Caspase-independent programmed cell death triggers Ca2PO4 deposition in an in vitro model of nephrocalcinosis

We provide evidence of caspase-independent cell death triggering the calcification process in GDNF-silenced HK-2 cells

Cell death in the kidney

Apoptotic cell death is usually a response to the cell’s microenvironment. In the kidney, apoptosis contributes to parenchymal cell loss in the course of acute and chronic renal injury, but does not trigger an inflammatory response. What distinguishes necrosis from apoptosis is the rupture of the plasma membrane, so necrotic cell death is accompanied by the release of unprocessed intracellular content, including cellular organelles, which are highly immunogenic proteins. The relative contribution of apoptosis and necrosis to injury varies, depending on the severity of the insult. Regulated cell death may result from immunologically silent apoptosis or from immunogenic necrosis. Recent advances have enhanced the most revolutionary concept of regulated necrosis. Several modalities of regulated necrosis have been described, such as necroptosis, ferroptosis, pyroptosis, and mitochondrial permeability transition-dependent regulated necrosis. We review the different modalities of apoptosis, necrosis, and regulated necrosis in kidney injury, focusing particularly on evidence implicating cell death in ectopic renal calcification. We also review the evidence for the role of cell death in kidney injury, which may pave the way for new therapeutic opportunities

Structure discovery in Atomic Force Microscopy imaging of ice

The interaction of water with surfaces is crucially important in a wide range of natural and technological settings. In particular, at low temperatures, unveiling the atomistic structure of adsorbed water clusters would provide valuable data for understanding the ice nucleation process. Using high-resolution Atomic Force Microscopy (AFM) and Scanning Tunnelling Microscopy, several studies have demonstrated the presence of water pentamers, hexamers, heptamers (and of their combinations) on a variety of metallic surfaces, as well the initial stages of 2D ice growth on an insulating surface. However, in all these cases, the observed structures were completely flat, providing a relatively straightforward path to interpretation. Here, we present high-resolution AFM measurements of several new water clusters on Au(111) and Cu(111), whose understanding presents significant challenges, due to both their highly 3D configuration and to their large size. For each of them, we use a combination of machine learning, atomistic modelling with neural network potentials and statistical sampling to propose an underlying atomic structure, finally comparing its AFM simulated images to the experimental ones. These results provide new insights into the early phases of ice formation, which is a ubiquitous phenomenon ranging from biology to astrophysics

Human parietal epithelial cells (PECs) and proteinuria in lupus nephritis: a role for ClC-5, megalin, and cubilin?

Background: Parietal epithelial cells are a heterogeneous population of cells located on Bowman’s capsule. These cells are known to internalize albumin with a still undetermined mechanism, although albumin has been shown to induce phenotypic changes in parietal epithelial cells. Proximal tubular cells are the main actors in albumin handling via the macromolecular complex composed by ClC-5, megalin, and cubilin. This study investigated the role of ClC-5, megalin, and cubilin in the parietal epithelial cells of kidney biopsies from proteinuric lupus nephritis patients and control subjects and identified phenotypical changes occurring in the pathological milieu. Methods: Immunohistochemistry and immunofluorescence analyses for ClC-5, megalin, cubilin, ANXA3, podocalyxin, CD24, CD44, HSA, and LTA marker were performed on 23 kidney biopsies from patients with Lupus Nephritis and 9 control biopsies (obtained from nephrectomies for renal cancer). Results: Two sub-populations of hypertrophic parietal epithelial cells ANXA3+/Podocalyxin−/CD44−, both expressing ClC-5, megalin, and cubilin and located at the tubular pole, were identified and characterized: the first one, CD24+/HSA−/LTA− had characteristics of human adult parietal epithelial multipotent progenitors, the second one, CD24−/LTA+/HSA+ committed to become phenotypically proximal tubular cells. The number of glomeruli presenting hypertrophic parietal epithelial cells positive for ClC-5, megalin, and cubilin were significantly higher in lupus nephritis patients than in controls. Conclusions: Our results may provide further insight into the role of hypertrophic parietal epithelial cells located at the tubular pole and their possible involvement in protein endocytosis in lupus nephritis patients. These data also suggest that the presence of hypertrophic parietal epithelial cells in Bowman's capsule represents a potential resource for responding to protein overload observed in other glomerulonephritis

