Primary pulmonary hypertension is associated with reduced pulmonary vascular expression of type II bone morphogenetic protein receptor

BACKGROUND: Mutations in the type II receptor for bone morphogenetic protein (BMPR-II), a receptor member of the transforming growth factor-beta (TGF-beta) superfamily, underlie many familial and sporadic cases of primary pulmonary hypertension (PPH). METHODS AND RESULTS: Because the sites of expression of BMPR-II in the normal and hypertensive lung are unknown, we studied the cellular localization of BMPR-II and the related type I and II receptors for TGF-beta by immunohistochemistry in lung sections from patients undergoing heart-lung transplantation for PPH (n=11, including 3 familial cases) or secondary pulmonary hypertension (n=6) and from unused donor lungs (n=4). In situ hybridization was performed for BMPR-II mRNA. Patients were screened for the presence of mutations in BMPR2. In normal lungs, BMPR-II expression was prominent on vascular endothelium, with minimal expression in airway and arterial smooth muscle. In pulmonary hypertension cases, the intensity of BMPR-II immunostaining varied between lesions but involved endothelial and myofibroblast components. Image analysis confirmed that expression of BMPR-II was markedly reduced in the peripheral lung of PPH patients, especially in those harboring heterozygous BMPR2 mutations. A less marked reduction was also observed in patients with secondary pulmonary hypertension. In contrast, there was no difference in level of staining for TGF-betaRII or the endothelial marker CD31. CONCLUSIONS: The cellular localization of BMPR-II is consistent with a role in the formation of pulmonary vascular lesions in PPH, and reduced BMPR-II expression may contribute to the process of vascular obliteration in severe pulmonary hypertension

UV Observations of the Powering Source of the Supergiant Shell in IC2574

A multi-band analysis of the region containing the supergiant HI shell in the nearby dwarf irregular galaxy IC2574 presents evidence of a causal relationship between a central star cluster, the surrounding expanding HI shell, and secondary star formation sites on the rim of the HI shell. Comparisons of the far-UV (FUV, 1521 A), optical broad-band, H-alpha, X-ray, and HI morphologies suggest that the region is in an auspicious moment of star formation triggered by the central stellar cluster. The derived properties of the HI shell, the central stellar cluster, and the star forming regions on the rim support this scenario: The kinematic age of the HI shell is <14 Myr and in agreement with the age of the central stellar cluster derived from the FUV observations (sim 11 Myr). An estimate for the mechanical energy input from SN and stellar winds of the central stellar cluster made from FUV photometry and the derived cluster age is 4.1 x 10^52 erg, roughly a few times higher than the kinetic energy of the HI shell. The requisite energy input needed to create the HI shell, derived in the `standard' fashion from the HI observations (using the numerical models of Chevalier), is 2.6 x 10^53 erg which is almost an order of magnitude higher than the estimated energy input as derived from the FUV data. Given the overwhelming observational evidence that the central cluster is responsible for the expanding HI shell, this discrepancy suggests that the required energy input is overestimated using the `standard' method. This may explain why some other searches for remnant stellar clusters in giant HI holes have been unsuccessful so far. Our observations also show that stellar clusters are indeed able to create supergiant HI shells, even at large galactocentric radii, a scenario which has recently been questioned by a number of authors.Comment: AJ, accepted, 16 pages, 6 figure

Axonal growth arrests after an increased accumulation of Schwann cells expressing senescence markers and stromal cells in acellular nerve allografts

Acellular nerve allografts (ANAs) and other nerve constructs do not reliably facilitate axonal regeneration across long defects (>3 cm). Causes for this deficiency are poorly understood. In this study, we determined what cells are present within ANAs before axonal growth arrest in nerve constructs and if these cells express markers of cellular stress and senescence. Using the Thy1-GFP rat and serial imaging, we identified the time and location of axonal growth arrest in long (6 cm) ANAs. Axonal growth halted within long ANAs by 4 weeks, while axons successfully regenerated across short (3 cm) ANAs. Cellular populations and markers of senescence were determined using immunohistochemistry, histology, and senescence-associated β-galactosidase staining. Both short and long ANAs were robustly repopulated with Schwann cells (SCs) and stromal cells by 2 weeks. Schwann cells (S100β(+)) represented the majority of cells repopulating both ANAs. Overall, both ANAs demonstrated similar cellular populations with the exception of increased stromal cells (fibronectin(+)/S100β(−)/CD68(−) cells) in long ANAs. Characterization of ANAs for markers of cellular senescence revealed that long ANAs accumulated much greater levels of senescence markers and a greater percentage of Schwann cells expressing the senescence marker p16 compared to short ANAs. To establish the impact of the long ANA environment on axonal regeneration, short ANAs (2 cm) that would normally support axonal regeneration were generated from long ANAs near the time of axonal growth arrest (“stressed” ANAs). These stressed ANAs contained mainly S100β(+)/p16(+) cells and markedly reduced axonal regeneration. In additional experiments, removal of the distal portion (4 cm) of long ANAs near the time of axonal growth arrest and replacement with long isografts (4 cm) rescued axonal regeneration across the defect. Neuronal culture derived from nerve following axonal growth arrest in long ANAs revealed no deficits in axonal extension. Overall, this evidence demonstrates that long ANAs are repopulated with increased p16(+) Schwann cells and stromal cells compared to short ANAs, suggesting a role for these cells in poor axonal regeneration across nerve constructs

