Soluble gC1qR is an autocrine signal that induces B1R expression on endothelial cells

Bradykinin (BK) is one of the most potent vasodilator agonists known and belongs to the kinin family of proinflammatory peptides. BK induces its activity via two G protein-coupled receptors: BK receptor 1 (B1R) and BK receptor 2. Although BK receptor 2 is constitutively expressed on endothelial cells (ECs), B1R is induced by IL-1β. The C1q receptor, receptor for the globular heads of C1q (gC1qR), which plays a role in BK generation, is expressed on activated ECs and is also secreted as soluble gC1qR (sgC1qR). Because sgC1qR can bind to ECs, we hypothesized that it may also serve as an autocrine/paracrine signal for the induction of B1R expression. In this study, we show that gC1qR binds to ECs via a highly conserved domain consisting of residues 174-180, as assessed by solid-phase binding assay and deconvolution fluorescence microscopy. Incubation of ECs (24 h, 37°C) with sgC1qR resulted in enhancement of B1R expression, whereas incubation with gC1qR lacking aa 174-180 and 154-162 had a diminished effect. Binding of sgC1qR to ECs was through surface-bound fibrinogen and was inhibited by anti-fibrinogen. In summary, our data suggest that, at sites of inflammation, sgC1qR can enhance vascular permeability by upregulation of B1R expression through de novo synthesis, as well as rapid translocation of preformed B1R

Long‐Term Variability and Tendencies in Middle Atmosphere Temperature and Zonal Wind From WACCM6 Simulations During 1850–2014

Long‐term variability of middle atmosphere temperature (T) and zonal wind (U) is investigated using a three‐member ensemble of historical simulations of NCAR's Whole Atmospheric Community Climate Model latest version 6 (WACCM6) for 1850–2014 (165 years). The model reproduces the climatological features of T and U. The contributions of Quasi Biennial Oscillation (QBO) at 10 and 30 hPa, solar cycle (SC), El Niño‐Southern Oscillation (ENSO), ozone depleting substances (ODS), carbon dioxide (CO2), and stratospheric sulfate aerosol (volcanic eruptions) to change in monthly zonal mean T and U are analyzed using multiple linear regression. The signal due to CO2 increase dominates as a predictor of the net multidecadal global annual mean temperature change at all levels in the middle atmosphere. Contributions from ODS also affect the net multidecadal global mean temperature trend in the stratosphere. Because of similarities in the time evolution of the emissions of CO2 and ODS, the analysis of existing model output cannot accurately separate the attributions of cooling to these two dominant forcing processes. On shorter time scales, solar flux variations are the largest source of variability in the mesosphere while volcanic eruptions are the largest in the stratosphere. In the stratosphere and mesosphere, both QBO and ENSO can significantly impact zonal mean temperature and zonal‐mean zonal wind depending on latitudes, but their impact on the multidecadal global mean temperature trend is very small

Long‐Term Variability and Tendencies in Migrating Diurnal Tide From WACCM6 Simulations During 1850–2014

Long‐term variability and tendencies in migrating diurnal tide (DW1) are investigated for the first time using a three‐member ensemble of historical simulations by NCAR's Whole Atmosphere Community Climate Model, latest Version 6 (WACCM6) for 1850–2014 (165 years). The model reproduces the climatological features of the tide in temperature (T), zonal wind (U), and meridional wind (V). The amplitudes peak in the upper mesosphere and lower thermosphere (above ~0.001 hPa) at the equator for T (~10 K) and over 20–30°N and S latitudes for U (~15 m/s) and V (~25 m/s). The contributions of solar cycle (SC), quasi biennial oscillation (QBO) at 10 and 30 hPa, El Niño–Southern Oscillation (ENSO), ozone depleting substances (ODS), carbon dioxide (CO2), and stratospheric sulfate aerosols (volcanic eruptions) to change in annual mean amplitudes are analyzed using multiple linear regression. The tidal amplitudes in three components show a long‐term increase in the upper stratosphere (0.95–10.7 hPa) and the upper mesosphere (0.0001–0.01 hPa), predominantly due to increasing CO2 with a smaller contribution from the trend in ENSO. Interestingly, the global mean tidal amplitude in T decreases sharply after 1950–1960 until 1995 and then increases in association with changes in ODSs. The seasonal differences in tidal responses to the above indices can be as large as the overall signals. All the responses are stronger in the upper mesosphere; however, there is also a pronounced negative response of temperature tide to ODSs over middle to high latitudes around the stratopause (~1 hPa) during all seasons

Tetralogy of Fallot with rheumatic mitral stenosis: A case report

<p>Abstract</p> <p>Introduction</p> <p>Rheumatic and congenital heart diseases account for the majority of hospital admissions for cardiac patients in India. Tetralogy of Fallot is the most common congenital heart disease with survival to adulthood. Infective endocarditis accounts for 4% of admissions to a specialized unit for adult patients with a congenital heart lesion. This report is unique in that a severe stenotic lesion of the mitral valve, probably of rheumatic aetiology, was noted in an adult male with Tetralogy of Fallot.</p> <p>Case presentation</p> <p>An unusual association of rheumatic mitral stenosis in an adult Indian male patient aged 35 years with Tetralogy of Fallot and subacute bacterial endocarditis of the aortic valve is presented.</p> <p>Conclusion</p> <p>In this case report the diagnostic implications, hemodynamic and therapeutic consequences of mitral stenosis in Tetralogy of Fallot are discussed. In addition, the morbidity and mortality of infective endocarditis in adult patients with congenital heart disease are summarized. The risk of a coincident rheumatic process in patients with congenital heart disease is highlighted and the need for careful attention to this possibility during primary and follow-up evaluation of such patients emphasized.</p

