Antiviral bioactivity of resveratrol against Zika virus infection in human retinal pigment epithelial cells

Resveratrol (RES) is a polyphenol with increasing interest for its inhibitory effects on a wide variety of viruses. Zika virus (ZIKV) is an arbovirus which causes a broad spectrum of ophthalmological manifestations in humans. Currently there is no certified therapy or vaccine to treat it, thus it has become a major global health threat. Retinal pigment epithelium (RPE) is highly permissive and susceptible to ZIKV. This work explored the protective effects of RES on ZIKV-infected human RPE cells. RES treatment resulted in a significant reduction of infectious viral particles in infected male ARPE-19 and female hTERT-RPE1 cells. This protection was positively influenced by the action of RES on mitochondrial dynamics. Also, docking studies predicted that RES has a high affinity for two enzymes of the rate-limiting steps of pyrimidine and purine biosynthesis and viral polymerase. This evidence suggests that RES might be a potential antiviral agent to treat ZIKV-induced ocular abnormalities.

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Initiation Factor-2 (eIF-2) Activity in Barley Embryos

The activity of eukaryotic initiation factor-2 (eIF-2), a polypeptidechain initiation factor, which forms a ternary complex withthe eukaryotic initiator methionyl-tRNA (Met-tRNAi) and GTPand which promotes the binding of Met-tRNAi to the 40Sribosomalsubunit, increases several fold in developing barley embryosduring the late stages of embryogenesis. The maximum increasetook place during the desiccation phase and, as a result, dryembryos contain a very large amount of eIF-2 activity. Thisactivity decreases and reaches a level that sustains proteinsynthesis during germination of the embryos. (Received October 19, 1982; Accepted December 30, 1982)     

Seed dispersal of a fleshy-fruited invasive shrub is affected by changes in the frugivorous bird assemblage along an elevational gradient

Seed dispersal by birds constitutes an essential mechanism for ornithochorous exotic plants to successfully invade a new system. New biotic associations with native birds might facilitate the upward spread of exotic plants from the foothills into the high mountains. However, environmental changes associated with elevation are known to drive changes in bird assemblages, and it is not clear how elevation changes impact the seed dispersal service of ornithochorous invaders. We evaluated changes in frugivorous bird assemblages of one of the exotic shrubs (Cotoneaster franchetii, Rosaceae) with the broadest elevation range among woody invaders in the Córdoba Mountains (Argentina). We quantified frugivory interactions (including absolute and proportional fruit consumption by seed dispersers, pulp consumers, and seed predators) using 4-h observations of focal C. franchetii shrubs distributed across low-elevation, mid-elevation, and high-elevation sites (700, 1100, and 1800 m a.s.l., respectively; 15 individuals per elevational band and one site per elevation). Seed disperser richness was highest at the low- and mid-elevation sites (three species vs. one at the high-elevation site), but proportional and absolute fruit consumption of C. franchetii was highest at the high-elevation site (39.1%, 88 seeds at high-elevation and 7.7%, 20 seeds at low-elevation). The Chiguanco Thrush (Turdus chiguanco, Turdidae) was the only seed disperser species found at the highest elevation site. Fruit consumption by seed dispersers was positively related to their abundance and elevation. In a high mountain system, a single abundant generalist seed disperser, rather than a high richness of seed disperser species, can uphold an effective dispersal service for an invasive ornithochorous shrub. This pattern may facilitate the spread of such plants across higher elevational ranges, thereby promoting the invasion of other exotic ornithochorous plants into upper elevations.     

Neutrophil Extracellular Traps are Involved in the Innate Immune Response to Infection with Leptospira

