Therapeutic use of a cationic antimicrobial peptide from the spider Acanthoscurria gomesiana in the control of experimental candidiasis

<p>Abstract</p> <p>Background</p> <p>Antimicrobial peptides are present in animals, plants and microorganisms and play a fundamental role in the innate immune response. Gomesin is a cationic antimicrobial peptide purified from haemocytes of the spider <it>Acanthoscurria gomesiana</it>. It has a broad-spectrum of activity against bacteria, fungi, protozoa and tumour cells. <it>Candida albicans</it> is a commensal yeast that is part of the human microbiota. However, in immunocompromised patients, this fungus may cause skin, mucosal or systemic infections. The typical treatment for this mycosis comprises three major categories of antifungal drugs: polyenes, azoles and echinocandins; however cases of resistance to these drugs are frequently reported. With the emergence of microorganisms that are resistant to conventional antibiotics, the development of alternative treatments for candidiasis is important. In this study, we evaluate the efficacy of gomesin treatment on disseminated and vaginal candidiasis as well as its toxicity and biodistribution.</p> <p>Results</p> <p>Treatment with gomesin effectively reduced <it>Candida albicans </it>in the kidneys, spleen, liver and vagina of infected mice. The biodistribution of gomesin labelled with technetium-99 m showed that the peptide is captured in the kidneys, spleen and liver. Enhanced production of TNF-α, IFN-γ and IL-6 was detected in infected mice treated with gomesin, suggesting an immunomodulatory activity. Moreover, immunosuppressed and <it>C. albicans</it>-infected mice showed an increase in survival after treatment with gomesin and fluconazole. Systemic administration of gomesin was also not toxic to the mic</p> <p>Conclusions</p> <p>Gomesin proved to be effective against experimental <it>Candida albicans</it> infection. It can be used as an alternative therapy for candidiasis, either alone or in combination with fluconazole. Gomesin's mechanism is not fully understood, but we hypothesise that the peptide acts through the permeabilisation of the yeast membrane leading to death and/or releasing the yeast antigens that trigger the host immune response against infection. Therefore, data presented in this study reinforces the potential of gomesin as a therapeutic antifungal agent in both humans and animals.</p

Integrative Model of Oxidative Stress Adaptation in the Fungal Pathogen Candida albicans

Acknowledgments We are grateful to the Ian Fraser Cytometry Centre and our Mass Spetrometry and qPCR Facilities for help with the flow cytometry, glutathione and qRT-PCR assays, respectively. We also thank our many colleagues in the CRISP Consortium and in the medical mycology and systems biology communities for insightful discussions. Funding: This work was supported by the CRISP project (Combinatorial Responses In Stress Pathways), which was funded by the UK Biotechnology and Biological Research Council (www.bbsrc.ac.uk): AJPB, KH, CG, ADM, NARG, MT, MCR. (Research Grants; BB/F00513X/1, BB/F005210/1-2). AJPB and JQ received additional support from the BBSRC (Research Grants; BB/K016393/1; BB/K017365/1). NARG and AJPB were also supported by the Wellcome Trust (www.wellcome.ac.uk), (Grants: 080088; 097377). AJPB was also supported by the European Research Council (http://erc.europa.eu/), (STRIFE Advanced Grant; ERC-2009-AdG-249793). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

Characterization of proteinases from the midgut of Rhipicephalus (Boophilus) microplus involved in the generation of antimicrobial peptides

Peer reviewedPublisher PD

Enzymatic Synthesis of a Novel Pterostilbene α-Glucoside by the Combination of Cyclodextrin Glucanotransferase and Amyloglucosidase

The synthesis of a novel α-glucosylated derivative of pterostilbene was performed by a transglycosylation reaction using starch as glucosyl donor, catalyzed by cyclodextrin glucanotransferase (CGTase) from Thermoanaerobacter sp. The reaction was carried out in a buffer containing 20% (v/v) DMSO to enhance the solubility of pterostilbene. Due to the formation of several polyglucosylated products with CGTase, the yield of monoglucoside was increased by the treatment with a recombinant amyloglucosidase (STA1) from Saccharomyces cerevisiae (var. diastaticus). This enzyme was not able to hydrolyze the linkage between the glucose and pterostilbene. The monoglucoside was isolated and characterized by combining ESI-MS and 2D-NMR methods. Pterostilbene α-d-glucopyranoside is a novel compound. The α-glucosylation of pterostilbene enhanced its solubility in water to approximately 0.1 g/L. The α-glucosylation caused a slight loss of antioxidant activity towards ABTS˙+ radicals. Pterostilbene α-d-glucopyranoside was less toxic than pterostilbene for human SH-S5Y5 neurons, MRC5 fibroblasts and HT-29 colon cancer cells, and similar for RAW 264.7 macrophages.This research was funded by the Spanish Ministry of Economy and Competitiveness (Grants BIO2016-76601-C3-1-R and BIO2016-76601-C3-3-R).Peer reviewe

Short-term low-severity spring grassland fire impacts on soil extractable elements and soil ratios in Lithuania.

