Terrane accretion and dispersal in the northern Gondwana margin. An Early Paleozoic analogue of a long-lived active margin

If reconstruction of major events in ancient orogenic belts is achieved in sufficient detail, the tectonic evolution of these belts can offer valuable information to widen our perspective of processes currently at work in modern orogens. Here, we illustrate this possibility taking the western European Cadomian–Avalonian belt as an example. This research is based mainly on the study and interpretation of U–Pb ages of more than 300 detrital zircons from Neoproterozoic and Early Paleozoic sedimentary rocks from Iberia and Brittany. Analyses have been performed using the laser ablation–ICP–MS technique. The U–Pb data record contrasting detrital zircon age spectra for various terranes of western Europe. The differences provide information on the processes involved in the genesis of the western European Precambrian terranes along the northern margin of Neoproterozoic Gondwana during arc construction and subduction, and their dispersal and re-amalgamation along the margin to form the Avalonia and Armorica microcontinents. The U–Pb ages reported here also support the alleged change from subduction to transform activity that led to the final break-up of the margin, the birth of the Rheic Ocean and the drift of Avalonia. We contend that the active northern margin of Gondwana evolved through several stages that match the different types of active margins recognised in modern settings

Expression and localization of epithelial aquaporins in the adult human lung

Aquaporins (AQPs) facilitate water transport across epithelia and play an important role in normal physiology and disease in the human airways. We used in situ hybridization and immunofluorescence to determine the expression and cellular localization of AQPs 5, 4, and 3 in human airway sections. In nose and bronchial epithelia, AQP5 is expressed at the apical membrane of columnar cells of the superficial epithelium and submucosal gland acinar cells. AQP4 was detected in basolateral membranes in ciliated ducts and by in situ in gland acinar cells. AQP3 is present on basal cells of both superficial epithelium and gland acinus. In these regions AQPs 5, 4, and 3 are appropriately situated to permit transepithelial water permeability. In the small airways (proximal and terminal bronchioles) AQP3 distribution shifts from basal cell to surface expression (i.e., localized to the apical membrane of proximal and terminal bronchioles) and is the only AQP identified in this region of the human lung. The alveolar epithelium has all three AQPs represented, with AQP5 and AQP4 localized to type I pneumocytes and AQP3 to type II cells. This study describes an intricate network of AQP expression that mediates water transport across the human airway epithelium

Permeabilization via the P2X7 purinoreceptor reveals the presence of a Ca2+ -activated Cl- conductance in the apical membrane of murine tracheal epithelial cells

Calcium-activated Cl- secretion is an important modulator of regulated ion transport in murine airway epithelium and is mediated by an unidentified Ca2+-stimulated Cl- channel. We have transfected immortalized murine tracheal epithelial cells with the cDNA encoding the permeabilizing P2X7 purinoreceptor (P2X7-R) to selectively permeabilize the basolateral membrane and thereby isolate the apical membrane Ca2+-activated Cl- current. In P2X7-R-permeabilized cells, we have demonstrated that UTP stimulates a Cl- current across the apical membrane of CF and normal murine tracheal epithelial cells. The magnitude of the UTP-stimulated current was significantly greater in CF than in normal cells. Ion substitution studies demonstrated that the current exhibited a permselectivity sequence of Cl- > I- > Br- > gluconate-. We have also determined a rank order of potency for putative Cl- channel blockers: niflumic acid ≥ 5-nitro-2-(3-phenylpropylamino)benzoic acid > 4,4'-diisothiocyanostilbene-2,2'-disulfonate > glybenclamide >> diphenlyamine-2-carboxylate, tamoxifen, and p-tetra-sulfonato-tetra-methoxy-calix[4]arene. Complete characterization of this current and the corresponding single channel properties could lead to the development of a new therapy to correct the defective airway surface liquid in cystic fibrosis patients

Transmembrane protein 16A (TMEM16A) is a Ca2+ -regulated Cl- secretory channel in mouse airways

For almost two decades, it has been postulated that calcium-activated Cl- channels (CaCCs) play a role in airway epithelial Cl- secretion, but until recently, the molecular identity of the airway CaCC(s) was unknown. Recent studies have unequivocally identified TMEM16A as a glandular epithelial CaCC. We have studied the airway bioelectrics of neonatal mice homozygous for a null allele of Tmem16a (Tmem16a-/ -) to investigate the role of this channel in Cl- secretion in airway surface epithelium. When compared with wild-type tracheas, the Tmem16a-/- tracheas exhibited a >60% reduction in purinoceptor (UTP)-regulated CaCC activity. Other members of the Tmem16 gene family,including Tmem16f and Tmem16k, were also detected by reverse transcription-PCR in neonatal tracheal epithelium, suggesting that other family members could be considered as contributing to the small residual UTP response. TMEM16A, however, appeared to contribute little to unstimulated Cl- secretion, whereas studies with cystic fibrosis transmembrane conductance regulator (CFTR)-deficient mice and wild-type littermates revealed that unstimulated Cl- secretion reflected ∼50% CFTR activity and ∼50% non-Tmem16a activity. Interestingly, the tracheas of both the Tmem16a-/- and the CFTR-/- mice exhibited similar congenital cartilaginous defects that may reflect a common Cl- secretory defect mediated by the molecularly distinct Cl- channels. Importantly, the residual CaCC activity in Tmem16a-/- mice appeared inadequate for normal airway hydration because Tmem16a-/- tracheas exhibited significant, neonatal, lumenal mucus accumulation. Our data suggest that TMEM16A CaCC-mediated Cl- secretion appears to be necessary for normal airway surface liquid homeostasis