Col-OSSOS: Colors of the Interstellar Planetesimal 1I/`Oumuamua

The recent discovery by Pan-STARRS1 of 1I/2017 U1 (`Oumuamua), on an unbound and hyperbolic orbit, offers a rare opportunity to explore the planetary formation processes of other stars, and the effect of the interstellar environment on a planetesimal surface. 1I/`Oumuamua's close encounter with the inner Solar System in 2017 October was a unique chance to make observations matching those used to characterize the small-body populations of our own Solar System. We present near-simultaneous g$^\prime$, r$^\prime$, and J photometry and colors of 1I/`Oumuamua from the 8.1-m Frederick C. Gillett Gemini North Telescope, and $gri$ photometry from the 4.2 m William Herschel Telescope. Our g$^\prime$r$^\prime$J observations are directly comparable to those from the high-precision Colours of the Outer Solar System Origins Survey (Col-OSSOS), which offer unique diagnostic information for distinguishing between outer Solar System surfaces. The J-band data also provide the highest signal-to-noise measurements made of 1I/`Oumuamua in the near-infrared. Substantial, correlated near-infrared and optical variability is present, with the same trend in both near-infrared and optical. Our observations are consistent with 1I/`Oumuamua rotating with a double-peaked period of $8.10 \pm 0.42$ hours and being a highly elongated body with an axial ratio of at least 5.3:1, implying that it has significant internal cohesion. The color of the first interstellar planetesimal is at the neutral end of the range of Solar System $g-r$ and $r-J$ solar-reflectance colors: it is like that of some dynamically excited objects in the Kuiper belt and the less-red Jupiter Trojans.Comment: Accepted to ApJ

Pennsylvania Folklife Vol. 26, No. 1

• Pennsylvania Folk Festivals in the 1930s • Rational Powwowing: An Examination of Choice among Medical Alternatives in Rural York County, Pennsylvania • Memories of a Moonshiner • The Pennsylvania Germans: Folklife Studies from Autobiographical Sources • Student Life at a Pennsylvania Dutch College • Pennsylvania German Astronomy & Astrology XIV: Health and the Heavens • A Traditional Family Reunion • Roads, Ferries, Fords and Bridges: Folk-Cultural Questionnaire No. 45https://digitalcommons.ursinus.edu/pafolklifemag/1070/thumbnail.jp

Development and implementation of an Internet-based survivorship care program for cancer survivors treated with hematopoietic stem cell transplantation.

The Internet provides a widely accessible modality for meeting survivorship care needs of cancer survivors. In this paper, we describe the development and implementation of an Internet site designed as a base from which to conduct a randomized controlled trial to meet psycho-educational needs of hematopoietic stem cell transplantation (HSCT) survivors

Wildfire ignition-distribution modelling: a comparative study in the Huron-Manistee National Forest, Michigan, USA

Abstract. Wildfire ignition distribution models are powerful tools for predicting the probability of ignitions across broad areas, and identifying their drivers. Several approaches have been used for ignition-distribution modelling, yet the performance of different model types has not been compared. This is unfortunate, given that conceptually similar speciesdistribution models exhibit pronounced differences among model types. Therefore, our goal was to compare the predictive performance, variable importance and the spatial patterns of predicted ignition-probabilities of three ignition-distribution model types: one parametric, statistical model (Generalised Linear Models, GLM) and two machine-learning algorithms (Random Forests and Maximum Entropy, Maxent). We parameterised the models using 16 years of ignitions data and environmental data for the Huron-Manistee National Forest in Michigan, USA. Random Forests and Maxent had slightly better prediction accuracies than did GLM, but model fit was similar for all three. Variables related to human population and development were the best predictors of wildfire ignition locations in all models (although variable rankings differed slightly), along with elevation. However, despite similar model performance and variables, the map of ignition probabilities generated by Maxent was markedly different from those of the two other models. We thus suggest that when accurate predictions are desired, the outcomes of different model types should be compared, or alternatively combined, to produce ensemble predictions