Composition Dependent Instabilities in Mixtures With Many Components

Understanding the phase behavior of mixtures with many components is important in many contexts, including as a key step toward a physics-based description of intracellular compartmentalization. Here, we study the instabilities of a mixture model where the second virial coefficients are taken as random Gaussian variables. Using tools from free probability theory we obtain the exact spinodal curve and the nature of instabilities for a mixture with an arbitrary composition, thus lifting the assumption of uniform mixture component densities pervading previous studies. We show that, by controlling the volume fraction of only a few components, one can systematically change the nature of the spinodal instability and achieve demixing for realistic scenarios by a strong {\em composition imbalance amplification}. This results from a non-trivial interplay of entropic effects due to non-uniform composition and complexity in the interactions. Our approach allows for the inclusion of any finite number of structured interactions, leading to a competition between different forms of demixing as density is varied

JNK Signalling Regulates Self-Renewal of Proliferative Urine-Derived Renal Progenitor Cells via Inhibition of Ferroptosis

With a global increase in chronic kidney disease patients, alternatives to dialysis and organ transplantation are needed. Stem cell-based therapies could be one possibility to treat chronic kidney disease. Here, we used multipotent urine-derived renal progenitor cells (UdRPCs) to study nephrogenesis. UdRPCs treated with the JNK inhibitor—AEG3482 displayed decreased proliferation and downregulated transcription of cell cycle-associated genes as well as the kidney progenitor markers—SIX2, SALL1 and VCAM1. In addition, levels of activated SMAD2/3, which is associated with the maintenance of self-renewal in UdRPCs, were decreased. JNK inhibition resulted in less efficient oxidative phosphorylation and more lipid peroxidation via ferroptosis, an iron-dependent non-apoptotic cell death pathway linked to various forms of kidney disease. Our study is the first to describe the importance of JNK signalling as a link between maintenance of self-renewal and protection against ferroptosis in SIX2-positive renal progenitor cells

Making hard choices easier: a prospective, multicentre study to assess the efficacy of a fertility-related decision aid in young women with early-stage breast cancer

BACKGROUND: Fertility is a priority for many young women with breast cancer. Women need to be informed about interventions to retain fertility before chemotherapy so as to make good quality decisions. This study aimed to prospectively evaluate the efficacy of a fertility-related decision aid (DA). METHODS: A total of 120 newly diagnosed early-stage breast cancer patients from 19 Australian oncology clinics, aged 18–40 years and desired future fertility, were assessed on decisional conflict, knowledge, decision regret, and satisfaction about fertility-related treatment decisions. These were measured at baseline, 1 and 12 months, and were examined using linear mixed effects models. RESULTS: Compared with usual care, women who received the DA had reduced decisional conflict (β=−1.51; 95%CI: −2.54 to 0.48; P=0.004) and improved knowledge (β=0.09; 95%CI: 0.01–0.16; P=0.02), after adjusting for education, desire for children and baseline uncertainty. The DA was associated with reduced decisional regret at 1 year (β=−3.73; 95%CI: −7.12 to −0.35; P=0.031), after adjusting for education. Women who received the DA were more satisfied with the information received on the impact of cancer treatment on fertility (P<0.001), fertility options (P=0.005), and rated it more helpful (P=0.002), than those who received standard care. CONCLUSION: These findings support widespread use of this DA shortly after diagnosis (before chemotherapy) among younger breast cancer patients who have not completed their families

Age-related differences in exercise and quality of life among breast cancer survivors

Purpose: Physical activity has become a focus of cancer recovery research as it has the potential to reduce treatment-related burden and optimize health-related quality of life (HRQoL). However, the potential for physical activity to influence recovery may be age-dependent. This paper describes physical activity levels and HRQoL among younger and older women after surgery for breast cancer and explores the correlates of physical inactivity. Methods: A population-based sample of breast cancer patients diagnosed in South-East Queensland, Australia, (n=287) were assessed once every three months, from 6 to 18 months post-surgery. The Functional Assessment of Cancer Therapy-Breast questionnaire (FACTB+4) and items from the Behavioral Risk Factor Surveillance System (BRFSS) questionnaire were used to measure HRQoL and physical activity, respectively. Physical activity was assigned metabolic equivalent task (MET) values, and categorized as 3, p<0.05). Conclusions: Age influences the potential to observe HRQoL benefits related to physical activity participation. These results also provide relevant information for the design of exercise interventions for breast cancer survivors and highlights that some groups of women are at greater risk of long-term sedentary behavior

