Direct numerical simulation of a 2D-stented aortic heart valve at physiological flow rates

We study the nonlinear interaction of an aortic heart valve, composed of hyperelastic corrugated leaflets of finite density attached to a stented vessel under physiological flow conditions. In our numerical simulations, we use a 2D idealised representation of this arrangement. Blood flow is caused by a time-varying pressure gradient that mimics that of the aortic valve and corresponds to a peak Reynolds number equal to 4050. Here, we fully account for the shear-thinning behaviour of the blood and large deformations and contact between the leaflets by solving the momentum and mass balances for blood and leaflets. The mixed finite element/Galerkin method along with linear discontinuous Lagrange multipliers for coupling the fluid and elastic domains is adopted. Moreover, a series of challenging numerical issues such as the finite length of the computational domain and the conditions that should be imposed on its inflow/outflow boundaries, the accurate time integration of the parabolic and hyperbolic momentum equations, the contact between the leaflets and the non-conforming mesh refinement in part of the domain are successfully resolved. Calculations for the velocity and the shear stress fields of the blood reveal that boundary layers appear on both sides of a leaflet. The one along the ventricular side transfers blood with high momentum from the core region of the vessel to the annulus or the sinusoidal expansion, causing the continuous development of flow instabilities. At peak systole, vortices are convected in the flow direction along the annulus of the vessel, whereas during the closure stage of the valve, an extremely large vortex develops in each half of the flow domain.     

Proteomics advances for precision therapy in ovarian cancer

ABSTRACT

Introduction: Due to the relatively low mutation rate and high frequency of copy number variation, finding actionable genetic drivers of high-grade serous carcinoma (HGSC) is a challenging task. Furthermore, emerging studies show that genetic alterations are frequently poorly represented at the protein level adding a layer of complexity. With improvements in large-scale proteomic technologies, proteomics studies have the potential to provide robust analysis of the pathways driving high HGSC behavior.

Areas covered: This review summarizes recent large-scale proteomics findings across adequately sized ovarian cancer sample sets. Key words combined with ‘ovarian cancer’ including ‘proteomics’, ‘proteogenomic’, ‘reverse-phase protein array’, ‘mass spectrometry’, and ‘adaptive response’, were used to search PubMed.

Expert opinion: Proteomics analysis of HGSC as well as their adaptive responses to therapy can uncover new therapeutic liabilities, which can reduce the emergence of drug resistance and potentially improve patient outcomes. There is a pressing need to better understand how the genomic and epigenomic heterogeneity intrinsic to ovarian cancer is reflected at the protein level and how this information could be used to improve patient outcomes.     

Climate change and the optimal flowering time of annual plants in seasonal environments

Long‐term phenology monitoring has documented numerous examples of changing flowering dates during the last century. A pivotal question is whether these phenological responses are adaptive or not under directionally changing climatic conditions. We use a classic dynamic growth model for annual plants, based on optimal control theory, to find the fitness‐maximizing flowering time, defined as the switching time from vegetative to reproductive growth. In a typical scenario of global warming, with advanced growing season and increased productivity, optimal flowering time advances less than the start of the growing season. Interestingly, increased temporal spread in production over the season may either advance or delay the optimal flowering time depending on overall productivity or season length. We identify situations where large phenological changes are necessary for flowering time to remain optimal. Such changes also indicate changed selection pressures. In other situations, the model predicts advanced phenology on a calendar scale, but no selection for early flowering in relation to the start of the season. We also show that the optimum is more sensitive to increased productivity when productivity is low than when productivity is high. All our results are derived using a general, graphical method to calculate the optimal flowering time applicable for a large range of shapes of the seasonal production curve. The model can thus explain apparent maladaptation in phenological responses in a multitude of scenarios of climate change. We conclude that taking energy allocation trade‐offs and appropriate time scales into account is critical when interpreting phenological patterns.     

