Wnt signaling is required for lineage commitment of glandular stem cells (SCs) during tracheal submucosal gland (SMG) morphogenesis from the surface airway epithelium (SAE). Whether similar ...Wnt-dependent processes coordinate SC expansion in adult SMGs following airway injury remains unknown. We found that two Wnt-reporters in mice (BAT-gal and TCF/Lef:H2B-GFP) are coexpressed in actively cycling SCs of primordial glandular placodes and in a small subset of adult SMG progenitor cells that enter the cell cycle 24 hours following airway injury. At homeostasis, these Wnt reporters showed nonoverlapping cellular patterns of expression in the SAE and SMGs. Following tracheal injury, proliferation was accompanied by dynamic changes in Wnt-reporter activity and the analysis of 56 Wnt-related signaling genes revealed unique temporal changes in expression within proximal (gland-containing) and distal (gland-free) portions of the trachea. Wnt stimulation in vivo and in vitro promoted epithelial proliferation in both SMGs and the SAE. Interestingly, slowly cycling nucleotide label-retaining cells (LRCs) of SMGs were spatially positioned near clusters of BAT-gal positive serous tubules. Isolation and culture of tet-inducible H2B-GFP LRCs demonstrated that SMG LRCs were more proliferative than SAE LRCs and culture expanded SMG-derived progenitor cells outcompeted SAE-derived progenitors in regeneration of tracheal xenograft epithelium using a clonal analysis competition assay. SMG-derived progenitors were also multipotent for cell types in the SAE and formed gland-like structures in xenografts. These studies demonstrate the importance of Wnt signals in modulating SC phenotypes within tracheal niches and provide new insight into phenotypic differences of SMG and SAE SCs. Stem Cells 2016;34:2758-2771.
Historical ecology is becoming an important focus in conservation biology and offers a promising tool to help guide ecosystem management. Here, we integrate data from multiple disciplines to ...illuminate the past, present, and future of biodiversity on California’s Channel Islands, an archipelago that has undergone a wide range of land-use and ecological changes. Our analysis spans approximately 20,000 years, from before human occupation and through Native American hunter–gatherers, commercial ranchers and fishers, the US military, and other land managers. We demonstrate how long-term, interdisciplinary research provides insight into conservation decisions, such as setting ecosystem restoration goals, preserving rare and endemic taxa, and reducing the impacts of climate change on natural and cultural resources. We illustrate the importance of historical perspectives for understanding modern patterns and ecological change and present an approach that can be applied generally in conservation management planning.
Bird-facilitated introduction of ticks and associated pathogens is postulated to promote invasion of tick-borne zoonotic diseases into urban areas. Results of a longitudinal study conducted in ...suburban Chicago, Illinois, USA, during 2005-2010 show that 1.6% of 6,180 wild birds captured in mist nets harbored ticks. Tick species in order of abundance were Haemaphysalis leporispalustris, Ixodes dentatus, and I. scapularis, but 2 neotropical tick species of the genus Amblyomma were sampled during the spring migration. I. scapularis ticks were absent at the beginning of the study but constituted the majority of ticks by study end and were found predominantly on birds captured in areas designated as urban green spaces. Of 120 ticks, 5 were infected with Borrelia burgdorferi, spanning 3 ribotypes, but none were infected with Anaplasma phagocytophilum. Results allow inferences about propagule pressure for introduction of tick-borne diseases and emphasize the large sample sizes required to estimate this pressure.
Primary graft dysfunction (PGD) is the leading cause of postoperative mortality in lung transplant recipients and the most important risk factor for development of chronic lung allograft dysfunction. ...The mechanistic basis for the variability in the incidence and severity of PGD between lung transplant recipients is not known. Using a murine orthotopic vascularized lung transplant model, we found that redundant activation of Toll-like receptors 2 and 4 (TLR2 and -4) on nonclassical monocytes activates MyD88, inducing the release of the neutrophil attractant chemokine CXCL2. Deletion of Itgam (encodes CD11b) in nonclassical monocytes enhanced their production of CXCL2 and worsened PGD, while a CD11b agonist, leukadherin-1, administered only to the donor lung prior to lung transplantation, abrogated CXCL2 production and PGD. The damage-associated molecular pattern molecule HMGB1 was increased in peripheral blood samples from patients undergoing lung transplantation after reperfusion and induced CXCL2 production in nonclassical monocytes via TLR4/MyD88. An inhibitor of HMGB1 administered to the donor and recipient prior to lung transplantation attenuated PGD. Our findings suggest that CD11b acts as a molecular brake to prevent neutrophil recruitment by nonclassical monocytes following lung transplantation, revealing an attractive therapeutic target in the donor lung to prevent PGD in lung transplant recipients.