A new framework for sign language alphabet hand posture recognition using geometrical features through artificial neural network (part 1)

Hand pose tracking is essential in sign languages. An automatic recognition of performed hand signs facilitates a number of applications, especially for people with speech impairment to communication with normal people. This framework which is called ASLNN proposes a new hand posture recognition technique for the American sign language alphabet based on the neural network which works on the geometrical feature extraction of hands. A user’s hand is captured by a three-dimensional depth-based sensor camera; consequently, the hand is segmented according to the depth analysis features. The proposed system is called depth-based geometrical sign language recognition as named DGSLR. The DGSLR adopted in easier hand segmentation approach, which is further used in segmentation applications. The proposed geometrical feature extraction framework improves the accuracy of recognition due to unchangeable features against hand orientation compared to discrete cosine transform and moment invariant. The findings of the iterations demonstrate the combination of the extracted features resulted to improved accuracy rates. Then, an artificial neural network is used to drive desired outcomes. ASLNN is proficient to hand posture recognition and provides accuracy up to 96.78% which will be discussed on the additional paper of this authors in this journal

IgM Promotes the Clearance of Small Particles and Apoptotic Microparticles by Macrophages

Background: Antibodies are often involved in enhancing particle clearance by macrophages. Although the mechanisms of antibody-dependent phagocytosis have been studied for IgG in greater detail, very little is known about IgM-mediated clearance. It has been generally considered that IgM does not support phagocytosis. Recent studies indicate that natural IgM is important to clear microbes and other bioparticles, and that shape is critical to particle uptake by macrophages; however, the relevance of IgM and particle size in their clearance remains unclear. Here we show that IgM has a sizedependent effect on clearance. Methodology/Principal Findings: We used antibody-opsonized sheep red blood cells, different size beads and apoptotic cells to determine the effect of human and mouse IgM on phagocytosis by mouse alveolar macrophages. Our microscopy (light, epifluorescence, confocal) and flow cytometry data show that IgM greatly enhances the clearance of small particles (about 1–2 micron) by these macrophages. There is an inverse relationship between IgM-mediated clearance by macrophages and the particle size; however, macrophages bind and internalize many different size particles coated with IgG. We also show that IgM avidly binds to small size late apoptotic cells or bodies (2–5 micron) and apoptotic microparticles (,2 mm) released from dying cells. IgM also promotes the binding and uptake of microparticle-coated beads. Conclusions/Significance: Therefore, while the shape of the particles is important for non-opsonized particle uptake, th

Translating evidence into policy for cardiovascular disease control in India

Cardiovascular diseases (CVD) are leading causes of premature mortality in India. Evidence from developed countries shows that mortality from these can be substantially prevented using population-wide and individual-based strategies. Policy initiatives for control of CVD in India have been suggested but evidence of efficacy has emerged only recently. These initiatives can have immediate impact in reducing morbidity and mortality. Of the prevention strategies, primordial involve improvement in socioeconomic status and literacy, adequate healthcare financing and public health insurance, effective national CVD control programme, smoking control policies, legislative control of saturated fats, trans fats, salt and alcohol, and development of facilities for increasing physical activity through better urban planning and school-based and worksite interventions. Primary prevention entails change in medical educational curriculum and improved healthcare delivery for control of CVD risk factors-smoking, hypertension, dyslipidemia and diabetes. Secondary prevention involves creation of facilities and human resources for optimum acute CVD care and secondary prevention. There is need to integrate various policy makers, develop effective policies and modify healthcare systems for effective delivery of CVD preventive care

Surfactant protein-D and pulmonary host defense

Surfactant protein-D (SP-D) participates in the innate response to inhaled microorganisms and organic antigens, and contributes to immune and inflammatory regulation within the lung. SP-D is synthesized and secreted by alveolar and bronchiolar epithelial cells, but is also expressed by epithelial cells lining various exocrine ducts and the mucosa of the gastrointestinal and genitourinary tracts. SP-D, a collagenous calcium-dependent lectin (or collectin), binds to surface glycoconjugates expressed by a wide variety of microorganisms, and to oligosaccharides associated with the surface of various complex organic antigens. SP-D also specifically interacts with glycoconjugates and other molecules expressed on the surface of macrophages, neutrophils, and lymphocytes. In addition, SP-D binds to specific surfactant-associated lipids and can influence the organization of lipid mixtures containing phosphatidylinositol in vitro. Consistent with these diverse in vitro activities is the observation that SP-D-deficient transgenic mice show abnormal accumulations of surfactant lipids, and respond abnormally to challenge with respiratory viruses and bacterial lipopolysaccharides. The phenotype of macrophages isolated from the lungs of SP-D-deficient mice is altered, and there is circumstantial evidence that abnormal oxidant metabolism and/or increased metalloproteinase expression contributes to the development of emphysema. The expression of SP-D is increased in response to many forms of lung injury, and deficient accumulation of appropriately oligomerized SP-D might contribute to the pathogenesis of a variety of human lung diseases