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1.
Nat Metab ; 6(4): 651-658, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38499765

RESUMEN

Metformin, a widely used first-line treatment for type 2 diabetes (T2D), is known to reduce blood glucose levels and suppress appetite. Here we report a significant elevation of the appetite-suppressing metabolite N-lactoyl phenylalanine (Lac-Phe) in the blood of individuals treated with metformin across seven observational and interventional studies. Furthermore, Lac-Phe levels were found to rise in response to acute metformin administration and post-prandially in patients with T2D or in metabolically healthy volunteers.


Asunto(s)
Diabetes Mellitus Tipo 2 , Metformina , Fenilalanina , Humanos , Metformina/farmacología , Metformina/uso terapéutico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/sangre , Fenilalanina/sangre , Fenilalanina/metabolismo , Hipoglucemiantes/uso terapéutico , Hipoglucemiantes/farmacología , Masculino , Femenino , Glucemia/metabolismo , Depresores del Apetito/uso terapéutico , Depresores del Apetito/farmacología , Apetito/efectos de los fármacos , Adulto , Persona de Mediana Edad , Periodo Posprandial
2.
Am Psychol ; 77(1): 147, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-35357860

RESUMEN

Memorializes Jerome L. Singer (1924-2019). Singer's seminal research, conducted over 50þ years, laid the foundations for virtually all modern investigations of stream of consciousness and mind wandering. During a time when daydreaming was considered pathological, Singer showed it to be a pervasive aspect of human experience that served positive social and creative functions, earning him the moniker "the father of daydreaming." After receiving his PhD in clinical psychology in 1951, Singer was certified as a psychoanalyst through the William Alanson White Institute, while also holding several part-time research appointments. In 1963, Singer became director of the clinical psychology program at City University, where he and collaborator John Antrobus studied "decoupled attention." Singer joined the faculty of Yale University in 1972 and assumed emeritus status in 2006. At Yale, he worked closely with his wife Dorothy (who was an exemplary developmental psychologist in her own right), where they codirected Yale's Family TV Research and Consultation Center for more than 30 years. He died on December 14, 2019. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Asunto(s)
Psicología Clínica , Canto , Femenino , Humanos , Universidades
3.
Fungal Genet Biol ; 159: 103669, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-35114379

RESUMEN

Phosphoinositides (PI) are essential components of eukaryotic membranes and function in a large number of signaling processes. While lipid second messengers are well studied in mammals and yeast, their role in filamentous fungi is poorly understood. We used fluorescent PI-binding molecular probes to localize the phosphorylated phosphatidylinositol species PI[3]P, PI[3,5]P2, PI[4]P and PI[4,5]P2 in hyphae of the endophyte Epichloë festucae in axenic culture and during interaction with its grass host Lolium perenne. We also analysed the roles of the phosphatidylinositol-4-phosphate 5-kinase MssD and the predicted phosphatidylinositol-3,4,5-triphosphate 3-phosphatase TepA, a homolog of the mammalian tumour suppressor protein PTEN. Deletion of tepA in E. festucae and in the root-infecting tomato pathogen Fusarium oxysporum had no impact on growth in culture or the host interaction phenotype. However, this mutation did enable the detection of PI[3,4,5]P3 in septa and mycelium of E. festucae and showed that TepA is required for chemotropism in F. oxysporum. The identification of PI[3,4,5]P3 in ΔtepA strains suggests that filamentous fungi are able to generate PI[3,4,5]P3 and that fungal PTEN homologs are functional lipid phosphatases. The F. oxysporum chemotropism defect suggests a conserved role of PTEN homologs in chemotaxis across protists, fungi and mammals.