Strength of bacterial adhesion on nanostructured surfaces quantified by substrate morphometry

Microbial adhesion and the subsequent formation of resilient biofilms at surfaces are decisively influenced by substrate properties, such as the topography. To date, studies that quantitatively link surface topography and bacterial adhesion are scarce, as both are not straightforward to quantify. To fill this gap, surface morphometry combined with single-cell force spectroscopy was performed on surfaces with irregular topographies on the nano-scale. As surfaces, hydrophobized silicon wafers were used that were etched to exhibit surface structures in the same size range as the bacterial cell wall molecules. The surface structures were characterized by a detailed morphometric analysis based on Minkowski functionals revealing both qualitatively similar features and quantitatively different extensions. We find that as the size of the nanostructures increases, the adhesion forces decrease in a way that can be quantified by the area of the surface that is available for the tethering of cell wall molecules. In addition, we observe a bactericidal effect, which is more pronounced on substrates with taller structures but does not influence adhesion. Our results can be used for a targeted development of 3D-structured materials for/against bio-adhesion. Moreover, the morphometric analysis can serve as a future gold standard for characterizing a broad spectrum of material structures. © The Royal Society of Chemistry 2019

The response of Monalisa apples to high CO2 storage conditions, harvest maturity and 1-MCP treatment.

This study aimed to determine the effects of harvest maturity, 1-MCP treatment and storage conditions with high CO2 partial pressures on ?Monalisa? apples physicochemical quality and susceptibility to physiological disorders and decay during long-term storage, plus 7 d of shelf life at 22 &#9702;C. The study was composed by two experiments. In Experiment 1, fruit were harvested in one growing season (2011) at the same maturity stage and were treated or not treated with 1-MCP (1 &#956;L L-1). In Experiment 2, fruit were harvested in two growing seasons (2019 and 2020), at two maturity stages. In both experiments, all fruit were stored under CA with four CO2 partial pressure (0.5, 1.5, 3.0 and 4.5 kPa) and regular air (RA, standard of comparison) for 6 or 7 months at 0.8 &#9702;C, plus 7 d shelf life at 22 &#9702;C. CA was very effective on delaying fruit ripening, senescent disorders and decay incidences, regardless of the CO2 partial pressure. However, under CA, ?Monalisa? apples were very susceptible to CO2 injury, expressed as dark flesh browning and cavities that were exacerbated with increasing CO2 partial pressures. Therefore, ?Monalisa? apples should be stored under CA with CO2 no higher than 0.5 kPa. The response of ?Monalisa? apples to high CO2 is more pronounced in late harvested fruit, which were also more prone to develop senescent flesh browning, cracking and rough skin. 1-MCP application had no effect on ?Monalisa? apple susceptibility to CO2 damages, while it reduced fruit softening and acidity loss in both RA and CA storages

Developing a digital intervention for cancer survivors: an evidence-, theory- and person-based approach

This paper illustrates a rigorous approach to developing digital interventions using an evidence-, theory- and person-based approach. Intervention planning included a rapid scoping review which identified cancer survivors’ needs, including barriers and facilitators to intervention success. Review evidence (N=49 papers) informed the intervention’s Guiding Principles, theory-based behavioural analysis and logic model. The intervention was optimised based on feedback on a prototype intervention through interviews (N=96) with cancer survivors and focus groups with NHS staff and cancer charity workers (N=31). Interviews with cancer survivors highlighted barriers to engagement, such as concerns about physical activity worsening fatigue. Focus groups highlighted concerns about support appointment length and how to support distressed participants. Feedback informed intervention modifications, to maximise acceptability, feasibility and likelihood of behaviour change. Our systematic method for understanding user views enabled us to anticipate and address important barriers to engagement. This methodology may be useful to others developing digital interventions

Hsp21potentiates antifungal drug tolerance in Candida albicans

Peer reviewedPublisher PD