NETosis is a process by which neutrophils extrude their DNA together with bactericidal proteins that trap and/or kill pathogens. In the present study, we evaluated the ability of Leptospira spp. to induce NETosis using human ex vivo and murine in vivo models. Microscopy and fluorometric studies showed that incubation of human neutrophils with Leptospira interrogans serovar Copenhageni strain Fiocruz L1-130 (LIC) resulted in the release of DNA extracellular traps (NETs). The bacteria number, pathogenicity and viability were relevant factors for induction of NETs, but bacteria motility was not. Entrapment of LIC in the NETs resulted in LIC death; however, pathogenic but not saprophytic Leptospira sp. exerted nuclease activity and degraded DNA. Mice infected with LIC showed circulating NETs after 2 days post-infection (dpi). Depletion of neutrophils with mAb1A8 significantly reduced the amount of intravascular NETs in LIC-infected mice, increasing bacteremia at 3 dpi. Although there was a low bacterial burden, scarce neutrophils and an absence of inflammation in the early stages of infection in the kidney and liver, at the beginning of the leptospiruric phase, the bacterial burden was significantly higher in kidneys of neutrophil-depleted-mice compared to non-depleted and infected mice. Surprisingly, interstitial nephritis was of similar intensity in both groups of infected mice. Taken together, these data suggest that LIC triggers NETs, and that the intravascular formation of these DNA traps appears to be critical not only to prevent early leptospiral dissemination but also to preclude further bacterial burden.     

Bovine lactoferrin inhibits Influenza A virus induced programmed cell death in vitro

Influenza is one of the main plagues worldwide. The statistical likelihood of a new pandemic outbreak, together with the alarming emergence of influenza virus strains that are resistant to available antiviral medications, highlights the need for new antiviral drugs. Lactoferrin, a 80 kDa bi-globular iron-binding glycoprotein, is a pleiotropic factor with potent antimicrobial and immunomodulatory activities. Although the antiviral effect of lactoferrin is one of its major biological functions, the mechanism of action is still under debate. In this research, we have analyzed the effect of bovine lactoferrin (bLf) on Influenza A virus infection in vitro. Our results showed that (i) Influenza virus infected cells died as a result of apoptosis, (ii) bLf treatment inhibited programmed cell death by interfering with function of caspase 3, a major virus-induced apoptosis effector, and (iii) bLf efficiently blocked nuclear export of viral ribonucleoproteins so preventing viral assembly. These results provide further insights on the antiviral activity of bLf and suggest novel strategies for treatment of Influenza virus infection.     

Protein metalation by metal-based drugs: reactions of cytotoxic gold compounds with cytochrome?c and lysozyme

Protein metalation processes are crucial for the mechanism of action of several anticancer metallodrugs and warrant deeper characterisation. We have explored the reactions of three cytotoxic gold(III) compounds??namely [(bipy^2Me)₂Au₂(??-O)₂][PF₆]₂ (where bipy^2Me is 6,6??-dimethyl-2,2??-bipyridine) (Auoxo6), [(phen^2Me)₂Au₂(??-O)₂][PF₆]₂ (where phen^2Me is 2,9-dimethyl-1,10-phenanthroline) (Au₂phen) and [(bipy^dmb-H)Au(OH)][PF₆] [where bipy^dmb-H is deprotonated 6-(1,1-dimethylbenzyl)-2,2??-bipyridine] (Aubipyc)??with two representative model proteins, i.e. horse heart cytochrome?c and hen egg white lysozyme, through UV?Cvisible absorption spectroscopy and electrospray ionisation mass spectrometry (ESI MS) to characterise the inherent protein metalation processes. Notably, Auoxo6 and Au₂phen produced stable protein adducts where one or more ??naked?? gold(I) ions are protein-coordinated; very characteristic is the case of cytochrome?c, which upon reaction with Auoxo6 or Au₂phen preferentially forms ??tetragold?? adducts with four protein-bound gold(I) ions. In turn, Aubipyc afforded monometalated protein adducts where the structural core of the gold(III) centre and its +3 oxidation state are conserved. Auranofin yielded protein derivatives containing the intact auranofin molecule. Additional studies were performed to assess the role played by a reducing environment in protein metalation. Overall, the approach adopted provides detailed insight into the formation of metallodrug?Cprotein derivatives and permits trends, peculiarities and mechanistic details of the underlying processes to be highlighted. In this respect, electrospray ionisation mass spectrometry is a very straightforward and informative research tool. The protein metalation processes investigated critically depend on the nature of both the metal compound and the interacting protein and also on the solution conditions used; thus, predicting with accuracy the nature and the amounts of the adducts formed for a given metallodrug?Cprotein pair is currently extremely difficult.