Asunto(s)
Endófitos , Simbiosis , Animales , Vías Biosintéticas , Endófitos/genética , Epichloe , Fusarium , Mamíferos , Fosfatidilinositoles , Poaceae , Simbiosis/genética
4.
G3 (Bethesda) ; 12(4)2022 04 04.
Artículo en Inglés | MEDLINE | ID: mdl-35191483

RESUMEN

Fungi from the genus Epichloë form systemic endobiotic infections of cool season grasses, producing a range of host-protective natural products in return for access to nutrients. These infections are asymptomatic during vegetative host growth, with associations between asexual Epichloë spp. and their hosts considered mutualistic. However, the sexual cycle of Epichloë spp. involves virulent growth, characterized by the envelopment and sterilization of a developing host inflorescence by a dense sheath of mycelia known as a stroma. Microscopic analysis of stromata revealed a dramatic increase in hyphal propagation and host degradation compared with asymptomatic tissues. RNAseq was used to identify differentially expressed genes in asymptomatic vs stromatized tissues from 3 diverse Epichloë-host associations. Comparative analysis identified a core set of 135 differentially expressed genes that exhibited conserved transcriptional changes across all 3 associations. The core differentially expressed genes more strongly expressed during virulent growth encode proteins associated with host suppression, digestion, adaptation to the external environment, a biosynthetic gene cluster, and 5 transcription factors that may regulate Epichloë stroma formation. An additional 5 transcription factor encoding differentially expressed genes were suppressed during virulent growth, suggesting they regulate mutualistic processes. Expression of biosynthetic gene clusters for natural products that suppress herbivory was universally suppressed during virulent growth, and additional biosynthetic gene clusters that may encode production of novel host-protective natural products were identified. A comparative analysis of 26 Epichloë genomes found a general decrease in core differentially expressed gene conservation among asexual species, and a specific decrease in conservation for the biosynthetic gene cluster expressed during virulent growth and an unusual uncharacterized gene.


Asunto(s)
Epichloe , Animales , Epichloe/genética , Estadios del Ciclo de Vida , Poaceae/genética , Simbiosis/genética , Transcriptoma
5.
J Pers Soc Psychol ; 123(2): 272-291, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35099201

RESUMEN

How should I greet her? Should I do what he requests? Newcomers to a culture learn its interpersonal norms at varying rates, largely through trial-and-error experience. Given that the culturally correct response often depends on conditions that are subtle and complex, we propose that newcomers' rate of acculturation depends on not only their explicit aptitude (e.g., reasoning ability) but also their implicit aptitude (e.g., pattern recognition ability). In Studies 1-3, participants experienced a range of influence situations sourced from a foreign culture. Across many trials, they decided whether or not to comply and then received accuracy feedback (based on what a majority of locals indicated to be the appropriate action in each situation). Across the 3 studies, stronger implicit aptitude was associated with greater improvement from trial-and-error experience, whereas stronger explicit aptitude was not. In Studies 4-6, participants experienced a range of greeting situations from a foreign culture. Across many trials, implicit aptitude predicted experiential learning, especially under conditions that impede reasoning: multiple cues, subliminal feedback, or inconsistent feedback. Study 7 found that the predictiveness of implicit aptitude was weaker under a condition that impedes associative processing: delayed feedback. These findings highlight the important role of implicit aptitude in helping people learn interpersonal norms from trial-and-error experience, particularly because in real-life intercultural interactions, the relevant cues are often complex, and the feedback is often fleeting and inconsistent but immediate. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Asunto(s)
Aprendizaje , Aprendizaje Basado en Problemas , Aptitud , Señales (Psicología) , Femenino , Humanos , Aprendizaje/fisiología , Masculino
6.
J Pers ; 90(5): 703-726, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-34860434

