4,120 research outputs found
The Temporins
No full textThe temporins belong to a family of short (8–17 amino acids),
hydrophobic, C-terminally α-amidated peptides with antibacterial
and antifungal properties that are synthesized in the skins of a
wide range of North American and Eurasian frogs of the Ranidae
family. Temporins adopt an α-helical conformation in hydrophobic
environments and have the ability to perturb the integrity of
target cell membranes. Not all temporins are cationic, but the number
of positively charged amino acids correlates with antimicrobial
potency. Temporins are mostly effective against Gram-positive
bacteria, but some are also active against Gram-negative bacteria.
Temporins show potential for development into therapeutically
valuable anti-infective agents, particularly for use against antibiotic-
resistant Gram-positive bacteria such as methicillin-resistant
Staphylococcus aureus (MRSA) and Enterococcus faecalis, against
anaerobic pathogens such as Clostridium difficile, and against the
protozoan parasite Leishmania spp. Although the clinical usefulness
of naturally occurring temporins is limited by high hemolytic
activity, noncytotoxic analogs have been designe
An immunomodulatory peptide related to frenatin 2 from skin secretions of the Tyrrhenian painted frog Discoglossus sardus (Alytidae)
No full textNorepinephrine-stimulated skin secretions of the Tyrrhenian painted frog Discoglossus sardus Tschudi, 1837 (Alytidae) did not contain any peptide with antimicrobial or hemolytic activity. However, peptidomic analysis of the secretions revealed the presence of an abundant peptide with structural similarity to frenatin 2, previously isolated from the Australian frog Litoria infrafrenata (Hylidae). The primary structure of the peptide, termed frenatin 2D, was established as DLLGTLGNLPLPFI.NH2 by automated Edman degradation and mass spectrometry with electron-transfer dissociation (ETD)-based fragmentation and confirmed by chemical synthesis. The structure of a second frenatin 2-related peptide, termed frenatin 2.1D, that was present in much lower abundance was established as GTLGNLPAPFPG. Frenatin 2D (20 μg/ml) significantly stimulated production of the proinflammatory cytokines TNF-α (P<0.05) and IL-1β (P<0.01) by mouse peritoneal macrophages but the peptide did not potentiate the stimulation produced by lipopolysaccharide (LPS). The peptide increased IL-12 production in both unstimulated (P<0.01) and LPS-stimulated (P<0.05) cells but stimulatory effects on IL-6 production were not significant. The biological role of frenatin 2D is unknown but it is speculated that the peptide acts on skin macrophages to produce a cytokine-mediated stimulation of the adaptive immune system in response to invasion by microorganisms
American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
No full text2R531-R53827
The SSC of the Generalised Jahangir’s Graph Jm,k and its Algebraic Characterizations
No full textIn this article, we present important combinatorial and algebraicproperties of spanning simplicial complex (SSC) of the generalised Jahangir’sgraph Jm,k. We describe the relation to find f−vectors associatedto Δs(Jm,k) and determine the Hilbert series for the SR-ring KΔs(Jm,k).In the end, we present the associated primes of the facet ideal IF(Δs(Jm,k))and the Cohen-Macaulay characterization of the SR-ring of Δs(Jm,k).AMS (MOS) Subject Classification Codes: Primary 13-P10, Secondary 13-F20, 13-C14, 13-H10.Corresponding Author: Agha KashifKey Words: Simplicial Complexes, f-vectors, Spanning Trees, Face Ring, Hilbert Series, CohenMacaulay
Conformational analysis and cytotoxic activities of the frog skin host-defense peptide, hymenochirin-1Pa
No full textHymenochirin-1Pa (LKLSPKTKDTLKKVLKGAIKGAIAIASMA-NH2) is a host-defense peptide first isolated from skin secretions of the frog Pseudhymenochirus merlini (Pipidae). A nuclear magnetic resonance structural investigation demonstrates that the peptide has a random coil conformation in water but, in the membrane-mimetic solvent 50% (v/ v) trifluoroethanol-water adopts a well-defined conformation characterized by two alpha-helical domains from residues K6 to G17 and from G21 to M28, with the N-terminal region unfolded. The presence of a GXXXG domain, the most common structural motif found at the interface between interacting trans-membrane helices, between residues 17 and 21, introduces a kink corresponding to a deviation from linearity of 93 +/- 31 degrees. Hymenochirin-1Pa shows broad spectrum anti-bacterial activity, including high potency against multidrug-resistant clinical isolates of Staphylococcus aureus, Acinetobacter baumannii, and Stenotrophomonas maltophilia. The peptide also shows high cytotoxic potency against human non-small lung adenocarcinoma A549 cells, breast adenocarcinoma MDA-MB-231 cells, and colorectal adenocarcinoma HT-29 cells but its therapeutic potential as an anti-cancer agent is limited by moderate hemolytic activity against human erythrocytes and lack of selectivity for tumor cells. Increasing cationicity of the peptide by substituting the Asp(9) residue by either L-Lys (K) or D-Lys (k) has relatively minor effects on antimicrobial and anti-tumor potencies but the [D9k] analog is non-hemolytic LC50 > 400 mu M. Thus, [D9k] hymenochirin-1Pa may serve as a template for the design of non-toxic antimicrobial agents for use against multidrug-resistant pathogenic bacteria. (C) 2014 Elsevier Inc. All rights reserved
