RESUMO
Rhodosporidium toruloides is a novel cell factory used to synthesis carotenoids, biosurfactants, and biofuel feedstocks. However, research on R. toruloides has generally centred on the manufacture of biochemicals, while analyses of its longevity have received scant attention. Understanding of R. toruloides longevity under different nutrient conditions could help to improve its biotechnological significance and metabolite production. Glucosylglycerol (GG) and proline are osmoprotectants that could revert the harmful effects of environmental stress. This study examined how GG and proline affect R. toruloides strain longevity under glucose nutrimental stress. Herein, we provide evidence that GG and proline enhance cell performance and viability. These compatible solutes neutralises the pro-ageing effects of high glucose (10% glucose) on the yeast cell and reverse its cellular stress. GG exhibits the greatest impact on lifespan extension at 100 mM, whereas proline exerts effect at 2 mM. Our data reveal that these compounds significantly affect the culture medium osmolarity. Moreso, GG and proline decreased ROS production and mitohormetic lifespan regulation, respectively. The data indicates that these solutes (proline and GG) support the longevity of R. toruloides at a pro-ageing high glucose culture condition.
Assuntos
Glucose , Longevidade , Rhodotorula , Glucose/farmacologia , Glucose/metabolismo , Glucosídeos/farmacologiaRESUMO
Viruses utilize host lipids to promote the viral life cycle, but much remains unknown as to how this is regulated. Zinc is a critical element for life, and few studies have linked zinc to lipid homeostasis. We demonstrated that Caenorhabditis elegans infection by Orsay virus is dependent upon lipids and that mutation of the master regulator of lipid biosynthesis, sbp-1, reduced Orsay virus RNA levels by ~236-fold. Virus infection could be rescued by dietary supplementation with lipids downstream of fat-6/fat-7. Mutation of a zinc transporter encoded by sur-7, which suppresses the lipid defect of sbp-1, also rescued Orsay virus infection. Furthermore, reducing zinc levels by chemical chelation in the sbp-1 mutant also increased lipids and rescued Orsay virus RNA levels. Finally, increasing zinc levels by dietary supplementation led to an ~1,620-fold reduction in viral RNA. These findings provide insights into the critical interactions between zinc and host lipids necessary for virus infection. IMPORTANCE Orsay virus is the only known natural virus pathogen of Caenorhabditis elegans, which shares many evolutionarily conserved pathways with humans. We leveraged the powerful genetic tractability of C. elegans to characterize a novel interaction between zinc, lipids, and virus infection. Inhibition of the Orsay virus replication in the sbp-1 mutant animals, explained by the lipid depletion, can be rescued by a genetic and pharmacological approach that reduces the zinc accumulation and rescues the lipid levels in this mutant animal. Interestingly, the human ortholog of sbp-1, srebp-1, has been reported to play a role for virus infection, and zinc has been shown to inhibit the virus replication of multiple viruses. However, the mechanism through which zinc is acting is not well understood. These results suggest that the lipid regulation mediated by zinc may play a relevant role during mammalian virus infection.
Assuntos
Proteínas de Caenorhabditis elegans , Nodaviridae , Viroses , Vírus , Animais , Humanos , Caenorhabditis elegans , Zinco/metabolismo , Nodaviridae/genética , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Vírus/genética , RNA Viral/genética , RNA Viral/metabolismo , Lipídeos , Mamíferos/genéticaRESUMO
Quercetin is a flavonoid with promising therapeutic applications; nonetheless, the phenotype exerted in some diseases is contradictory. For instance, anticancer properties may be explained by a cytotoxic mechanism, whereas antioxidant-related neuroprotection is a pro-survival process. According to the available literature, quercetin exerts a redox interaction with the electron transport chain (ETC) in the mitochondrion, affecting its membrane potential. It also affects ATP generation by oxidative phosphorylation, where ATP deprivation could partly explain its cytotoxic effect. Moreover, quercetin may support the generation of free radicals through redox reactions, causing a prooxidant effect. The nutrimental stress and prooxidant effect induced by quercetin might promote pro-survival properties such as antioxidant processes. Thus, in this review, we discuss the evidence supporting that quercetin redox interaction with the ETC could explain its beneficial and toxic properties.
