Leukocyte-specific protein 1 regulates T-cell migration in rheumatoid arthritis

Copy number variations (CNVs) have been implicated in human diseases. However, it remains unclear how they affect immune dysfunction and autoimmune diseases, including rheumatoid arthritis (RA). Here, we identified a novel leukocyte-specific protein 1 (LSP1) deletion variant for RA susceptibility located in 11p15.5. We replicated that the copy number of LSP1 gene is significantly lower in patients with RA, which correlates positively with LSP1 protein expression levels. Differentially expressed genes in Lsp1-deficient primary T cells represent cell motility and immune and cytokine responses. Functional assays demonstrated that LSP1, induced by T-cell receptor activation, negatively regulates T-cell migration by reducing ERK activation in vitro. In mice with T-cell-dependent chronic inflammation, loss of Lsp1 promotes migration of T cells into the target tissues as well as draining lymph nodes, exacerbating disease severity. Moreover, patients with RA show diminished expression of LSP1 in peripheral T cells with increased migratory capacity, suggesting that the defect in LSP1 signaling lowers the threshold for T-cell activation. To our knowledge, our work is the first to demonstrate how CNVs result in immune dysfunction and a disease phenotype. Particularly, our data highlight the importance of LSP1 CNVs and LSP1 insufficiency in the pathogenesis of RA and provide previously unidentified insights into the mechanisms underlying T-cell migration toward the inflamed synovium in RA.1187Ysciescopu

Molecular lens applied to benzene and carbon disulfide molecular beams

A molecular lens of the nonresonant dipole force formed by focusing a nanosecond IR laser pulse has been applied to benzene and CS2 molecular beams. Using the velocity map imaging technique for molecular ray tracing, characteristic molecular lens parameters including the focal length (f ), minimum beam width (W), and distance to the minimum beam width position (D) were determined. The laser intensity dependence of the observed lens parameters was in good agreement with theoretical predictions. W was independent of the laser peak intensity (I-0), whereas f and D varied linearly with 1/I-0. The differences in lens parameters between the molecular species were well correlated with the polarizability per mass values of the molecules. A high chromatographic resolution of Rs = 0.84 was achieved between the images of benzene molecular beams undeflected and deflected by the lens. The possibilities for a new type of chromatography are discussed.open293

W5ater desalination using graphene-enhanced electrospun nanofiber membrane via air gap membrane distillation

© 2016 This study demonstrates the preparation and desalination performance via air gap membrane distillation (AGMD) of a graphene-loaded electrospun nanofiber membrane. Different concentrations of graphene (0–10 wt%) were incorporated in/on electrospun polyvinylidene fluoride-co-hexafluoropropylene (PH) membrane to obtain a robust, and superhydrophobic nanocomposite membrane. The results showed that graphene incorporation has significantly enhanced the membrane structure and properties with an optimal concentration of 5 wt% (i.e., G5PH). Characterization of G5PH revealed membrane porosity of >88%, contact angle of >162° (superhydrophobic), and high liquid entry pressure (LEP) of >186 kPa. These favourable properties led to a high and stable AGMD flux of 22.9 L/m2 h or LMH (compared with ~4.8 LMH for the commercial PVDF flat-sheet membrane) and excellent salt rejection (100%) for 60 h of operation using 3.5 wt% NaCl solution as feed (feed and coolant inlet temperatures of 60 and 20 °C, respectively). A two-dimensional dynamic model to investigate the flux profile of the graphene/PH membrane is also introduced. The present study suggests that exploiting the interesting properties of nanofibers and graphene nanofillers through a facile electrospinning technique provides high potential towards the fabrication of a robust and high-performance AGMD membrane

3D printing technology to control BMP-2 and VEGF delivery spatially and temporally to promote large-volume bone regeneration

When large engineered tissue structures are used to achieve tissue regeneration, formation of vasculature is an essential process. We report a technique that combines 3D printing with spatial and temporal control of dual growth factors to prevascularize bone tissue. Human dental pulp stem cells (DPSCs) that have both osteogenic and vasculogenic potential were printed with bone morphogenetic protein-2 (BMP- 2) in the peripheral zone of the 3D printed construct, and with the vascular endothelial growth factor (VEGF) in the central zone, in which a hypoxic area forms. The structure was implanted in the back of a mouse and tissue regeneration was assessed after 28 d. Microvessels were newly formed in the hypoxic area of the printed large volume structure, and angiogenesis from the host tissue was also observed. Bone regeneration was faster in prevascularized structures than in nonvascularized structures. The 3D-printed prevascularized structure could be a promising approach to overcome the size limitation of tissue implants and to enhance bone regeneration.open114635sciescopu

Graphene/PVDF flat-sheet membrane for the treatment of RO brine from coal seam gas produced water by air gap membrane distillation

