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MicroRNA regulation of type 2 innate lymphoid cell homeostasis and function in allergic inflammation.
MicroRNAs (miRNAs) exert powerful effects on immunity through coordinate regulation of multiple target genes in a wide variety of cells. Type 2 innate lymphoid cells (ILC2s) are tissue sentinel mediators of allergic inflammation. We established the physiological requirements for miRNAs in ILC2 homeostasis and immune function and compared the global miRNA repertoire of resting and activated ILC2s and T helper type 2 (TH2) cells. After exposure to the natural allergen papain, mice selectively lacking the miR-17∼92 cluster in ILC2s displayed reduced lung inflammation. Moreover, miR-17∼92-deficient ILC2s exhibited defective growth and cytokine expression in response to IL-33 and thymic stromal lymphopoietin in vitro. The miR-17∼92 cluster member miR-19a promoted IL-13 and IL-5 production and inhibited expression of several targets, including SOCS1 and A20, signaling inhibitors that limit IL-13 and IL-5 production. These findings establish miRNAs as important regulators of ILC2 biology, reveal overlapping but nonidentical miRNA-regulated gene expression networks in ILC2s and TH2 cells, and reinforce the therapeutic potential of targeting miR-19 to alleviate pathogenic allergic responses
Comprehensive Analyses of Coagulation Parameters in Patients with Vascular Anomalies.
BACKGROUND
Vascular anomalies comprise a diverse group of rare diseases with altered blood flow and are often associated with coagulation disorders. The most common example is a localized intravascular coagulopathy in venous malformations leading to elevated D-dimers. In severe cases, this may progress to a disseminated intravascular coagulopathy with subsequent consumption of fibrinogen and thrombocytes predisposing to serious bleeding. A separate coagulopathy is the Kasabach-Merritt phenomenon in kaposiform hemangioendothelioma characterized by platelet trapping leading to thrombocytopenia and eventually consumptive coagulopathy. Our previous work showed impaired von Willebrand factor and platelet aggregometry due to abnormal blood flow, i.e., in ventricular assist devices or extracorporeal membrane oxygenation. With altered blood flow also present in vascular anomalies, we hypothesized that, in particular, the von Willebrand factor parameters and the platelet function may be similarly impacted.
METHODS
We prospectively recruited 73 patients with different vascular anomaly entities and analyzed their coagulation parameters.
RESULTS
Acquired von Willebrand syndrome was observed in both of our patients with Kasabach-Merritt phenomenon. In six out of nine patients with complex lymphatic anomalies, both the vWF antigen and activity were upregulated. Platelet aggregometry was impaired in both patients with Kasabach-Merritt phenomenon and in seven out of eight patients with an arteriovenous malformation.
CONCLUSIONS
The analysis of coagulation parameters in our patients with vascular anomalies advanced our understanding of the underlying pathophysiologies of the observed coagulopathies. This may lead to new treatment options for the, in part, life-threatening bleeding risks in these patients in the future
Interplay between developmental cues and rhizosphere signals from mycorrhizal fungi shape root anatomy, impacting crop productivity
Background: The rhizosphere is the interface between roots and the soil and the site of nutrient and water uptake for plant growth. Root anatomy and the physical, chemical, and biological components of the rhizosphere interact to influence plant growth. Several root developmental and rhizosphere signals combine in the patterning of root cortical anatomy and have implications for the plant’s hydro-mineral nutrition and carbon partitioning and therefore crop productivity, especially in edaphic stress. Scope: Here, we highlight how mutualistic mycorrhizal fungi from the rhizosphere mobilize plant molecular actors controlling root anatomical traits, including cortical cell size, to facilitate their establishment and accommodation within the cortex. We explore the effects on plant growth and stress tolerance that may result from the changes in root anatomy driven by interactions with arbuscular mycorrhizal fungi, including altering the metabolic efficiency required for nutrient exploitation. We also discuss opportunities for understanding the genetic control of root anatomy and rhizosphere interactions to enable a comprehensive understanding of the benefits and trade-offs of root-rhizosphere interactions for more productive crops
Future roots for future soils
Mechanical impedance constrains root growth in most soils. Crop cultivation changed the impedance characteristics of native soils, through topsoil erosion, loss of organic matter, disruption of soil structure and loss of biopores. Increasing adoption of Conservation Agriculture in high-input agroecosystems is returning cultivated soils to the soil impedance characteristics of native soils, but in the low-input agroecosystems characteristic of developing nations, ongoing soil degradation is generating more challenging environments for root growth. We propose that root phenotypes have evolved to adapt to the altered impedance characteristics of cultivated soil during crop domestication. The diverging trajectories of soils under Conservation Agriculture and low-input agroecosystems have implications for strategies to develop crops to meet global needs under climate change. We present several root ideotypes as breeding targets under the impedance regimes of both high-input and low-input agroecosystems, as well as a set of root phenotypes that should be useful in both scenarios. We argue that a ‘whole plant in whole soil’ perspective will be useful in guiding the development of future crops for future soils
Genetic control of root architectural plasticity in maize
© 2020 The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Experimental Biology. Root phenotypes regulate soil resource acquisition; however, their genetic control and phenotypic plasticity are poorly understood. We hypothesized that the responses of root architectural phenes to water deficit (stress plasticity) and different environments (environmental plasticity) are under genetic control and that these loci are distinct. Root architectural phenes were phenotyped in the field using a large maize association panel with and without water deficit stress for three seasons in Arizona and without water deficit stress for four seasons in South Africa. All root phenes were plastic and varied in their plastic response. We identified candidate genes associated with stress and environmental plasticity and candidate genes associated with phenes in well-watered conditions in South Africa and in well-watered and water-stress conditions in Arizona. Few candidate genes for plasticity overlapped with those for phenes expressed under each condition. Our results suggest that phenotypic plasticity is highly quantitative, and plasticity loci are distinct from loci that control phene expression in stress and non-stress, which poses a challenge for breeding programs. To make these loci more accessible to the wider research community, we developed a public online resource that will allow for further experimental validation towards understanding the genetic control underlying phenotypic plasticity