RESUMO
The Crabtree effect molecular regulation comprehension could help to improve ethanol production with biotechnological purposes and a better understanding of cancer etiology due to its similarity with the Warburg effect. Snf1p/Hxk2p/Mig1p pathway has been linked with the transcriptional regulation of the hexose transporters and phenotypes associated with the Crabtree effect. Nevertheless, direct evidence linking the genetic control of the hexose transporters with modulation of the Crabtree effect phenotypes by the Snf1p/Hxk2p/Mig1p pathway is still lacking. In this sense, we provide evidence that SNF1 and HXK2 genes deletion affects exponential growth, mitochondrial respiration, and transcript levels of hexose transporters in a glucose-dependent manner. The Vmax of the hexose transporters with the high transcript levels was correlated positively with the exponential growth and negatively with the mitochondrial respiration. HXT2 gene transcript levels were the most affected by the deletion of the SNF1/HXK2/MIG1 pathway. Deleting the orthologous genes SNF1 and HXK2 in Kluyveromyces marxianus (Crabtree negative yeast) has an opposite effect compared to Saccharomyces cerevisiae in growth and mitochondrial respiration. Overall, these results indicate that the SNF1/HXK2/MIG1 pathway regulates transcript levels of the hexose transporters, which shows an association with the exponential growth and mitochondrial respiration in a glucose-dependent manner.
Assuntos
Hexoquinase , Proteínas Serina-Treonina Quinases , Proteínas Repressoras , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae , Glucose/metabolismo , Hexoquinase/genética , Hexoquinase/metabolismo , Proteínas de Transporte de Monossacarídeos/genética , Proteínas de Transporte de Monossacarídeos/metabolismo , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Respiração , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismoRESUMO
The antioxidant phenotype caused by resveratrol has been recognized as a key piece in the health benefits exerted by this phytochemical in diseases related to aging. It has recently been proposed that a mitochondrial pro-oxidant mechanism could be the cause of resveratrol antioxidant properties. In this regard, the hypothesis that resveratrol impedes electron transport to complex III of the electron transport chain as its main target suggests that resveratrol could increase reactive oxygen species (ROS) generation through reverse electron transport or by the semiquinones formation. This idea also explains that cells respond to resveratrol oxidative damage, inducing their antioxidant systems. Moreover, resveratrol pro-oxidant properties could accelerate the aging process, according to the free radical theory of aging, which postulates that organism's age due to the accumulation of the harmful effects of ROS in cells. Nonetheless, there is no evidence linking the chronological lifespan (CLS) shorten occasioned by resveratrol with a pro-oxidant mechanism. Hence, this study aimed to evaluate whether resveratrol shortens the CLS of Saccharomyces cerevisiae due to a pro-oxidant activity. Herein, we provide evidence that supplementation with 100 µM of resveratrol at 5% glucose: (1) shortened the CLS of ctt1Δ and yap1Δ strains; (2) decreased ROS levels and increased the catalase activity in WT strain; (3) maintained unaffected the ROS levels and did not change the catalase activity in ctt1Δ strain; and (4) lessened the exponential growth of ctt1Δ strain, which was restored with the adding of reduced glutathione. These results indicate that resveratrol decreases CLS by a pro-oxidant mechanism.