Ecological research in the Large Scale Biosphere Atmosphere Experiment in Amazonia: A discussion of early results

The Large-scale Biosphere–Atmosphere Experiment in Amazonia (LBA) is a multinational, interdisciplinary research program led by Brazil. Ecological studies in LBA focus on how tropical forest conversion, regrowth, and selective logging influence carbon storage, nutrient dynamics, trace gas fluxes, and the prospect for sustainable land use in the Amazon region. Early results from ecological studies within LBA emphasize the variability within the vast Amazon region and the profound effects that land-use and land-cover changes are having on that landscape. The predominant land cover of the Amazon region is evergreen forest; nonetheless, LBA studies have observed strong seasonal patterns in gross primary production, ecosystem respiration, and net ecosystem exchange, as well as phenology and tree growth. The seasonal patterns vary spatially and interannually and evidence suggests that these patterns are driven not only by variations in weather but also by innate biological rhythms of the forest species. Rapid rates of deforestation have marked the forests of the Amazon region over the past three decades. Evidence from ground-based surveys and remote sensing show that substantial areas of forest are being degraded by logging activities and through the collapse of forest edges. Because forest edges and logged forests are susceptible to fire, positive feedback cycles of forest degradation may be initiated by land-use-change events. LBA studies indicate that cleared lands in the Amazon, once released from cultivation or pasture usage, regenerate biomass rapidly. However, the pace of biomass accumulation is dependent upon past land use and the depletion of nutrients by unsustainable land-management practices. The challenge for ongoing research within LBA is to integrate the recognition of diverse patterns and processes into general models for prediction of regional ecosystem function

Fire-Protection Research for Energy-Technology Projects: FY 1981 year-end report

This report summarizes research conducted in fiscal year 1981 for the DOE-supported project, Fire Protection Research for Energy Technology Projects. Initiated in 1977, this ongoing research program was conceived to advance fire protection strategies for Energy Technology Projects to keep abreast of the unique fire problems that are developing with the complexity of energy technology research. We are developing an analytical methodology through detailed study of fusion energy experiments at Lawrence Livermore National Laboratory (LLNL). Employing these facilities as models for methodology development, we are simultaneously advancing three major task areas: (1) determination of unique fire hazards of current fusion energy facilities; (2) evaluation of the ability of accepted fire management measures to meet and negate hazards; and (3) performance of unique research into problem areas we have identified to provide input into analytical fire-growth and damage-assessment models

Fire-protection research for DOE facilities: FY 82 year-end report

We summarize our research in FY 82 for the DOE-sponsored project, Fire Protection Research for DOE Facilities. This research program was initiated in 1977 to advance fire-protection strategies for energy technology facilities to keep abreast of the unique fire problems that develop along with energy technology research. Since 1977, the program has broadened its original scope, as reflected in previous year-end reports. We are developing an analytical methodology through detailed study of fusion energy experiments at Lawrence Livermore National Laboratory (LLNL). Using these experiments as models for methodology development, we are concurrently advancing three major task areas: (1) the identification of fire hazards unique to current fusion energy facilities; (2) the evaluation of accepted fire-management measures to meet and negate hazards; and (3) the performance of unique research into problem areas we have identified to provide input into analytical fire-growth and damage-assessment models

Fire protection research for DOE facilities: FY 83 year-end report

We summarize our research in FY 83 for the DOE-sponsored project, Fire Protection Research for DOE Facilities. This research program was initiated in 1977 to advance fire-protection strategies of energy technology facilities in order to keep abreast of the unique fire problems that develop along with energy technology research. Since 1977, the program has broadened its original scope, as reflected in previous year-end reports. We are developing an analytical methodology through detailed study of fusion energy experiments at Lawrence Livermore National Laboratory (LLNL). Using these experiments as models for methodology development, we are currently advancing three major task areas: (1) the identification of fire hazards unique to fusion energy facilities, (2) the evaluation of accepted fire-management measures to meet the negate hazards, and (3) the performance of unique research into problem areas we have identified to provide input into analytical fire-growth and damage-assessment models