Spring grassland fires are common in boreal areas as a consequence of slash and burn agriculture used to remove dry grass to increase soil nutrient properties and crop production. However, fewworks have investigated fire impacts on these grassland ecosystems, especially in the immediate period after the fire. The objective of this work was to study the short-termimpacts of a spring grassland fire in Lithuania. Four days after the firewe established a 400 m2 sampling grid within the burned area and in an adjacent unburned area with the same topographical, hydrological and pedological characteristics. Wecollected topsoil samples immediately after the fire (0 months), 2, 5, 7 and 9 months after the fire. We analysed soil pH, electrical conductivity (EC), major nutrients including calcium(Ca), magnesium(Mg), sodium(Na), and potassium(K), and theminor elements aluminium(Al), manganese (Mn), iron (Fe) and zinc (Zn). We also calculated the soil Na and K adsorption ratio (SPAR), Ca:Mg and Ca:Al. The results showed that this low-severity grassland fire significantly decreased soil pH, Al, and Mn but increased EC, Ca,Mg, and K,. There was no effect on Na, Fe, and Zn. Therewas a decrease of EC, Ca,Mg, and Na from 0months after the fire until 7 months after the fire,with an increase during the last sampling period. Fire did not significantly affect SPAR. Ca:Mg decreased significantly immediately after the fire, but not to critical levels. Ca:Al increased after the fire, reducing the potential effects of Al on plants. Overall, fire impactsweremainly limited to the immediate period after the fire

Chromatin regulation by Histone H4 acetylation at Lysine 16 during cell death and differentiation in the myeloid compartment

Histone H4 acetylation at Lysine 16 (H4K16ac) is a key epigenetic mark involved in gene regulation, DNA repair and chromatin remodeling, and though it is known to be essential for embryonic development, its role during adult life is still poorly understood. Here we show that this lysine is massively hyperacetylated in peripheral neutrophils. Genome-wide mapping of H4K16ac in terminally differentiated blood cells, along with functional experiments, supported a role for this histone post-translational modification in the regulation of cell differentiation and apoptosis in the hematopoietic system. Furthermore, in neutrophils, H4K16ac was enriched at specific DNA repeats. These DNA regions presented an accessible chromatin conformation and were associated with the cleavage sites that generate the 50 kb DNA fragments during the first stages of programmed cell death. Our results thus suggest that H4K16ac plays a dual role in myeloid cells as it not only regulates differentiation and apoptosis, but it also exhibits a non-canonical structural role in poising chromatin for cleavage at an early stage of neutrophil cell death

Carbon sequestration potential of second-growth forest regeneration in the Latin American tropics

Regrowth of tropical secondary forests following complete or nearly complete removal of forest vegetation actively stores carbon in aboveground biomass, partially counterbalancing carbon emissions from deforestation, forest degradation, burning of fossil fuels, and other anthropogenic sources. We estimate the age and spatial extent of lowland second-growth forests in the Latin American tropics and model their potential aboveground carbon accumulation over four decades. Our model shows that, in 2008, second-growth forests (1 to 60 years old) covered 2.4 million km2 of land (28.1%of the total study area).Over 40 years, these lands can potentially accumulate a total aboveground carbon stock of 8.48 Pg C (petagrams of carbon) in aboveground biomass via low-cost natural regeneration or assisted regeneration, corresponding to a total CO2 sequestration of 31.09 Pg CO2. This total is equivalent to carbon emissions from fossil fuel use and industrial processes in all of Latin America and the Caribbean from1993 to 2014. Ten countries account for 95% of this carbon storage potential, led by Brazil, Colombia, Mexico, and Venezuela. We model future land-use scenarios to guide national carbon mitigation policies. Permitting natural regeneration on 40% of lowland pastures potentially stores an additional 2.0 Pg C over 40 years. Our study provides information and maps to guide national-level forest-based carbon mitigation plans on the basis of estimated rates of natural regeneration and pasture abandonment. Coupled with avoided deforestation and sustainable forestmanagement, natural regeneration of second-growth forests provides a low-costmechanism that yields a high carbon sequestration potential with multiple benefits for biodiversity and ecosystem services. © 2016 The Authors

Intraerythrocytic stages of Plasmodium falciparum biosynthesize menaquinone

Herein, we show that intraerythrocytic stages of Plasmodium falciparum have an active pathway for biosynthesis of menaquinone. Kinetic assays confirmed that plasmodial menaquinone acts at least in the electron transport. Similarly to Escherichia coli, we observed increased levels of menaquinone in parasites kept under anaerobic conditions. Additionally, the mycobacterial inhibitor of menaquinone synthesis Ro 48-8071 also suppressed menaquinone biosynthesis and growth of parasites, although off-targets may play a role in this growth-inhibitory effect. Due to its absence in humans, the menaquinone biosynthesis can be considered an important drug target for malaria. (c) 2010 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)FAPESPConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)National Institutes of Health, NIAID/NIH, USA[AI049151]U.S. National Institutes of Health (NIH

Sodium Nitroprusside Treatment of Clozapine-Refractory Schizophrenia

Univ Sao Paulo, Sao Paulo, BrazilNatl Inst Sci & Technol Translat Med, Sao Paulo, BrazilUniv Fed Rio Grande do Norte, Rio Grande Do Norte, BrazilUniv Rio Grande Sul, Rio Grande Do Sul, BrazilNatl Inst Sci & Technol Translat Med, Rio Grande Do Sul, BrazilUniv Fed Sao Paulo, Sao Paulo, BrazilSchizophrenia Program, Sao Paulo, BrazilInterdisciplinary Lab Clin Neurosci, Sao Paulo, BrazilUniv Alberta, Dept Psychiat, Neurochem Res Unit, Edmonton, AB T6G 2M7, CanadaAlberta Hosp, Alberta Hlth Serv, Ctr Psychiat Assessment & Therapeut, Edmonton, AB, CanadaUniv Fed Sao Paulo, Sao Paulo, BrazilWeb of Scienc