Assuntos
Longevidade , Saccharomyces cerevisiae , Antioxidantes/farmacologia , Catalase/metabolismo , Catalase/farmacologia , Glucose/farmacologia , Longevidade/genética , Estresse Oxidativo , Espécies Reativas de Oxigênio , Resveratrol/farmacologia , Saccharomyces cerevisiae/genéticaRESUMO
Quercetin is a flavonol ubiquitously present in fruits and vegetables that shows a potential therapeutic use in non-transmissible chronic diseases, such as cancer and diabetes. Although this phytochemical has shown promising health benefits, the molecular mechanism behind this compound is still unclear. Interestingly, quercetin displays toxic properties against phylogenetically distant organisms such as bacteria and eukaryotic cells, suggesting that its molecular target resides on a highly conserved pathway. The cytotoxicity of quercetin could be explained by energy depletion occasioned by mitochondrial respiration impairment and its concomitant pleiotropic effect. Thereby, the molecular basis of quercetin cytotoxicity could shed light on potential molecular mechanisms associated with its health benefits. Nonetheless, the evidence supporting this hypothesis is still lacking. Thus, this study aimed to evaluate whether quercetin supplementation affects mitochondrial respiration and whether this is related to quercetin cytotoxicity. Saccharomyces cerevisiae was used as a study model to assess the effect of quercetin on energetic metabolism. Herein, we provide evidence that quercetin supplementation: (1) decreased the exponential growth of S. cerevisiae in a glucose-dependent manner; (2) affected diauxic growth in a similar way to antimycin A (complex III inhibitor of electron transport chain); (3) suppressed the growth of S. cerevisiae cultures supplemented with non-fermentable carbon sources (glycerol and lactate); (4) promoted a glucose-dependent inhibition of the basal, maximal, and ATP-linked respiration; (5) diminished complex II and IV activities. Altogether, these data indicate that quercetin disturbs mitochondrial respiration between the ubiquinone pool and cytochrome c, and this phenotype is associated with its cytotoxic properties.
Assuntos
Quercetina , Saccharomyces cerevisiae , Saccharomyces cerevisiae/metabolismo , Quercetina/farmacologia , Quercetina/metabolismo , Mitocôndrias/metabolismo , Glucose/metabolismo , RespiraçãoRESUMO
Lipases are hydrolytic enzymes that break the ester bonds of triglycerides, generating free fatty acids and glycerol. Extracellular lipase activity has been reported for the nonconventional yeast Kluyveromyces marxianus, grown in olive oil as a substrate, and the presence of at least eight putative lipases has been detected in its genome. However, to date, there is no experimental evidence on the physiological role of the putative lipases nor their structural and catalytic properties. In this study, a bioinformatic analysis of the genes of the putative lipases from K. marxianus L-2029 was performed, particularly identifying and characterizing the extracellular expected enzymes, due to their biotechnological relevance. The amino acid sequence of 10 putative lipases, obtained by in silico translation, ranged between 389 and 773 amino acids. Two of the analysed putative proteins showed a signal peptide, 25 and 33 amino acids long for KmYJR107Wp and KmLIP3p, and a molecular weight of 44.53 and 58.23 kDa, respectively. The amino acid alignment of KmLIP3p and KmYJR107Wp with the crystallized lipases from a patatin and the YlLip2 lipase from Yarrowia lipolytica, respectively, revealed the presence of the hydrolase characteristic motifs. From the 3D models of putative extracellular K. marxianus L-2029 lipases, the conserved pentapeptide of each was determined, being GTSMG for KmLIP3p and GHSLG for KmYJR107Wp; besides, the genes of these two enzymes (LIP3 and YJR107W) are apparently regulated by oleate response elements. The phylogenetic analysis of all K. marxianus lipases revealed evolutionary affinities with lipases from abH15.03, abH23.01, and abH23.02 families.
