Defective Tmprss3-Associated Hair Cell Degeneration in Inner Ear Organoids

Mutations in the gene encoding the type II transmembrane protease 3 (TMPRSS3) cause human hearing loss, although the underlying mechanisms that result in TMPRSS3-related hearing loss are still unclear. We combined the use of stem cell-derived inner ear organoids with single-cell RNA sequencing to investigate the role of TMPRSS3. Defective Tmprss3 leads to hair cell apoptosis without altering the development of hair cells and the formation of the mechanotransduction apparatus. Prior to degeneration, Tmprss3-KO hair cells demonstrate reduced numbers of BK channels and lower expressions of genes encoding calcium ion-binding proteins, suggesting a disruption in intracellular homeostasis. A proteolytically active TMPRSS3 was detected on cell membranes in addition to ER of cells in inner ear organoids. Our in vitro model recapitulated salient features of genetically associated inner ear abnormalities and will serve as a powerful tool for studying inner ear disorders

Beyond the angle of repose: A review and synthesis of landslide processes in response to rapid uplift, Eel River, Northern California

In mountainous settings, increases in rock uplift are often followed by a commensurate uptick in denudation as rivers incise and steepen hillslopes, making them increasingly prone to landsliding as slope angles approach a limiting value. For decades, the threshold slope model has been invoked to account for landslide-driven increases in sediment flux that limit topographic relief, but the manner by which slope failures organize themselves spatially and temporally in order for erosion to keep pace with rock uplift has not been well documented. Here, we review past work and present new findings from remote sensing, cosmogenic radionuclides, suspended sediment records, and airborne lidar data, to decipher patterns of landslide activity and geomorphic processes related to rapid uplift along the northward-migrating Mendocino Triple Junction in Northern California. From historical air photos and airborne lidar, we estimated the velocity and sediment flux associated with active, slow-moving landslides (or earthflows) in the mélange- and argillite-dominated Eel River watershed using the downslope displacement of surface markers such as trees and shrubs. Although active landslides that directly convey sediment into the channel network account for only 7% of the landscape surface, their sediment flux amounts to more than 50% of the suspended load recorded at downstream sediment gaging stations. These active slides tend to exhibit seasonal variations in velocity as satellite-based interferometry has demonstrated that rapid acceleration commences within 1 to 2 months of the onset of autumn rainfall events before slower deceleration ensues in the spring and summer months. Curiously, this seasonal velocity pattern does not appear to vary with landslide size, suggesting that complex hydrologic–mechanical feedbacks (rather than 1-D pore pressure diffusion) may govern slide dynamics. A new analysis of 14 yrs of discharge and sediment concentration data for the Eel River indicates that the characteristic mid-winter timing of earthflow acceleration corresponds with increased suspended concentration values, suggesting that the seasonal onset of landslide motion each year may be reflected in the export of sediments to the continental margin. The vast majority of active slides exhibit gullied surfaces and the gully networks, which are also seasonally active, may facilitate sediment export although the proportion of material produced by this pathway is poorly known. Along Kekawaka Creek, a prominent tributary to the Eel River, new analyses of catchment-averaged erosion rates derived from cosmogenic radionuclides reveal rapid erosion (0.76 mm/yr) below a prominent knickpoint and slower erosion (0.29 mm/yr) upstream. Such knickpoints are frequently observed in Eel tributaries and are usually comprised of massive (> 10 m) interlocking resistant boulders that likely persist in the landscape for long periods of time (> 105 yr). Upstream of these knickpoints, active landslides tend to be less frequent and average slope angles are slightly gentler than in downstream areas, which indicates that landslide density and average slope angle appear to increase with erosion rate. Lastly, we synthesize evidence for the role of large, catastrophic landslides in regulating sediment flux and landscape form. The emergence of resistant blocks within the mélange bedrock has promoted large catastrophic slides that have dammed the Eel River and perhaps generated outburst events in the past. The frequency and impact of these landslide dams likely depend on the spatial and size distributions of resistant blocks relative to the width and drainage area of adjacent valley networks. Overall, our findings demonstrate that landslides within the Eel River catchment do not occur randomly, but instead exhibit spatial and temporal patterns related to baselevel lowering, climate forcing, and lithologic variations. Combined with recent landscape evolution models that incorporate landslides, these results provide predictive capability for estimating erosion rates and managing hazards in mountainous regions

