52 research outputs found
Activation of podocyte Notch mediates early Wt1 glomerulopathy
The Wilms' tumor suppressor gene, WT1, encodes a zinc finger protein that regulates podocyte development and is highly expressed in mature podocytes. Mutations in the WT1 gene are associated with the development of renal failure due to the formation of scar tissue within glomeruli, the mechanisms of which are poorly understood. Here, we used a tamoxifen-based CRE-LoxP system to induce deletion of Wt1 in adult mice to investigate the mechanisms underlying evolution of glomerulosclerosis. Podocyte apoptosis was evident as early as the fourth day post-induction and increased during disease progression, supporting a role for Wt1 in mature podocyte survival. Podocyte Notch activation was evident at disease onset with upregulation of Notch1 and its transcriptional targets, including Nrarp. There was repression of podocyte FoxC2 and upregulation of Hey2 supporting a role for a Wt1/FoxC2/Notch transcriptional network in mature podocyte injury. The expression of cleaved Notch1 and HES1 proteins in podocytes of mutant mice was confirmed in early disease. Furthermore, induction of podocyte HES1 expression was associated with upregulation of genes implicated in epithelial mesenchymal transition, thereby suggesting that HES1 mediates podocyte EMT. Lastly, early pharmacological inhibition of Notch signaling ameliorated glomerular scarring and albuminuria. Thus, loss of Wt1 in mature podocytes modulates podocyte Notch activation, which could mediate early events in WT1-related glomerulosclerosis
Inhibition of VCP preserves retinal structure and function in autosomal dominant retinal degeneration
Due to continuously high production rates of rhodopsin (RHO) and high metabolic activity, photoreceptor neurons are especially vulnerable to defects in proteostasis. A proline to histidine substitution at position 23 (P23H) leads to production of structurally misfolded RHO, causing the most common form of autosomal dominant Retinitis Pigmentosa (adRP) in North America. The AAA-ATPase valosin-containing protein (VCP) extracts misfolded proteins from the ER membrane for cytosolic degradation. Here, we provide the first evidence that inhibition of VCP activity rescues degenerating P23H rod cells and improves their functional properties in P23H transgenic rat and P23H knock-in mouse retinae, both in vitro and in vivo. This improvement correlates with the restoration of the physiological RHO localization to rod outer segments (OS) and properly-assembled OS disks. As a single intravitreal injection suffices to deliver a long-lasting benefit in vivo, we suggest VCP inhibition as a potential therapeutic strategy for adRP patients carrying mutations in the RHO gene
Towards an end-to-end analysis and prediction system for weather, climate, and marine applications in the Red Sea
Author Posting. © American Meteorological Society, 2021. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Bulletin of the American Meteorological Society 102(1), (2021): E99-E122, https://doi.org/10.1175/BAMS-D-19-0005.1.The Red Sea, home to the second-longest coral reef system in the world, is a vital resource for the Kingdom of Saudi Arabia. The Red Sea provides 90% of the Kingdom’s potable water by desalinization, supporting tourism, shipping, aquaculture, and fishing industries, which together contribute about 10%–20% of the country’s GDP. All these activities, and those elsewhere in the Red Sea region, critically depend on oceanic and atmospheric conditions. At a time of mega-development projects along the Red Sea coast, and global warming, authorities are working on optimizing the harnessing of environmental resources, including renewable energy and rainwater harvesting. All these require high-resolution weather and climate information. Toward this end, we have undertaken a multipronged research and development activity in which we are developing an integrated data-driven regional coupled modeling system. The telescopically nested components include 5-km- to 600-m-resolution atmospheric models to address weather and climate challenges, 4-km- to 50-m-resolution ocean models with regional and coastal configurations to simulate and predict the general and mesoscale circulation, 4-km- to 100-m-resolution ecosystem models to simulate the biogeochemistry, and 1-km- to 50-m-resolution wave models. In addition, a complementary probabilistic transport modeling system predicts dispersion of contaminant plumes, oil spill, and marine ecosystem connectivity. Advanced ensemble data assimilation capabilities have also been implemented for accurate forecasting. Resulting achievements include significant advancement in our understanding of the regional circulation and its connection to the global climate, development, and validation of long-term Red Sea regional atmospheric–oceanic–wave reanalyses and forecasting capacities. These products are being extensively used by academia, government, and industry in various weather and marine studies and operations, environmental policies, renewable energy applications, impact assessment, flood forecasting, and more.The development of the Red Sea modeling system is being supported by the Virtual Red Sea Initiative and the Competitive Research Grants (CRG) program from the Office of Sponsored Research at KAUST, Saudi Aramco Company through the Saudi ARAMCO Marine Environmental Center at KAUST, and by funds from KAEC, NEOM, and RSP through Beacon Development Company at KAUST
MATLAB-based algorithm to estimate depths of isolated thin dike-like sources using higher-order horizontal derivatives of magnetic anomalies