Assuntos
Proteínas de Bactérias/química , Biologia Computacional , Kluyveromyces/enzimologia , Lipase/química , Sequência de Aminoácidos , Proteínas de Bactérias/genética , Biocatálise , Hidrólise , Kluyveromyces/genética , Lipase/genéticaRESUMO
The switch between mitochondrial respiration and fermentation as the main ATP production pathway through an increase glycolytic flux is known as the Crabtree effect. The elucidation of the molecular mechanism of the Crabtree effect may have important applications in ethanol production and lay the groundwork for the Warburg effect, which is essential in the molecular etiology of cancer. A key piece in this mechanism could be Snf1p, which is a protein that participates in the nutritional response including glucose metabolism. Thus, this work aimed to recognize the role of the SNF1 gene on the glycolytic flux and mitochondrial respiration through the glucose concentration variation to gain insights about its relationship with the Crabtree effect. Herein, we found that SNF1 deletion in Saccharomyces cerevisiae cells grown at 1% glucose, decreased glycolytic flux, increased NAD(P)H concentration, enhanced HXK2 gene transcription, and decreased mitochondrial respiration. Meanwhile, the same deletion increased the mitochondrial respiration of cells grown at 10% glucose. Altogether, these findings indicate that SNF1 is important to respond to glucose concentration variation and is involved in the switch between mitochondrial respiration and fermentation.
Assuntos
Glucose/metabolismo , Mitocôndrias/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Saccharomyces cerevisiae/metabolismo , Fermentação , Glucose/análise , Glicólise , Hexoquinase/genética , NAD/metabolismo , Proteínas Serina-Treonina Quinases/genética , Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Deleção de Sequência , Transcrição GênicaRESUMO
Diet plays a key role in determining the longevity of the organisms since it has been demonstrated that glucose restriction increases life span whereas a high-glucose diet decreases it. However, the molecular basis of how diet leads to the aging process is currently unknown. We propose that the quantity of glucose that fuels respiration influences reactive oxygen species generation and glutathione levels, and both chemical species impact in the aging process. Herein, we provide evidence that mutation of the gene GSH1 in Saccharomyces cerevisiae diminishes glutathione levels. Moreover, glutathione levels were higher with 0.5% than in 10% glucose in the gsh1Δ and wild-type strains. Interestingly, the chronological life span was lowered in the gsh1Δ strain cultured with 10% glucose but not under dietary restriction. The gsh1Δ strain also showed inhibition of the mitochondrial respiration in 0.5 and 10% glucose but only increased the H2 O2 levels under dietary restriction. These results correlate well with the GSH/GSSG ratio, which showed a decrease in gsh1Δ strain cultured with 0.5% glucose. Together, these data indicate that glutathione exhaustion impact negatively both the electron transport chain function and the chronological life span of yeast, the latter occurring when a low threshold level of this antioxidant is reached, independently of the H2 O2 levels.
Assuntos
Glucose/metabolismo , Glutationa/metabolismo , Saccharomyces cerevisiae/metabolismo , Meios de Cultura/metabolismo , Transporte de Elétrons/efeitos dos fármacos , Glutamato-Cisteína Ligase/genética , Glutamato-Cisteína Ligase/metabolismo , Peróxido de Hidrogênio/farmacologia , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Saccharomyces cerevisiae/efeitos dos fármacos , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/crescimento & desenvolvimento , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismoRESUMO
Nutritional homeostasis is fundamental for alcoholic fermentation in Saccharomyces cerevisiae. Carbon and nitrogen have been related to this metabolic process; nevertheless, little is known about their interactions with the media and the energetic metabolism. Rim15p kinase is a point of convergence among different nutrient-activated signaling pathways; this makes it a target to investigate the relationship between nutritional status and energetic metabolism. To improve the current knowledge of nutrient interactions and their association with RIM15, we validated the doubling time as an indicator of growth phenotype, confirming that this kinetic parameter can be related to the cellular bioenergetic status. This endorses the usefulness of a threshold in doubling time values as an indicator of fermentative (≤ 6.5 h) and respiratory growth (≥ 13.2 h). Using the doubling time as response variable, we find that (i) two second-order interactions between type and concentration of carbon and nitrogen sources significantly affected the growth phenotype of S. cerevisiae; (ii) these metabolic interactions changed when RIM15 was deleted, suggesting a dependence on this gene; (iii) high concentration of ammonium (5% w/v) is toxic for S. cerevisiae cells; (iv) proline prompted fermentative growth phenotype regardless presence or absence of RIM15; (v) RIM15 deletion reverted ammonium toxicity when cells were grown in glucose (10% w/v); and (vi) RIM15 deletion improves fermentative metabolism probably by a partial inhibition of the respiration capacity. This study reveals the existence of synergic and diverse roles of carbon and nitrogen sources that are affected by RIM15, influencing the fermentative and respiratory growth of S. cerevisiae.