Seawater softening of suture zones inhibits fracture propagation in Antarctic ice shelves

Suture zones are abundant on Antarctic ice shelves and widely observed to impede fracture propagation, greatly enhancing ice-shelf stability. Using seismic and radar observations on the Larsen C Ice Shelf of the Antarctic Peninsula, we confirm that such zones are highly heterogeneous, consisting of multiple meteoric and marine ice bodies of diverse provenance fused together. Here we demonstrate that fracture detainment is predominantly controlled by enhanced seawater content in suture zones, rather than by enhanced temperature as previously thought. We show that interstitial seawater can reduce fracture-driving stress by orders of magnitude, promoting both viscous relaxation and the development of micro cracks, the incidence of which scales inversely with stress intensity. We show how simple analysis of viscous buckles in ice-penetrating radar data can quantify the seawater content of suture zones and their modification of the ice-shelf’s stress regime. By limiting fracture, enhancing stability and restraining continental ice discharge into the ocean, suture zones act as vital regulators of Antarctic mass balance

Flow-line model code for accumulation of ice along velocity-based trajectories

The flow-line model was designed to enable estimation of the age and surface origin for various ice bodies identified within hot-water drilled boreholes on Larsen C Ice Shelf. Surface fluxes are accumulated, converted to thicknesses, and advected down flow from a fixed number of selected points. The model requires input datasets of surface mass balance, surface velocity, vertical strain rates, ice-shelf thickness, and a vertical density profile. This model is part of a larger project. Input datasets such as density profiles and trajectory vectors are available separately. Resolution is dependent on the input datasets. Funding was provided by the NERC grant NE/L005409/1

Hysteresis of Electronic Transport in Graphene Transistors

Graphene field effect transistors commonly comprise graphene flakes lying on SiO2 surfaces. The gate-voltage dependent conductance shows hysteresis depending on the gate sweeping rate/range. It is shown here that the transistors exhibit two different kinds of hysteresis in their electrical characteristics. Charge transfer causes a positive shift in the gate voltage of the minimum conductance, while capacitive gating can cause the negative shift of conductance with respect to gate voltage. The positive hysteretic phenomena decay with an increase of the number of layers in graphene flakes. Self-heating in helium atmosphere significantly removes adsorbates and reduces positive hysteresis. We also observed negative hysteresis in graphene devices at low temperature. It is also found that an ice layer on/under graphene has much stronger dipole moment than a water layer does. Mobile ions in the electrolyte gate and a polarity switch in the ferroelectric gate could also cause negative hysteresis in graphene transistors. These findings improved our understanding of the electrical response of graphene to its surroundings. The unique sensitivity to environment and related phenomena in graphene deserve further studies on nonvolatile memory, electrostatic detection and chemically driven applications.Comment: 13 pages, 6 Figure

Chronic psychosocial and financial burden accelerates 5-year telomere shortening: findings from the Coronary Artery Risk Development in Young Adults Study.

Leukocyte telomere length, a marker of immune system function, is sensitive to exposures such as psychosocial stressors and health-maintaining behaviors. Past research has determined that stress experienced in adulthood is associated with shorter telomere length, but is limited to mostly cross-sectional reports. We test whether repeated reports of chronic psychosocial and financial burden is associated with telomere length change over a 5-year period (years 15 and 20) from 969 participants in the Coronary Artery Risk Development in Young Adults (CARDIA) Study, a longitudinal, population-based cohort, ages 18-30 at time of recruitment in 1985. We further examine whether multisystem resiliency, comprised of social connections, health-maintaining behaviors, and psychological resources, mitigates the effects of repeated burden on telomere attrition over 5 years. Our results indicate that adults with high chronic burden do not show decreased telomere length over the 5-year period. However, these effects do vary by level of resiliency, as regression results revealed a significant interaction between chronic burden and multisystem resiliency. For individuals with high repeated chronic burden and low multisystem resiliency (1 SD below the mean), there was a significant 5-year shortening in telomere length, whereas no significant relationships between chronic burden and attrition were evident for those at moderate and higher levels of resiliency. These effects apply similarly across the three components of resiliency. Results imply that interventions should focus on establishing strong social connections, psychological resources, and health-maintaining behaviors when attempting to ameliorate stress-related decline in telomere length among at-risk individuals

