Single-Cell Transcriptomic Profiling of Pluripotent Stem Cell-Derived SCGB3A2+ Airway Epithelium.

Lung epithelial lineages have been difficult to maintain in pure form in vitro, and lineage-specific reporters have proven invaluable for monitoring their emergence from cultured pluripotent stem cells (PSCs). However, reporter constructs for tracking proximal airway lineages generated from PSCs have not been previously available, limiting the characterization of these cells. Here, we engineer mouse and human PSC lines carrying airway secretory lineage reporters that facilitate the tracking, purification, and profiling of this lung subtype. Through bulk and single-cell-based global transcriptomic profiling, we find PSC-derived airway secretory cells are susceptible to phenotypic plasticity exemplified by the tendency to co-express both a proximal airway secretory program as well as an alveolar type 2 cell program, which can be minimized by inhibiting endogenous Wnt signaling. Our results provide global profiles of engineered lung cell fates, a guide for improving their directed differentiation, and a human model of the developing airway

Deep GALEX Imaging of the HST/COSMOS Field: A First Look at the Morphology of z~0.7 Star-forming Galaxies

We present a study of the morphological nature of redshift z~0.7 star-forming galaxies using a combination of HST/ACS, GALEX and ground-based images of the COSMOS field. Our sample consists of 8,146 galaxies, 5,777 of which are detected in the GALEX near-ultraviolet band down to a limiting magnitude of 25.5 (AB). We make use of the UV to estimate star formation rates, correcting for the effect of dust using the UV-slope, and compute, from the ACS F814W images, the C,A,S,G,M20 morphological parameters for all objects in our sample. We observe a morphological bimodality in the galaxy population and show that it has a strong correspondence with the FUV - g color bimodality. We conclude that UV-optical color predominantly evolves concurrently with morphology. We observe many of the most star-forming galaxies to have morphologies approaching that of early-type galaxies, and interpret this as evidence that strong starburst events are linked to bulge growth and constitute a process through which galaxies can be brought from the blue to the red sequence while simultaneously modifying their morphology accordingly. We conclude that the red sequence has continued growing at z~<0.7. We also observe z~0.7 galaxies to have physical properties similar to that of local galaxies, except for higher star formation rates. Whence we infer that the dimming of star-forming galaxies is responsible for most of the evolution in the star formation rate density of the Universe since that redshift, although our data are also consistent with a mild number evolution. [abridged]Comment: 29 pages including 22 figures. Accepted for publication in ApJS COSMOS Special Issue. A copy of the paper with high resolution figures is available at http://www.astro.columbia.edu/~michel/galex_cosmos_paper.pd

Crossing the Dripline to 11N Using Elastic Resonance Scattering

The level structure of the unbound nucleus 11N has been studied by 10C+p elastic resonance scattering in inverse geometry with the LISE3 spectrometer at GANIL, using a 10C beam with an energy of 9.0 MeV/u. An additional measurement was done at the A1200 spectrometer at MSU. The excitation function above the 10C+p threshold has been determined up to 5 MeV. A potential-model analysis revealed three resonance states at energies 1.27 (+0.18-0.05) MeV (Gamma=1.44 +-0.2 MeV), 2.01(+0.15-0.05) MeV, (Gamma=0.84 +-$0.2 MeV) and 3.75(+-0.05) MeV, (Gamma=0.60 +-0.05 MeV) with the spin-parity assignments I(pi) =1/2+, 1/2- and 5/2+, respectively. Hence, 11N is shown to have a ground state parity inversion completely analogous to its mirror partner, 11Be. A narrow resonance in the excitation function at 4.33 (+-0.05) MeV was also observed and assigned spin-parity 3/2-.Comment: 14 pages, 9 figures, twocolumn Accepted for publication in PR

Revision and Update of the Consensus Definitions of Invasive Fungal Disease From the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium.

BACKGROUND: Invasive fungal diseases (IFDs) remain important causes of morbidity and mortality. The consensus definitions of the Infectious Diseases Group of the European Organization for Research and Treatment of Cancer and the Mycoses Study Group have been of immense value to researchers who conduct clinical trials of antifungals, assess diagnostic tests, and undertake epidemiologic studies. However, their utility has not extended beyond patients with cancer or recipients of stem cell or solid organ transplants. With newer diagnostic techniques available, it was clear that an update of these definitions was essential. METHODS: To achieve this, 10 working groups looked closely at imaging, laboratory diagnosis, and special populations at risk of IFD. A final version of the manuscript was agreed upon after the groups' findings were presented at a scientific symposium and after a 3-month period for public comment. There were several rounds of discussion before a final version of the manuscript was approved. RESULTS: There is no change in the classifications of "proven," "probable," and "possible" IFD, although the definition of "probable" has been expanded and the scope of the category "possible" has been diminished. The category of proven IFD can apply to any patient, regardless of whether the patient is immunocompromised. The probable and possible categories are proposed for immunocompromised patients only, except for endemic mycoses. CONCLUSIONS: These updated definitions of IFDs should prove applicable in clinical, diagnostic, and epidemiologic research of a broader range of patients at high-risk

Multiple dose-dependent roles for Sox2 in the patterning and differentiation of anterior foregut endoderm