Quantitation and localization of ENaC subunit expression in fetal, newborn, and adult mouse lung

The newborn lung is cleared of fetal liquid by active Na+ transport. The heterotrimeric (α, β, γ) epithelial Na+ channel, ENaC, mediates this process. To understand the role of individual ENaC subunits in Na+ transport during development, we quantified murine ENaC (mENaC) subunit messenger RNA (mRNA) expression levels of fetal, neonatal, and adult mouse lung by Northern blot analysis and studied regional expression by in situ hybridization. αmENaC and γmENaC mRNA expression increased sharply in late fetal gestation and reached near-adult levels by Day 1 of postnatal life. βmENaC expression increased more gradually through late fetal and early postnatal life and increased progressively until adulthood. In situ hybridization studies showed similar localization patterns of αmENaC and γmENaC subunit expression in fetal and postnatal lung. γmENaC and αmENaC subunits were initially localized to fetal lung bud tubules and by late gestation both subunits were expressed in all regions (acinar and bronchiolar) of the distal lung epithelium. βmENaC was detected from 16 d gestation onward and was expressed most intensely in small airways. There was little expression of βmENaC in the alveolar region. In postnatal lung all three subunits were expressed intensely in small airways. In adult lung, αmENaC and γmENaC were expressed in a pattern consistent with an alveolar type II (ATII) cell distribution. The timing of quantitative changes in mENaC subunit expression is consistent with a role of Na+ transport in liquid clearance of the perinatal lung. Intense expression of mENaC subunits in medium and small airway epithelium and in ATII cells suggests that these regions are a primary location for liquid absorption in the perinatal and post-natal murine lung

Continuation-Passing C: compiling threads to events through continuations

In this paper, we introduce Continuation Passing C (CPC), a programming language for concurrent systems in which native and cooperative threads are unified and presented to the programmer as a single abstraction. The CPC compiler uses a compilation technique, based on the CPS transform, that yields efficient code and an extremely lightweight representation for contexts. We provide a proof of the correctness of our compilation scheme. We show in particular that lambda-lifting, a common compilation technique for functional languages, is also correct in an imperative language like C, under some conditions enforced by the CPC compiler. The current CPC compiler is mature enough to write substantial programs such as Hekate, a highly concurrent BitTorrent seeder. Our benchmark results show that CPC is as efficient, while using significantly less space, as the most efficient thread libraries available.Comment: Higher-Order and Symbolic Computation (2012). arXiv admin note: substantial text overlap with arXiv:1202.324

Regulation of murine airway surface liquid volume by CFTR and Ca2+-activated Cl- conductances

Two Cl- conductances have been described in the apical membrane of both human and murine proximal airway epithelia that are thought to play predominant roles in airway hydration: (1) CFTR, which is cAMP regulated and (2) the Ca2+-activated Cl- conductance (CaCC) whose molecular identity is uncertain. In addition to second messenger regulation, cross talk between these two channels may also exist and, whereas CFTR is absent or defective in cystic fibrosis (CF) airways, CaCC is preserved, and may even be up-regulated. Increased CaCC activity in CF airways is controversial. Hence, we have investigated the effects of CFTR on CaCC activity and have also assessed the relative contributions of these two conductances to airway surface liquid (ASL) height (volume) in murine tracheal epithelia. We find that CaCC is up-regulated in intact murine CF tracheal epithelia, which leads to an increase in UTP-mediated Cl-/volume secretion. This up-regulation is dependent on cell polarity and is lost in nonpolarized epithelia. We find no role for an increased electrical driving force in CaCC up-regulation but do find an increased Ca2+ signal in response to mucosal nucleotides that may contribute to the increased Cl-/volume secretion seen in intact epithelia. CFTR plays a critical role in maintaining ASL height under basal conditions and accordingly, ASL height is reduced in CF epithelia. In contrast, CaCC does not appear to significantly affect basal ASL height, but does appear to be important in regulating ASL height in response to released agonists (e.g., mucosal nucleotides). We conclude that both CaCC and the Ca2+ signal are increased in CF airway epithelia, and that they contribute to acute but not basal regulation of ASL height

Gossip in organisations: Contexts, consequences and controversies

This article examines the key themes surrounding gossip including its contexts, the various outcomes (positive and negative) of gossip as well as a selection of challenges and controversies. The challenges which are highlighted revolve around definitional issues, methodological approaches, and ethical considerations. Our analysis suggests that the characteristics and features of gossip lend itself to a process-oriented approach whereby the beginning and, particularly, end points of gossip are not always easily identified. Gossip about a subject or person can temporarily disappear only for it to re-surface at some later stage. In addition, questions pertaining to the effects of gossip and ethical-based arguments depend on the nature of the relationships within the gossip triad (gossiper, listener/respondent and target)

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes