Hematological features in children with systemic lupus erythematosus: are they more common than appreciated?

PubMe

Proerythroblast Cells of Diamond-Blackfan Anemia Patients With RPS19 and CECR1 Mutations Have Similar Transcriptomic Signature

Diamond Blackfan Anemia (DBA) is an inherited bone marrow (BM) failure syndrome, characterized by a paucity of erythroid differentiation. DBA is mainly caused by the mutations in ribosomal protein genes, hence classified as ribosomopathy. However, in approximately 30% of patients, the molecular etiology cannot be discovered. RPS19 germline mutations caused 25% of the cases. On the other hand, CECR1 mutations also cause phenotypes similar to DBA but not being a ribosomopathy. Due to the blockade of erythropoiesis in the BM, we investigated the transcriptomic profile of three different cell types of BM resident cells of DBA patients and compared them with healthy donors. From BM aspirates BM mononuclear cells (MNCs) were isolated and hematopoietic stem cells (HSC) [CD71–CD34+ CD38mo/lo], megakaryocyte–erythroid progenitor cells (MEP) [CD71–CD34+ CD38hi] and Proerythroblasts [CD71+ CD117+ CD38+] were sorted and analyzed with a transcriptomic approach. Among all these cells, proerythroblasts had the most different transcriptomic profile. The genes associated with cellular stress/immune responses were increased and some of the transcription factors that play a role in erythroid differentiation had altered expression in DBA proerythroblasts. We also showed that gene expression levels of ribosomal proteins were decreased in DBA proerythroblasts. In addition to these, colony formation assay (CFU-E) provided functional evidence of the failure of erythroid differentiation in DBA patients. According to our findings that all patients resembling both RPS19 and CECR1 mutations have common transcriptomic signatures, it may be possible that inflammatory BM niche may have a role in DBA pathogenesis

Bottom-Up Assembly of Hydrogels from Bacteriophage and Au Nanoparticles: The Effect of Cis- and Trans-Acting Factors

Hydrogels have become a promising research focus because of their potential for biomedical application. Here we explore the long-range, electrostatic interactions by following the effect of trans-acting (pH) and cis-acting factors (peptide mutation) on the formation of Au-phage hydrogels. These bioinorganic hydrogels can be generated from the bottom-up assembly of Au nanoparticles (Au NP) with either native or mutant bacteriophage (phage) through electrostatic interaction of the phage pVIII major capsid proteins (pVIII). The cis-acting factor consists of a peptide extension displayed on the pVIII that mutates the phage. Our results show that pH can dictate the direct-assembly and stability of Au-phage hydrogels in spite of the differences between the native and the mutant pVIII. The first step in characterizing the interactions of Au NP with phage was to generate a molecular model that identified the charge distribution and structure of the native and mutant pVIII. This model indicated that the mutant peptide extension carried a higher positive charge relative to the native pVIII at all pHs. Next, by monitoring the Au-phage interaction by means of optical microscopy, elastic light scattering, fractal dimension analysis as well as Uv-vis and surface plasmon resonance spectroscopy, we show that the positive charge of the mutant peptide extension favors the opposite charge affinity between the phage and Au NP as the pH is decreased. These results show the versatility of this assembly method, where the stability of these hydrogels can be achieved by either adjusting the pH or by changing the composition of the phage pVIII without the need of phage display libraries

Loss of C2orf69 defines a fatal autoinflammatory syndrome in humans and zebrafish that evokes a glycogen-storage-associated mitochondriopathy

Summary Human C2orf69 is an evolutionarily conserved gene whose function is unknown. Here, we report eight unrelated families from which 20 children presented with a fatal syndrome consisting of severe autoinflammation and progredient leukoencephalopathy with recurrent seizures; 12 of these subjects, whose DNA was available, segregated homozygous loss-of-function C2orf69 variants. C2ORF69 bears homology to esterase enzymes, and orthologs can be found in most eukaryotic genomes, including that of unicellular phytoplankton. We found that endogenous C2ORF69 (1) is loosely bound to mitochondria, (2) affects mitochondrial membrane potential and oxidative respiration in cultured neurons, and (3) controls the levels of the glycogen branching enzyme 1 (GBE1) consistent with a glycogen-storage-associated mitochondriopathy. We show that CRISPR-Cas9-mediated inactivation of zebrafish C2orf69 results in lethality by 8 months of age due to spontaneous epileptic seizures, which is preceded by persistent brain inflammation. Collectively, our results delineate an autoinflammatory Mendelian disorder of C2orf69 deficiency that disrupts the development/homeostasis of the immune and central nervous systems

