Vaccinia virus immune evasion: mechanisms, virulence and immunogenicity

Virus infection of mammalian cells is sensed by pattern recognition receptors and leads to an innate immune response that restricts virus replication and induces adaptive immunity. In response, viruses have evolved many countermeasures that enable them to replicate and be transmitted to new hosts, despite the host innate immune response. Poxviruses, such as vaccinia virus (VACV), have large DNA genomes and encode many proteins that are dedicated to host immune evasion. Some of these proteins are secreted from the infected cell, where they bind and neutralize complement factors, interferons, cytokines and chemokines. Other VACV proteins function inside cells to inhibit apoptosis or signalling pathways that lead to the production of interferons and pro-inflammatory cytokines and chemokines. In this review, these VACV immunomodulatory proteins are described and the potential to create more immunogenic VACV strains by manipulation of the gene encoding these proteins is discussed

Myrtucommulone from Myrtus communis exhibits potent anti-inflammatory effectiveness in vivo.

Myrtucommulone a nonprenylated acylphloroglucinol contained in the leaves of myrtle (Myrtus communis), has been reported to suppress the biosynthesis of eicosanoids by inhibition of 5-lipoxygenase and cyclooxygenase-1 in vitro and to inhibit the release of elastase and the formation of reactive oxygen species in activated polymorphonuclear leukocytes. Here, in view of the ability of MC to suppress typical proinflammatory cellular responses in vitro, we have investigated the effects of MC in in vivo models of inflammation. MC was administered to mice intraperitoneally, and paw edema and pleurisy were induced by the subplantar and intrapleural injection of carrageenan, respectively. MC (0.5, 1.5, and 4.5 mg/kg i.p.) reduced the development of mouse carrageenan-induced paw edema in a dose-dependent manner. Moreover, MC (4.5 mg/kg i.p. 30 min before and after carrageenan) exerted anti-inflammatory effects in the pleurisy model. In particular, 4 h after carrageenan injection in the pleurisy model, MC reduced: 1) the exudate volume and leukocyte numbers; 2) lung injury (histological analysis) and neutrophil infiltration (myeloperoxidase activity); 3) the lung intercellular adhesion molecule-1 and P-selectin immunohistochemical localization; 4) the cytokine levels (tumor necrosis factor-α and interleukin-1 β in the pleural exudate and their immunohistochemical localization in the lung; 5) the leukotriene B 4, but not prostaglandin E2, levels in the pleural exudates; and 6) lung peroxidation (thiobarbituric acid-reactant substance) and nitrotyrosine and poly (ADP-ribose) immunostaining. In conclusion, our results demonstrate that MC exerts potent anti-inflammatory effects in vivo and offer a novel therapeutic approach for the management of acute inflammation. Copyright © 2009 by The American Society for Pharmacology and Experimental Therapeutics

Floristic composition of weeds in different winter and summer covers.

The usage of cover crops is an adopted cultural measure that shows positive effects when associated with the no-till system and weed management. During the cycle of the plants there might be competition within them for water, solar radiation and nutrients and effects of allelopathic substances released by leaching, volatilization and/or root exudation in the environment might also coexist. The study aimed to quantify the floristic composition of weed species in an cultivated area with cover crops during winter and summer, for two years, 2011/12 and 2012/13, in an experimental area of UFSM, Campus of Frederico Westphalen ? RS state, Brazil. The treatments consisted of Italian ryegrass, wild radish, black oat, vetch, wheat and uncultivated, in winter, and, sorghum, sunflower, black velvet bean, dwarf velvet bean, gray velvet bean and green velvet bean in the summer. In the first year of the experiment, a diversity of weeds in winter was observed, especially occuring Stellaria media and Bowlesia incana. In summer, the weeds of higher importance were Ipomoea spp. and Bidens spp., both of utter importance in agricultural systems. Winter cover crops of wild radish and Italian ryegrass and summer cover crops of sorghum and sunflower provided a lower weed infestatio

Relative yield of wheat in coexistence with concurrent plants as indicator of competitiveness.

