Superresolution microscopy reveals a dynamic picture of cell polarity maintenance during directional growth

Polar (directional) cell growth, a key cellular mechanism shared among a wide range of species, relies on targeted insertion of new material at specific locations of the plasma membrane. How these cell polarity sites are stably maintained during massive membrane insertion has remained elusive. Conventional live-cell optical microscopy fails to visualize polarity site formation in the crowded cell membrane environment because of its limited resolution. We have used advanced live-cell imaging techniques to directly observe the localization, assembly, and disassembly processes of cell polarity sites with high spatiotemporal resolution in a rapidly growing filamentous fungus, Aspergillus nidulans. We show that the membrane-associated polarity site marker TeaR is transported on microtubules along with secretory vesicles and forms a protein cluster at that point of the apical membrane where the plus end of the microtubule touches. There, a small patch of membrane is added through exocytosis, and the TeaR cluster gets quickly dispersed over the membrane. There is an incessant disassembly and reassembly of polarity sites at the growth zone, and each new polarity site locus is slightly offset from preceding ones. On the basis of our imaging results and computational modeling, we propose a transient polarity model that explains how cell polarity is stably maintained during highly active directional growth

Superresolution microscopy reveals a dynamic picture of cell polarity maintenance during directional growth

Polar (directional) cell growth, a key cellular mechanism shared among a wide range of species, relies on targeted insertion of new material at specific locations of the plasma membrane. How these cell polarity sites are stably maintained during massive membrane insertion has remained elusive. Conventional live-cell optical microscopy fails to visualize polarity site formation in the crowded cell membrane environment because of its limited resolution. We have used advanced live-cell imaging techniques to directly observe the localization, assembly, and disassembly processes of cell polarity sites with high spatiotemporal resolution in a rapidly growing filamentous fungus, Aspergillus nidulans. We show that the membrane-associated polarity site marker TeaR is transported on microtubules along with secretory vesicles and forms a protein cluster at that point of the apical membrane where the plus end of the microtubule touches. There, a small patch of membrane is added through exocytosis, and the TeaR cluster gets quickly dispersed over the membrane. There is an incessant disassembly and reassembly of polarity sites at the growth zone, and each new polarity site locus is slightly offset from preceding ones. On the basis of our imaging results and computational modeling, we propose a transient polarity model that explains how cell polarity is stably maintained during highly active directional growth

Ensuring meiotic DNA break formation in the mouse pseudoautosomal region

In mice, the pseudoautosomal region of the sex chromosomes undergoes a dynamic structural rearrangement to promote a high rate of DNA double-strand breaks and to ensure X-Y recombination. Sex chromosomes in males of most eutherian mammals share only a small homologous segment, the pseudoautosomal region (PAR), in which the formation of double-strand breaks (DSBs), pairing and crossing over must occur for correct meiotic segregation(1,2). How cells ensure that recombination occurs in the PAR is unknown. Here we present a dynamic ultrastructure of the PAR and identify controlling cis- and trans-acting factors that make the PAR the hottest segment for DSB formation in the male mouse genome. Before break formation, multiple DSB-promoting factors hyperaccumulate in the PAR, its chromosome axes elongate and the sister chromatids separate. These processes are linked to heterochromatic mo-2 minisatellite arrays, and require MEI4 and ANKRD31 proteins but not the axis components REC8 or HORMAD1. We propose that the repetitive DNA sequence of the PAR confers unique chromatin and higher-order structures that are crucial for recombination. Chromosome synapsis triggers collapse of the elongated PAR structure and, notably, oocytes can be reprogrammed to exhibit spermatocyte-like levels of DSBs in the PAR simply by delaying or preventing synapsis. Thus, the sexually dimorphic behaviour of the PAR is in part a result of kinetic differences between the sexes in a race between the maturation of the PAR structure, formation of DSBs and completion of pairing and synapsis. Our findings establish a mechanistic paradigm for the recombination of sex chromosomes during meiosis.Peer reviewe

Underwater Leidenfrost nanochemistry for creation of size-tailored zinc peroxide cancer nanotherapeutics

The dynamic underwater chemistry seen in nature is inspiring for the next generation of eco-friendly nanochemistry. In this context, green synthesis of size-tailored nanoparticles in a facile and scalable manner via a dynamic process is an interesting challenge. Simulating the volcano-induced dynamic chemistry of the deep ocean, here we demonstrate the Leidenfrost dynamic chemistry occurring in an underwater overheated confined zone as a new tool for customized creation of nanoclusters of zinc peroxide. The hydrodynamic nature of the phenomenon ensures eruption of the nanoclusters towards a much colder region, giving rise to growth of monodisperse, size-tailored nanoclusters. Such nanoparticles are investigated in terms of their cytotoxicity on suspension and adherent cells to prove their applicability as cancer nanotherapeutics. Our research can pave the way for employment of the dynamic green nanochemistry in facile, scalable fabrication of size-tailored nanoparticles for biomedical applications.Peer reviewe

Economic hardship associated with managing chronic illness: a qualitative inquiry