RESUMEN

OBJECTIVE: Narcissism can manifest in grandiose and vulnerable patterns of experience and behavior. While largely unrelated in the general population, individuals with clinically relevant narcissism are thought to display both. Our previous studies showed that trait measures of grandiosity and vulnerability were unrelated at low-to-moderate levels of grandiose narcissism, but related at high levels. METHOD: We replicate and extend these findings in a preregistered individual data meta-analysis ("mega-analysis") using data from the Narcissistic Personality Inventory (NPI)/Hypersensitive Narcissism Scale (HSNS; N = 10,519, k = 28) and the Five-Factor Narcissism Inventory (FFNI; N = 7,738, k = 17). RESULTS: There was strong evidence for the hypothesis in the FFNI (ßGrandiose < 1 SD  = .08, ßGrandiose > 1 SD  = .36, ßGrandiose > 2 SD  = .53), and weaker evidence in the NPI/HSNS (ßGrandiose < 1 SD  = .00, ßGrandiose > 1 SD  = .12, ßGrandiose > 2 SD  = .32). Nonlinearity increased with age but was invariant across other moderators. Higher vulnerability was predicted by elevated antagonistic and low agentic narcissism at subfactor level. CONCLUSION: Narcissistic vulnerability increases at high levels of grandiosity. Interpreted along Whole Trait Theory, the effects are thought to reflect state changes echoing in trait measures and can help to link personality and clinical models.


Asunto(s)
Narcisismo , Trastornos de la Personalidad , Humanos , Trastornos del Humor , Personalidad , Inventario de Personalidad
7.
Mol Plant Microbe Interact ; 34(10): 1181-1192, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34058838

RESUMEN

Epichloë festucae forms a mutualistic symbiotic association with Lolium perenne. This biotrophic fungus systemically colonizes the intercellular spaces of aerial tissues to form an endophytic hyphal network and also grows as an epiphyte. However, little is known about the cell wall-remodeling mechanisms required to avoid host defense and maintain intercalary growth within the host. Here, we use a suite of molecular probes to show that the E. festucae cell wall is remodeled by conversion of chitin to chitosan during infection of L. perenne seedlings, as the hyphae switch from free-living to endophytic growth. When hyphae transition from endophytic to epiphytic growth, the cell wall is remodeled from predominantly chitosan to chitin. This conversion from chitin to chitosan is catalyzed by chitin deacetylase. The genome of E. festucae encodes three putative chitin deacetylases, two of which (cdaA and cdaB) are expressed in planta. Deletion of either of these genes results in disruption of fungal intercalary growth in the intercellular spaces of plants infected with these mutants. These results establish that these two genes are required for maintenance of the mutualistic symbiotic interaction between E. festucae and L. perenne.[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.


Asunto(s)
Epichloe , Lolium , Amidohidrolasas , Pared Celular/metabolismo , Quitina , Epichloe/genética , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Regulación Fúngica de la Expresión Génica , Simbiosis
8.
J Exp Bot ; 72(9): 3410-3426, 2021 04 13.
Artículo en Inglés | MEDLINE | ID: mdl-33630999

RESUMEN

Plants secrete various defence-related proteins into the apoplast, including proteases. Papain-like cysteine proteases (PLCPs) are central components of the plant immune system. To overcome plant immunity and successfully colonize their hosts, several plant pathogens secrete effector proteins inhibiting plant PLCPs. We hypothesized that not only pathogens, but also mutualistic microorganisms interfere with PLCP-meditated plant defences to maintain endophytic colonization with their hosts. Epichloë festucae forms mutualistic associations with cool season grasses and produces a range of secondary metabolites that protect the host against herbivores. In this study, we performed a genome-wide identification of Lolium perenne PLCPs, analysed their evolutionary relationship, and classified them into nine PLCP subfamilies. Using activity-based protein profiling, we identified four active PLCPs in the apoplast of L. perenne leaves that are inhibited during endophyte interactions. We characterized the L. perenne cystatin LpCys1 for its inhibitory capacity against ryegrass PLCPs. LpCys1 abundance is not altered during the mutualistic interaction and it mainly inhibits LpCP2. However, since the activity of other L. perenne PLCPs is not sensitive to LpCys1, we propose that additional inhibitors, likely of fungal origin, are involved in the suppression of apoplastic PLCPs during E. festucae infection.


