Rhinoviruses (RVs), which are the most common cause of virally induced asthma exacerbations, account for much of the burden of asthma in terms of morbidity, mortality, and associated cost. ...Interleukin-25 (IL-25) activates type 2-driven inflammation and is therefore potentially important in virally induced asthma exacerbations. To investigate this, we examined whether RV-induced IL-25 could contribute to asthma exacerbations. RV-infected cultured asthmatic bronchial epithelial cells exhibited a heightened intrinsic capacity for IL-25 expression, which correlated with donor atopic status. In vivo human IL-25 expression was greater in asthmatics at baseline and during experimental RV infection. In addition, in mice, RV infection induced IL-25 expression and augmented allergen-induced IL-25. Blockade of the IL-25 receptor reduced many RV-induced exacerbation-specific responses including type 2 cytokine expression, mucus production, and recruitment of eosinophils, neutrophils, basophils, and T and non-T type 2 cells. Therefore, asthmatic epithelial cells have an increased intrinsic capacity for expression of a pro-type 2 cytokine in response to a viral infection, and IL-25 is a key mediator of RV-induced exacerbations of pulmonary inflammation.
White Island volcano, New Zealand, produced two periods (January–February and July 2013) of episodic and persistent eruptions through a viscous shallow mud/sulphur pool. The eruptions included an ...initial hemispherical bubble burst, which was intermittently followed by an up-channel gas jet, and finally a late stage heaving of a mud/sulphur/water suspension. The late stage heave was systematically directed south-eastward as far as 30–40m from the vent.
The associated infrasound time-series included harmonic tremor on permanent stations WIZ and WSRZ. Detailed inspection showed that the tremor was composed of numerous discrete double pulse events without a strong periodic event repetition. The first pulse had highly similar waveforms event-to-event and a notable distortion of the waveform period between the two infrasound stations located on opposites sides from the directed eruption source. The second pulse occurred about 1.5–2.5s later and was weakly observed on station WSRZ.
Where the video can be rigorously linked to the double pulse infrasound signals we interpret aspects of the distinctive eruptive regimes. For this case, the regime dynamics are driven by the propagation of numerous discrete gas slugs though the shallow viscous muddy crater lake, each generating a distinct bubble burst with subsequent eruption heave and associated double pulse infrasound events. The double pulse events are the source of the persistent harmonic tremor having fundamental and overtone spectral frequencies but are not interpreted as related to cavity resonance or a repetitious comb function. Instead the activity is produced by a single event producing a specific two pulse source time function. The observed distortion in the first pulse wave period at WIZ and WSRZ may be ascribed to a Doppler shift associated with the directivity observed in the initial jet/heave eruption process. We surmise that double pulse source dynamics and directivity effects may be generically extended to some examples of subsurface seismic tremor or for tremor associated with geyser eruptions, mud volcano eruptions, fire fountains from lava lakes and strombolian eruptions.
•Infrasound tremor observed during periods of persistent bubble bursts through viscous shallow Crater Lake.•Infrasound double pulse source dynamics are linked to gas slug burst dynamics.•Observed directivity of eruptions are consistent with Doppler shift observed at infrasound sensors.•Harmonic tremor may be produced without comb function or resonant cavity.
The balance and distribution of epithelial cell types is required to maintain tissue homeostasis. A hallmark of airway diseases is epithelial remodeling, leading to increased goblet cell numbers and ...an overproduction of mucus. In the conducting airway, basal cells act as progenitors for both secretory and ciliated cells. To identify mechanisms regulating basal cell fate, we developed a screenable 3D culture system of airway epithelial morphogenesis. We performed a high-throughput screen using a collection of secreted proteins and identified inflammatory cytokines that specifically biased basal cell differentiation toward a goblet cell fate, culminating in enhanced mucus production. We also demonstrate a specific requirement for Notch2 in cytokine-induced goblet cell metaplasia in vitro and in vivo. We conclude that inhibition of Notch2 prevents goblet cell metaplasia induced by a broad range of stimuli and propose Notch2 neutralization as a therapeutic strategy for preventing goblet cell metaplasia in airway diseases.
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•Airway basal cells differentiate into goblet and ciliated cells in 3D cultures•Inflammatory cytokines bias airway basal cell fate to drive goblet cell metaplasia•Notch2 is a key node required for goblet cell metaplasia•Targeting Notch2 prevents goblet cell metaplasia, regardless of the stimulus
Goblet cell metaplasia, resulting in excessive mucus production, is a hallmark of airway diseases. Here, Danahay et al. demonstrate that inhibition of Notch2 prevents goblet cell metaplasia in response to diverse stimuli in vitro and in vivo, validating Notch2 blockade as a therapeutic strategy for airway diseases.
The structures and textures preserved in lava domes reflect underlying magmatic and eruptive processes, and may provide evidence of how eruptions initiate and evolve. This study explores the ...remarkable cycles in lava extrusion style produced between 1922 and 2012 at the Santiaguito lava dome complex, Guatemala. By combining an examination of eruptive lava morphologies and textures with a review of historical records, we aim to constrain the processes responsible for the range of erupted lava type and morphologies. The Santiaguito lava dome complex is divided into four domes (El Caliente, La Mitad, El Monje, El Brujo), containing a range of proximal structures (e.g., spines) from which a series of structurally contrasting lava flows originate. Vesicular lava flows (with a'a like, yet non-brecciated flow top) have the highest porosity with interconnected spheroidal pores and may transition into blocky lava flows. Blocky lava flows are high volume and texturally variable with dense zones of small tubular aligned pore networks and more porous zones of spheroidal shaped pores. Spines are dense and low volume and contain small skeletal shaped pores, and subvertical zones of sigmoidal pores. We attribute the observed differences in pore shapes to reflect shallow inflation, deflation, flattening, or shearing of the pore fraction. Effusion rate and duration of the eruption define the amount of time available for heating or cooling, degassing and outgassing prior to and during extrusion, driving changes in pore textures and lava type. Our new textural data when reviewed with all the other published data allow a cyclic model to be developed. The cyclic eruption models are influenced by viscosity changes resulting from (1) initial magmatic composition and temperature, and (2) effusion rate which in turn affects degassing, outgassing and cooling time in the conduit. Each lava type presents a unique set of hazards and understanding the morphologies and dome progression is useful in hazard forecasting.