One of the factors that limit the yield of wheat is the weed competition, being the competitive potential of plants affected by their morphophysiological characteristics. The objective of this study was to determine the competitiveness of wheat when in coexistence with Italian ryegrass (Lolium multiflorum) and radish (Raphanus sativus) competitive plants or with wheat as simulator competition plant. There were realized four experiments in the greenhouse of the Agricultural Department of Environmental Sciences of the UFSM, Campus of Frederico Westphalen ? RS, during July to September, 2012. The treatments were arranged in a replacement series, in the proportions of 100:00 (wheat monoculture), 75:25, 50:50, 25:75 and 100:00 (competitor plant monoculture) for wheat plants (cv. Fundacep Cristalino) and for Italian ryegrass, radish and wheat (cv. BRS Guamirim) as competitor plants. The wheat is more competitive than Italian ryegrass in initial coexistence, even in the smallest proportion of plants. The radish when intercropped with wheat demonstrates similar competitive potential for environmental resources to the crop. There is mutual beneficial effect when wheat cultivars Fundacep Cristalino and BRS Guamirim coexisted, and each cultivar seems to have mechanism to avoid competition

Higher Fano manifolds

In this paper we address Fano manifolds with positive higher Chern characters. They are expected to enjoy stronger versions of several of the nice properties of Fano manifolds. For instance, they should be covered by higher dimensional rational varieties, and families of higher Fano manifolds over higher dimensional bases should admit meromorphic sections (modulo the Brauer obstruction). Aiming at finding new examples of higher Fano manifolds, we investigate positivity of higher Chern characters of rational homogeneous spaces. We determine which rational homogeneous spaces of Picard rank $1$ have positive second Chern character, and show that the only rational homogeneous spaces of Picard rank $1$ having positive second and third Chern characters are projective spaces and quadric hypersurfaces. We also classify Fano manifolds of large index having positive second and third Chern characters. We conclude by discussing conjectural characterizations of projective spaces and complete intersections in terms of these higher Fano conditions

Fertilizer Potential of Organic-Based Soil Amendments on cv. Sangiovese (V. vinifera L.) Vines: Preliminary Results

The intensification of highly specialized viticulture has led to a dramatic decrease of soil fertility that can be restored by increasing soil organic matter using organic fertilizers. The aim of the present experiment was to evaluate the effect of different organic amendments on vine vegetative growth and nutritional status, soil N availability and microbial biomass, as well as on yield and grape quality. The experiment was carried out in 2020 and 2021, on cv. Sangiovese (Vitis vinifera L.) vines grafted on 110 Richter (V. berlandieri × V. rupestris) planted in February 2019. Plants were fer-tilized yearly in spring with (1) mineral fertilization (MIN), (2) municipal organic waste compost (MOW), and (3) sewage sludge compost (SS). The application of SS increased nitrate availability in both years, while the supply of organic matter (no matter the source) enhanced soil microbial bio-mass content. Plant nutritional status was in the optimal range for all treatments, with an increase of N in SS and K in MOW. Fruit yield in 2020 was not influenced by treatments, while in 2021 it was enhanced by MIN and MOW, which also induced a higher berry quality. Plant vegetative growth was stimulated by the application of SS. In conclusion, from these preliminary results we observed a higher N availability as a consequence of SS supply that resulted in a higher plant biomass, but reduced yield and berry quality, supporting the theory that for vineyards, N should be carefully managed to reach an equilibrium between vegetative and reproductive activity

Glycogen Synthase Kinase-3β Inhibition Attenuates the Development of Bleomycin-Induced Lung Injury:

Glycogen synthase kinase-3 (GSK-3) is an ubiquitous serine-threonine protein kinase that participates in a multitude of cellular processes and has recently been implicated in the pathophysiology of a number of diseases. The aim of this study is to investigate the effects of TDZD-8, a potent and selective GSK-3β inhibitor, on the development of lung injury caused by administration of bleomycin (BLM). Mice subjected to intra-tracheal administration of BLM developed significant lung injury characterized by marked neutrophil infiltration and tissue edema. An increase in immunoreactivity to nitrotyrosine, iNOS, TNF-α and IL-1β was also observed in the lungs of BLM-treated mice. In contrast, administration of BLM-treated mice with TDZD-8 (1 mg/kg daily) significantly reduced (I) the degree of lung injury, (II) the increase in staining (immunohistochemistry) for myeloperoxidase (MPO), nitrotyrosine, iNOS, TNF-α and IL-1β and (III) the degree of apoptosis, as evaluated by Bax and Bcl-2 immunoreactivity and TUNEL staining. Taken together, these results clearly demonstrate treatment with the GSK-3β inhibitor TDZD-8 reduces the development of lung injury and inflammation induced by BLM in mice