Asunto(s)
Proteasas de Cisteína , Epichloe , Lolium , Proteínas de Plantas , Lolium/enzimología , Simbiosis
9.
Environ Microbiol ; 23(4): 2116-2131, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33350014

RESUMEN

Recent studies have identified key genes that control the symbiotic interaction between Epichloë festucae and Lolium perenne. Here we report on the identification of specific E. festucae genes that control host infection. Deletion of setB, which encodes a homologue of the H3K36 histone methyltransferase Set2/KMT3, reduced histone H3K36 trimethylation and led to severe defects in colony growth and hyphal development. The E. festucae ΔclrD mutant, which lacks the gene encoding the homologue of the H3K9 methyltransferase KMT1, displays similar developmental defects. Both mutants are completely defective in their ability to infect L. perenne. Alleles that complement the culture and plant phenotypes of both mutants also complement the histone methylation defects. Co-inoculation of either ΔsetB or ΔclrD with the wild-type strain enables these mutants to colonize the host. However, successful colonization by the mutants resulted in death or stunting of the host plant. Transcriptome analysis at the early infection stage identified four fungal candidate genes, three of which encode small-secreted proteins, that are differentially regulated in these mutants compared to wild type. Deletion of crbA, which encodes a putative carbohydrate binding protein, resulted in significantly reduced host infection rates by E. festucae.


Asunto(s)
Epichloe , Epichloe/genética , Epichloe/metabolismo , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Regulación Fúngica de la Expresión Génica , Histonas/genética , Metiltransferasas/genética , Poaceae , Simbiosis/genética
10.
Mol Microbiol ; 114(4): 626-640, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32634260

RESUMEN

The endophytic fungus Epichloë festucae systemically colonizes the intercellular spaces of cool-season grasses to establish a mutualistic symbiosis. Hyphal growth of the endophyte within the host plant is tightly regulated and synchronized with the growth of the host plant. A genetic screen to identify symbiotic genes identified mutant FR405 that had an antagonistic interaction with the host plant. Perennial ryegrass infected with the FR405 mutant were stunted and underwent premature senescence and death. The disrupted gene in FR405 encodes a nuclear-localized protein, designated as NsiA for nuclear protein for symbiotic infection. Like previously isolated symbiotic mutants the nsiA mutant is defective in hyphal cell fusion. NsiA interacts with Ste12, a C2H2 zinc-finger transcription factor, and a MAP kinase MpkB. Both are known as essential components for cell fusion in other fungal species. In E. festucae, MpkB, but not Ste12, is essential for cell fusion. Expression of several genes required for cell fusion and symbiosis, including proA/adv-1, pro41/ham-6, ham7, ham8, and ham9 were downregulated in the nsiA mutant. However, the NsiA ortholog in Neurospora crassa was not essential for hyphal cell fusion. These results demonstrate that the roles of NsiA and Ste12 orthologs in hyphal cell fusion are distinctive between fungal species.


Asunto(s)
Epichloe/metabolismo , Fusión Celular , Epichloe/enzimología , Epichloe/genética , Proteínas Fúngicas/metabolismo , Regulación Fúngica de la Expresión Génica/genética , Hifa/crecimiento & desarrollo , Lolium/metabolismo , Lolium/microbiología , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Proteínas Nucleares/genética , Simbiosis/genética , Factores de Transcripción/metabolismo
11.
Front Psychol ; 11: 1006, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32528378

RESUMEN

Selfishness is often regarded as an undesirable or even immoral characteristic, whereas altruism is typically considered universally desirable and virtuous. However, human history as well as the works of humanistic and psychodynamic psychologists point to a more complex picture: not all selfishness is necessarily bad, and not all altruism is necessarily good. Based on these writings, we introduce new scales for the assessment of individual differences in two paradoxical forms of selfishness that have lacked measurement in the field - healthy selfishness (HS) and pathological altruism (PA). In two studies (N 1 = 370, N 2 = 891), we constructed and validated the HS and PA scales. The scales showed good internal consistency and a clear two-dimensional structure across both studies. HS was related to higher levels of psychological well-being and adaptive psychological functioning as well as a genuine prosocial orientation. PA was associated with maladaptive psychological outcomes, vulnerable narcissism, and selfish motivations for helping others. These results underpin the paradoxical nature of both constructs. We discuss the implications for future research, including clinical implications.

