22 research outputs found

    Clusterin in the eye: An old dog with new tricks at the ocular surface

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    Experimental Determination of Hydraulic Conductivity at Unsaturated Soil Column

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    Hydraulic Conductivity (K) is an important hydraulic parameter as it affects the environment by controlling infiltration, irrigation rate, and consequently the water movement through the ground. In order to determine Hydraulic Conductivity in a soil column during unsaturated flow, experiments were performed in the laboratory. A sandy (S) soil sample of known Hydraulic Conductivity at saturation (KS) was placed uniformly in a transparent column. Using a pump, water was applied at the surface of the soil column in certain supplies (Qi), while soil moisture (θ) was measured using TDR probes. At the same time, soil pore pressure (h) was measured using pressure transducers. The cumulative volume of the outgoing water (V) of the column was measured. Experimental data were fitted by Van Genuhten's Hydraulic Conductivity model. The results of the above experimental procedure constitute useful tools for the simulation of water movement in unsaturated soils and can be the outset for further research

    Toward better application of minimum area requirements in conservation planning

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    The Minimum Area Requirements (MAR) of species is a concept that explicitly addresses area and therefore can be highly relevant for conservation planning and policy. This study compiled a comprehensive database of MAR estimates from the literature, covering 216 terrestrial animal species from 80 studies. We obtained estimates from (a) Population Viability Analyses (PVAs) which explored a range of area-related scenarios, (b) PVAs that provided a fixed value – either MAR or the minimum viable population size (MVP) alongside other area-relevant information, and (c) empirical studies of occupancy patterns in islands or isolated habitat patches across area. We assessed the explanatory power of life-history traits (body mass, feeding guild, generation length and offspring size), environmental variables (average precipitation and temperature), research approach and phylogenetic group on MAR estimates. PVAs exploring area showed strong correlation between MAR and body mass. One to two additional variables further improved the predictive power. PVA reporting fixed MAR, and occupancy-based studies, were better explained by the combination of feeding guild, climatic variables and additional life history traits. Phylogeny had a consistent but usually small contribution to the predictive power of models. Our work demonstrates that estimating the MAR across species and taxa is achievable but requires cautious interpretation. We further suggest that occupancy patterns are likely sensitive to transient dynamics and are therefore risky to use for estimating MAR. PVA-based evaluations enable considering time horizon and extinction probability, two aspects that are critical for future implementation of the MAR concept into policy and management

    Mixed Systems of Hydrophobically Modified Polyelectrolytes: Controlling Rheology by Charge and Hydrophobe Stoichiometry and Interaction Strength

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    Rheology and phase separation were investigated for aqueous mixtures of two oppositely charged hydrophobically modified polyelectrolytes. The typical phase separation, normally seen for oppositely charged polymer mixtures, is dramatically reduced by the presence of hydrophobic modification, and phase separation is only detected close to the point of charge neutralization. While the two polyelectrolytes separately can give high viscosities and a gel-like behavior, a pronounced maximum in viscosity and storage modulus with the mixing ratio of the polyelectrolytes is observed; the maximum is located between the points of charge and hydrophobe stoichiometry and reflects a combination of hydrophobic and electrostatic association. Lowering the charge density of the anionic polymer leads to a strengthened association at first, but at lower charge densities there is a weakened association due to the onset of phase separation. The strength of the electrostatic interaction was modified by adding salt. Increased ionic strength can lead to phase separation and to increased or decreased viscosity depending on the polyelectrolyte mixing ratio

    Cell-autonomous inflammation of BRCA1-deficient ovarian cancers drives both tumor-intrinsic immunoreactivity and immune resistance through STING

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    We investigated mechanisms leading to inflammation and immunoreactivity in ovarian tumors with homologous recombination deficiency. BRCA1lossis found to lead to transcriptional reprogramming in tumor cells and cell-intrinsic inflammation involving type I IFN and STING.BRCA1-mutated (BRCA1mut) tumors are thus T-cell inflamed at baseline. Genetic deletion or methylation of DNA-sensing/IFN genes or CCL5chemokineare identified as potential mechanism to attenuate T cell inflammation. Alternatively, in BRCA1mutcancersretaining inflammation, STING up regulates VEGF-A, mediating immune resistance and tumor progression. Tumor intrinsic STING elimination reduces neoangiogenesis, increasesCD8+T cell infiltration and reverts therapeutic resistance to dual immune checkpoint blockade(ICB). VEGF-A blockade phenocopies genetic STING loss and synergizes with IC Band/or PARP inhibitors to control the outgrowth of Trp53-/-Brca1-/-but notBrca1+/+ovarian tumors in vivo, offering rational combinatorial therapies for HRD cancer

    Clusterin in the eye: an old dog with new tricks at the ocular surface

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    The multifunctional protein clusterin (CLU) was first described in 1983 as a secreted glycoprotein present in ram rete testis fluid that enhanced aggregation (\u27clustering\u27) of a variety of cells in vitro. It was also independently discovered in a number of other systems. By the early 1990s, CLU was known under many names and its expression had been demonstrated throughout the body, including in the eye. Its homeostatic activities in proteostasis, cytoprotection, and anti-inflammation have been well documented, however its roles in health and disease are still not well understood. CLU is prominent at fluid-tissue interfaces, and in 1996 it was demonstrated to be the most highly expressed transcript in the human cornea, the protein product being localized to the apical layers of the mucosal epithelia of the cornea and conjunctiva. CLU protein is also present in human tears. Using a preclinical mouse model for desiccating stress that mimics human dry eye disease, the authors recently demonstrated that CLU prevents and ameliorates ocular surface barrier disruption by a remarkable sealing mechanism dependent on attainment of a critical all-or-none concentration in the tears. When the CLU level drops below the critical all-or-none threshold, the barrier becomes vulnerable to desiccating stress. CLU binds selectively to the ocular surface subjected to desiccating stress in vivo, and in vitro to LGALS3 (galectin-3), a key barrier component. Positioned in this way, CLU not only physically seals the ocular surface barrier, but it also protects the barrier cells and prevents further damage to barrier structure. CLU depletion from the ocular surface epithelia is seen in a variety of inflammatory conditions in humans and mice that lead to squamous metaplasia and a keratinized epithelium. This suggests that CLU might have a specific role in maintaining mucosal epithelial differentiation, an idea that can now be tested using the mouse model for desiccating stress. Most excitingly, the new findings suggest that CLU could serve as a novel biotherapeutic for dry eye disease
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