The Cellular and Physiological Basis for Lung Repair and Regeneration: Past, Present, and Future.

The respiratory system, which includes the trachea, airways, and distal alveoli, is a complex multi-cellular organ that intimately links with the cardiovascular system to accomplish gas exchange. In this review and as members of the NIH/NHLBI-supported Progenitor Cell Translational Consortium, we discuss key aspects of lung repair and regeneration. We focus on the cellular compositions within functional niches, cell-cell signaling in homeostatic health, the responses to injury, and new methods to study lung repair and regeneration. We also provide future directions for an improved understanding of the cell biology of the respiratory system, as well as new therapeutic avenues

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

Heterogeneity in Readouts of Canonical Wnt Pathway Activity within Intestinal Crypts

BACKGROUND: Canonical Wnt pathway signaling is necessary for maintaining the proliferative capacity of mammalian intestinal crypt base columnar stem cells (CBCs). Furthermore, dysregulation of the Wnt pathway is a major contributor to disease, including oncogenic transformation of the intestinal epithelium. Given the critical importance of this pathway, numerous tools have been used as proxy measures for Wnt pathway activity, yet the relationship between Wnt target gene expression and reporter allele activity within individual cells at the crypt base remains unclear. RESULTS: Here, we describe a novel Axin2-CreERT2-tdTomato allele that efficiently marks both WntHigh CBCs and radioresistant reserve intestinal stem cells. We analyze the molecular and functional identity of Axin2-CreERT2-tdTomato-marked cells using single cell gene expression profiling and tissue regeneration assays and find that Axin2 reporter activity does not necessarily correlate with expression of Wnt target genes and, furthermore, that Wnt target genes themselves vary in their expression patterns at the crypt base. CONCLUSIONS: Wnt target genes and reporter alleles can vary greatly in their cell-type specificity, demonstrating that these proxies cannot be used interchangeably. Furthermore, Axin2-CreERT2-tdTomato is a robust marker of both active and reserve intestinal stem cells and is thus useful for understanding the intestinal stem cell compartment

Health Care Consumers: Choices and Constraints

This article summarizes the research and data currently available on different dimensions of consumer choice. These dimensions include not only whether to participate in a health care plan and which plan to select if given a choice but also the decisions that lead to having a choice and the implications of making the choice. Data are presented on what choices consumers face, how many are given what kinds of choices, what constraints they face, what we know about how they make these choices, and what information they are given and what they use. The majority of Americans are offered some kind of health insurance plan either through their place of employment or as a dependent on someone else’s employer-sponsored health plan. About half of those offered health insurance are offered a choice, usually of only two or three plans. The majority elect to participate in one of those plans.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68465/2/10.1177_107755879905600102.pd

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

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

Adverse Selection in the Children’s Health Insurance Program

This study investigates whether new enrollees in the Alabama Children’s Health Insurance Program have different claims experience from renewing enrollees who do not have a lapse in coverage and from continuing enrollees. The analysis compared health services utilization in the first month of enrollment for new enrollees (who had not been in the program for at least 12 months) with utilization among continuing enrollees. A second analysis compared first-month utilization of those who renew immediately with those who waited at least 2 months to renew. A 2-part model estimated the probability of usage and then the extent of usage conditional on any utilization. Claims data for 826 866 child-years over the period from 1999 to 2012 were used. New enrollees annually constituted a stable 40% share of participants. Among those enrolled in the program, 13.5% renewed on time and 86.5% of enrollees were late to renew their enrollment. In the multivariate 2-part models, controlling for age, gender, race, income eligibility category, and year, new enrollees had overall first-month claims experience that was nearly $29 less than continuing enrollees. This was driven by lower ambulatory use. Late renewals had overall first-month claims experience that was$10 less than immediate renewals. However, controlling for the presence of chronic health conditions, there was no statistically meaningful difference in the first-month claims experience of late and early renewals. Thus, differences in claims experience between new and continuing enrollees and between early and late renewals are small, with greater spending found among continuing and early renewing participants. Higher claims experience by early renewals is attributable to having chronic health conditions

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