Purpose
– The purpose of this paper is to investigate the relationship between work placements and employability, through an analysis of the impact of a work placement on students’ self-efficacy.
...Design/methodology/approach
– The basis of this paper is a large-scale work-based learning module at the University of Birmingham, the “Professional Development Module”. Students completed questionnaires both before and after they undertaken their placements and the results from the questionnaires were compared. These results were then combined with the results of semi-structured interviews undertaken with students.
Findings
– The paper's findings support the view that a work placement has a positive impact on students’ self-efficacy, especially in relation to their confidence in making applications and/or attending interviews, and in articulating their skills and strengths.
Research limitations/implications
– While the relatively small sample size means that the paper's conclusions must remain provisional, it highlights the need for careers practitioners to encourage students to engage in critical self-reflection. The paper suggests that it is important for careers practitioners and researchers to engage in more collaborative projects in order for a fully rounded picture of the relationship between placements and employability to emerge. The paper shows that more research is needed into the relative impact of short- and long-term placements.
Originality/value
– The paper demonstrates the value of assessing students’ views both before and after their work placements so that these views can be compared directly.
Italian ryegrass is a major weed problem in wheat (Triticum aestivum L.) production worldwide. Two separate studies were conducted in Stoneville, Mississippi to evaluate: (1) the efficacy of ...herbicides available to Mississippi producers for controlling glyphosate-resistant (GR) Italian ryegrass (control study), and (2) fall burndown herbicide seed suppression study. Results of the control study showed that flufenacet/metribuzin EPOST followed by (fb) pinoxaden LPOST (standard treatment) provided 93% control of GR Italian ryegrass. Some other treatments provided comparable Italian ryegrass control (92% to 97%) as the standard treatment in 2017. Italian ryegrass control in the seed suppression study was 100%, 100%, 67.5%, 97%, and 99.5% from the application of the following treatments: (1) S-metolachlor + flumioxazin + paraquat in October–November fb glyphosate + clethodim in January–February fb gramoxone as needed (weed-free check); (2) S-metolachlor + flumioxazin + paraquat in October–November; (3) field cultivator (disk) in October–November; (4) glyphosate + clethodim in January–February; and (5) field cultivator in October–November fb glyphosate + clethodim in January–February, respectively. The remaining Italian ryegrass from the application of treatments 3, 4, and 5 produced 65,700; 1008; and 9 seeds m−2, respectively. Seed suppression study highlights the importance of 100% control that is required to manage GR Italian grass.
Latitudinal gradients in species abundance and diversity have been postulated for nearshore taxa but few analyses have been done over sufficiently broad geographic scales incorporating various ...nearshore depth strata to empirically test these gradients. Typically, gradients are based on literature reviews and species lists and have focused on alpha diversity across the entire nearshore zone. No studies have used a standardized protocol in the field to examine species density among sites across a large spatial scale while also focusing on particular depth strata. The present research used field collected samples in the northern hemisphere to explore the relationships between macroalgal species density and biomass along intertidal heights and subtidal depths and latitude. Results indicated no overall correlations between either estimates of species density or biomass with latitude, although the highest numbers of both were found at mid-latitudes. However, when strata were examined separately, significant positive correlations were found for both species numbers and biomass at particular strata, namely the intertidal ones. While the data presented in this paper have some limitations, we show that latitudinal macroalgal trends in species density and biomass do exist for some strata in the northern hemisphere with more taxa and biomass at higher latitudes.
The world of singing has changed. The COVID-19 pandemic’s effects are only beginning to be understood, predicted demographic shifts will bring significant enrollment challenges in higher education, ...and today’s learners demand that we confront our historical biases and the institutional barriers to learning. In the 2014 article that preceded this publication the authors asked if collegiate voice pedagogy was adequately serving the needs of our singers. In this piece the authors present an updated analysis of this question, taking into consideration changes in the current educational climate.
Abstract
Costello syndrome (CS) is caused by heterozygous
HRAS
germline mutations. Most patients share the HRAS variant p.Gly12Ser that is associated with a typical, homogeneous phenotype. Rarer ...pathogenic HRAS variants (e.g., p.Thr56Ile) were identified in individuals with attenuated CS phenotypes. The obvious phenotypical variability reflects different dysfunctional consequences of distinct HRAS variants. We report on two boys with the novel
de novo HRAS
variant c.466 C > T p.(Phe156Leu). Both had severe feeding difficulties, airway obstruction and developmental delay, which are typical findings in CS. They showed subtle facial and dermatologic features consistent with attenuated CS. They significantly differed in their musculoskeletal, cardiovascular and endocrinologic manifestations underscoring the clinical variability of individuals with identical, in particular rarer pathogenic HRAS variants. Functional studies revealed enhanced effector-binding, increased downstream signaling activation and impaired growth factor-induced signaling dynamics in cells expressing HRAS
Phe156Leu
. Our data further illustrate the molecular and phenotypic variability of CS.
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