Complement-mediated injury reversibly disrupts glomerular epithelial cell actin microfilaments and focal adhesions.
Foot process effacement and condensation of the glomerular epithelial cell (GEC) ...cytoskeleton are manifestations of passive Heymann nephritis, a model of complement-mediated membranous nephropathy.
To study the effects of complement on the actin cytoskeleton in this model, we have used an in vitro system in which GECs are sublethally injured using a combination of complement-fixing anti-Fx1A IgG and human serum as a source of complement. We examined the effects of this injury on the organization of the cytoskeleton and focal contacts using immunohistology and immunochemistry.
By immunofluorescence, sublethal complement-mediated injury was accompanied by a loss of actin stress fibers and focal contacts but retention of matrix-associated integrins. Full recovery was seen after 18hours. Western blot analysis showed no change in the cellular content of the focal contact proteins. Inhibition of the calcium-dependent protease calpain did not prevent injury. In addition, cycloheximide during recovery did not inhibit the reassembly of stress fibers or focal contacts. Injury was associated with a reduction in tyrosine phosphorylation of paxillin and a currently unidentified 200kDa protein, but inhibition of tyrosine phosphatase activity with sodium vanadate did not prevent injury. Cellular adenosine triphosphate content was significantly reduced in injured cells.
These results document reversible, complement-dependent disruption of actin microfilaments and focal contacts leading to the dissociation of the cytoskeleton from matrix-attached integrins. This may explain the altered cell–matrix relationship accompanying podocyte effacement in membranous nephropathy.
Landsat 8, a NASA and USGS collaboration, acquires global moderate-resolution measurements of the Earth's terrestrial and polar regions in the visible, near-infrared, short wave, and thermal ...infrared. Landsat 8 extends the remarkable 40year Landsat record and has enhanced capabilities including new spectral bands in the blue and cirrus cloud-detection portion of the spectrum, two thermal bands, improved sensor signal-to-noise performance and associated improvements in radiometric resolution, and an improved duty cycle that allows collection of a significantly greater number of images per day. This paper introduces the current (2012–2017) Landsat Science Team's efforts to establish an initial understanding of Landsat 8 capabilities and the steps ahead in support of priorities identified by the team. Preliminary evaluation of Landsat 8 capabilities and identification of new science and applications opportunities are described with respect to calibration and radiometric characterization; surface reflectance; surface albedo; surface temperature, evapotranspiration and drought; agriculture; land cover, condition, disturbance and change; fresh and coastal water; and snow and ice. Insights into the development of derived ‘higher-level’ Landsat products are provided in recognition of the growing need for consistently processed, moderate spatial resolution, large area, long-term terrestrial data records for resource management and for climate and global change studies. The paper concludes with future prospects, emphasizing the opportunities for land imaging constellations by combining Landsat data with data collected from other international sensing systems, and consideration of successor Landsat mission requirements.
•Initial understanding of Landsat 8 capabilities, new science and applications.•Landsat Science Team identified priorities.•Derived ‘higher-level’ Landsat products.•International synergies with other moderate resolution remote sensing satellites.•Successor Landsat mission requirements.
The origin of cometary matter and the potential contribution of comets to inner-planet atmospheres are long-standing problems. During a series of dedicated low-altitude orbits, the Rosetta Orbiter ...Spectrometer for Ion and Neutral Analysis (ROSINA) on the Rosetta spacecraft analyzed the isotopes of xenon in the coma of comet 67P/Churyumov-Gerasimenko. The xenon isotopic composition shows deficits in heavy xenon isotopes and matches that of a primordial atmospheric component. The present-day Earth atmosphere contains 22 ± 5% cometary xenon, in addition to chondritic (or solar) xenon.
Effects of black gram (vigna mungo L.cv. Barimash 3) seed treatments with 400 torr dielectric barrier discharge (DBD) air plasma on seed surface morphology, seed germination, seedling growth and ...antioxidant enzyme activities in the roots, shoots and leaves were investigated. The plasma discharge voltage, frequency, electrode spacing, gas temperature and power were 5kV, 4.5kHz, 60mm, 310K and 45W, respectively. The seeds were treated for the duration ranging from 20 to 180 s. Seed germination rate, seedling growth, total chlorophyll content, total soluble protein and sugar concentrations in the seedlings grown from the treated seeds were found to increase 13.67%, 37.13%, 37.26%,53.60% and 51.71%, respectively, with respect to control. This study reveals that the DBD air plasma was involved in the enhancement of nitrogen complex in the seed coat of black gram which upregulated the protein through nitrogen conversion that was ultimately responsible for the increased seed germination and seedling growth of black gram.
The development of a portfolio of COVID-19 vaccines to vaccinate the global population remains an urgent public health imperative
. Here we demonstrate the capacity of a subunit vaccine, comprising ...the SARS-CoV-2 spike protein receptor-binding domain displayed on an I53-50 protein nanoparticle scaffold (hereafter designated RBD-NP), to stimulate robust and durable neutralizing-antibody responses and protection against SARS-CoV-2 in rhesus macaques. We evaluated five adjuvants including Essai O/W 1849101, a squalene-in-water emulsion; AS03, an α-tocopherol-containing oil-in-water emulsion; AS37, a Toll-like receptor 7 (TLR7) agonist adsorbed to alum; CpG1018-alum, a TLR9 agonist formulated in alum; and alum. RBD-NP immunization with AS03, CpG1018-alum, AS37 or alum induced substantial neutralizing-antibody and CD4 T cell responses, and conferred protection against SARS-CoV-2 infection in the pharynges, nares and bronchoalveolar lavage. The neutralizing-antibody response to live virus was maintained up to 180 days after vaccination with RBD-NP in AS03 (RBD-NP-AS03), and correlated with protection from infection. RBD-NP immunization cross-neutralized the B.1.1.7 SARS-CoV-2 variant efficiently but showed a reduced response against the B.1.351 variant. RBD-NP-AS03 produced a 4.5-fold reduction in neutralization of B.1.351 whereas the group immunized with RBD-NP-AS37 produced a 16-fold reduction in neutralization of B.1.351, suggesting differences in the breadth of the neutralizing-antibody response induced by these adjuvants. Furthermore, RBD-NP-AS03 was as immunogenic as a prefusion-stabilized spike immunogen (HexaPro) with AS03 adjuvant. These data highlight the efficacy of the adjuvanted RBD-NP vaccine in promoting protective immunity against SARS-CoV-2 and have led to phase I/II clinical trials of this vaccine (NCT04742738 and NCT04750343).
Nineteen insertion/deletion and restriction site polymorphisms on autosomal and mitochondrial genomes and mitochondrial DNA hypervariable segment 1 sequences were used to study genetic diversities ...and affinities among four endogamous groups of Punjab, India. High values of heterozygosity were noted in all four groups, both in the autosomal and mitochondrial genomes. The coefficient of gene differentiation among the groups, however, was found to be low. Genetic distance and phylogenetic analyses based on these data indicated that inferences on affinities among the populations were different when the two sets of loci (autosomal and mitochondrial) were considered separately. We have interpreted these results on the basis of some known historical data on migrations into this region. The results of this study when compared with the findings of some previous studies indicate that there are regional differences in the patterns of correlation between genomic and sociocultural affinities within India.
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