Assuntos
Carbono/metabolismo , Nitrogênio/metabolismo , Proteínas Quinases/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/fisiologia , Fermentação , Glucose/metabolismo , Saccharomyces cerevisiae/crescimento & desenvolvimentoRESUMO
A broad range of health benefits have been attributed to resveratrol (RSV) supplementation in mammalian systems, including the increases in longevity. Nonetheless, despite the growing number of studies performed with RSV, the molecular mechanism by which it acts still remains unknown. Recently, it has been proposed that inhibition of the oxidative phosphorylation activity is the principal mechanism of RSV action. This mechanism suggests that RSV might induce mitochondrial dysfunction resulting in oxidative damage to cells with a concomitant decrease of cell viability and cellular life span. To prove this hypothesis, the chronological life span (CLS) of Saccharomyces cerevisiae was studied as it is accepted as an important model of oxidative damage and aging. In addition, oxygen consumption, mitochondrial membrane potential, and hydrogen peroxide (H2O2) release were measured in order to determine the extent of mitochondrial dysfunction. The results demonstrated that the supplementation of S. cerevisiae cultures with 100 µM RSV decreased CLS in a glucose-dependent manner. At high-level glucose, RSV supplementation increased oxygen consumption during the exponential phase yeast cultures, but inhibited it in chronologically aged yeast cultures. However, at low-level glucose, oxygen consumption was inhibited in yeast cultures in the exponential phase as well as in chronologically aged cultures. Furthermore, RSV supplementation promoted the polarization of the mitochondrial membrane in both cultures. Finally, RSV decreased the release of H2O2 with high-level glucose and increased it at low-level glucose. Altogether, this data supports the hypothesis that RSV supplementation decreases CLS as a result of mitochondrial dysfunction and this phenotype occurs in a glucose-dependent manner.
Assuntos
Longevidade/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Saccharomyces cerevisiae/citologia , Estilbenos/farmacologia , Antioxidantes/farmacologia , Glucose/farmacologia , Peróxido de Hidrogênio/metabolismo , Fosforilação Oxidativa/efeitos dos fármacos , Consumo de Oxigênio , Resveratrol , Saccharomyces cerevisiae/efeitos dos fármacosRESUMO
The metabolic effects induced by resveratrol have been associated mainly with the consumption of high-calorie diets; however, its effects with standard or low-calorie diets remain unclear. To better understand the interactions between resveratrol and cellular energy levels, we used Saccharomyces cerevisiae as a model. Herein it is shown that resveratrol: (a) decreased cell viability in an energy-dependent manner; (b) lessening of cell viability occurred specifically when cells were under cellular respiration; and (c) inhibition of oxygen consumption in state 4 occurred at low and standard energy levels, whereas at high energy levels oxygen consumption was promoted. These findings indicate that the effects of resveratrol are dependent on the cellular energy status and linked to metabolic respiration. Importantly, our study also revealed that S. cerevisiae is a suitable and useful model to elucidate the molecular targets of resveratrol under different nutritional statuses. Copyright © 2016 John Wiley & Sons, Ltd.
Assuntos
Metabolismo Energético/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Saccharomyces cerevisiae/efeitos dos fármacos , Saccharomyces cerevisiae/metabolismo , Estilbenos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Consumo de Oxigênio , ResveratrolRESUMO
Resveratrol (3,4',5-trihydroxy-trans-stilbene, RSV) has emerged as an important molecule in the biomedical area. This is due to its antioxidant and health benefits exerted in mammals. Nonetheless, early studies have also demonstrated its toxic properties toward plant-pathogenic fungi of this phytochemical. Both effects appear to be opposed and caused by different molecular mechanisms. However, the inhibition of cellular respiration is a hypothesis that might explain both toxic and beneficial properties of resveratrol, since this phytochemical: (1) decreases the production of energy of plant-pathogenic organisms, which prevents their proliferation; (2) increases adenosine monophosphate/adenosine diphosphate (AMP/ADP) ratio that can lead to AMP protein kinase (AMPK) activation, which is related to its health effects, and (3) increases the reactive oxygen species generation by the inhibition of electron transport. This pro-oxidant effect induces expression of antioxidant enzymes as a mechanism to counteract oxidative stress. In this review, evidence is discussed that supports the hypothesis that cellular respiration is the main target of resveratrol.
