Spatial and temporal changes in extracellular elastin and laminin distribution during lung alveolar development

Lung alveolarization requires precise coordination of cell growth with extracellular matrix (ECM) synthesis and deposition. The role of extracellular matrices in alveogenesis is not fully understood, because prior knowledge is largely extrapolated from two-dimensional structural analysis. Herein, we studied temporospatial changes of two important ECM proteins, laminin and elastin that are tightly associated with alveolar capillary growth and lung elastic recoil respectively, during both mouse and human lung alveolarization. By combining protein immunofluorescence staining with two- and three-dimensional imaging, we found that the laminin network was simplified along with the thinning of septal walls during alveogenesis, and more tightly associated with alveolar endothelial cells in matured lung. In contrast, elastin fibers were initially localized to the saccular openings of nascent alveoli, forming a ring-like structure. Then, throughout alveolar growth, the number of such alveolar mouth ring-like structures increased, while the relative ring size decreased. These rings were interconnected via additional elastin fibers. The apparent patches and dots of elastin at the tips of alveolar septae found in two-dimensional images were cross sections of elastin ring fibers in the three-dimension. Thus, the previous concept that deposition of elastin at alveolar tips drives septal inward growth may potentially be conceptually challenged by our data

Extreme Kuiper Belt Object 2001 QG298 and the Fraction of Contact Binaries

Extensive time-resolved observations of Kuiper Belt object 2001 QG298 show a lightcurve with a peak-to-peak variation of 1.14 +-0.04 magnitudes and single-peaked period of 6.8872 +- 0.0002 hr. The mean absolute magnitude is 6.85 magnitudes which corresponds to a mean effective radius of 122 (77) km if an albedo of 0.04 (0.10) is assumed. This is the first known Kuiper Belt object and only the third minor planet with a radius > 25 km to display a lightcurve with a range in excess of 1 magnitude. We find the colors to be typical for a Kuiper Belt object (B-V = 1.00 +- 0.04, V-R = 0.60 +- 0.02) with no variation in color between minimum and maximum light. The large light variation, relatively long double-peaked period and absence of rotational color change argue against explanations due to albedo markings or elongation due to high angular momentum. Instead, we suggest that 2001 QG298 may be a very close or contact binary similar in structure to what has been independently proposed for the Trojan asteroid 624 Hektor. If so, its rotational period would be twice the lightcurve period or 13.7744 +- 0.0004 hr. By correcting for the effects of projection, we estimate that the fraction of similar objects in the Kuiper Belt is at least 10% to 20% with the true fraction probably much higher. A high abundance of close and contact binaries is expected in some scenarios for the evolution of binary Kuiper Belt objects.Comment: 15 text pages,6 figures(Color),5 Tables, Accepted to AJ for May 200

A First-Principles Approach to Insulators in Finite Electric Fields

We describe a method for computing the response of an insulator to a static, homogeneous electric field. It consists of iteratively minimizing an electric enthalpy functional expressed in terms of occupied Bloch-like states on a uniform grid of k points. The functional has equivalent local minima below a critical field E_c that depends inversely on the density of k points; the disappearance of the minima at E_c signals the onset of Zener breakdown. We illustrate the procedure by computing the piezoelectric and nonlinear dielectric susceptibility tensors of III-V semiconductors.Comment: 4 pages, with 1 postscript figure embedded. Uses REVTEX and epsf macros. Also available at http://www.physics.rutgers.edu/~dhv/preprints/is_ef/index.htm

Human epicardial adipose tissue expresses a pathogenic profile of adipocytokines in patients with cardiovascular disease

Introduction: Inflammation contributes to cardiovascular disease and is exacerbated with increased adiposity, particularly omental adiposity; however, the role of epicardial fat is poorly understood. Methods: For these studies the expression of inflammatory markers was assessed in epicardial fat biopsies from coronary artery bypass grafting (CABG) patients using quantitative RT-PCR. Further, the effects of chronic medications, including statins, as well as peri-operative glucose, insulin and potassium infusion, on gene expression were also assessed. Circulating resistin, CRP, adiponectin and leptin levels were determined to assess inflammation. Results: The expression of adiponectin, resistin and other adipocytokine mRNAs were comparable to that in omental fat. Epicardial CD45 expression was significantly higher than control depots (p < 0.01) indicating significant infiltration of macrophages. Statin treated patients showed significantly lower epicardial expression of IL-6 mRNA, in comparison with the control abdominal depots (p < 0.001). The serum profile of CABG patients showed significantly higher levels of both CRP (control: 1.28 ± 1.57 μg/mL vs CABG: 9.11 ± 15.7 μg/mL; p < 0.001) and resistin (control: 10.53 ± 0.81 ng/mL vs CABG: 16.8 ± 1.69 ng/mL; p < 0.01) and significantly lower levels of adiponectin (control: 29.1 ± 14.8 μg/mL vs CABG: 11.9 ± 6.0 μg/mL; p < 0.05) when compared to BMI matched controls. Conclusion: Epicardial and omental fat exhibit a broadly comparable pathogenic mRNA profile, this may arise in part from macrophage infiltration into the epicardial fat. This study highlights that chronic inflammation occurs locally as well as systemically potentially contributing further to the pathogenesis of coronary artery disease

Deep learning-based fully automatic segmentation of wrist cartilage in MR images

The study objective was to investigate the performance of a dedicated convolutional neural network (CNN) optimized for wrist cartilage segmentation from 2D MR images. CNN utilized a planar architecture and patch-based (PB) training approach that ensured optimal performance in the presence of a limited amount of training data. The CNN was trained and validated in twenty multi-slice MRI datasets acquired with two different coils in eleven subjects (healthy volunteers and patients). The validation included a comparison with the alternative state-of-the-art CNN methods for the segmentation of joints from MR images and the ground-truth manual segmentation. When trained on the limited training data, the CNN outperformed significantly image-based and patch-based U-Net networks. Our PB-CNN also demonstrated a good agreement with manual segmentation (Sorensen-Dice similarity coefficient (DSC) = 0.81) in the representative (central coronal) slices with large amount of cartilage tissue. Reduced performance of the network for slices with a very limited amount of cartilage tissue suggests the need for fully 3D convolutional networks to provide uniform performance across the joint. The study also assessed inter- and intra-observer variability of the manual wrist cartilage segmentation (DSC=0.78-0.88 and 0.9, respectively). The proposed deep-learning-based segmentation of the wrist cartilage from MRI could facilitate research of novel imaging markers of wrist osteoarthritis to characterize its progression and response to therapy

Structure-function mapping of a heptameric module in the nuclear pore complex.

The nuclear pore complex (NPC) is a multiprotein assembly that serves as the sole mediator of nucleocytoplasmic exchange in eukaryotic cells. In this paper, we use an integrative approach to determine the structure of an essential component of the yeast NPC, the ~600-kD heptameric Nup84 complex, to a precision of ~1.5 nm. The configuration of the subunit structures was determined by satisfaction of spatial restraints derived from a diverse set of negative-stain electron microscopy and protein domain-mapping data. Phenotypic data were mapped onto the complex, allowing us to identify regions that stabilize the NPC's interaction with the nuclear envelope membrane and connect the complex to the rest of the NPC. Our data allow us to suggest how the Nup84 complex is assembled into the NPC and propose a scenario for the evolution of the Nup84 complex through a series of gene duplication and loss events. This work demonstrates that integrative approaches based on low-resolution data of sufficient quality can generate functionally informative structures at intermediate resolution