Interaction between integrin α9β1 and vascular cell adhesion molecule-1 (VCAM-1) inhibits neutrophil apoptosis

According to the prevailing paradigm, neutrophils are short-lived cells that undergo spontaneous apoptosis within 24 hours of their release from the bone marrow. However, neutrophil survival can be significantly prolonged within inflamed tissue by cytokines, inflammatory mediators, and hypoxia. During screening experiments aimed at identifying the effect of the adhesive microenvironment on neutrophil survival, we found that VCAM-1 (CD106) was able to delay both spontaneous and Fas-induced apoptosis. VCAM-1-mediated survival was as efficient as that induced by the cytokine IFN-β and provided an additive, increased delay in apoptosis when given in combination with IFN-β. VCAM-1 delivered its antiapoptotic effect through binding the integrin α9β1. The α9β 1 signaling pathway shares significant features with the IFN-β survival signaling pathway, requiring PI3 kinase, NF-κB activation, as well as de novo protein synthesis, but the kinetics of NF-κB activation by VCAM-1 were slower and more sustained compared with IFN-β. This study demonstrates a novel functional role for α9β1 in neutrophil biology and suggests that adhesive signaling pathways provide an important extrinsic checkpoint for the resolution of inflammatory responses in tissues

MHCII-mediated dialog between group 2 innate lymphoid cells and CD4+ T cells potentiates type 2 immunity and promotes parasitic helminth expulsion

Group 2 innate lymphoid cells (ILC2s) release interleukin-13 (IL-13) during protective immunity to helminth infection and detrimentally during allergy and asthma. Using two mouse models to deplete ILC2s in vivo, we demonstrate that T helper 2 (Th2) cell responses are impaired in the absence of ILC2s. We show that MHCII-expressing ILC2s interact with antigen-specific T cells to instigate a dialog in which IL-2 production from T cells promotes ILC2 proliferation and IL-13 production. Deletion of MHCII renders IL-13-expressing ILC2s incapable of efficiently inducing Nippostrongylus brasiliensis expulsion. Thus, during transition to adaptive T cell-mediated immunity, the ILC2 and T cell crosstalk contributes to their mutual maintenance, expansion and cytokine production. This interaction appears to augment dendritic-cell-induced T cell activation and identifies a previously unappreciated pathway in the regulation of type-2 immunity

A p53-dependent mechanism underlies macrocytic anemia in a mouse model of human 5q- syndrome.

The identification of the genes associated with chromosomal translocation breakpoints has fundamentally changed understanding of the molecular basis of hematological malignancies. By contrast, the study of chromosomal deletions has been hampered by the large number of genes deleted and the complexity of their analysis. We report the generation of a mouse model for human 5q- syndrome using large-scale chromosomal engineering. Haploinsufficiency of the Cd74-Nid67 interval (containing Rps14, encoding the ribosomal protein S14) caused macrocytic anemia, prominent erythroid dysplasia and monolobulated megakaryocytes in the bone marrow. These effects were associated with defective bone marrow progenitor development, the appearance of bone marrow cells expressing high amounts of the tumor suppressor p53 and increased bone marrow cell apoptosis. Notably, intercrossing with p53-deficient mice completely rescued the progenitor cell defect, restoring common myeloid progenitor and megakaryocytic-erythroid progenitor, granulocyte-monocyte progenitor and hematopoietic stem cell bone marrow populations. This mouse model suggests that a p53-dependent mechanism underlies the pathophysiology of the 5q- syndrome

A Disposable Copper (II) Ion Biosensor Based on Self-Assembly of L-Cysteine on Gold Nanoparticle-Modified Screen-Printed Carbon Electrode

A disposable copper (II) ion biosensor based on self-assembly of L-cysteine on gold nanoparticle-modified screen-printed carbon electrode was fabricated. The electrode was modified by attaching gold nanoparticles onto the surface of screen-printed carbon electrode through seed mediated growth method followed by self-assembly of L-cysteine. As demonstrated by differential pulse voltammetry, the sensor exhibited high sensitivity to copper (II) ion down to ppb (parts per billion) levels. Optimization of various experimental parameters such as pH, buffer concentration, and preconcentration time, which influenced the performance of the biosensor, was investigated. The sensor demonstrated a wide linear response range from 10 to 0.005 ppm (r=0.9870), with a lower detection limit of 8 ppb using 10 min of preconcentration time. The sensor based on screen-printed electrode provides a cost-effective means of application of copper ion sensor for the detection of ppb level of copper ions in water

In vitro digestion and swelling kinetics of thymoquinone-loaded pickering emulsions incorporated in alginate-chitosan hydrogel beads

The present work aimed to investigate the swelling behavior, in vitro digestion, and release of a hydrophobic bioactive compound, thymoquinone (TQ), loaded in Pickering emulsion incorporated in alginate-chitosan hydrogel beads using a simulated gastrointestinal model. In this study, oil-in-water Pickering emulsions of uniform micron droplet sizes were formulated using 20% red palm olein and 0.5% (w/v) cellulose nanocrystals-soy protein isolate (CNC/SPI) complex followed by encapsulation within beads. FT-IR was used to characterize the bonding between the alginate, chitosan, and Pickering emulsion. 2% (w/v) alginate-1% (w/v) chitosan hydrogel beads were found to be spherical with higher stability against structural deformation. The alginate-chitosan beads displayed excellent stability in simulated gastric fluid (SGF) with a low water uptake of ~19%. The hydrogel beads demonstrated a high swelling degree (85%) with a superior water uptake capacity of ~593% during intestinal digestion in simulated intestinal fluid (SIF). After exposure to SIF, the microstructure transformation was observed, causing erosion and degradation of alginate/chitosan wall materials. The release profile of TQ up to 83% was achieved in intestinal digestion, and the release behavior was dominated by diffusion via the bead swelling process. These results provided useful insight into the design of food-grade colloidal delivery systems using protein-polysaccharide complex-stabilized Pickering emulsions incorporated in alginate-chitosan hydrogel beads