Pressure wave propagation in pressurized thin-walled circular tubes under axial impact

WOS: 000469155700011The pressurized thin-walled tubes are called as a member of adaptive energy absorbers of which energy absorbing performance can be controlled by variation of internal pressure. in this context, this study numerically investigates the axial impact performance of pressurized thin-walled circular tubes. For the realistic modeling of the compressed air, the ALE model was developed in LS-DYNA, which enabled an opportunity to investigate both pressure wave propagation in pressurized air and fluid-structure interaction effects between tube-wall and air. in addition, the models were run by taking into account both states, whether pressure regulator, which is an adjustable valve to control internal pressure value, was active. To validate the numerical models, the axial impact tests on Aluminum Aerosol cans were carried out using a light gas gun set-up. the results showed that at the onset of impact, a radial pressure wave, as well as an axial pressure one, simultaneously emerged. Whereas a radial pressure wave propagated towards the center from the tube-wall, the other one propagated along the centerline of the tube. Therefore, a complex pressure distribution and wave propagation occurred in the pressurized tubes. the pressure distribution obtained in the model with a pressure regulator revealed different behavior from the corresponding one obtained without pressure regulator. Also, the results showed that there is no distinct interaction between strain energy absorbed by tube-wall and pressure wave propagation although the total absorbed energy of pressurized tubes increases to some extent with the effects of wave propagation in the pressurized medium

COMPRESSIVE MECHANICAL BEHAVIORS OF HYBRID COMPOSITE MATERIALS BASED ON MICRO LATTICE STRUCTURE AND RUBBERLIKE MATERIALS

ABSTRACT This article investigates compressive and energy absorption characteristics for composites obtained by filling stainless steel micro lattice materials, manufactured via the selective laser melting method, with three different rubbers, including room temperature vulcanization silicone, natural rubber, and neoprene rubber. At the stage of building the composites with natural and neoprene rubbers, an experimental setup was designed for these two rubbers to be infiltrated into lattice spaces under vulcanization temperatures and high pressures. The results showed that the composites with silicone and neoprene matrix had a quite similar response as well as a seriously enhanced energy absorbing capacity and plateau stresses, in comparison with the corresponding lattice structures, for especially small sized lattice components. Also, the compression tests of the composite with natural rubber matrix clearly show that there should be no large differences between the individual mechanical properties of each component in the composite, and, in this way, the contribution of each component on the mechanical behavior of composite should be guaranteed to provide the satisfying performance.</jats:p

Investigation of wear resistance of the porcelain tile bodies by solid particle impingement using alumina particles

WOS:000532990000018Wear resistance is of great importance for many industries related with minerals. The particles seen in these industries may cause erosion. These particles may have various sizes, shapes, and hardness, and may also impact the surface at various angles and speeds. Wear resistance is also important for the ceramic tile industry because the materials, which are also used in building facades, must withstand all kinds of weather conditions. In this study, the wear resistance of the porcelain tile bodies was investigated by solid particle impingement using alumina particles. The effects of technological, mechanical, and microstructural properties on wear resistance were also investigated. It was determined that the technological, mechanical, and microstructural properties were improved with the addition of spodumene, which also caused that the wear rates were reduced

Investigation of wear resistance of the porcelain tile bodies by solid particle impingement using alumina particles

WOS: 000532990000018Wear resistance is of great importance for many industries related with minerals. The particles seen in these industries may cause erosion. These particles may have various sizes, shapes, and hardness, and may also impact the surface at various angles and speeds. Wear resistance is also important for the ceramic tile industry because the materials, which are also used in building facades, must withstand all kinds of weather conditions. In this study, the wear resistance of the porcelain tile bodies was investigated by solid particle impingement using alumina particles. The effects of technological, mechanical, and microstructural properties on wear resistance were also investigated. It was determined that the technological, mechanical, and microstructural properties were improved with the addition of spodumene, which also caused that the wear rates were reduced