Bone morphogenetic protein receptor signaling is necessary for normal murine postnatal bone formation

Functions of bone morphogenetic proteins (BMPs) are initiated by signaling through specific type I and type II serine/threonine kinase receptors. In previous studies, we have demonstrated that the type IB BMP receptor (BMPR-IB) plays an essential and specific role in osteoblast commitment and differentiation. To determine the role of BMP receptor signaling in bone formation in vivo, we generated transgenic mice, which express a truncated dominant-negative BMPR-IB targeted to osteoblasts using the type I collagen promoter. The mice are viable and fertile. Tissue-specific expression of the truncated BMPR-IB was demonstrated. Characterization of the phenotype of these transgenic mice showed impairment of postnatal bone formation in 1-mo-old homozygous transgenic mice. Bone mineral density, bone volume, and bone formation rates were severely reduced, but osteoblast and osteoclast numbers were not significantly changed in the transgenic mice. To determine whether osteoblast differentiation is impaired, we used primary osteoblasts isolated from the transgenic mice and showed that BMP signaling is blocked and BMP2-induced mineralized bone matrix formation was inhibited. These studies show the effects of alterations in BMP receptor function targeted to the osteoblast lineage and demonstrate a necessary role of BMP receptor signaling in postnatal bone growth and bone formation in vivo

Case Report: A Case of Wood-Smoke–Related Pulmonary Disease

CONTEXT: Biomass serves as a major fuel source for > 50% of the world’s population. The global burden of disease attributed to indoor air pollution from biomass combustion accounts for approximately 3% of worldwide disability-adjusted life-years lost. This is due to pneumonia in children and chronic obstructive pulmonary disease and lung cancer in women. CASE PRESENTATION: A 53-year-old man from Mexico was referred to the pulmonary clinic for evaluation of chronic productive cough and pulmonary nodules. In his youth, he worked at a charcoal plant in Mexico, where he burned wood and was exposed to massive amounts of smoke. His evaluation revealed thickened bronchovascular bundles with nodules on thoracic computed tomography, dark black plaques in large airways on bronchoscopy, and carbon-laden macrophages and fibrotic scars on lung biopsy. DISCUSSION: The patient was diagnosed with “hut lung,” a term that refers to the noninfectious, nonmalignant respiratory manifestations of chronic, high-level exposures to biomass smoke. This is the first reported case of hut lung associated with charcoal production. This case highlights that histopathologic abnormalities of the lung parenchyma may be present in patients with only mild symptoms and that clinical progression is likely a function of both the duration and intensity of exposure. RELEVANCE TO CLINICAL PRACTICE: As residents of lesser developed countries continue to be exposed to high levels of biomass smoke at work or at home and continue to immigrate to developed countries, it is important that health care providers in developed countries be aware of biomass-smoke–related pulmonary disease

The integrin αvβ8 mediates epithelial homeostasis through MT1-MMP–dependent activation of TGF-β1

Întegrins, matrix metalloproteases (MMPs), and the cytokine TGF-β have each been implicated in homeostatic cell behaviors such as cell growth and matrix remodeling. TGF-β exists mainly in a latent state, and a major point of homeostatic control is the activation of TGF-β. Because the latent domain of TGF-β1 possesses an integrin binding motif (RGD), integrins have the potential to sequester latent TGF-β (SLC) to the cell surface where TGF-β activation could be locally controlled. Here, we show that SLC binds to αvβ8, an integrin expressed by normal epithelial and neuronal cells in vivo. This binding results in the membrane type 1 (MT1)-MMP–dependent release of active TGF-β, which leads to autocrine and paracrine effects on cell growth and matrix production. These data elucidate a novel mechanism of cellular homeostasis achieved through the coordination of the activities of members of three major gene families involved in cell–matrix interactions

Microvessel stenosis, enlarged perivascular spaces, and fibrinogen deposition are associated with ischemic periventricular white matter hyperintensities

Periventricular white matter hyperintensities (pvWMH) are neuroimaging abnormalities surrounding the lateral ventricles that are apparent on magnetic resonance imaging (MRI). They are associated with age, neurodegenerative disease, and cerebrovascular risk factors. While pvWMH ultimately represent a loss of white matter structural integrity, the pathological causes are heterogeneous in nature, and currently, cannot be distinguished using neuroimaging alone. pvWMH could occur because of a combination of small vessel disease (SVD), ependymal loss, blood–brain barrier dysfunction, and microgliosis. In this study we aimed to characterize microvascular stenosis, fibrinogen extravasation, and microgliosis within pvWMH with and without imaging evidence of periventricular infarction. Using postmortem neuroimaging of human brains (n = 20), we identified pvWMH with and without periventricular infarcts (PVI). We performed histological analysis of microvessel stenosis, perivascular spaces, microgliosis, and immunohistochemistry against fibrinogen as a measure of serum protein extravasation. Herein, we report distinctions between pvWMH with and without periventricular infarcts based on associations with microvessel stenosis, enlarged perivascular spaces, and fibrinogen IHC. Microvessel stenosis was significantly associated with PVI and with cellular deposition of fibrinogen in the white matter. The presence of fibrinogen was associated with PVI and increased number of microglia. These findings suggest that neuroimaging-based detection of infarction within pvWMH may help distinguish more severe lesions, associated with underlying microvascular disease and BBB dysfunction, from milder pvWMH that are a highly frequent finding on MRI