Assuntos
Respiração Celular/efeitos dos fármacos , Estilbenos/farmacologia , Animais , Antioxidantes , Humanos , Estresse Oxidativo , ResveratrolRESUMO
Evidence suggests that AMP protein kinase (AMPK) is the main target of the phytochemical resveratrol (RSV) in mammalian cells. Data also indicates that RSV stimulates glucose metabolism; however, the molecular link between RSV and glucose uptake remains unknown. Herein, we provide evidence indicating that RSV stimulates glycolysis via sucrose non-fermenting 1 gene (SNF1, Saccharomyces cerevisiae orthologous of AMPK). S. cerevisiae cultures treated with 30 µM RSV showed an increase in extracellular acidification rate compared to untreated cells, indicating an elevated glycolytic flux. Also, RSV treatment increased transcription levels of two key glycolytic genes, hexokinase 2 (HXK2) and phosphofructokinase 1 (PFK1), as well as production of NADH. Moreover, RSV treatment inhibited mitochondrial respiration when glucose was used as a carbon source. Importantly, the effects of RSV on glycolysis were dependent of SNF1. Taken together, these findings suggest that SNF1 (AMPK in mammalian systems) is the molecular target of RSV in S. cerevisiae.
Assuntos
Glicólise/efeitos dos fármacos , Mitocôndrias/metabolismo , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Saccharomyces cerevisiae/metabolismo , Estilbenos/farmacologia , Transcrição Gênica/efeitos dos fármacos , Hexoquinase/biossíntese , Hexoquinase/genética , Mitocôndrias/genética , Consumo de Oxigênio/efeitos dos fármacos , Fosfofrutoquinase-1/biossíntese , Fosfofrutoquinase-1/genética , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Resveratrol , Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/biossíntese , Proteínas de Saccharomyces cerevisiae/genéticaRESUMO
Alsophila firma is a tree fern that is distributed mainly in tropical montane cloud forest (TMCF) and is considered as a threatened species. Arbuscular mycorrrhizal fungi (AMF) have been proposed as an alternative in rescue programs of endangered species. However, our knowledge about diversity of AMF and mycorrhizal status of the species of TMCF is limited. In Mexico TMCF shows different degrees of conservation because of fragmentation and land use change. In this study, we evaluated the level of colonization, richness and abundances of spores of AMF in three fragments with different conservation status: conserved (100 years), secondary vegetation (17 years) and disturbed. For this, soil samples and roots were collected from five individuals of A. firma per site, with at least 100 m away from each other; a total of 100 cm of roots were analysed per site. Root samples showed AMF and occasionally dark septate fungi (DSF) colonizations. For the overall study, 19 species of AMF were recorded: Gigaspora (7), Acaulospora (4), Glomus (4), Funneliformis (2), Sclerocystis (1) and Scutellospora (1). The dominant species in the three sites were Funneliformis geosporum and Acaulospora scrobiculata. The highest diversity (H') and evenness (J') (p < 0.05) were found in the conserved site (H' = 1.7, J' = 0.66), when compared to the secondary vegetation (H' = 1.5, J' = 0.61), and the disturbed site (H' = 0.74, J' = 0.41). Statistical analysis showed that the AMF degree of colonization was significantly higher (p < 0.05) in the conserved site; although, the disturbed site showed low richness and abundances of AMF, the degree of root colonization did not differ statistically (p < 0.05) with the secondary vegetation site. Chao2 (Richness estimation model) showed that the number of analysed samples were sufficient to represent the structure of the AME communities with values > 90%. The present study confirmed that A. firma is a mycorrhizal species that exhibits high levels of colonization even in disturbed sites. We suggest that F. geosporum and A. scrobiculata may have the potential to inoculate the gametophyte and young sporophyte of A. firma, to support restoration programs, because of their abundances and high tolerance to disturbed sites.
