Hydrogen Desorption below 150 °c in MgH2-TiH2 Composite Nanoparticles: Equilibrium and Kinetic Properties

Reversible hydrogen sorption coupled with the MgH2 <-> Mg phase transformation was achieved in the remarkably low 340-425 K temperature range using MgH2-TiH2 composite nanoparticles obtained by reactive gas-phase condensation of Mg Ti vapors under He/H-2 atmosphere. The equilibrium pressures determined by in situ measurements at low temperature were slightly above those predicted using enthalpy Delta H and entropy Delta S of bulk magnesium. A single van't Hoff fit over a range extended up to 550 K yields the thermodynamic parameters Delta H = 68.1 0.9 kJ/molH(2) and Delta S = 119 2 J/(Kmo1H2) for hydride decomposition. A desorption rate of 0.18 wt % H-2/min was measured at T = 423 K and p(H-2) approximate to 1 mbar, i.e., close to equilibrium, without using a Pd catalysts. The nanoparticles displayed a small absorption desorption pressure hysteresis even at low temperatures. We critically discuss the influence exerted by nanostructural features such as interface free energy, elastic clamping, and phase mixing at the single nanopartide level on equilibrium and kinetic properties of hydrogen sorption

Biological application of Compressed Sensing Tomography in the Scanning Electron Microscope

The three-dimensional tomographic reconstruction of a biological sample, namely collagen fibrils in human dermal tissue, was obtained from a set of projection-images acquired in the Scanning Electron Microscope. A tailored strategy for the transmission imaging mode was implemented in the microscope and proved effective in acquiring the projections needed for the tomographic reconstruction. Suitable projection alignment and Compressed Sensing formulation were used to overcome the limitations arising from the experimental acquisition strategy and to improve the reconstruction of the sample. The undetermined problem of structure reconstruction from a set of projections, limited in number and angular range, was indeed supported by exploiting the sparsity of the object projected in the electron microscopy images. In particular, the proposed system was able to preserve the reconstruction accuracy even in presence of a significant reduction of experimental projections

Automatic segmentation of optical coherence tomography pullbacks of coronary arteries treated with bioresorbable vascular scaffolds: Application to hemodynamics modeling

Automatic algorithms for stent struts segmentation in optical coherence tomography (OCT) images of coronary arteries have been developed over the years, particularly with application on metallic stents. The aim of this study is three-fold: (1) to develop and to validate a segmentation algorithm for the detection of both lumen contours and polymeric bioresorbable scaffold struts from 8-bit OCT images, (2) to develop a method for automatic OCT pullback quality assessment, and (3) to demonstrate the applicability of the segmentation algorithm for the creation of patient-specific stented coronary artery for local hemodynamics analysis

Treatment with 1,25-dihydroxyvitamin D3 preserves glomerular slit diaphragm-associated protein expression in experimental glomerulonephritis

In this study, we investigated the effect of 1,25(OH)2D3on proteinuria and on the alteration of slit diaphragm-associated proteins induced by anti-Thy 1.1 in Wistar rats. Four groups of animals were studied: group I, anti-Thy 1.1 treated rats; group II, anti-Thy1.1 treated group that at day 2, after the onset of overt proteinuria, started the treatment with 1,25(OH)2D3; group III, normal control rats injected with vehicle alone; group IV, rats that received only 1,25(OH)2D3. At day 2, in group I and II, before the administration of 1,25(OH)2D3, protein excretion was significantly increased when compared to controls. Overt proteinuria was maintained until day 14 in group I whereas in group II protein excretion was significantly reduced from day 3 to day 14. Moreover, treatment with 1,25(OH)2D3abrogated podocytes injury, detected as desmin expression and loss of nephrin and zonula occludens-1 (ZO-1), two slit diaphragm-associated proteins, and glomerular polyanion staining, that were observed in group I. In conclusion, these results suggest that 1,25(OH)2D3administrated with a therapeutic regiment may revert proteinuria, counteracting glomerular podocyte injury

