effects make the Nk4 sequence an attractive candidate for gene therapy of cancer. This study investigates the inhibition of tumour metasasis by gene therapy mediated production of Nk4 by the primary tumour. Optimal delivery of anti-cancer genes is vital in order to achieve the highest therapeutic responses. Non-viral plasmid delivery methods have the advantage of safety and ease of production, providing immediate transgene expression, albeit short-lived in most tumours. Sustained presence of anti-angiogenic molecules is preferable with anti-angiogenic therapies, and the long-term expression mediated by Adeno-associated Virus (AAV) might represent a more appropriate delivery in this respect. However, the incubation time required by AAV vectors to reach appropriate gene expression levels hampers efficacy in many fast-growing murine tumour models. Here, we describe murine trials assessing the effects of Nk4 on the spontaneously metastatic Lewis Lung Carcinoma (LLC) model when delivered to primary tumour via plasmid lipofection or AAV2 vector. Intratumoural AAV-Nk4 administration produced the highest therapeutic response with significant reduction in both primary tumour growth and incidence of lung metastases. Plasmid-mediated therapy also significantly reduced metastatic growth, but with moderate reduction in primary subcutaneous tumour growth. Overall, this study demonstrates the potential for Nk4 gene therapy of metastatic tumours, when delivered by AAV or non-viral methods