Ecological research in the Large-scale Biosphere-Atmosphere Experiment in Amazonia: Early results

Copyright by the Ecological Society of America ©2004 Michael Keller, Ane Alencar, Gregory P. Asner, Bobby Braswell, Mercedes Bustamante, Eric Davidson, Ted Feldpausch, Erick Fernandes, Michael Goulden, Pavel Kabat, Bart Kruijt, Flavio Luizão, Scott Miller, Daniel Markewitz, Antonio D. Nobre, Carlos A. Nobre, Nicolau Priante Filho, Humberto da Rocha, Pedro Silva Dias, Celso von Randow, and George L. Vourlitis 2004. ECOLOGICAL RESEARCH IN THE LARGE-SCALE BIOSPHERE– ATMOSPHERE EXPERIMENT IN AMAZONIA: EARLY RESULTS. Ecological Applications 14:3–16. http://dx.doi.org/10.1890/03-6003The Large-scale Biosphere–Atmosphere Experiment in Amazonia (LBA) is a multinational, interdisciplinary research program led by Brazil. Ecological studies in LBA focus on how tropical forest conversion, regrowth, and selective logging influence carbon storage, nutrient dynamics, trace gas fluxes, and the prospect for sustainable land use in the Amazon region. Early results from ecological studies within LBA emphasize the variability within the vast Amazon region and the profound effects that land-use and land-cover changes are having on that landscape. The predominant land cover of the Amazon region is evergreen forest; nonetheless, LBA studies have observed strong seasonal patterns in gross primary production, ecosystem respiration, and net ecosystem exchange, as well as phenology and tree growth. The seasonal patterns vary spatially and interannually and evidence suggests that these patterns are driven not only by variations in weather but also by innate biological rhythms of the forest species. Rapid rates of deforestation have marked the forests of the Amazon region over the past three decades. Evidence from ground-based surveys and remote sensing show that substantial areas of forest are being degraded by logging activities and through the collapse of forest edges. Because forest edges and logged forests are susceptible to fire, positive feedback cycles of forest degradation may be initiated by land-use-change events. LBA studies indicate that cleared lands in the Amazon, once released from cultivation or pasture usage, regenerate biomass rapidly. However, the pace of biomass accumulation is dependent upon past land use and the depletion of nutrients by unsustainable land-management practices. The challenge for ongoing research within LBA is to integrate the recognition of diverse patterns and processes into general models for prediction of regional ecosystem function

Branch xylem density variations across Amazonia

International audienceMeasurements of branch xylem density, Dx, were made for 1466 trees representing 503 species, sampled from 80 sites across the Amazon basin. Measured values ranged from 240 kg m?3 for a Brosimum parinarioides from Tapajos in West Pará, Brazil to 1130 kg m?3 for an Aiouea sp. from Caxiuana, Central Pará, Brazil. Analysis of variance showed significant differences in average Dx across the sample plots as well as significant differences between families, genera and species. A partitioning of the total variance in the dataset showed that geographic location and plot accounted for 33% of the variation with species identity accounting for an additional 27%; the remaining "residual" 40% of the variance accounted for by tree to tree (within species) variation. Variations in plot means, were, however, hardly accountable at all by differences in species composition. Rather, it would seem that variations of xylem density at plot level must be explained by the effects of soils and/or climate. This conclusion is supported by the observation that the xylem density of the more widely distributed species varied systematically from plot to plot. Thus, as well as having a genetic component branch xylem density is a plastic trait that, for any given species, varies according to where the tree is growing and in a predictable manner. Exceptions to this general rule may be some pioneers belonging to Pourouma and Miconia and some species within the genera Brosimum, Rinorea and Trichillia which seem to be more constrained in terms of this plasticity than most species sampled as part of this study