Sox2 is expressed in developing foregut endoderm, with highest levels in the future esophagus and anterior stomach. By contrast, Nkx2.1 (Titf1) is expressed ventrally, in the future trachea. In humans, heterozygosity for SOX2 is associated with anopthalmiaesophageal-genital syndrome (OMIM 600992), a condition including esophageal atresia (EA) and tracheoesophageal fistula (TEF), in which the trachea and esophagus fail to separate. Mouse embryos heterozygous for the null allele, Sox2EGFP, appear normal. However, further reductions in Sox2, using Sox2LP and Sox2COND hypomorphic alleles, result in multiple abnormalities. Approximately 60% of Sox2EGFP/COND embryos have EA with distal TEF in which Sox2 is undetectable by immunohistochemistry or western blot. The mutant esophagus morphologically resembles the trachea, with ectopic expression of Nkx2.1, a columnar, ciliated epithelium, and very few p63+ basal cells. By contrast, the abnormal foregut of Nkx2.1-null embryos expresses elevated Sox2 and p63, suggesting reciprocal regulation of Sox2 and Nkx2.1 during early dorsal/ventral foregut patterning. Organ culture experiments further suggest that FGF signaling from the ventral mesenchyme regulates Sox2 expression in the endoderm. In the 40% Sox2EGFP/COND embryos in which Sox2 levels are ~18% of wild type there is no TEF. However, the esophagus is still abnormal, with luminal mucus-producing cells, fewer p63+ cells, and ectopic expression of genes normally expressed in glandular stomach and intestine. In all hypomorphic embryos the forestomach has an abnormal phenotype, with reduced keratinization, ectopic mucus cells and columnar epithelium. These findings suggest that Sox2 plays a second role in establishing the boundary between the keratinized, squamous esophagus/forestomach and glandular hindstomach

Catholic Healthcare Organizations and the Articulation of Their Identity

Contains fulltext : 69947.pdf (publisher's version ) (Open Access

Hemodynamic Forces Sculpt Developing Heart Valves through a KLF2-WNT9B Paracrine Signaling Axis.

Hemodynamic forces play an essential epigenetic role in heart valve development, but how they do so is not known. Here, we show that the shear-responsive transcription factor KLF2 is required in endocardial cells to regulate the mesenchymal cell responses that remodel cardiac cushions to mature valves. Endocardial Klf2 deficiency results in defective valve formation associated with loss of Wnt9b expression and reduced canonical WNT signaling in neighboring mesenchymal cells, a phenotype reproduced by endocardial-specific loss of Wnt9b. Studies in zebrafish embryos reveal that wnt9b expression is similarly restricted to the endocardial cells overlying the developing heart valves and is dependent upon both hemodynamic shear forces and klf2a expression. These studies identify KLF2-WNT9B signaling as a conserved molecular mechanism by which fluid forces sensed by endothelial cells direct the complex cellular process of heart valve development and suggest that congenital valve defects may arise due to subtle defects in this mechanotransduction pathway.journal articleresearch support, non-u.s. gov'tresearch support, n.i.h., extramural2017 11 062017 10 19importe

Immunohistochemical detection and regulation of α5 nicotinic acetylcholine receptor (nAChR) subunits by FoxA2 during mouse lung organogenesis

<p>Abstract</p> <p>Background</p> <p>α₅nicotinic acetylcholine receptor (nAChR) subunits structurally stabilize functional nAChRs in many non-neuronal tissue types. The expression of α₅nAChR subunits and cell-specific markers were assessed during lung morphogenesis by co-localizing immunohistochemistry from embryonic day (E) 13.5 to post natal day (PN) 20. Transcriptional control of α₅nAChR expression by FoxA2 and GATA-6 was determined by reporter gene assays.</p> <p>Results</p> <p>Steady expression of α₅nAChR subunits was observed in distal lung epithelial cells during development while proximal lung expression significantly alternates between abundant prenatal expression, absence at PN4 and PN10, and a return to intense expression at PN20. α₅expression was most abundant on luminal edges of alveolar type (AT) I and ATII cells, non-ciliated Clara cells, and ciliated cells in the proximal lung at various periods of lung formation. Expression of α₅nAChR subunits correlated with cell differentiation and reporter gene assays suggest expression of α₅is regulated in part by FoxA2, with possible cooperation by GATA-6.</p> <p>Conclusions</p> <p>Our data reveal a highly regulated temporal-spatial pattern of α₅nAChR subunit expression during important periods of lung morphogenesis. Due to specific regulation by FoxA2 and distinct identification of α₅in alveolar epithelium and Clara cells, future studies may identify possible mechanisms of cell differentiation and lung homeostasis mediated at least in part by α₅-containing nAChRs.</p

Physician and Clinical Integration Among Rural Hospitals

The pressures for closer alignment between physicians and hospitals in both rural and urban areas are increasing. This study empirically specifies independent dimensions of physician and clinical integration and compares the extent to which such activities are practiced between rural and urban hospitals and among rural hospitals in different organizational and market contexts. Results suggest that both rural and urban hospitals practice physician integration, although each emphasizes different types of strategies. Second, urban hospitals engage in clinical integration with greater frequency than their rural counterparts. Finally, physician integration approaches in rural hospitals are more common among larger rural hospitals, those proximate to urban facilities, those with system affiliations, and those not under public control.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72074/1/j.1748-0361.1998.tb00637.x.pd

The Effect of Medicare Eligibility on Spousal Insurance Coverage

A majority of married couples in the United States take advantage of the fact that employers often provide health insurance coverage to spouses. When the older spouses become eligible for Medicare, however, many of them can no longer provide their younger spouses with coverage. In this paper, we study how spousal eligibility for Medicare affects the health insurance and health care access of the younger spouse. We find spousal eligibility for Medicare results in the younger spouse having worse insurance coverage and reduced access to health care services