Upward ant distribution shift corresponds with minimum,not maximum,temperature tolerance

Rapid climate change may prompt species distribution shifts upward and poleward, but species movement in itself is not sufficient to establish climate causation. Other dynamics, such as disturbance history, may prompt species distribution shifts resembling those expected from rapid climate change. Links between species distributions, regional climate trends and physiological mechanism are needed to convincingly establish climate‐induced species shifts. We examine a 38‐year shift (1974–2012) in an elevation ecotone between two closely related ant species, Aphaenogaster picea and A. rudis. Even though A. picea and A. rudis are closely related with North American distributions that sometimes overlap, they also exhibit local‐ and regional‐scale differences in temperature requirements so that A. rudis is more southerly and inhabits lower elevations whereas A. picea is more northerly and inhabits high elevations. We find considerable movement by the warm‐habitat species upward in elevation between 1974 and 2012 with A. rudis, replacing the cold‐habitat species, A. picea, along the southern edge of the Appalachian Mountain chain in north Georgia, USA. Concomitant with the distribution shifts, regional mean and maximum temperatures remain steady (1974–2012), but minimum temperatures increase. We collect individuals from the study sites and subject them to thermal tolerance testing in a controlled setting and find that maximum and minimum temperature acclimatization occurs along the elevation gradient in both species, but A. rudis consistently becomes physiologically incapacitated at minimum and maximum temperatures 2 °C higher than A. picea. These results indicate that rising minimum temperatures allow A. rudis to move upward in elevation and displace A. picea. Given that Aphaenogaster ants are the dominant woodland seed dispersers in eastern deciduous forests, and that their thermal tolerances drive distinct differences in temperature‐cued synchrony with early blooming plants, these climate responses not only impact ant‐ant interactions, but might have wide implications for ant‐plant interactions.     

Shaping up for action

The Malpighian tubule is the main organ for excretion and osmoregulation in most insects. During a short period of embryonic development the tubules of Drosophila are shaped, undergo differentiation and become precisely positioned in the body cavity, so they become fully functional at the time of larval hatching a few hours later. In this review I explore three developmental events on the path to physiological maturation. First, I examine the molecular and cellular mechanisms that generate organ shape, focusing on the process of cell intercalation that drives tubule elongation, the roles of the cytoskeleton, the extracellular matrix and how intercalation is coordinated at the tissue level. Second, I look at the genetic networks that control the physiological differentiation of tubule cells and consider how distinctive physiological domains in the tubule are patterned. Finally, I explore how the organ is positioned within the body cavity and consider the relationship between organ position and function.     

Exogenous strigolactones impact metabolic profiles and phosphate starvation signalling in roots

Strigolactones (SLs) are important ex-planta signalling molecules in the rhizosphere, promoting the association with beneficial microorganisms, but also affecting plant interactions with harmful organisms. They are also plant hormones in-planta, acting as modulators of plant responses under nutrient-deficient conditions, mainly phosphate (Pi) starvation. In the present work, we investigate the potential role of SLs as regulators of early Pi starvation signalling in plants. A short-term pulse of the synthetic SL analogue 2′-epi-GR24 promoted SL accumulation and the expression of Pi starvation markers in tomato and wheat under Pi deprivation. 2′-epi-GR24 application also increased SL production and the expression of Pi starvation markers under normal Pi conditions, being its effect dependent on the endogenous SL levels. Remarkably, 2′-epi-GR24 also impacted the root metabolic profile under these conditions, promoting the levels of metabolites associated to plant responses to Pi limitation, thus partially mimicking the pattern observed under Pi deprivation. The results suggest an endogenous role for SLs as Pi starvation signals. In agreement with this idea, SL-deficient plants were less sensitive to this stress. Based on the results, we propose that SLs may act as early modulators of plant responses to P starvation.     

Alveolar mimics with periodic strain and its effect on the cell layer formation

We report on the development of a new model of alveolar air–tissue interface on a chip. The model consists of an array of suspended hexagonal monolayers of gelatin nanofibers supported by microframes and a microfluidic device for the patch integration. The suspended monolayers are deformed to a central displacement of 40–80 µm at the air–liquid interface by application of air pressure in the range of 200–1,000 Pa. With respect to the diameter of the monolayers, that is, 500 µm, this displacement corresponds to a linear strain of 2–10% in agreement with the physiological strain range in the lung alveoli. The culture of A549 cells on the monolayers for an incubation time of 1–3 days showed viability in the model. We exerted a periodic strain of 5% at a frequency of 0.2 Hz for 1 hr to the cells. We found that the cells were strongly coupled to the nanofibers, but the strain reduced the coupling and induced remodeling of the actin cytoskeleton, which led to a better tissue formation. Our model can serve as a versatile tool in lung investigations such as in inhalation toxicology and therapy.