Fungal strategies for dealing with environment- and agriculture-induced stresses

The Fungal Kingdom is responsible for many ecosystem services as well as many industrial and agricultural products. Nevertheless, how these fungal species function and carry out these services is dependent on their capacity to grow under different stress conditions caused by a variety of abiotic factors such as ionizing radiation, UV radiation, extremes of temperature, acidity and alkalinity, and environments of low nutritional status, low water activity, or polluted with, e.g. toxic metals or xenobiotics. This article reviews some natural or synthetic environments where fungi thrive under stress and have important impacts in agriculture and forestry.</p

Treating Cancer as an Infectious Disease—Viral Antigens as Novel Targets for Treatment and Potential Prevention of Tumors of Viral Etiology

Nearly 20% of human cancers worldwide have an infectious etiology with the most prominent examples being hepatitis B and C virus-associated hepatocellular carcinoma and human papilloma virus-associated cervical cancer. There is an urgent need to find new approaches to treatment and prevention of virus-associated cancers.Viral antigens have not been previously considered as targets for treatment or prevention of virus-associated cancers. We hypothesized that it was possible to treat experimental HPV16-associated cervical cancer (CC) and Hepatitis B-associated hepatocellular carcinoma (HCC) by targeting viral antigens expressed on cancer cells with radiolabeled antibodies to viral antigens. Treatment of experimental CC and HCC tumors with (188)Re-labeled mAbs to E6 and HBx viral proteins, respectively, resulted in significant and dose-dependent retardation of tumor growth in comparison with untreated mice or mice treated with unlabeled antibodies.This strategy is fundamentally different from the prior uses of radioimmunotherapy in oncology, which targeted tumor-associated human antigens and promises increased specificity and minimal toxicity of treatment. It also raises an exciting possibility to prevent virus-associated cancers in chronically infected patients by eliminating cells infected with oncogenic viruses before they transform into cancer

The second International Symposium on Fungal Stress:ISFUS

The topic of 'fungal stress' is central to many important disciplines, including medical mycology, chronobiology, plant and insect pathology, industrial microbiology, material sciences, and astrobiology. The International Symposium on Fungal Stress (ISFUS) brought together researchers, who study fungal stress in a variety of fields. The second ISFUS was held in May 8-11 2017 in Goiania, Goias, Brazil and hosted by the Instituto de Patologia Tropical e Satide Pablica at the Universidade Federal de Goias. It was supported by grants from CAPES and FAPEG. Twenty-seven speakers from 15 countries presented their research related to fungal stress biology. The Symposium was divided into seven topics: 1. Fungal biology in extreme environments; 2. Stress mechanisms and responses in fungi: molecular biology, biochemistry, biophysics, and cellular biology; 3. Fungal photobiology in the context of stress; 4. Role of stress in fungal pathogenesis; 5. Fungal stress and bioremediation; 6. Fungal stress in agriculture and forestry; and 7. Fungal stress in industrial applications. This article provides an overview of the science presented and discussed at ISFUS-2017. (C) 2017 British Mycological Society. Published by Elsevier Ltd. All rights reserved.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundacao de Amparo a Pesquisa do Estado de Goias of BrazilAlders English Serv, BR-74810908 Goiania, Go, BrazilUniv Fed Goias, Lab Biol Mol, Inst Ciencias Biol, BR-74690900 Goiania, Go, BrazilUniv Fed Sao Carlos, Dept Genet & Evolucao, Ctr Ciencias Biol & Saude, Lab Bioquim & Genet Aplicada, BR-90040060 Sao Carlos, SP, BrazilChinese Acad Sci, Shanghai Inst Plant Physiol & Ecol, CAS Key Lab Insect Dev & Evolutionary Biol, Shanghai 200032, Peoples R ChinaUniv Fed Rio Grande do Sul, Dept Mol Biol & Biotechnol, Ctr Biotechnol, BR-13565905 Porto Alegre, RS, BrazilUniv Saskatchewan, Coll Pharm & Nutr, Saskatoon, SK S7N 5E5, CanadaUniv Helsinki, Dept Agr Sci, POB 27, FI-00014 Helsinki, FinlandUniv Fed Rio de Janeiro, Inst Chem, BR-21941901 Rio De Janeiro, RJ, BrazilUniv Fed Goias, Inst Patol Trop & Saude Publ, BR-74605050 Goiania, Go, BrazilUniv Dundee, Sch Life Sci, Geomicrobiol Grp, Dundee DD1 5EH, ScotlandUniv Gottingen, Inst Microbiol & Genet, Dept Mol Microbiol & Genet, D-37077 Gottingen, GermanyUniv Gottingen, Gottingen Ctr Mol Biosci, D-37077 Gottingen, GermanyUniv Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Dept Anal Clin Toxicol & Bromatol, BR-14040903 Ribeirao Preto, SP, BrazilUniv Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Dept Ciencias Farmaceut, BR-14040903 Ribeirao Preto, SP, BrazilUniv Fed Sao Carlos, Dept Genet & Evolucao, Ctr Ciencias Biol & Saude, BR-13565905 Sao Carlos, SP, BrazilQueens Univ Belfast, Inst Global Food Secur, Sch Biol Sci, MBC, Belfast BT9 7BL, Antrim, North IrelandUtah State Univ, Dept Biol, Logan, UT 84322 USAGeisel Sch Med Dartmouth, Dept Mol & Syst Biol, Hanover, NH 03755 USAUniv Tuscia, Dept Ecol & Biol Sci DEB, I-01100 Viterbo, ItalyUniv Seville, Fac Biol, Dept Genet, Seville 41012, SpainUniv Estadual Paulista, Inst Quim, Dept Bioquim & Tecnol Quim, BR-14800060 Araraquara, SP, BrazilAIT Austrian Inst Technol GmbH, Ctr Hlth & Bioresources, Konrad Lorenz Str 24, A-3430 Tulin, AustriaCONICET Univ Nacl La Plata UNLP, Inst Invest Bioquim La Plata INIBIOLP, CCT La Plata Consejo Nacl Invest Cient & Tecn, Calles 60 & 120, RA-1900 La Plata, ArgentinaUniv Autonoma Metropolitana Iztapalapa, Dept Biotechnol, Mexico City 09340, DF, MexicoSwedish Univ Agr Sci, Uppsala Bioctr, Dept Forest Mycol & Plant Pathol, Box 7026, S-75007 Uppsala, SwedenUniv Estadual Maringa, Dept Biochem, BR-87020900 Maringa, PR, BrazilUniv Estadual Paulista, Inst Quim, Dept Bioquim & Tecnol Quim, BR-14800060 Araraquara, SP, BrazilFAPESP: 2010/06374-1FAPESP: 2013/50518-6FAPESP: 2014/01229-4CNPq: PQ2 302312/2011-0CNPq: PQ1D 308436/2014-8CAPES: PAEP 88881.123209/2016-01Fundacao de Amparo a Pesquisa do Estado de Goias of Brazil: 20171026700011