The link of biocompatibility to cytokine production

The link of biocompatibility to cytokine production. Recent studies suggest that chronic inflammation plays a role in the pathogenesis of cardiovascular disease. Cytokines released from jeopardized tissues stimulate the liver to synthesize acute phase proteins, including C-reactive protein (CRP). Baseline levels of CRP in apparently healthy persons or in persons with unstable angina constitute an independent risk factor for cardiovascular events. More recently, it has been suggested that CRP is useful not only as a marker of the acute phase response, but is also involved in the pathogenesis of the disease. CRP may, in fact, directly interact with the atherosclerotic vessels or ischemic myocardium by activation of the complement system, thereby promoting inflammation and thrombosis. Several studies in uremic patients have implicated CRP as a marker of malnutrition, resistance to erythropoietin, and chronic stimulation in hemodialysis. An increased cytokine production secondary to blood interaction with bioincompatible dialysis components has been reported by several studies; interleukin-1 (IL-1), tumor necrosis factor-α (TNF-α), and mainly IL-6 are the three proinflammatory cytokines involved in the pathogenesis of hemodialysis-related disease. We have provided evidence for the occurrence of high CRP and IL-6 levels in chronic dialytic patients exposed to contaminate dialysate and suggest that backfiltration may induce a chronic, slowly developing inflammatory state that may be abrogated by avoiding backfiltration of contaminate dialysate. Therefore, CRP is implicated as a marker linking bioincompatibility associated with backfiltration and increased cytokine production with a clinical state of chronic inflammation

A framework for computational fluid dynamic analyses of patient-specific stented coronary arteries from optical coherence tomography images

The clinical challenge of percutaneous coronary interventions (PCI) is highly dependent on the recognition of the coronary anatomy of each individual. The classic imaging modality used for PCI is angiography, but advanced imaging techniques that are routinely performed during PCI, like optical coherence tomography (OCT), may provide detailed knowledge of the pre-intervention vessel anatomy as well as the post-procedural assessment of the specific stent-to-vessel interactions. Computational fluid dynamics (CFD) is an emerging investigational tool in the setting of optimization of PCI results. In this study, an OCT-based reconstruction method was developed for the execution of CFD simulations of patient-specific coronary artery models which include the actual geometry of the implanted stent. The method was applied to a rigid phantom resembling a stented segment of the left anterior descending coronary artery. The segmentation algorithm was validated against manual segmentation. A strong correlation was found between automatic and manual segmentation of lumen in terms of area values. Similarity indices resulted >96% for the lumen segmentation and >77% for the stent strut segmentation. The 3D reconstruction achieved for the stented phantom was also assessed with the geometry provided by X-ray computed micro tomography scan, used as ground truth, and showed the incidence of distortion from catheter-based imaging techniques. The 3D reconstruction was successfully used to perform CFD analyses, demonstrating a great potential for patient-specific investigations. In conclusion, OCT may represent a reliable source for patient-specific CFD analyses which may be optimized using dedicated automatic segmentation algorithms

Nkx2-5+Islet1+ Mesenchymal Precursors Generate Distinct Spleen Stromal Cell Subsets and Participate in Restoring Stromal Network Integrity

SummarySecondary lymphoid organ stromal cells comprise different subsets whose origins remain unknown. Herein, we exploit a genetic lineage-tracing approach to show that splenic fibroblastic reticular cells (FRCs), follicular dendritic cells (FDCs), marginal reticular cells (MRCs), and mural cells, but not endothelial cells, originate from embryonic mesenchymal progenitors of the Nkx2-5+Islet1+ lineage. This lineage include embryonic mesenchymal cells with lymphoid tissue organizer (LTo) activity capable also of supporting ectopic lymphoid-like structures and a subset of resident spleen stromal cells that proliferate and regenerate the splenic stromal microenvironment following resolution of a viral infection. These findings identify progenitor cells that generate stromal diversity in spleen development and repair and suggest the existence of multipotent stromal progenitors in the adult spleen with regenerative capacity

METTL1 Promotes let-7 MicroRNA Processing via m7G Methylation.