Towards an end-to-end analysis and prediction system for weather, climate, and Marine applications in the Red Sea
AbstractThe Red Sea, home to the second-longest coral reef system in the world, is a vital resource for the Kingdom of Saudi Arabia. The Red Sea provides 90% of the Kingdom’s potable water by desalinization, supporting tourism, shipping, aquaculture, and fishing industries, which together contribute about 10%–20% of the country’s GDP. All these activities, and those elsewhere in the Red Sea region, critically depend on oceanic and atmospheric conditions. At a time of mega-development projects along the Red Sea coast, and global warming, authorities are working on optimizing the harnessing of environmental resources, including renewable energy and rainwater harvesting. All these require high-resolution weather and climate information. Toward this end, we have undertaken a multipronged research and development activity in which we are developing an integrated data-driven regional coupled modeling system. The telescopically nested components include 5-km- to 600-m-resolution atmospheric models to address weather and climate challenges, 4-km- to 50-m-resolution ocean models with regional and coastal configurations to simulate and predict the general and mesoscale circulation, 4-km- to 100-m-resolution ecosystem models to simulate the biogeochemistry, and 1-km- to 50-m-resolution wave models. In addition, a complementary probabilistic transport modeling system predicts dispersion of contaminant plumes, oil spill, and marine ecosystem connectivity. Advanced ensemble data assimilation capabilities have also been implemented for accurate forecasting. Resulting achievements include significant advancement in our understanding of the regional circulation and its connection to the global climate, development, and validation of long-term Red Sea regional atmospheric–oceanic–wave reanalyses and forecasting capacities. These products are being extensively used by academia, government, and industry in various weather and marine studies and operations, environmental policies, renewable energy applications, impact assessment, flood forecasting, and more.</jats:p
Deciphering transmissivity and hydraulic conductivity of the aquifer by vertical electrical sounding (VES) experiments in Northwest Bangladesh
Favourable uranium–phosphate exploration trends guided by the application of statistical factor analysis technique on the aerial gamma spectrometric data in Syrian desert (Area-1), Syria
New insight on the recent instrumental seismic activity along the Serghaya fault, Syria
En este trabajo se presentan observaciones y análisis basados en datos instrumentales de actividad sísmica a lo largo de la falla Serghaya. La actividad sísmica registrada por estaciones de período corto entre 1995 y 2009, muestra una actividad significativa que se ha asociado con trazos superficiales conocidos de “steps-over” a lo largo de la falla Serghaya. Los enjambres espaciales podrían relacionarse con el “step-over” de la falla, por ejemplo en Deir el Acheir y Ham. Algunos enjambres se observaron en la región de Hermel, pudiéndose relacionar con una posible extensión de la falla Serghaya en el NE de Líbano. La zona sismogénica pudo coincidir con la supuesta localización de unión desde la falla Serghaya hasta las fallas de Jhar y Bishri. Esta evidencia completa los resultados de estudios anteriores que demostraron que el último sismo destructivo se localizó en la falla Serghaya y pudo ser anterior a los sismos de la falla Yammouneh. La falla Serghaya es probablemente la fuente más plausible de riesgo sísmico en Siria y Líbano.
doi: https://doi.org/10.22201/igeof.00167169p.2017.56.3.181
Evaluation of the leakage origin in Abu Baara earthen dam using electrical resistivity tomography, northwestern Syria
An integrated geophysical approach is proposed herewith to identify the potentialleakage zones within the substructure bedrock close to the dam body. Such an approach includes geophysicalsurveys using Electrical Resistivity Tomography (ERT), and traditional VES soundings. Geophysical measurements were carried out at the Abu Baara earth fill dam, located at the southern margins of Al-Ghab plain northwest of Syria.Three long ERT profiles(P1, P2, and P3)were implemented in parallel with the dam embankment in up and down stream reservoir as well as on the dam crest.The acquired geophysical results were interpreted by using different interpretative techniques, particularly the Pichgin and Habibullaev technique one. Three main major blocks, characterizing the geological substructural rocks were distinguished in the surrounding of the studied dam. The alluvial deposits overlaya resistiveand fractured limestone and dolomite bedrock with resistivity values ranging between 300 and 1200 Ωm. Several structural anomalous features were identified within the hard carbonate bedrock. These features are almost related to tectonic elements such as faults, fractures or karstic cavities. The central second block seems to be related to a faulted or subsidence structure coinciding with the main valley, completely filled by alluvial deposits of more than 50m thickness.The detected features represented by faulted structures, fractures and the karstic occurrences, developed within the dam bedrock are therefore regarded as the main responsible causes of the leakage processes from the dam. The integrated geophysical approach presented and proposed in this paper could be easily applied in another similar dams suffering from leakage problems.
doi: https://doi.org/10.22201/igeof.00167169p.2018.57.4.210
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