3,996 research outputs found
Role of protein kinase C-delta in the regulation of collagen gene expression in scleroderma fibroblasts
Working with cultured dermal fibroblasts derived from control individuals and patients with systemic sclerosis (SSc), we have examined the effects of protein kinase C-delta (PKC-delta) on type I collagen biosynthesis and steady-state levels of COL1A1 and COL3A1 mRNAs. Rottlerin, a specific inhibitor of PKC-delta, exerted a powerful, dose-dependent inhibition of type I and type III collagen gene expression in normal and SSc cells. Optimal rottlerin concentrations caused a 70-90% inhibition of type I collagen production, a \u3e80% reduction in COL1A1 mRNA, and a \u3e70% reduction in COL3A1 mRNA in both cell types. In vitro nuclear transcription assays and transient transfections with COL1A1 promoter deletion constructs demonstrated that rottlerin profoundly reduced COL1A1 transcription and that this effect required a 129-bp promoter region encompassing nucleotides -804 to -675. This COL1A1 segment imparted rottlerin sensitivity to a heterologous promoter. Cotransfections of COL1A1 promoter constructs with a dominant-negative PKC-delta expression plasmid showed that suppression of this kinase silenced COL1A1 promoter activity. The results indicate that PKC-delta participates in the upregulation of collagen gene transcription in SSc and suggest that treatment with PKC-delta inhibitors could suppress fibrosis in this disease
Hydrothermal Decomposition of Amino Acids and Origins of Prebiotic Meteoritic Organic Compounds
The organic compounds found in carbonaceous chondrite meteorites provide insight into primordial solar system chemistry. Evaluating the formation and decomposition mechanisms of meteoritic amino acids may aid our understanding of the origins of life and homochirality on Earth. The amino acid glycine is widespread in meteorites and other extraterrestrial environments; other amino acids, such as isovaline, are found with enantiomeric excesses in some meteorites. The relationship between meteoritic amino acids and other compounds with similar molecular structures, such as aliphatic monoamines and monocarboxylic acids is unclear; experimental results evaluating the decomposition of amino acids have produced inconclusive results about the preferred pathways, reaction intermediates, and if the conditions applied may be compatible with those occurring inside meteoritic parent bodies. In this work, we performed extensive tandem metadynamics, umbrella sampling, and committor analysis to simulate the neutral mild hydrothermal decomposition mechanisms of glycine and isovaline and put them into context for the origins of meteoritic organic compounds. Our ab initio simulations aimed to determine free energy profiles and decomposition pathways for glycine and isovaline. We found that under our modeled conditions, methylammonium, glycolic acid, and sec-butylamine are the most likely decomposition products. These results suggest that meteoritic aliphatic monocarboxylic acids are not produced from decomposition of meteoritic amino acids. Our results also indicate that the decomposition of L-isovaline prefers an enantioselective pathway resulting in the production of (S)-sec-butylamine
Implicit neural representations for unsupervised super-resolution and denoising of 4D flow MRI
4D flow MRI is a non-invasive imaging method that can measure blood flow velocities over time. However, the velocity fields detected by this technique have limitations due to low resolution and measurement noise. Coordinate-based neural networks have been researched to improve accuracy, with SIRENs being suitable for super-resolution tasks. Our study investigates SIRENs for time-varying 3-directional velocity fields measured in the aorta by 4D flow MRI, achieving denoising and super-resolution. We trained our method on voxel coordinates and benchmarked our approach using synthetic measurements and a real 4D flow MRI scan. Our optimized SIREN architecture outperformed state-of-the-art techniques, producing denoised and super-resolved velocity fields from clinical data. Our approach is quick to execute and straightforward to implement for novel cases, achieving 4D super-resolution
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Potential of Human Umbilical Cord Blood Mesenchymal Stem Cells to Heal Damaged Corneal Endothelium
Purpose: To test the feasibility of altering the phenotype of umbilical cord blood mesenchymal stem cells (UCB MSCs) toward that of human corneal endothelial cells (HCEC) and to determine whether UCB MSCs can “home” to sites of corneal endothelial cell injury using an ex vivo corneal wound model. Methods: RNA was isolated and purified from UCB MSCs and HCECs. Baseline information regarding the relative gene expression of UCB MSCs and HCEC was obtained by microarray analysis. Quantitative real-time PCR (q-PCR) verified the microarray findings for a subset of genes. The ability of different culture media to direct UCB MSCs toward a more HCEC-like phenotype was tested in both tissue culture and ex vivo corneal endothelial wound models using three different media: MSC basal medium (MSCBM), a basal medium used to culture lens epithelial cells (LECBM), or lens epithelial cell-conditioned medium (LECCM). Morphology of the MSCs was observed by phase-contrast microscopy or by light microscopic observation of crystal violet-stained cells. Immunolocalization of the junction-associated proteins, zonula occludins-1 (ZO1) and N-cadherin, was visualized by fluorescence confocal microscopy. Formation of cell-cell junctions was tested by treatment with the calcium chelator, EGTA. A second microarray analysis compared gene expression between UCB MSCs grown in LECBM and LECCM to identify changes induced by the lens epithelial cell-conditioned culture medium. The ability of UCB MSCs to “home” to areas of endothelial injury was determined using ZO1 immunolocalization patterns in ex vivo corneal endothelial wounds. Results: Baseline microarray analysis provided information regarding relative gene expression in UCB MSCs and HCECs. MSCs attached to damaged, but not intact, corneal endothelium in ex vivo corneal wounds. The morphology of MSCs was consistently altered when cells were grown in the presence of LECCM. In tissue culture and in ex vivo corneal wounds, UCB MSC treated with LECCM were elongated and formed parallel sheets of closely apposed cells. In both tissue culture and ex vivo corneal endothelial wounds, ZO1 and N-cadherin localized mainly to the cytoplasm of UCB MSCs in the presence of MSCBM. However, both proteins localized to cell borders when UCB MSCs were grown in either LECBM or LECCM. This localization was lost when extracellular calcium levels were reduced by treatment with EGTA. A second microarray analysis showed that, when UCB MSCs were grown in LECCM instead of LECBM, the relative expression of a subset of genes markedly differed, suggestive of a more HCEC-like phenotype. Conclusions: Results indicate that UCB MSCs are able to “home” to areas of injured corneal endothelium and that the phenotype of UCB MSCs can be altered toward that of HCEC-like cells. Further study is needed to identify the specific microenvironmental conditions that would permit tissue engineering of UCB MSCs to replace damaged or diseased corneal endothelium
Performance of Pheromone-Baited Traps to Monitor the Seasonal Abundance of Tortrix Moths in Chestnut Groves.