7-methylguanosine (m7G) is present at mRNA caps and at defined internal positions within tRNAs and rRNAs. However, its detection within low-abundance mRNAs and microRNAs (miRNAs) has been hampered by a lack of sensitive detection strategies. Here, we adapt a chemical reactivity assay to detect internal m7G in miRNAs. Using this technique (Borohydride Reduction sequencing [BoRed-seq]) alongside RNA immunoprecipitation, we identify m7G within a subset of miRNAs that inhibit cell migration. We show that the METTL1 methyltransferase mediates m7G methylation within miRNAs and that this enzyme regulates cell migration via its catalytic activity. Using refined mass spectrometry methods, we map m7G to a single guanosine within the let-7e-5p miRNA. We show that METTL1-mediated methylation augments let-7 miRNA processing by disrupting an inhibitory secondary structure within the primary miRNA transcript (pri-miRNA). These results identify METTL1-dependent N7-methylation of guanosine as a new RNA modification pathway that regulates miRNA structure, biogenesis, and cell migration

Promoter-bound METTL3 maintains myeloid leukaemia by m6A-dependent translation control.

N6-methyladenosine (m6A) is an abundant internal RNA modification in both coding and non-coding RNAs that is catalysed by the METTL3-METTL14 methyltransferase complex. However, the specific role of these enzymes in cancer is still largely unknown. Here we define a pathway that is specific for METTL3 and is implicated in the maintenance of a leukaemic state. We identify METTL3 as an essential gene for growth of acute myeloid leukaemia cells in two distinct genetic screens. Downregulation of METTL3 results in cell cycle arrest, differentiation of leukaemic cells and failure to establish leukaemia in immunodeficient mice. We show that METTL3, independently of METTL14, associates with chromatin and localizes to the transcriptional start sites of active genes. The vast majority of these genes have the CAATT-box binding protein CEBPZ present at the transcriptional start site, and this is required for recruitment of METTL3 to chromatin. Promoter-bound METTL3 induces m6A modification within the coding region of the associated mRNA transcript, and enhances its translation by relieving ribosome stalling. We show that genes regulated by METTL3 in this way are necessary for acute myeloid leukaemia. Together, these data define METTL3 as a regulator of a chromatin-based pathway that is necessary for maintenance of the leukaemic state and identify this enzyme as a potential therapeutic target for acute myeloid leukaemia

RNA modifications detection by comparative Nanopore direct RNA sequencing.

RNA molecules undergo a vast array of chemical post-transcriptional modifications (PTMs) that can affect their structure and interaction properties. In recent years, a growing number of PTMs have been successfully mapped to the transcriptome using experimental approaches relying on high-throughput sequencing. Oxford Nanopore direct-RNA sequencing has been shown to be sensitive to RNA modifications. We developed and validated Nanocompore, a robust analytical framework that identifies modifications from these data. Our strategy compares an RNA sample of interest against a non-modified control sample, not requiring a training set and allowing the use of replicates. We show that Nanocompore can detect different RNA modifications with position accuracy in vitro, and we apply it to profile m6A in vivo in yeast and human RNAs, as well as in targeted non-coding RNAs. We confirm our results with orthogonal methods and provide novel insights on the co-occurrence of multiple modified residues on individual RNA molecules.The Kouzarides laboratory is supported by Cancer Research UK (grant reference RG72100) and core support from the Wellcome Trust (core grant reference WT203144) and Cancer Research UK (grant reference C6946/A24843). PPA was supported by a Borysiewicz Biomedical Sciences postdoctoral fellowship (University of Cambridge) and AL by a COFUND Marie Skłodowska-Curie Actions postdoctoral fellowship (EMBL). FW and TS are supported by the Francis Crick Institute, which receives its core funding from Cancer Research UK (FC001203), the UK Medical Research Council (FC001203), and the Wellcome Trust (FC001203). IB and V Miano are supported by Cancer Research UK (grant reference RG86786) and by the Joseph Mitchell Fund