Abstract
Construction durations of magma reservoirs are commonly inferred from U–Pb zircon geochronology using various statistical methods to interpret zircon U–Pb age spectra (e.g. weighted mean ...ages of concordant zircon populations). However, in compositionally different magmas, zircon saturation and crystallization are predicted to occur at different times relative to other mineral phases and the geological event of interest; for instance, magma emplacement. The timescales of these processes can be predicted by numerical modeling and measured using U–Pb zircon thermal ionization mass spectrometry (TIMS) geochronology, therefore creating an opportunity to quantify magma emplacement in space and time to constrain the size and longevity of magma reservoirs during pluton construction. The Jurassic tilted, bimodal (gabbroic and granitic) Guadalupe igneous complex (GIC) in the Sierra Nevada arc presents an exceptional opportunity to study the construction duration of a shallow (1–10 km) magma reservoir comprising multiple magma batches. We present a new workflow to constrain emplacement ages from zircon geochronology of compositionally different magma batches and evaluate melt-present timescales. High-precision U–Pb chemical ablation isotope dilution (CA-ID)-TIMS zircon ages are combined with MELTS modeling to calculate zircon saturation ages for each dated sample. Bayesian statistics are then used to compare calculated zircon saturation distributions with zircon age distributions from TIMS data to predict time, temperature, and melt fraction at zircon saturation and solidus. In addition, we use mineral thermometry and cooling rate calculations to relate zircon saturation ages to emplacement ages for felsic and mafic rocks, resulting in a best estimate for the total construction duration of 295 ± 110 kyr for the GIC. Rhyolites exposed at the top of the GIC are ∼2–3 Myr older and thus not part of the same magmatic system. The good agreement between Ti-in-zircon crystallization temperatures and calculated zircon saturation temperatures by MELTS implies that bulk-rock compositions of both mafic and felsic rocks are close to liquid compositions. Mafic and felsic magmas experienced extensive mingling at the emplacement level in a magma chamber (which, as defined here, has temperatures above the solidus of the respective rock composition) encompassing ∼60% of the exposed map area of the complex shortly after construction. Melt was present within the system for a total duration of ∼550 kyr as constrained by two-dimensional thermal finite-difference modeling using an incremental growth and sill emplacement model. The construction and melt-present timescales calculated in this study for the shallow GIC have implications for the potential of in situ differentiation, mixing and mingling timescales and eruption in shallow magmatic systems.
Reconstructing climates of the past relies on a variety of evidence from a large number of sites to capture the varied features of climate and the spatial heterogeneity of climate change. This review ...summarizes available information from diverse Holocene paleoenvironmental records across eastern Beringia (Alaska, westernmost Canada and adjacent seas), and it quantifies the primary trends of temperature- and moisture-sensitive records based in part on midges, pollen, and biogeochemical indicators (compiled in the recently published Arctic Holocene database, and updated here to v2.1). The composite time series from these proxy records are compared with new summaries of mountain-glacier and lake-level fluctuations, terrestrial water-isotope records, sea-ice and sea-surface-temperature analyses, and peatland and thaw-lake initiation frequencies to clarify multi-centennial- to millennial-scale trends in Holocene climate change. To focus the synthesis, the paleo data are used to frame specific questions that can be addressed with simulations by Earth system models to investigate the causes and dynamics of past and future climate change. This systematic review shows that, during the early Holocene (11.7–8.2 ka; 1 ka = 1000 cal yr BP), rather than a prominent thermal maximum as suggested previously, temperatures were highly variable, at times both higher and lower than present (approximate mid-20th-century average), with no clear spatial pattern. Composited pollen, midge and other proxy records average out the variability and show the overall lowest summer and mean-annual temperatures across the study region during the earliest Holocene, followed by warming over the early Holocene. The sparse data available on early Holocene glaciation show that glaciers in southern Alaska were as extensive then as they were during the late Holocene. Early Holocene lake levels were low in interior Alaska, but moisture indicators show pronounced differences across the region. The highest frequency of both peatland and thaw-lake initiation ages also occurred during the early Holocene. During the middle Holocene (8.2–4.2 ka), glaciers retreated as the regional average temperature increased to a maximum between 7 and 5 ka, as reflected in most proxy types. Following the middle Holocene thermal maximum, temperatures decreased starting between 4 and 3 ka, signaling the onset of Neoglacial cooling. Glaciers in the Brooks and Alaska Ranges advanced to their maximum Holocene extent as lakes generally rose to modern levels. Temperature differences for averaged 500-year time steps typically ranged by 1–2 °C for individual records in the Arctic Holocene database, with a transition to a cooler late Holocene that was neither abrupt nor spatially coherent. The longest and highest-resolution terrestrial water isotope records previously interpreted to represent changes in the Aleutian low-pressure system around this time are here shown to be largely contradictory. Furthermore, there are too few records with sufficient resolution to identify sub-centennial-scale climate anomalies, such as the 8.2 ka event. The review concludes by suggesting some priorities for future paleoclimate research in the region.
•We summarize diverse Holocene paleoclimate records from Alaska and NW Canada.•Proxy types include midges, pollen, biogeochemistry, glaciers, isotopes, lake levels.•Early Holocene (11.5–8.0 ka) temperatures were highly variable, but cold on average.•Regional average temperature increased to a maximum between 7 and 5 ka.•Priorities for future paleoclimate research in the region are suggested.
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