Pre-Clinical Evaluation of a 213Bi-Labeled 2556 Antibody to HIV-1 gp41 Glycoprotein in HIV-1 Mouse Models as a Reagent for HIV Eradication

Any strategy for curing HIV infection must include a method to eliminate viral-infected cells. Based on our earlier proof-of-principle results targeting HIV-1 infected cells with radiolabeled antibody (mAb) to gp41 viral antigen, we embarked on identifying a suitable candidate mAb for preclinical development.Among the several human mAbs to gp41 tested, mAb 2556 was found to have high affinity, reactivity with multimeric forms of gp41 present on both the surface of virus particles and cells expressing HIV-1 Env, and recognition of a highly conserved epitope of gp41 shared by all HIV-1 subtypes. Also, mAb 2556 was the best in competition with HIV-1+ serum antibodies, which is an extremely important consideration for efficacy in the treatment of HIV patients. When radiolabeled with alpha-emitting radionuclide 213-Bismuth ((213)Bi) - (213)Bi-2556 efficiently and specifically killed ACH-2 human lymphocytes chronically infected with HIV-1, and HIV-1 infected human peripheral blood mononuclear cells (hPBMCs). The number of binding sites for (213)Bi-2556 on the surface of the infected cells was >10(6). The in vivo experiments were performed in two HIV-1 mouse models--splenic and intraperitoneal. In both models, the decrease in HIV-1 infected hPBMCs from the spleens and peritoneum, respectively, was dose-dependent with the most pronounced killing of hPBMCs observed in the 100 µCi (213)Bi-2556 group (P = 0.01). Measurement of the blood platelet counts and gross pathology of the treated mice demonstrated the lack of toxicity for (213)Bi-2556.We describe the preclinical development of a novel radiolabeled mAb reagent that could potentially be part of an HIV eradication strategy that is ready for translation into the clinic as the next step in its development. As viral antigens are very different from "self" human antigens - this approach promises high selectivity, increased efficacy and low toxicity, especially in comparison to immunotoxins

