| 1. |
- Zamora, Juan Carlos, et al.
(författare)
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Considerations and consequences of allowing DNA sequence data as types of fungal taxa
- 2018
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Ingår i: IMA Fungus. - : INT MYCOLOGICAL ASSOC. - 2210-6340 .- 2210-6359. ; 9:1, s. 167-185
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Tidskriftsartikel (refereegranskat)abstract
- Nomenclatural type definitions are one of the most important concepts in biological nomenclature. Being physical objects that can be re-studied by other researchers, types permanently link taxonomy (an artificial agreement to classify biological diversity) with nomenclature (an artificial agreement to name biological diversity). Two proposals to amend the International Code of Nomenclature for algae, fungi, and plants (ICN), allowing DNA sequences alone (of any region and extent) to serve as types of taxon names for voucherless fungi (mainly putative taxa from environmental DNA sequences), have been submitted to be voted on at the 11th International Mycological Congress (Puerto Rico, July 2018). We consider various genetic processes affecting the distribution of alleles among taxa and find that alleles may not consistently and uniquely represent the species within which they are contained. Should the proposals be accepted, the meaning of nomenclatural types would change in a fundamental way from physical objects as sources of data to the data themselves. Such changes are conducive to irreproducible science, the potential typification on artefactual data, and massive creation of names with low information content, ultimately causing nomenclatural instability and unnecessary work for future researchers that would stall future explorations of fungal diversity. We conclude that the acceptance of DNA sequences alone as types of names of taxa, under the terms used in the current proposals, is unnecessary and would not solve the problem of naming putative taxa known only from DNA sequences in a scientifically defensible way. As an alternative, we highlight the use of formulas for naming putative taxa (candidate taxa) that do not require any modification of the ICN.
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| 2. |
- Lara-Gonzalez, Samuel, et al.
(författare)
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Substrate-induced dimerization of engineered monomeric variants of triosephosphate isomerase from trichomonas vaginalis
- 2015
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- The dimeric nature of triosephosphate isomerases (TIMs) is maintained by an extensive surface area interface of more than 1600 Å2. TIMs from Trichomonas vaginalis (TvTIM) are held in their dimeric state by two mechanisms: A ball and socket interaction of residue 45 of one subunit that fits into the hydrophobic pocket of the complementary subunit and by swapping of loop 3 between subunits. TvTIMs differ from other TIMs in their unfolding energetics. In TvTIMs the energy necessary to unfold a monomer is greater than the energy necessary to dissociate the dimer. Herein we found that the character of residue I45 controls the dimer-monomer equilibrium in TvTIMs. Unfolding experiments employing monomeric and dimeric mutants led us to conclude that dimeric TvTIMs unfold following a four state model denaturation process whereas monomeric TvTIMs follow a three state model. In contrast to other monomeric TIMs, monomeric variants of TvTIM1 are stable and unexpectedly one of them (I45A) is only 29-fold less active than wild-type TvTIM1. The high enzymatic activity of monomeric TvTIMs contrast with the marginal catalytic activity of diverse monomeric TIMs variants. The stability of the monomeric variants of TvTIM1 and the use of cross-linking and analytical ultracentrifugation experiments permit us to understand the differences between the catalytic activities of TvTIMs and other marginally active monomeric TIMs. As TvTIMs do not unfold upon dimer dissociation, herein we found that the high enzymatic activity of monomeric TvTIM variants is explained by the formation of catalytic dimeric competent species assisted by substrate binding.
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| 3. |
- Sánchez-Sandoval, Maria E., et al.
