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Transmembrane protein GARP binds latent TGF-β1 to form GARP:(latent)TGF-β1 complexes on the surface of several cell types including Tregs, B-cells, and platelets. Upon stimulation, these cells release active TGF-β1. Blocking TGF-β1 activation by Tregs with anti-GARP:TGF-β1 mAbs overcomes resistance to PD1/PD-L1 blockade and induces immune-mediated regressions of murine tumors, indicating that Treg-derived TGF-β1 inhibits anti-tumor immunity. TGF-β1 exerts a vast array of effects on immune responses. For example, it favors differentiation of TH17 cells and B-cell switch to IgA production, two important processes for mucosal immunity. Here, we sought to determine whether treatment with anti-GARP:TGF-β1 mAbs would perturb immune responses to intestinal bacterial infection. We observed no aggravation of intestinal disease, no systemic dissemination, and no alteration of innate or adaptative immune responses upon oral gavage of C. rodentium in highly susceptible Il22r−/− mice treated with anti-GARP:TGF-β1 mAbs. To examine the effects of GARP:TGF-β1 blockade on Ig production, we compared B cell- and TH cell- responses to OVA or CTB protein immunization in mice carrying deletions of Garp in Tregs, B cells, or platelets. No alteration of adaptive immune responses to protein immunization was observed in the absence of GARP on any of these cells. Altogether, we show that antibody-mediated blockade of GARP:TGF-β1 or genetic deletion of Garp in Tregs, B cells or platelets, do not alter innate or adaptive immune responses to intestinal bacterial infection or protein immunization in mice. Anti-GARP:TGF-β1 mAbs, currently tested for cancer immunotherapy, may thus restore anti-tumor immunity without severely impairing other immune defenses. Précis: Immunotherapy with GARP:TGF-β1 mAbs may restore anti-tumor immunity without impairing immune or inflammatory responses required to maintain homeostasis or host defense against infection, notably at mucosal barriers. [ABSTRACT FROM AUTHOR]

We develop a fast collocation method for a static bond-based peridynamic model. Based on the analysis of the structure of the stiffness matrix, a fast matrix-vector multiplication technique was found, which can be used in the Krylov subspace iteration method. In this paper, we also present an effective preconditioner to accelerate the convergence of the Krylov subspace iteration method. Using the block-Toeplitz–Toeplitz-block (BTTB)-type structure of the stiffness matrix, we give a block-circulant-circulant-block (BCCB)-type preconditioner. The numerical experiments show the utility of the preconditioned fast collocation method. [ABSTRACT FROM AUTHOR]

In this paper, a fast collocation method is developed for a two-dimensional variable-coefficient linear nonlocal diffusion model. By carefully dealing with the variable coefficient in the integral operator and then analyzing the structure of the coefficient matrix, we can reduce the computational operations in each Krylov subspace iteration from O (N 2) to O (N log N) and the memory requirement for the coefficient matrix from O (N 2) to O (N) . Numerical experiments are carried out to show the utility of the fast collocation method. [ABSTRACT FROM AUTHOR]

Bacillus velezensis ZY-1-1 was isolated from the larval gut of the lignocellulose-rich diet-fed scarab beetle, Holotrichia parallela, and confirmed to possess extremely high xylanase (48153.8 ± 412.1 U/L) and relatively moderate cellulase activity (610.1 ± 8.2 U/L). Notably, these xylanase and cellulase activities were enhanced by xylan (1.4 and 5.8-fold, respectively) and cellulose (1.1 and 3.5-fold, respectively), which indicated the hemicellulosic/cellulosic substrate-inducible lignocellulolytic activities of this strain. The complete genome of B. velezensis ZY-1-1 comprises of 3,899,251 bp in a circular chromosome with a G + C content of 46.6%. Among the predicted 3688 protein-coding genes, 24 genes are involved in the degradation of lignocellulose and other polysaccharides, including 8, 7 and 2 critical genes for the degradation of xylan, cellulose and lignin, respectively. This genome-based analysis will facilitate our understanding of the mechanism underlying the biodegradation of lignocellulose and the biotechnological application of this novel lignocellulolytic bacteria or related enzymes. [ABSTRACT FROM AUTHOR]