Human iPS cell–derived alveolar epithelium repopulates lung extracellular matrix

The use of induced pluripotent stem cells (iPSCs) has been postulated to be the most effective strategy for developing patient-specific respiratory epithelial cells, which may be valuable for lung-related cell therapy and lung tissue engineering. We generated a relatively homogeneous population of alveolar epithelial type II (AETII) and type I (AETI) cells from human iPSCs that had phenotypic properties similar to those of mature human AETII and AETI cells. We used these cells to explore whether lung tissue can be regenerated in vitro. Consistent with an AETII phenotype, we found that up to 97% of cells were positive for surfactant protein C, 95% for mucin-1, 93% for surfactant protein B, and 89% for the epithelial marker CD54. Additionally, exposing induced AETII to a Wnt/β-catenin inhibitor (IWR-1) changed the iPSC-AETII–like phenotype to a predominantly AETI-like phenotype. We found that of induced AET1 cells, more than 90% were positive for type I markers, T1α, and caveolin-1. Acellular lung matrices were prepared from whole rat or human adult lungs treated with decellularization reagents, followed by seeding these matrices with alveolar cells derived from human iPSCs. Under appropriate culture conditions, these progenitor cells adhered to and proliferated within the 3D lung tissue scaffold and displayed markers of differentiated pulmonary epithelium

Changing forest water yields in response to climate warming: results from long-term experimental watershed sites across North America

Climate warming is projected to affect forest water yields but the effects are expected to vary. We investigated how forest type and age affect water yield resilience to climate warming. To answer this question, we examined the variability in historical water yields at long-term experimental catchments across Canada and the United States over 5-year cool and warm periods. Using the theoretical framework of the Budyko curve, we calculated the effects of climate warming on the annual partitioning of precipitation (P) into evapotranspiration (ET) and water yield. Deviation (d) was defined as a catchment’s change in actual ET divided by P [AET/P; evaporative index (EI)] coincident with a shift from a cool to a warm period – a positive d indicates an upward shift in EI and smaller than expected water yields, and a negative d indicates a downward shift in EI and larger than expected water yields. Elasticity was defined as the ratio of inter annual variation in potential ET divided by P (PET/P; dryness index) to inter annual variation in the EI – high elasticity indicates low d despite large range in drying index (i.e., resilient water yields), low elasticity indicates high d despite small range in drying index (i.e., non-resilient water yields). Although the data needed to fully evaluate ecosystems based on these metrics are limited, we were able to identify some characteristics of response among forest types. Alpine sites showed the greatest sensitivity to climate warming with any warming leading to increased water yields. Conifer forests included catchments with lowest elasticity and stable to larger water yields. Deciduous forests included catchments with intermediate elasticity and stable to smaller water yields. Mixed coniferous/deciduous forests included catchments with highest elasticity and stable water yields. Forest type appeared to influence the resilience of catchment water yields to climate warming, with conifer and deciduous catchments more susceptible to climate warming than the more diverse mixed forest catchments

Revival of the magnetar PSR J1622-4950: observations with MeerKAT, Parkes, XMM-Newton, Swift, Chandra, and NuSTAR

New radio (MeerKAT and Parkes) and X-ray (XMM-Newton, Swift, Chandra, and NuSTAR) observations of PSR J1622-4950 indicate that the magnetar, in a quiescent state since at least early 2015, reactivated between 2017 March 19 and April 5. The radio flux density, while variable, is approximately 100x larger than during its dormant state. The X-ray flux one month after reactivation was at least 800x larger than during quiescence, and has been decaying exponentially on a 111+/-19 day timescale. This high-flux state, together with a radio-derived rotational ephemeris, enabled for the first time the detection of X-ray pulsations for this magnetar. At 5%, the 0.3-6 keV pulsed fraction is comparable to the smallest observed for magnetars. The overall pulsar geometry inferred from polarized radio emission appears to be broadly consistent with that determined 6-8 years earlier. However, rotating vector model fits suggest that we are now seeing radio emission from a different location in the magnetosphere than previously. This indicates a novel way in which radio emission from magnetars can differ from that of ordinary pulsars. The torque on the neutron star is varying rapidly and unsteadily, as is common for magnetars following outburst, having changed by a factor of 7 within six months of reactivation.Comment: Published in ApJ (2018 April 5); 13 pages, 4 figure