(författare)
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Phospholipid signaling pathway in Capsicum chinense suspension cells as a key response to consortium infection
- 2021
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Ingår i: BMC Plant Biology. - : Springer Science and Business Media LLC. - 1471-2229. ; 21
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Tidskriftsartikel (refereegranskat)abstract
- Background: Mexico is considered the diversification center for chili species, but these crops are susceptible to infection by pathogens such as Colletotrichum spp., which causes anthracnose disease and postharvest decay in general. Studies have been carried out with isolated strains of Colletotrichum in Capsicum plants; however, under growing conditions, microorganisms generally interact with others, resulting in an increase or decrease of their ability to infect the roots of C. chinense seedlings and thus, cause disease. Results: Morphological changes were evident 24 h after inoculation (hai) with the microbial consortium, which consisted primarily of C. ignotum. High levels of diacylglycerol pyrophosphate (DGPP) and phosphatidic acid (PA) were found around 6 hai. These metabolic changes could be correlated with high transcription levels of diacylglycerol-kinase (CchDGK1 and CchDG31) at 3, 6 and 12 hai and also to pathogen gene markers, such as CchPR1 and CchPR5. Conclusions: Our data constitute the first evidence for the phospholipids signalling events, specifically DGPP and PA participation in the phospholipase C/DGK (PI-PLC/DGK) pathway, in the response of Capsicum to the consortium, offering new insights on chilis’ defense responses to damping-off diseases.
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| 4. |
- Argüelles, Nancy, et al.
(författare)
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Design, synthesis, and docking of highly hypolipidemic agents: Schizosaccharomyces pombe as a new model for evaluating α-asarone-based HMG-CoA reductase inhibitors
- 2010
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Ingår i: Bioorganic and Medicinal Chemistry. - : Elsevier BV. - 0968-0896. ; 18, s. 4238-4248
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Tidskriftsartikel (refereegranskat)abstract
- A series of α-asarone-based analogues was designed by conducting docking experiments with published crystal structures of human HMG-CoA reductase. Indeed, synthesis and evaluation of this series showed a highly hypocholesterolemic in vivo activity in a murine model, as predicted by previous docking studies. In agreement with this model, the polar groups attached to the benzene ring could play a key role in the enzyme binding and probably also in its biological activity, mimicking the HMG-moiety of the natural substrate. The hypolipidemic action mechanism of these compounds was investigated by developing a simple, efficient, and novel model for determining HMG-CoA reductase inhibition. The partial purification of the enzyme from Schizosaccharomyces pombe allowed for testing of α-asarone- and fibrate-based analogues, resulting in positive and significant inhibitory activity. © 2010 Elsevier Ltd. All rights reserved.
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| 5. |
- Mehmedovic, Majda, et al.
(författare)
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Disease causing mutation (P178L) in mitochondrial transcription factor A results in impaired mitochondrial transcription initiation
- 2022
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Ingår i: Biochimica Et Biophysica Acta-Molecular Basis of Disease. - : Elsevier BV. - 0925-4439 .- 1879-260X. ; 1868:10
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Tidskriftsartikel (refereegranskat)abstract
- Mitochondrial transcription factor A (TFAM) is essential for the maintenance, expression, and packaging of mitochondrial DNA (mtDNA). Recently, a pathogenic homozygous variant in TFAM (P178L) has been associated with a severe mtDNA depletion syndrome leading to neonatal liver failure and early death. We have performed a biochemical characterization of the TFAM variant P178L in order to understand the molecular basis for the pathogenicity of this mutation. We observe no effects on DNA binding, and compaction of DNA is only mildly affected by the P178L amino acid change. Instead, the mutation severely impairs mtDNA transcription initiation at the mitochondrial heavy and light strand promoters. Molecular modeling suggests that the P178L mutation affects promoter sequence recognition and the interaction between TFAM and the tether helix of POLRMT, thus explaining transcription initiation deficiency.
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| 6. |
- Andrade-Pavón, Dulce, et al.