Intermittent bulk release of human cytomegalovirus
Human Cytomegalovirus (HCMV) can infect a variety of cell types by using virions of varying glycoprotein compositions. It is still unclear how this diversity is generated, but spatio-temporally separated envelopment and egress pathways might play a role. So far, one egress pathway has been described in which HCMV particles are individually enveloped into small vesicles and are subsequently exocytosed continuously. However, some studies have also found enveloped virus particles inside multivesicular structures but could not link them to productive egress or degradation pathways. We used a novel 3D-CLEM workflow allowing us to investigate these structures in HCMV morphogenesis and egress at high spatio-temporal resolution. We found that multiple envelopment events occurred at individual vesicles leading to multiviral bodies (MViBs), which subsequently traversed the cytoplasm to release virions as intermittent bulk pulses at the plasma membrane to form extracellular virus accumulations (EVAs). Our data support the existence of a novel bona fide HCMV egress pathway, which opens the gate to evaluate divergent egress pathways in generating virion diversity
Probing for Exoplanets Hiding in Dusty Debris Disks: Disk Imaging, Characterization, and Exploration with HST/STIS Multi-Roll Coronagraphy
Spatially resolved scattered-light images of circumstellar (CS) debris in
exoplanetary systems constrain the physical properties and orbits of the dust
particles in these systems. They also inform on co-orbiting (but unseen)
planets, systemic architectures, and forces perturbing starlight-scattering CS
material. Using HST/STIS optical coronagraphy, we have completed the
observational phase of a program to study the spatial distribution of dust in
ten CS debris systems, and one "mature" protoplanetrary disk all with HST
pedigree, using PSF-subtracted multi-roll coronagraphy. These observations
probe stellocentric distances > 5 AU for the nearest stars, and simultaneously
resolve disk substructures well beyond, corresponding to the giant planet and
Kuiper belt regions in our Solar System. They also disclose diffuse very
low-surface brightness dust at larger stellocentric distances. We present new
results inclusive of fainter disks such as HD92945 confirming, and better
revealing, the existence of a narrow inner debris ring within a larger diffuse
dust disk. Other disks with ring-like sub-structures, significant asymmetries
and complex morphologies include: HD181327 with a posited spray of ejecta from
a recent massive collision in an exo-Kuiper belt; HD61005 suggested interacting
with the local ISM; HD15115 & HD32297, discussed also in the context of
environmental interactions. These disks, and HD15745, suggest debris system
evolution cannot be treated in isolation. For AU Mic's edge-on disk,
out-of-plane surface brightness asymmetries at > 5 AU may implicate one or more
planetary perturbers. Time resolved images of the MP Mus proto-planetary disk
provide spatially resolved temporal variability in the disk illumination. These
and other new images from our program enable direct inter-comparison of the
architectures of these exoplanetary debris systems in the context of our own
Solar System.Comment: 109 pages, 43 figures, accepted for publication in the Astronomical
Journa
Soil penetration by maize roots is negatively related to ethylene-induced thickening
Radial expansion is a classic response of roots to a mechanical impedance that has generally been assumed to aid penetration. We analysed the response of maize nodal roots to impedance to test the hypothesis that radial expansion is not related to the ability of roots to cross a compacted soil layer. Genotypes varied in their ability to cross the compacted layer, and those with a steeper approach to the compacted layer or less radial expansion in the compacted layer were more likely to cross the layer and achieve greater depth. Root radial expansion was due to cortical cell size expansion, while cortical cell file number remained constant. Genotypes and nodal root classes that exhibited radial expansion in the compacted soil layer generally also thickened in response to exogenous ethylene in hydroponic culture, that is, radial expansion in response to ethylene was correlated with the thickening response to impedance in soil. We propose that ethylene insensitive roots, that is, those that do not thicken and can overcome impedance, have a competitive advantage under mechanically impeded conditions as they can maintain their elongation rates. We suggest that prolonged exposure to ethylene could function as a stop signal for axial root growth
A six-country study of coaches’ perspectives of girls’ body image concerns in sport and intervention preferences: Template analysis of survey and focus group data
Coaches are a key influence of athletes’ body image, but often feel ill-equipped to address body image concerns and can perpetuate harmful body ideals. Limited research has investigated coaches’ attitudes and opinions and few effective resources are available. The current study explored coaches’ perspectives of body image among girls in sport, as well as their preferences for body image interventions. Thirty-four coaches (41% women; Mage=31.6 yrs; SD=10.5) from France, India, Japan, Mexico, the United Kingdom, and the United States took part in semi-structured focus groups and completed an online survey. Template analysis of survey and focus group data resulted in eight first-order themes grouped under three categories: (1) perspectives of body image among girls in sport (objectification and surveillance, impact of puberty, the role of the coach); (2) preferences for intervention design (content of the intervention, accessibility of the intervention, incentives for taking part); and (3) cross-cultural considerations (acknowledging your privilege, cultural and societal norms). Two integrative themes were defined: (1) girls’ disengagement from sport and (2) the role of community. Coaches perceived body image to be a significant barrier for girls in sport and a need to address this in a formal and accessible intervention
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