(1) Background: Pammene fasciana (L.), Cydia fagiglandana (Zeller), and C. splendana (Hübner) (Lepidoptera: Tortricidae) are considered key moth pests of chestnut in Europe. (2) Methods: Investigations were performed in 2018–2019 in northern Italy. Sticky traps and commercially available pheromones were used for monitoring; moreover, two experimental pheromone blends were tested. All specimens were identified according to male genitalia and molecular analyses. Newly formed chestnut husks and fruits were randomly collected to evaluate the presence of larvae and/or feeding damage, by comparing it to trap catches. (3) Results: P. fasciana was present in all the sites, whereas Cydia species were recorded in three sites of six, with differences in abundance related to pheromone blends studied. Several non-target species, such as Oegoconia novimundi (Busck) and Cydia ilipulana (Walsingham), were present. Data about the seasonal flight activity are provided. (4) Conclusions: This research contributes to ascertaining the presence and abundance of tortrix moths in Italian chestnut groves, and the presence of non-target species highlights the risk of overestimating catches. Fruit damage recorded did not always reflect catches made by pheromone traps, suggesting that monitoring may underestimate the real size of moths’ populations. All of the data acquired are important for planning specific control measures
Multiple plasmon resonances in naturally-occurring multiwall nanotubes: infrared spectra of chrysotile asbestos
Chrysotile asbestos is formed by densely packed bundles of multiwall hollow
nanotubes. Each wall in the nanotubes is a cylindrically wrapped layer of . We show by experiment and theory that the infrared spectrum
of chrysotile presents multiple plasmon resonances in the Si-O stretching
bands. These collective charge excitations are universal features of the
nanotubes that are obtained by cylindrically wrapping an anisotropic material.
The multiple plasmons can be observed if the width of the resonances is
sufficiently small as in chrysotile.Comment: 4 pages, 5 figures. Revtex4 compuscript. Misprint in Eq.(6) correcte
The DSC monitoring of oil melting to follow the oil curing
The drying of an oil paint is due to the polyunsaturations of the oil in the binder. Polyunsaturated oils dry trough an autoxidation process in which the double bonds of linolenic and linoleic acids naturally react with the oxygen present in the atmosphere. The gradual conversion of the liquid oil through a soft gel to a rubbery solid occurs as a result of a multistep free radical chain reaction. During the propagation step, hydroperoxides are formed. A method frequently used to follow the oil curing is the DSC monitoring of the peroxide decomposition peak during time. Since the oil polymerization affects its crystallinity, we propose here an altemative method to asses the oil curing. The melting peak of linseed oil samples is measured at different times of curing and compared with the pro\ufb01le of the peroxide decomposition peak over time. The comparison shows that the two phenomena are strongly correlated and that, when the maximum of the peroxide content is reached, the melting peak disappears. The study of the DSC melting peak is therefore proposed as a valid alternative tool to monitor the curing of an oil paint
Development, optimization and characterization of Eudraguard®-based microparticles for colon delivery
Development of pH-dependent systems for colon delivery of natural active ingredients is an attractive area of research in the field of nutraceutical products. This study was focused on Eudraguard® resins, that are methacrylate copolymers approved as “food grade” by European Commission and useful for the production of food supplements. In particular, Eudraguard® Biotic (EUG-B), characterized by a pH-dependent solubility and Eudraguard® Control (EUG-C), whose chemical properties support a prolonged release of the encapsulated compounds, were tested. To obtain EUG microparticles, different preparation techniques were tested, in order to optimize the preparation method and observe the effect upon drug encapsulation and specific colonic release. Unloaded microparticles were initially produced to evaluate the influence of polymer characteristics on the formulation process; subsequently microparticles loaded with quercetin (QUE) as a low solubility model drug were prepared. The characterization of microparticles in the solid-state (FT-IR spectroscopy, differential scanning calorimetry and X-ray diffractometry) indicated that QUE was uniformly dispersed in a non-crystalline state in the polymeric network, without strong signs of chemical interactions. Finally, to assess the ability of EUG-C and EUG-B to control the drug release in the gastric environment, and to allow an increased release at a colonic level, suitable in vitro release tests were carried out by simulating the pH variations along the gastro-intestinal tract. Among the evaluated preparation methods, those in which an aqueous phase was not present, and in particular the emulsion-solvent evaporation method produced the best microparticle systems. The in vitro tests showed a limited drug release at a gastric level and a good specific colon release
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