(författare)
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Inhibition of recombinant enzyme 3-hydroxy-3-methylglutaryl-CoA reductase from Candida glabrata by α-asarone-based synthetic compounds as antifungal agents
- 2019
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Ingår i: Journal of Biotechnology. - : Elsevier BV. - 0168-1656 .- 1873-4863. ; 292, s. 64-67
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Tidskriftsartikel (refereegranskat)abstract
- Due to increasing resistance of Candida species to antifungal drugs, especially azoles, new drugs are needed. The proposed compounds 3 and 4 are analogous to α-asarone (2), a naturally occurring potent inhibitor of HMGR with hypolipidemic and antifungal activity. We used the recombinant enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase of Candida glabrata (CgHMGR) as a model to test the effectiveness of the test compounds. Compounds 3 and 4 demonstrated inhibitory kinetics, having lower IC 50 values (42.65 μM and 28.77 μM, respectively) than compound 2 (>100 μM). The docking studies showed better binding energies for compounds 3 and 4 (−5.35 and −6.1 kcal/mol, respectively) than for compound 2 (−4.53 kcal/mol). These findings suggest that the tested compounds are better than their natural analogue. Plaque assays were performed on the C. glabrata strain CBS138 by applying ergosterol or cholesterol to evaluate the possible reversal of the inhibition induced by compounds 2, 3 and 4. Inhibition was easily suppressed in all three cases, recovering the viability of C. glabrata. These results reveal that the CgHMGR model is excellent for testing antifungals. Compound 4 produced the best effect and is herein proposed as a new potent antifungal agent.
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| 7. |
- Andrade-Pavón, Dulce, et al.
(författare)
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Inhibitors of 3-Hydroxy-3-methylglutaryl Coenzyme A Reductase Decrease the Growth, Ergosterol Synthesis and Generation of petite Mutants in Candida glabrata and Candida albicans
- 2023
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Ingår i: International Journal of Molecular Sciences. - 1661-6596 .- 1422-0067. ; 24:23
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Tidskriftsartikel (refereegranskat)abstract
- Candida glabrata and Candida albicans, the most frequently isolated candidiasis species in the world, have developed mechanisms of resistance to treatment with azoles. Among the clinically used antifungal drugs are statins and other compounds that inhibit 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR), resulting in decreased growth and ergosterol levels in yeasts. Ergosterol is a key element for the formation of the yeast cell membrane. However, statins often cause DNA damage to yeast cells, facilitating mutation and drug resistance. The aim of the current contribution was to synthesize seven series of compounds as inhibitors of the HMGR enzyme of Candida ssp., and to evaluate their effect on cellular growth, ergosterol synthesis and generation of petite mutants of C. glabrata and C. albicans. Compared to the reference drugs (fluconazole and simvastatin), some HMGR inhibitors caused lower growth and ergosterol synthesis in the yeast species and generated fewer petite mutants. Moreover, heterologous expression was achieved in Pichia pastoris, and compounds 1a, 1b, 6g and 7a inhibited the activity of recombinant CgHMGR and showed better binding energy values than for α-asarone and simvastatin. Thus, we believe these are good candidates for future antifungal drug development.
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| 8. |
- Andrade-Pavón, Dulce, et al.
(författare)
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The 3-hydroxy-3-methylglutaryl coenzyme-A reductases from fungi: A proposal as a therapeutic target and as a study model
- 2014
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Ingår i: Revista Iberoamericana de Micologia. - : Elsevier BV. - 1130-1406 .- 2173-9188. ; 31, s. 81-85
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Tidskriftsartikel (refereegranskat)abstract
- The enzyme 3-hydroxy-3-methylglutaryl coenzyme-A reductase (HMGR) catalyzes the conversion of HMG-Co-A into mevalonate. This step is the limiting point for the synthesis of cholesterol in mammals and ergosterol in fungi. We describe in this article the genome organization of HMGR coding genes and those deduced from different fungi, recount the evidence showing statins as HMGR inhibitors for ergosterol synthesis and its effect in yeast viability, and propose fungal HMGR (HMGRf) as a model to study the use of pharmaceutical compounds to inhibit cholesterol and ergosterol synthesis. Bibliographical search and bioinformatic analyses were performed and discussed. HMGRfs belong to the class I with a high homology in the catalytic region. The sterol biosynthetic pathway in humans and fungi share many enzymes in the initial steps (such as the HMGR enzyme), but in the last steps enzymes are different rendering the two final products: cholesterol in mammals and ergosterol in fungi. With regards to inhibitors such as statins and other compounds, these affect also fungal viability. Since HMGR from Schizosaccharomyces pombe and Ustilago maydis are very similar to the human HMGR in the catalytic regions, we propose that fungal enzymes can be used to test inhibitors for a potential use in humans. We consider that HMGRf is a good therapeutic target to design and test new antifungal compounds.This manuscript is part of the series of works presented at the "V International Workshop: Molecular genetic approaches to the study of human pathogenic fungi" (Oaxaca, Mexico, 2012). © 2013 Revista Iberoamericana de Micología.