© 2016 Elsevier B.V. Brine management of coal seam gas (CSG) produced water is a significant concern for the sustainable production of CSG in Australia. Membrane distillation (MD) has shown the potential to further reduce the volume of CSG reverse osmosis (RO) brine. However, despite its potential, the lack of appropriate MD membranes limits its industrial use. Therefore, this study was aimed on the fabrication of a robust membrane for the treatment of real RO brine from CSG produced water via an air gap MD (AGMD) process. Here, graphene/polyvinylidene fluoride (G/PVDF) membranes at various graphene loadings 0.1-2.0 wt% w.r.t. to PVDF) were prepared through a phase inversion method. Surface characterization revealed that all G/PVDF membranes exhibited favorable membrane properties having high porosity (>78%), suitable mean pore size (3.66 bar). AGMD test results (feed inlet: 60.0±1.5 °C; coolant inlet: 20.0±1.5 °C) for 24 h operation indicated a high water vapor flux and salt rejection of 20.5 L/m2h and 99.99%, respectively for the optimal graphene loading of 0.5 wt%, i.e., G/PVDF-0.5 membrane (compared to 11.6 L/m2h and 99.96% for neat PVDF membrane). Long-term AGMD operation of 10 days further revealed the robustness of G/PVDF membrane with superior performance compared to commercial PVDF membrane (85.3% final normalized flux/99.99% salt rejection against 51.4%/99.95% for commercial membrane). Incorporation of graphene has resulted to improved wetting resistance and more robust membrane that has the potential for the treatment of RO brine from CSG produced water via AGMD

The impacts of aerosol emissions on historical climate in ukesm1

As one of the main drivers for climate change, it is important to understand changes in anthropogenic aerosol emissions and evaluate the climate impact. Anthropogenic aerosols have affected global climate while exerting a much larger influence on regional climate by their short lifetime and heterogeneous spatial distribution. In this study, the effective radiative forcing (ERF), which has been accepted as a useful index for quantifying the effect of climate forcing, was evaluated to understand the effects of aerosol on regional climate over a historical period (1850–2014). Eastern United States (EUS), Western European Union (WEU), and Eastern Central China (ECC), are regions that predominantly emit anthropogenic aerosols and were analyzed using Coupled Model Intercomparison Project 6 (CMIP6) simulations implemented within the framework of the Aerosol Chemistry Model Intercomparison Project (AerChemMIP) in the UK’s Earth System Model (UKESM1). In EUS and WEU, where industrialization occurred relatively earlier, the negative ERF seems to have been recovering in recent decades based on the decreasing trend of aerosol emissions. Conversely, the radiative cooling in ECC seems to be strengthened as aerosol emission continuously increases. These aerosol ERFs have been largely attributed to atmospheric rapid adjustments, driven mainly by aerosol-cloud interactions rather than direct effects of aerosol such as scattering and absorption.</jats:p

Effect of Cytoskeletal Disruption on Mechanotransduction of Hydrostatic Pressure by C3H10T1/2 Murine Fibroblasts

Cyclic hydrostatic pressure of physiological magnitude (< 10 MPa) stimulates chondrogenic differentiation of mesenchymal stem cells, but mechanotransduction mechanisms are not well understood. It was hypothesized that an intact cytoskeleton would be required for uninhibited mechanotransduction of hydrostatic pressure. Therefore we examined the effects of drugs which selectively interfere with actin and tubulin polymerization on pressure-induced upregulation of aggrecan and col2a1 (type II collagen) mRNA expression. C3H10T1/2 cells were cultured as pellets in either 4µM cytochalasin D or 4µM nocodazole and subjected to 3 days of cyclic hydrostatic compression (1 Hz, 5 MPa, 2 h per day). Phalloidin staining and indirect immunostaining with anti α-tubulin antibody confirmed disruption of microfilament and microtubule assemblies, respectively. Real time RT-PCR revealed that both drugs substantially lowered the basal level of aggrecan and col2a1 mRNA, but that neither drug prevented a pressure-stimulated increase in gene expression relative to the altered basal state. Thus upregulation of macromolecular gene expression by cyclic hydrostatic pressure did not require a completely intact cytoskeleton

Gastrointestinal Stromal Tumor Mimicking Arteriovenous Malformation of the Jejunum

There have been case reports of small intestinal gastrointestinal stromal tumors (GISTs) complicated with arteriovenous malformation (AVM) and angiodysplasia and exhibiting intense tumor staining. Herein we report a GIST of the small intestine that showed tumor staining and early venous return on imaging studies, and so the patient was suspected to have AVM. A 62-year-old male presented with intermittent pain in the left abdominal region. Contrast-enhanced computed tomography revealed a 15-mm-long spindle-shaped mass showing intense tumor staining and early venous return through the jejunal vein. In the arterial phase, the attenuation value of the tumor was 250 Hounsfield units. Color Doppler ultrasonography simultaneously delineated vessels extending from the serosal side and turbulent signals showing a mosaic pattern in the tumor. On angiography, intense staining was observed in the peripheral part of the second branch of the jejunal artery. Although these findings suggested AVM, the tumor was diagnosed as a GIST based on pathological examination of the resected specimens. In this case, no AVM or change in vascular density was noted despite the careful examination of pathological specimens, and the cause of the tumor staining remained unknown

Theoretical and experimental evidence for a post-perovskite phase of MgSiO3 in Earth's D" layer

The Earth's lower mantle is believed to be composed mainly of (Mg,Fe)SiO3 perovskite, with lesser amounts of (Mg,Fe)O and CaSiO3). But it has not been possible to explain many unusual properties of the lowermost 150 km of the mantle (the D" layer) with this mineralogy. Here, using ab initio simulations and high-pressure experiments, we show that at pressures and temperatures of the D" layer, MgSiO3 transforms from perovskite into a layered CaIrO3-type post-perovskite phase. The elastic properties of the post-perovskite phase and its stability field explain several observed puzzling properties of the D" layer: its seismic anisotropy, the strongly undulating shear-wave discontinuity at its top and possibly the anticorrelation between shear and bulk sound velocities.Comment: PUBLISHED IN Nature 430, 445-448 (2004