Assuntos
Gleiquênias/microbiologia , Micorrizas/fisiologia , Ecossistema , Florestas , México , Micorrizas/classificação , Clima TropicalRESUMO
Surface lattice resonances (SLRs) sustained by ordered metal arrays are characterized by their narrow spectral features, remarkable quality factors, and the ability to tune their spectral properties based on the periodicity of the array. However, the majority of these structures are fabricated using classical lithographic processes or require postannealing steps at high temperatures to enhance the quality of the metal. These limitations hinder the widespread utilization of these periodic metal arrays in various applications. In this work, we use the scalable technique of template-assisted assembly of metal colloids to produce plasmonic supercrystals over centimeter areas capable of sustaining SLRs with high Q factors reaching up to 270. Our approach obviates the need for any postprocessing, offering a streamlined and efficient fabrication route. Furthermore, our method enables extensive tunability across the entire visible and near-infrared spectral ranges, empowering the design of tailored plasmonic resonant structures for a wide range of applications.
RESUMO
During the COVID-19 pandemic, bioethical concerns were raised and there was even a â³resurgence of bioethics. â³ In this work, we review the scientific articles published by Spanish authors in relation to bioethical issues in the three years following the declaration of the pandemic. Seventy publications have been selected. Of all of them, the topic that lent itself to the most debate was that of prioritization in the use of health resources. A consensus was reached that ruled out that age could be considered as a sole exclusion criterion in healthcare or in a possible admission to the ICU. And the importance of taking special care of the most vulnerable and adapting care to the conditions of each patient without excluding anyone was recalled. Other relevant topics were the contrast between autonomy and the common good, the immune passport, vaccination, rigor in research and the publication of results, the professionalism of health personnel, misinformation, care for nursing homes, telemedicine, and the importance of the exercise of virtues. After the experience of both vulnerability and the need to exercise solidarity, many works raise the desire and the possibility of being able to overcome the pandemic being better.
Assuntos
Temas Bioéticos , COVID-19 , Pandemias , COVID-19/epidemiologia , Humanos , Espanha , Pandemias/ética , Autonomia Pessoal , SARS-CoV-2 , Telemedicina/ética , Populações Vulneráveis , Fatores Etários , Vacinação/ética , Casas de Saúde/éticaRESUMO
Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, much effort has been dedicated to identifying effective antivirals against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A number of calpain inhibitors show excellent antiviral activities against SARS-CoV-2 by targeting the viral main protease (Mpro), which plays an essential role in processing viral polyproteins. In this study, we found that calpain inhibitors potently inhibited the infection of a chimeric vesicular stomatitis virus (VSV) encoding the SARS-CoV-2 spike protein but not Mpro. In contrast, calpain inhibitors did not exhibit antiviral activities toward the wild-type VSV with its native glycoprotein. Genetic knockout of calpain-2 by CRISPR/Cas9 conferred resistance of the host cells to the chimeric VSV-SARS-CoV-2 virus and a clinical isolate of wild-type SARS-CoV-2. Mechanistically, calpain-2 facilitates SARS-CoV-2 spike protein-mediated cell attachment by positively regulating the cell surface levels of ACE2. These results highlight an Mpro-independent pathway targeted by calpain inhibitors for efficient viral inhibition. We also identify calpain-2 as a novel host factor and a potential therapeutic target responsible for SARS-CoV-2 infection at the entry step. IMPORTANCE: Many efforts in small-molecule screens have been made to counter SARS-CoV-2 infection by targeting the viral main protease, the major element that processes viral proteins after translation. Here, we discovered that calpain inhibitors further block SARS-CoV-2 infection in a main protease-independent manner. We identified the host cysteine protease calpain-2 as an important positive regulator of the cell surface levels of SARS-CoV-2 cellular receptor ACE2 and, thus, a facilitator of viral infection. By either pharmacological inhibition or genetic knockout of calpain-2, the SARS-CoV-2 binding to host cells is blocked and viral infection is decreased. Our findings highlight a novel mechanism of ACE2 regulation, which presents a potential new therapeutic target. Since calpain inhibitors also potently interfere with the viral main protease, our data also provide a mechanistic understanding of the potential use of calpain inhibitors as dual inhibitors (entry and replication) in the clinical setting of COVID-19 diseases. Our findings bring mechanistic insights into the cellular process of SARS-CoV-2 entry and offer a novel explanation to the mechanism of activities of calpain inhibitors.