12.
Neuroimage ; 220: 117011, 2020 10 15.
Artículo en Inglés | MEDLINE | ID: mdl-32504814

RESUMEN

An influential model of the neural mechanisms of creative thought suggests that creativity is manifested in the joint contributions of the Default Mode Network (DMN; a set of regions in the medial PFC, lateral and medial parietal cortex, and the medial temporal lobes) and the executive networks within the dorsolateral PFC. Several empirical reports have offered support for this model by showing that complex interactions between these brain systems account for individual differences in creative performance. The present study examined whether the engagement of these regions in idea generation is modulated by one's eminence in a creativity-related field. Twenty (n â€‹= â€‹20) healthy eminent creators from diverse fields of expertise and a 'smart' comparison group of sixteen (n â€‹= â€‹16) age- and education-matched non-eminent thinkers were administered a creative generation task (an adaptation of the Alternative Uses Task) and a control perceptual task, while undergoing functional magnetic resonance imaging (fMRI). The participants' verbal responses were recorded through a noise-canceling microphone and were later coded for fluency and accuracy. Behavioral and fMRI analyses revealed commonalities between groups, but also distinct patterns of activation in default mode and executive brain regions between the eminent and the non-eminent participants during creative thinking. We interpret these findings in the context of the well-documented contributions of these regions in the generation of creative ideas as modulated, in this study, by participants' creative eminence.


Asunto(s)
Encéfalo/fisiología , Creatividad , Red Nerviosa/fisiología , Pensamiento/fisiología , Adulto , Anciano , Encéfalo/diagnóstico por imagen , Mapeo Encefálico , Cognición/fisiología , Femenino , Neuroimagen Funcional , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Red Nerviosa/diagnóstico por imagen
13.
Neuroimage ; 218: 116921, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32438051

RESUMEN

Nearly everyone has the ability for creative thought. Yet, certain individuals create works that propel their fields, challenge paradigms, and advance the world. What are the neurobiological factors that might underlie such prominent creative achievement? In this study, we focus on morphometric differences in brain structure between high creative achievers from diverse fields of expertise and a 'smart' comparison group of age-, intelligence-, and education-matched average creative achievers. Participants underwent a high-resolution structural brain imaging scan and completed a series of intelligence, creative thinking, personality, and creative achievement measures. We examined whether high and average creative achievers could be distinguished based on the relationship between morphometric brain measures (cortical area and thickness) and behavioral measures. Although participants' performance on the behavioral measures did not differ between the two groups aside from creative achievement, the relationship between posterior parietal cortex morphometry and creativity, intelligence, and personality measures depended on group membership. These results suggest that extraordinary creativity may be associated with measurable structural brain differences, especially within parietal cortex.


Asunto(s)
Encéfalo/anatomía & histología , Creatividad , Adulto , Mapeo Encefálico/métodos , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad
14.
New Phytol ; 227(2): 559-571, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32155669