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| 9. |
- González-Mendoza, Victor M., et al.
(författare)
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Biochemical characterization of phospholipases C from Coffea arabica in response to aluminium stress
- 2020
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Ingår i: Journal of Inorganic Biochemistry. - : Elsevier BV. - 0162-0134 .- 1873-3344. ; 204
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Tidskriftsartikel (refereegranskat)abstract
- Signal transduction in plants determines their successful adaptation to diverse stress factors. Our group employed suspension cells to study the phosphoinositide pathway, which is triggered by aluminium stress. We investigated about members of the PI-specific phospholipase C (PLC) family and evaluated their transcription profiles in Coffea arabica (Ca) suspension cells after 14 days of culture when treated or not with 100 μM AlCl3. The four CaPLC1-4 members showed changes in their transcript abundance upon AlCl3 treatment. The expression profiles of CaPLC1/2 exhibited a rapid and transitory increase in abundance. In contrast, CaPLC3 and CaPLC4 showed that transcript levels were up-regulated in short times (at 30 s), while only CaPLC4 kept high levels and CaPLC3 was reduced to basal after 3 h of treatment. CaPLC proteins were heterologously expressed, and CaPLC2 and CaPLC4 were tested for in vitro activity in the presence or absence of AlCl3 and compared to Arabidopsis PLC2 (AtPLC2). A crude extract was isolated from coffee cells. CaPLC2 showed a similar inhibition (30%) as in AtPLC2 and in the crude extract, while in CaPLC4, the activity was enhanced by AlCl3. Additionally, we visualized the yellow fluorescent protein PH domain of human PLCδ1 (YFP-PHPLCδ1) subcellular localization in cells that were treated or not with AlCl3. In non-treated cells, we observed a polar fluorescence signal towards the fused membrane. However, when cells were treated with AlCl3, these signals were disrupted. Finally, this is the first time that PLC activity has been shown to be stimulated in vitro by AlCl3.
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| 10. |
- Gonzalez-Mendoza, V. M., et al.
(författare)
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Phospholipases C and D and Their Role in Biotic and Abiotic Stresses
- 2021
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Ingår i: Plants-Basel. - : MDPI AG. - 2223-7747. ; 10:5
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Tidskriftsartikel (refereegranskat)abstract
- Plants, as sessile organisms, have adapted a fine sensing system to monitor environmental changes, therefore allowing the regulation of their responses. As the interaction between plants and environmental changes begins at the surface, these changes are detected by components in the plasma membrane, where a molecule receptor generates a lipid signaling cascade via enzymes, such as phospholipases (PLs). Phospholipids are the key structural components of plasma membranes and signaling cascades. They exist in a wide range of species and in different proportions, with conversion processes that involve hydrophilic enzymes, such as phospholipase-C (PLC), phospholipase-D (PLD), and phospholipase-A (PLA). Hence, it is suggested that PLC and PLD are highly conserved, compared to their homologous genes, and have formed clusters during their adaptive history. Additionally, they generate responses to different functions in accordance with their protein structure, which should be reflected in specific signal transduction responses to environmental stress conditions, including innate immune responses. This review summarizes the phospholipid systems associated with signaling pathways and the innate immune response.
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