To <i>JM</i> on Its 75th Anniversary
No full text This article discusses how Journal of Marketing ( JM) has influenced marketing science and practice by publishing articles on substantive topics relevant to customers, managers, organizations, markets, and society. The journal's 75th anniversary coincides with the 50th anniversary of the Marketing Science Institute (MSI). Frequently, JM and MSI have collaborated to address important substantive marketing issues identified in MSI's Research Priorities. The author highlights seminal articles on brand equity; business-to-business marketing (including sales force management); connecting marketing information, metrics, and strategy; consumer behavior; innovation, new product development. and product management; marketing orientation and capabilities; and market research, methodology and services. She also draws attention to articles that have won the Sheth Foundation/ JM Award and the H. Paul Root Award. The article describes how JM‘s knowledge dissemination is amplified by powerful social network effects. Ideas in JM articles diffuse through the business community, influencing the mind-set of managers worldwide. </jats:p
Conformational analysis of the frog skin peptide, plasticin-L1, and its effects on production of proinflammatory cytokines by macrophages
No full textPlasticin-L1 (GLVNGLLSSVLGGGQGGGGLLGGIL) is a conformationally flexible glycine/leucine-rich peptide originally isolated from norepinephrine-stimulated skin secretions of the South-American Santa Fe frog Leptodactylus laticeps (Leptodactylidae). A nuclear magnetic resonance/molecular dynamics characterization of plasticin-L1 in the presence of dodecylphosphocholine (DPC) and DPC/sodium dodecylsulphate micelles as membrane-mimetic models showed that the peptide has affinity for both neutral and anionic membranes. The peptide adopts a stable helical conformation at the N-terminal region and a more disordered helix at the C-terminal region, separated by an unstructured loop wherein the highest number of glycines is localized. In both micelle environments, plasticin-L1 slowly inserts between the detergent head groups but always remains localized at the micelle/water interface. Plasticin-L1 lacks direct antimicrobial activity but stimulates cytokine production by macrophages. Incubation with plasticin-L1 (20 μg/mL) significantly (P < 0.05) increased the production of the proinflammatory cytokines IL-1β, IL-12, IL-23, and TNF-α from unstimulated peritoneal macrophages from both C57BL/6 and BALB/C mice. The peptide also increased IL-6 production by unstimulated (P < 0.01) and lipopolysaccharide-stimulated (P < 0.01) macrophages, whereas the effects on production of the anti-inflammatory cytokine IL-10 were not significant. These findings suggest that plasticin-L1 may play an immunomodulatory role in vivo by stimulating cytokine production from frog skin macrophages in response to microbial pathogens. This peptide may represent a template for the design of peptides with therapeutic applications as immunostimulatory agent
JM-20, a Benzodiazepine-Dihydropyridine Hybrid Molecule, Inhibits the Formation of Alpha-Synuclein-Aggregated Species
No full text\ua9 2022, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.Studies showed that JM-20, a benzodiazepine-dihydropyridine hybrid molecule, protects against rotenone and 6-hydroxydopamine neurotoxicity. However, its protective effects against cytotoxicity induced by endogenous neurotoxins involved in Parkinson’s disease (PD) pathogenesis have never been investigated. In this study, we evaluated the ability of JM-20 to inhibit alpha-synuclein (aSyn) aggregation. We also evaluated the interactions of JM-20 with aSyn by molecular docking and molecular dynamics and assessed the protective effect of JM-20 against aminochrome cytotoxicity. We demonstrated that JM-20 induced the formation of heterogeneous amyloid fibrils, which were innocuous to primary cultures of mesencephalic cells. Moreover, JM-20 reduced the average size of aSyn positive inclusions in H4 cells transfected with SynT wild-type and synphilin-1-V5, but not in HEK cells transfected with synphilin-1-GFP. In silico studies showed the interaction between JM-20 and the aSyn-binding site. Additionally, we showed that JM-20 protects SH-SY5Y cells against aminochrome cytotoxicity. These results reinforce the potential of JM-20 as a neuroprotective compound for PD and suggest aSyn as a molecular target for JM-20
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