Ultra-sharp pinnacles sculpted by natural convective dissolution.

The evolution of landscapes, landforms, and other natural structures involves highly interactive physical and chemical processes that often lead to intriguing shapes and recurring motifs. Particularly intricate and fine-scale features characterize the so-called karst morphologies formed by mineral dissolution into water. An archetypal form is the tall, slender, and sharply tipped karst pinnacle or rock spire that appears in multitudes in striking landforms called stone forests, but whose formative mechanisms remain unclear due to complex, fluctuating, and incompletely understood developmental conditions. Here, we demonstrate that exceedingly sharp spires also form under the far-simpler conditions of a solid dissolving into a surrounding liquid. Laboratory experiments on solidified sugars in water show that needlelike pinnacles, as well as bed-of-nails-like arrays of pinnacles, emerge robustly from the dissolution of solids with smooth initial shapes. Although the liquid is initially quiescent and no external flow is imposed, persistent flows are generated along the solid boundary as dense, solute-laden fluid descends under gravity. We use these observations to motivate a mathematical model that links such boundary-layer flows to the shape evolution of the solid. Dissolution induces these natural convective flows that, in turn, enhance dissolution rates, and simulations show that this feedback drives the shape toward a finite-time singularity or blow-up of apex curvature that is cut off once the pinnacle tip reaches microscales. This autogenic mechanism produces ultra-fine structures as an attracting state or natural consequence of the coupled processes at work in the closed solid-fluid system.

Anomalous Convective Flows Carve Pinnacles and Scallops in Melting Ice.

We report on the shape dynamics of ice suspended in cold fresh water and subject to the natural convective flows generated during melting. Experiments reveal shape motifs for increasing far-field temperature: Sharp pinnacles directed downward at low temperatures, scalloped waves for intermediate temperatures between 5 °C and 7 °C, and upward pointing pinnacles at higher temperatures. Phase-field simulations reproduce these morphologies, which are closely linked to the anomalous density-temperature profile of liquid water. Boundary layer flows yield pinnacles that sharpen with accelerating growth of tip curvature while scallops emerge from a Kelvin-Helmholtz-like instability caused by counterflowing currents that roll up to form vortex arrays. By linking the molecular-scale effects underlying water's density anomaly to the macroscale flows that imprint the surface, these results show that the morphology of melted ice is a sensitive indicator of ambient temperature.

Aryl amino acetamides prevent Plasmodium falciparum ring development via targeting the lipid-transfer protein PfSTART1.

With resistance to most antimalarials increasing, it is imperative that new drugs are developed. We previously identified an aryl acetamide compound, MMV006833 (M-833), that inhibited the ring-stage development of newly invaded merozoites. Here, we select parasites resistant to M-833 and identify mutations in the START lipid transfer protein (PF3D7_0104200, PfSTART1). Introducing PfSTART1 mutations into wildtype parasites reproduces resistance to M-833 as well as to more potent analogues. PfSTART1 binding to the analogues is validated using organic solvent-based Proteome Integral Solubility Alteration (Solvent PISA) assays. Imaging of invading merozoites shows the inhibitors prevent the development of ring-stage parasites potentially by inhibiting the expansion of the encasing parasitophorous vacuole membrane. The PfSTART1-targeting compounds also block transmission to mosquitoes and with multiple stages of the parasite's lifecycle being affected, PfSTART1 represents a drug target with a new mechanism of action.

Respiratory-related displacement of the trachea in obstructive sleep apnea.

Tracheal displacement is thought to be the primary mechanism by which changes in lung volume influence upper airway patency. Caudal tracheal displacement during inspiration may help preserve the integrity of the upper airway in response to increasing negative airway pressure by stretching and stiffening pharyngeal tissues. However, tracheal displacement has not been previously quantified in obstructive sleep apnea (OSA). Accordingly, we aimed to measure tracheal displacements in awake individuals with and without OSA. The upper head and neck of 34 participants [apnea-hypopnea index (AHI) = 2-74 events/h] were imaged in the midsagittal plane using dynamic magnetic resonance imaging (MRI) during supine awake quiet breathing. MRI data were analyzed to identify peak tracheal displacement and its timing relative to inspiration. Epiglottic pressure was measured separately for a subset of participants (n = 30) during similar experimental conditions. Nadir epiglottic pressure and its timing relative to inspiration were quantified. Peak tracheal displacement ranged from 1.0-9.6 mm, with a median (25th-75th percentile) of 2.3 (1.7-3.5) mm, and occurred at 89 (78-99)% of inspiratory time. Peak tracheal displacement increased with increasing OSA severity (AHI) (R2 = 0.28, P = 0.013) and increasing negative nadir epiglottic pressure (R2 = 0.47, P = 0.023). Relative inspiratory timing of peak tracheal displacement also correlated with OSA severity, with peak displacement occurring earlier in inspiration with increasing AHI (R2 = 0.36, P = 0.002). Tracheal displacements during quiet breathing are larger in individuals with more severe OSA and tend to reach peak displacement earlier in the inspiratory cycle. Increased tracheal displacement may contribute to maintenance of upper airway patency during wakefulness in OSA, particularly in those with severe disease.NEW & NOTEWORTHY Tracheal displacement is thought to play an important role in stabilizing the upper airway by stretching/stiffening the pharyngeal musculature. Using dynamic magnetic resonance imaging, this study shows that caudal tracheal displacement is more pronounced during inspiration in obstructive sleep apnea (OSA) compared with healthy individuals. Softer pharyngeal muscles and greater inspiratory forces in OSA may underpin greater tracheal excursion. These findings suggest that tracheal displacement may contribute to maintenance of pharyngeal patency during wakefulness in OSA.