Characterization of the pathophysiological role of CD47 in uveal melanoma

Uveal melanoma (UM) represents the most frequent primary intraocular tumor, however, limited therapeutic options are still available. We have previously shown that cluster of differentiation 47 (CD47) is significantly upregulated in UM cells following inflammatory stimuli and that it represents a predictor of disease progression. Here, we aimed to better characterize the pathophysiological role of CD47 in UM. We show that CD47 is not modulated at different cancer stages, although patients with the lowest expression of CD47 show significant better progression-free survival, after correcting for the presence of BAP1, GNAQ, and GNA11 mutations. By stratifying patients based on the expression of CD47 in the tumor, we observed that patients with high levels of CD47 have a significant increase in immune score as compared to patients with low levels of CD47. In particular, deconvolution analysis of infiltrating immune cell populations revealed that a significantly higher number of CD4+ and CD8+ T cells can be found in patients with high CD47 levels, with the most enriched populations being the Th2, Treg, and CD8+ Tcm cells. We also show that a large number of transcripts are significantly modulated between the groups of patients with high and low levels of CD47, with a significant enrichment of interferon IFN-alpha regulated genes. The results from this study may propel the development of anti-CD47 therapies for UM patients

GW0742, a high affinity PPAR-β/δ agonist reduces lung inflammation induced by bleomycin instillation in mice.

Peroxisome Proliferator-Activated Receptor β/δ belongs to a family of ligand-activated transcription factors. Recent data have clarified its metabolic roles and enhanced the potential role of this receptor as a pharmacological target. Moreover, although its role in acute inflammation remains unclear, being the nuclear receptor PPAR β/δ widely expressed in many tissues, including the vascular endothelium, we assume that the infiltration of PMNs into tissues, a prominent feature in inflammation, may also be related to PPAR β/δ. Mice subjected to intratracheal instillation of bleomycin (BLEO, 1 mg/kg), a glycopeptide produced by the bacterium Streptomyces verticillus, develop lung inflammation and injury characterized by a significant neutrophil infiltration and tissue oedema. Therefore, the aim of this study is to investigate the effects of GW0742, a synthetic high affinity PPAR β/δ agonist, and its possible role in preventing the advance of inflammatory and apoptotic processes induced by bleomycin, that long-term leads to the appearance of pulmonary fibrosis. Our data showed that GW0742-treatment (0.3 mg/Kg, 10% DMSO, i.p.) has therapeutic effects on pulmonary damage, decreasing many inflammatory and apoptotic parameters detected by measurement of: 1) cytokine production; 2) leukocyte accumulation, indirectly measured as decrease of myeloperoxidase (MPO) activity; 3) IκBα degradation and NF-κB nuclear translocation; 4) ERK phosphorylation; 5) stress oxidative by NO formation due to iNOS expression; 6) nitrotyrosine and PAR localization; 7) the degree of apoptosis, evaluated by Bax and Bcl2 balance, FAS ligand expression and TUNEL staining. Taken together, our results clearly show that GW0742 reduces the lung injury and inflammation due to the intratracheal BLEO-instillation in mice

The ground beetle Pseudoophonus rufipes gut microbiome is influenced by the farm management system

: Intensive conventional farm management, characterized by high agrochemicals input, could alter the composition of microbial communities with potential negative effects on both functional traits and the ecosystem services provided. In this study, we investigated the gut microbial composition of a high ecological relevance carabid Pseudoophonus rufipes, sampled in two fields subjected to conventional and organic management practices. Carabids' gut microbiota was analyzed via qPCR and NGS. Profound differences between the microbial composition of organic and conventional samples were detected: the abundance of Tenericutes and Proteobacteria was significant higher in organic and conventional samples, respectively. Spiroplasmataceae and Bifidobacteriaceae families were significantly more abundant in samples from organic management, while Enterococcaceae, Morganellaceae and Yersiniaceae were more abundant in samples from conventional management. The diverse gut microbial composition of insects between the two management systems is related to the pressure of environmental stressors and it may representing an important bioindication of ecological functions and services provided by a carabid species