<p>Abstract</p> <p>Background</p> <p>Chronic illness and disability can have damaging, even catastrophic, socioeconomic effects on individuals and their households. We examined the experiences of people affected by chronic heart failure, complicated diabetes and chronic obstructive pulmonary disease to inform patient centred policy development. This paper provides a first level, qualitative understanding of the economic impact of chronic illness.</p> <p>Methods</p> <p>Interviews were conducted with patients aged between 45 and 85 years who had one or more of the index conditions and family carers from the Australian Capital Territory and Western Sydney, Australia (n = 66). Content analysis guided the interpretation of data.</p> <p>Results</p> <p>The affordability of medical treatments and care required to manage illness were identified as the key aspects of economic hardship, which compromised patients' capacity to proactively engage in self-management and risk reduction behaviours. Factors exacerbating hardship included ineligibility for government support, co-morbidity, health service flexibility, and health literacy. Participants who were on multiple medications, from culturally and linguistically diverse or Indigenous backgrounds, and/or not in paid employment, experienced economic hardship more harshly and their management of chronic illness was jeopardised as a consequence. Economic hardship was felt among not only those ineligible for government financial supports but also those receiving subsidies that were insufficient to meet the costs of managing long-term illness over and above necessary daily living expenses.</p> <p>Conclusion</p> <p>This research provides insights into the economic stressors associated with managing chronic illness, demonstrating that economic hardship requires households to make difficult decisions between care and basic living expenses. These decisions may cause less than optimal health outcomes and increased costs to the health system. The findings support the necessity of a critical analysis of health, social and welfare policies to identify cross-sectoral strategies to alleviate such hardship and improve the affordability of managing chronic conditions. In a climate of global economic instability, research into the economic impact of chronic illness on individuals' health and well-being and their disease management capacity, such as this study, provides timely evidence to inform policy development.</p

Drivers of Health Care Expenditure: Does Baumol's Cost Disease Loom Large?

According to Baumol (1993) health care epitomises Baumol's cost disease. Sectors that suffer from Baumol's cost disease are characterised by slow productivity growth due to a high labour coefficient. As a result, unit costs of these sectors rise inexorably if the respective wages increase with productivity growth of the progressive industries such as manufacturing. Thus, according to Baumol (1993) the secular rise in health-care expenditure has been unavoidable. This present paper demonstrates that health care is contracted by Baumol's cost disease, but only to a minor extent. Consequently, policy-makers have more leeway to curbever-increasing health-care expenditure than is suggested by Baumol (1993) and other authors. In addition, we test the implications of Baumol's cost disease for health care by avoiding the well-known flaws in constructing medical price indices. Therefore, the adjusted Baumol variable derived in this paper is also extremely appropriate to test the validity of Baumol's cost diseases of other service industries such as education or the live performing arts. Additionally, our analysis suggests that health care is rather a necessity than a luxury at the national level, which conflicts with macroeconomic evidence provided in the relevant literature

Measuring Distributional Effects of Fiscal Reforms

The purpose of this paper is to provide an overview of how to analyse the distributional effects of fiscal reforms. Thereby, distributional effects shall be differentiated by four subconcepts, i.e. 1.) the traditional concept of inequality, 2.) the rather novel concept of polarisation, 3.) the concept of progression in taxation, and 4.) the concepts of income poverty and richness. The concept of inequality and the concept of income poverty are the by far most widely applied concepts in empirical analyses, probably since they appear to be the most transparent ones in their structure as well as the most controversial ones in political affairs. However, the concepts of richness, polarisation and progression in taxation shall additionally be subject of this analysis, since they appear to be useful devices on the course of analysing cause and effect of the other two concepts

Effect of the relative shift between the electron density and temperature pedestal position on the pedestal stability in JET-ILW and comparison with JET-C

The electron temperature and density pedestals tend to vary in their relative radial positions, as observed in DIII-D (Beurskens et al 2011 Phys. Plasmas 18 056120) and ASDEX Upgrade (Dunne et al 2017 Plasma Phys. Control. Fusion 59 14017). This so-called relative shift has an impact on the pedestal magnetohydrodynamic (MHD) stability and hence on the pedestal height (Osborne et al 2015 Nucl. Fusion 55 063018). The present work studies the effect of the relative shift on pedestal stability of JET ITER-like wall (JET-ILW) baseline low triangularity (\u3b4) unseeded plasmas, and similar JET-C discharges. As shown in this paper, the increase of the pedestal relative shift is correlated with the reduction of the normalized pressure gradient, therefore playing a strong role in pedestal stability. Furthermore, JET-ILW tends to have a larger relative shift compared to JET carbon wall (JET-C), suggesting a possible role of the plasma facing materials in affecting the density profile location. Experimental results are then compared with stability analysis performed in terms of the peeling-ballooning model and with pedestal predictive model EUROPED (Saarelma et al 2017 Plasma Phys. Control. Fusion). Stability analysis is consistent with the experimental findings, showing an improvement of the pedestal stability, when the relative shift is reduced. This has been ascribed mainly to the increase of the edge bootstrap current, and to minor effects related to the increase of the pedestal pressure gradient and narrowing of the pedestal pressure width. Pedestal predictive model EUROPED shows a qualitative agreement with experiment, especially for low values of the relative shift