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Background: The anticancer activities of host defense peptides (HDPs) are mainly attributed to their cell penetrating activity. Accordingly, several approaches based on machine learning, calculating the membrane pore formation ability, have been proposed for the anti-cancer peptide identification. Since the membranolytic activity can lead to nonspecific effects, like hemolysis, the therapeutic application of such molecules is limited. In this context, we considered the immunomodulatory activity of HDPs, which is regulated by specific membrane targets and immunomodulatory pathways in immune cells. As many immunomodulators are aberrantly expressed in cancer cells, the possibility of the activation of an immunomodulatory pathway was investigated for a novel anticancer HDP, SSTP1.Methods: The fourteen mature peptides identified by shotgun cloning from the frog-skin secretions were screened for cytotoxicity in oral cancer cells. The mechanism of action of the selected peptide, SSTP1 was investigated in comparison to its inactive mutant, SSTP2. An RNA-Seq coupled with pathway enrichment analysis was performed to identify the upstream signaling leading to the mitochondrial pathway of apoptosis. Since the activation of the IL6/IL6R pathway was suggested, we performed in silico docking studies to find the binding of SSTP1 to the IL6/IL6Rα/gp130 complex. The dynamic simulation predicted the conformational changes in the active site residues. The confocal co-localization studies, pull-down assay, FRET analysis, western blot and reporter assays were performed to elucidate the role of the IL6/IL6R pathway in SSTP1-induced apoptosis. Specific small molecule inhibitors and neutralizing antibodies were used to ascertain the role of the IL6/IL6Rα/gp130 complex in the activation of JNK/AP1 pathway-dependent cell death.Results: SSTP1, a novel temporin, modulates the IL6 pathway and induces apoptosis when it binds to IL6Rα on the active IL6/IL6Rα/gp130 complex, rearranging the active site residues. In contrast to the IL6 blockers inhibiting JAK/STAT activity, SSTP1 shifts the proliferative IL6/JAK/STAT signaling to the apoptotic IL6/JNK/AP1 pathway. In IL6Rα-overexpressing cancer cells, apoptosis is preferred over the membranolytic activity, upon SSTP1 treatment.Conclusions: Here, we provide the evidence of an HDP-induced signaling through immunomodulators, leading to apoptosis in cancer cells. Our study also implies the importance of identifying the targets of HDPs for their clinical application

Gonad inhibiting hormone (GIH), type II class of the CHH family neuropeptides, is released by the neurohaemal XO-SG complex of the eyestalk. The inhibitory function of GIH has a pivotal role in gonad development and reproduction. In this study, we report the expression and production of a thioredoxin-fused mature GIH protein (mf-PmGIH) of Penaeus monodon in a bacterial system and its use as antigen to raise polyclonal antiserum (anti-mf-PmGIH). The mature GIH gene of 237bp that codes for 79 amino acids, was cloned into the Escherichia coli thioredoxin gene fusion expression system. The expression vector construct (mf-PmGIH+pEt32a+) upon induction produced 32.16kDa mature GIH fusion protein (mf-PmGIH)·The purified fusion protein was used as exogenous GIH and as antigen to raise polyclonal antisera. The fusion protein when injected into juvenile shrimp significantly reduced vitellogenin/vitellin levels by 31.55% within 72h in comparison to the controls showing the gonad inhibiting property. Vitellogenin/vitellin levels were significantly induced by 74.10% within 6h when polyclonal antiserum (anti-mf-PmGIH - 1:500) was injected in P. monodon. Anti-mf-PmGIH immunolocalized GIH producing neurosecretory cells in the eyestalk of P. monodon. The present manuscript reports an innovative means of gonad inhibition and vitellogenin/vitellin induction with thioredoxin fused GIH and antisera developed.

RANGE AND GROUP MONOTONICITY OF OPERATORS

The positive invertibility of operators between Banach spaces, ordered by special closed cones, is characterized by the existence of splittings for the operators into the difference of two operators with appropriate spectral properties. Some results, up to now known only for matrices, are generalized to operators and to order intervals of operators., №1 (2018)

For A ? ?n�n and q ? ?n, the linear complementarity problem LCP(A; q) is to determine if there is x ? ?n such that x ? 0; y = Ax+q ? 0 and xT y = 0. Such an x is called a solution of LCP(A; q). A is called an R 0-matrix if LCP(A; 0) has zero as the only solution. In this article, the class of R0-matrices is extended to include typically singular matrices, by requiring in addition that the solution x above belongs to a subspace of ?n. This idea is then extended to semidefinite linear complementarity problems, where a characterization is pre-sented for the multplicative transformation.

The concept of the Moore-Penrose inverse in an indefinite inner product space is introduced. Extensions of some of the formulae in the Euclidean space to an indefinite inner product space are studied. In particular range-hermitianness is completely characterized. Equivalence of a weighted generalized inverse and the Moore-Penrose inverse is proved. Finally, methods of computing the Moore-Penrose inverse are presented. ? 2005 Korean Society for Computational & Applied Mathematics and Korean SIGCAM.