Receptor-stimulated oxidation of SHP-2 promotes T-cell adhesion through SLP-76-ADAP

Receptor-stimulated generation of intracellular reactive oxygen species (ROS) modulates signal transduction, although the mechanism(s) is unclear. One potential basis is the reversible oxidation of the active site cysteine of protein tyrosine phosphatases (PTPs). Here, we show that activation of the antigen receptor of T cells (TCR), which induces production of ROS, induces transient inactivation of the SH2 domain-containing PTP, SHP-2, but not the homologous SHP-1. SHP-2 is recruited to the LAT-Gads-SLP-76 complex and directly regulates the phosphorylation of key signaling proteins Vav1 and ADAP. Furthermore, the association of ADAP with the adapter SLP-76 is regulated by SHP-2 in a redox-dependent manner. The data indicate that TCR-mediated ROS generation leads to SHP-2 oxidation, which promotes T-cell adhesion through effects on an SLP-76-dependent signaling pathway to integrin activation.     

Expression of trefoil peptides in the subtypes of intestinal metaplasia

We studied the expression of trefoil peptides in the different types of intestinal metaplasia of the stomach. Endoscopic biopsy was performed in 132 patients with dyspepsia. Intestinal metaplasia subtype was classified according to the pattern of alcian blue/PAS staining and high iron diamine staining. Expression of trefoil peptides was measured by immunohistochemistry. TFF1 and TFF3 were mainly expressed in goblet cells and TFF2 in columnar cells in all the types of intestinal metaplasia. There was a gradual decrease of TFF1 and TFF3, and increase of TFF2, during the progression of intestinal metaplasia from type I to type III via the type II intermediate.     

Differential expression of the chsE gene encoding a chitin synthase of Aspergillus nidulans in response to developmental status and growth conditions

Expression of chsE encoding one of the five chitin synthases of Aspergillus nidulans was analyzed. Expression of chsE was moderate in conidiophores, but somewhat weaker in vegetative mycelia. During sexual development, chsE was expressed strongly in young cleistothecia and hülle cells, but little in mature sexual structures. Deletion of chsE caused a significant decrease in the chitin content of the cell wall during early sexual development. Expression of chsE was increased by substituting glucose with lactose or by addition of 0.6M KCl or NaCl, but affected little by substituting glucose with sodium acetate. Consequently, chsE was shown to have a mode of expression distinct from those of the other chitin synthase genes, chsA, chsB and chsC.     

Dendritic Cell-Based Immunotherapy for Solid Tumors

As a treatment for solid tumors, dendritic cell (DC)-based immunotherapy has not been as effective as expected. Here, we review the reasons underlying the limitations of DC-based immunotherapy for solid tumors and ask what can be done to improve immune cell-based cancer therapies. Several reports show that, rather than a lack of immune induction, the limited efficacy of DC-based immunotherapy in cases of renal cell carcinoma (RCC) likely results from inhibition of immune responses by tumor-secreted TGF-β and an increase in the number of regulatory T (Treg) cells in and around the solid tumor. Indeed, unlike DC therapy for solid tumors, cytotoxic T lymphocyte (CTL) responses induced by DC therapy inhibit tumor recurrence after surgery; CTL responses also limit tumor metastasis induced by additional tumor-challenge in RCC tumor-bearing mice. Here, we discuss the mechanisms underlying the poor efficacy of DC-based therapy for solid tumors and stress the need for new and improved DC immunotherapies and/or combination therapies with killer cells to treat resistant solid tumors.     

The role of extracellular polymeric substances in reducing copper inhibition to nitrification in activated sludge

This study presents the role of extracellular polymeric substances (EPS) in reducing the inhibitory effects of copper towards nitrifying activated sludge. EPS could ameliorate copper toxicity in activated sludge by binding metal ions. A series of copper inhibition experiments were conducted with activated sludge taken from laboratoryscale sequencing batch reactor (SBR) systems operated under different feast-famine cycles, which provided the different conditions to the EPS-producing heterotrophic populations. The toxicity of copper to both nitrifiers and heterotrophs decreased with increasing the feast-famine period. Average EPS contents were substantially higher in SBR sludge with longer feast-famine periods indicating that the decrease in the toxicity of copper at a longer feastfamine period was attributed to the presence of higher amounts of EPS. Comparison of the responses of nitrifiers and heterotrophs to free copper suggests that nitrifiers were no more sensitive to copper than heterotrophs.     

Lipophorin uptake by the larval fat body and adult ovary in the wax moth Galleria mellonella

Lipophorin (Lp) acts in the circulation of insects to selectively deliver lipids to target tissues. In the present study, we wanted to show that Lp is taken up into larval fat body cells and the adult ovary in Galleria mellonella. Larval fat body and adult ovary tissues were incubated at room temperature for 30 min with fluorescein isothiocyanate (FITC)‐labeled Lp. Fluorescence microscopy and sodium dodecylsulfate (SDS)–polyacrylamide gel electrophoresis (PAGE) revealed that fat body and ovary tissues internalize fluorescence‐labeled Lp. The results suggest that both lipids and proteins are taken up by fat body cells and the ovary and also that large amounts of proteins and lipids taken up can serve as building blocks and as a source of energy. Immunological relationships with other insects were investigated using western blotting. The data showed that the Lp of Galleria mellonella is related to that of Hyphantria cunea.     

Key Role of Disulfide Bridges in the Antimicrobial Activity of Beta-Defensin from Olive Flounder

International Journal of Peptide Research and Therapeutics - Proteins that contain multiple disulfide bonds (SS bonds) expressed in Escherichia coli are usually problematic. This study reports the...