Chiral symmetry breaking and effective lagrangians for softly broken supersymmetric QCD

We study supersymmetric QCD with N_f<N_c in the limit of small supersymmetry-breaking masses and smaller quark masses using the weak-coupling Kahler potential. We calculate the full spectrum of this theory, which manifests a chiral symmetry breaking pattern similar to that caused by the strong interactions of the standard model. We derive the chiral effective lagrangian for the pion degrees of freedom, and discuss the behavior in the formal limit of large squark and gluino masses and for large N_c. We show that the resulting scalings of the pion decay constant and pion masses in these limits differ from those expected in ordinary nonsupersymmetric QCD. Although there is no weak coupling expansion with N_f=N_c, we extend our results to this case by constructing a superfield quantum modified constraint in the presence of supersymmetry breaking.Comment: 16 pages, LaTe

Adherence to the updated guidelines for the prevention of perinatal Group B streptococcal disease

In 2010, the Centers for Disease Control and Prevention updated the Guidelines for the Prevention of Perinatal Group B Streptococcal (GBS) Disease. Previous studies of adherence to GBS guidelines have focused on the treatment of carriers of GBS. Our objective was to determine whether there was any difference in adherence to the guidelines for screening and treatment of women who delivered at our institution between the beginning of 2011 and the end of 2011 as the revised guidelines were published in November 2010. Our secondary outcome was to determine whether any differences in adherence occurred between prenatal provider types (OB/Gyn, Certified Nurse Midwives, and Family Practice)

Right coronary wall cmr in the older asymptomatic advance cohort: positive remodeling and associations with type 2 diabetes and coronary calcium

<p>Abstract</p> <p>Background</p> <p>Coronary wall cardiovascular magnetic resonance (CMR) is a promising noninvasive approach to assess subclinical atherosclerosis, but data are limited in subjects over 60 years old, who are at increased risk. The purpose of the study was to evaluate coronary wall CMR in an asymptomatic older cohort.</p> <p>Results</p> <p>Cross-sectional images of the proximal right coronary artery (RCA) were acquired using spiral black-blood coronary CMR (0.7 mm resolution) in 223 older, community-based patients without a history of cardiovascular disease (age 60-72 years old, 38% female). Coronary measurements (total vessel area, lumen area, wall area, and wall thickness) had small intra- and inter-observer variabilities (r = 0.93~0.99, all p < 0.0001), though one-third of these older subjects had suboptimal image quality. Increased coronary wall thickness correlated with increased coronary vessel area (p < 0.0001), consistent with positive remodeling. On multivariate analysis, type 2 diabetes was the only risk factor associated with increased coronary wall area and thickness (p = 0.03 and p = 0.007, respectively). Coronary wall CMR measures were also associated with coronary calcification (p = 0.01-0.03).</p> <p>Conclusions</p> <p>Right coronary wall CMR in asymptomatic older subjects showed increased coronary atherosclerosis in subjects with type 2 diabetes as well as coronary calcification. Coronary wall CMR may contribute to the noninvasive assessment of subclinical coronary atherosclerosis in older, at-risk patient groups.</p

Analysis of close conjunctions between dayside polar cap airglow patches and flow channels by all-sky imager and DMSP

Recent imager and radar observations in the nightside polar cap have shown evidence that polar cap patches are associated with localized flow channels. To understand how flow channels propagate from the dayside auroral oval into the polar cap, we use an all-sky imager in Antarctica and DMSP (F13, F15, F16, F17 and F18) to determine properties of density and flows associated with dayside polar cap patches. We identified 50 conjunction events during the southern winter seasons of 2007–2011. In a majority (45) of events, longitudinally narrow flow enhancements directed anti-sunward are found to be collocated with the patches, have velocities (up to a few km/s) substantially larger than the large-scale background flows (~500 m/s) and have widths comparable to patch widths (~400 km). While the patches start with poleward moving auroral forms (PMAFs) as expected, many PMAFs propagate azimuthally away from the noon over a few hours of MLT, resulting in formation of polar cap patches quite far away from the noon, as early as ~6 MLT. The MLT separation from the noon is found to be proportional to the IMF |By|. Fast polar cap flows of \u3e~1500 m/s are predominantly seen during large IMF |By| and small |Bz|. The presence of fast, anti-sunward flow channels associated with the polar cap patches suggests that the flow channels form in the dayside auroral oval through transient reconnection and can be the source of flow channels propagating into the polar cap