Fungal Melanins Differ in Planar Stacking Distances

Melanins are notoriously difficult to study because they are amorphous, insoluble and often associated with other biological materials. Consequently, there is a dearth of structural techniques to study this enigmatic pigment. Current models of melanin structure envision the stacking of planar structures. X ray diffraction has historically been used to deduce stacking parameters. In this study we used X ray diffraction to analyze melanins derived from Cryptococcus neoformans, Aspergillus niger, Wangiella dermatitides and Coprinus comatus. Analysis of melanin in melanized C. neoformans encapsulated cells was precluded by the fortuitous finding that the capsular polysaccharide had a diffraction spectrum that was similar to that of isolated melanin. The capsular polysaccharide spectrum was dominated by a broad non-Bragg feature consistent with origin from a repeating structural motif that may arise from inter-molecular interactions and/or possibly gel organization. Hence, we isolated melanin from each fungal species and compared diffraction parameters. The results show that the inferred stacking distances of fungal melanins differ from that reported for synthetic melanin and neuromelanin, occupying intermediate position between these other melanins. These results suggest that all melanins have a fundamental diffracting unit composed of planar graphitic assemblies that can differ in stacking distance. The stacking peak appears to be a distinguishing universal feature of melanins that may be of use in characterizing these enigmatic pigments

Physico-Chemical Evaluation of Rationally Designed Melanins as Novel Nature-Inspired Radioprotectors

Melanin, a high-molecular weight pigment that is ubiquitous in nature, protects melanized microorganisms against high doses of ionizing radiation. However, the physics of melanin interaction with ionizing radiation is unknown.We rationally designed melanins from either 5-S-cysteinyl-DOPA, L-cysteine/L-DOPA, or L-DOPA with diverse structures as shown by elemental analysis and HPLC. Sulfur-containing melanins had higher predicted attenuation coefficients than non-sulfur-containing melanins. All synthetic melanins displayed strong electron paramagnetic resonance (2.14.10(18), 7.09.10(18), and 9.05.10(17) spins/g, respectively), with sulfur-containing melanins demonstrating more complex spectra and higher numbers of stable free radicals. There was no change in the quality or quantity of the stable free radicals after high-dose (30,000 cGy), high-energy ((137)Cs, 661.6 keV) irradiation, indicating a high degree of radical stability as well as a robust resistance to the ionizing effects of gamma irradiation. The rationally designed melanins protected mammalian cells against ionizing radiation of different energies.We propose that due to melanin's numerous aromatic oligomers containing multiple pi-electron system, a generated Compton recoil electron gradually loses energy while passing through the pigment, until its energy is sufficiently low that it can be trapped by stable free radicals present in the pigment. Controlled dissipation of high-energy recoil electrons by melanin prevents secondary ionizations and the generation of damaging free radical species

Protection of Melanized Cryptococcus neoformans from Lethal Dose Gamma Irradiation Involves Changes in Melanin's Chemical Structure and Paramagnetism

Certain fungi thrive in highly radioactive environments including the defunct Chernobyl nuclear reactor. Cryptococcus neoformans (C. neoformans), which uses L-3,4-dihydroxyphenylalanine (L-DOPA) to produce melanin, was used here to investigate how gamma radiation under aqueous aerobic conditions affects the properties of melanin, with the aim of gaining insight into its radioprotective role. Exposure of melanized fungal cell in aqueous suspensions to doses of γ-radiation capable of killing 50 to 80% of the cells did not lead to a detectable loss of melanin integrity according to EPR spectra of melanin radicals. Moreover, upon UV-visible (Xe-lamp) illumination of melanized cells, the increase in radical population was unchanged after γ-irradiation. Gamma-irradiation of frozen cell suspensions and storage of samples for several days at 77 K however, produced melanin modification noted by a reduced radical population and reduced photoresponse. More direct evidence for structural modification of melanin came from the detection of soluble products with absorbance maxima near 260 nm in supernatants collected after γ-irradiation of cells and cell-free melanin. These products, which include thiobarbituric acid (TBA)-reactive aldehydes, were also generated by Fenton reagent treatment of cells and cell-free melanin. In an assay of melanin integrity based on the metal (Bi+3) binding capacity of cells, no detectable loss in binding was detected after γ-irradiation. Our results show that melanin in C. neoformans cells is susceptible to some damage by hydroxyl radical formed in lethal radioactive aqueous environments and serves a protective role in melanized fungi that involves sacrificial breakdown