Assuntos
COVID-19 , SARS-CoV-2 , Humanos , Calpaína/metabolismo , Calpaína/farmacologia , Enzima de Conversão de Angiotensina 2/metabolismo , Glicoproteína da Espícula de Coronavírus/metabolismo , Antivirais/farmacologia , Internalização do VírusRESUMO
Microbial assemblages under the sea ice of the Dease Strait, Canadian Arctic, were sequenced for metagenomes of a small size fraction (0.2-3 µm). The community from early March was typical for this season, with Alpha- and Gammaproteobacteria as the dominant taxa, followed by Thaumarchaeota and Bacteroidetes. Toward summer, Bacteroidetes, and particularly the genus Polaribacter, became increasingly dominant, followed by the Gammaproteobacteria. Analysis of genes responsible for microbial acquisition of iron showed an abundance of ABC transporters for divalent cations and ferrous iron. The most abundant transporters, however, were the outer membrane TonB-dependent transporters of iron-siderophore complexes. The abundance of iron acquisition genes suggested this element was essential for the microbial assemblage. Interestingly, Gammaproteobacteria were responsible for most of the siderophore synthesis genes. On the contrary, Bacteroidetes did not synthesize siderophores but accounted for most of the transporters, suggesting a role as cheaters in the competition for siderophores as public goods. This cheating ability of the Bacteroidetes may have contributed to their dominance in the summer.
RESUMO
Introduction: Genetic variants that control dopamine have been associated with obesity in children through loss of control of satiety and impulses, the manifestation of addictive eating behaviors, and specific personality traits. The variants include FTO-rs9939609 and the MAO-A 30 pb u-VNTR low-transcription alleles (LTA). Objective: To evaluate the genetic association of FTO-rs9939609 and the MAO-A LTA, along with personality traits and eating behavior with obesity in Mayan children from Mexico. Methods: We cross-sectionally evaluated 186 children (70 with obesity and 116 with normal weight) 6-12 years old from Yucatan, Mexico. Nutritional status was defined with body mass index (BMI) percentiles. Personality traits were evaluated with the Conners and TMCQ tests; eating behavior was evaluated with the CEBQ test. Genotyping with real-time PCR and TaqMan probes was used for FTO-rs9939609, whereas PCR amplification was used for MAO-A u-VNTR. Results: High-intensity pleasure (p = 0.013) and moderate appetite (p = 0.032) differed according to nutritional status. Heterozygous FTO-rs9939609 T/A children showed higher mean scores of low-intensity pleasure (p = 0.002) and moderate appetite (p = 0.027) than homozygous T/T. Hemizygous boys having MAO-A LTA showed significantly higher mean scores of anxiety (p = 0.001) and impulsivity (p = 0.008). In multivariate models, only LTA alleles of MAO-A explained obesity in boys (OR = 4.44; 95% CI = 1.18-16.63). Conclusion: In the present study, MAO-A u-VNTR alleles were associated with obesity in multivariate models only in boys. These alleles might also have a role in personality traits such as anxiety and impulsivity, which secondly contribute to developing obesity in Mayan boys.