RESUMEN

Epichloë festucae is an endophytic fungus that forms a symbiotic association with Lolium perenne. Here we analysed how the metabolome of the ryegrass apoplast changed upon infection of this host with sexual and asexual isolates of E. festucae. A metabolite fingerprinting approach was used to analyse the metabolite composition of apoplastic wash fluid from uninfected and infected L. perenne. Metabolites enriched or depleted in one or both of these treatments were identified using a set of interactive tools. A genetic approach in combination with tandem MS was used to identify a novel product of a secondary metabolite gene cluster. Metabolites likely to be present in the apoplast were identified using MarVis in combination with the BioCyc and KEGG databases, and an in-house Epichloë metabolite database. We were able to identify the known endophyte-specific metabolites, peramine and epichloëcyclins, as well as a large number of unknown markers. To determine whether these methods can be applied to the identification of novel Epichloë-derived metabolites, we deleted a gene encoding a NRPS (lgsA) that is highly expressed in planta. Comparative MS analysis of apoplastic wash fluid from wild-type- vs mutant-infected plants identified a novel Leu/Ile glycoside metabolite present in the former.


Asunto(s)
Epichloe , Lolium , Epichloe/genética , Proteínas Fúngicas , Metabolómica , Simbiosis
15.
Mol Microbiol ; 113(6): 1101-1121, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32022309

RESUMEN

Although lipid signaling has been shown to serve crucial roles in mammals and plants, little is known about this process in filamentous fungi. Here we analyze the contribution of phospholipase D (PLD) and its product phosphatidic acid (PA) in hyphal morphogenesis and growth of Epichloë festucae and Neurospora crassa, and in the establishment of a symbiotic interaction between E. festucae and Lolium perenne. Growth of E. festucae and N. crassa PLD deletion strains in axenic culture, and for E. festucae in association with L. perenne, were analyzed by light-, confocal- and electron microscopy. Changes in PA distribution were analyzed in E. festucae using a PA biosensor and the impact of these changes on the endocytic recycling and superoxide production investigated. We found that E. festucae PldB, and the N. crassa ortholog, PLA-7, are required for polarized growth and cell fusion and contribute to ascospore development, whereas PldA/PLA-8 are dispensable for these functions. Exogenous addition of PA rescues the cell-fusion phenotype in E. festucae. PldB is also crucial for E. festucae to establish a symbiotic association with L. perenne. This study identifies a new component of the cell-cell communication and cell fusion signaling network for hyphal morphogenesis and growth of filamentous fungi.


Asunto(s)
Epichloe/crecimiento & desarrollo , Lolium/microbiología , Neurospora crassa/crecimiento & desarrollo , Ácidos Fosfatidicos/metabolismo , Fosfolipasa D/metabolismo , Técnicas Biosensibles , Comunicación Celular , Fusión Celular , Epichloe/fisiología , Eliminación de Gen , Regulación Fúngica de la Expresión Génica/genética , Hifa/crecimiento & desarrollo , Lolium/fisiología , Fosfatidilcolinas/metabolismo , Transducción de Señal/fisiología , Esporas Fúngicas/crecimiento & desarrollo , Superóxidos/metabolismo , Simbiosis/fisiología
16.
J Pers Disord ; 34(1): 107-130, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-30179576

RESUMEN

There is broad consensus that there are at least two different dimensions of narcissism: vulnerable and grandiose. In this study, the authors use a new trifurcated, three-factor model of narcissism to examine relations between aspects of narcissism and an array of clinically relevant criteria related to psychopathology, the self, authenticity, and well-being. Neurotic and antagonistic aspects of narcissism emerged as the most clinically relevant dimensions of narcissism, bearing relations with outcomes relating to interpersonal guilt, insecure attachment styles, cognitive distortions, maladaptive defense mechanisms, experiential avoidance, impostor syndrome, weak sense of self, inauthenticity, low self-esteem, and reduced psychological well-being. Grandiose narcissism was not correlated with most forms of psychopathology and was even positively associated with life satisfaction. Nevertheless, a surprising link was found between grandiose narcissism and multiple indicators of inauthenticity. Implications for the appropriate conceptualization, assessment, and treatment of pathological narcissism are discussed.


Asunto(s)
Deluciones/psicología , Control Interno-Externo , Narcisismo , Trastornos de la Personalidad/diagnóstico , Personalidad , Adulto , Mecanismos de Defensa , Deluciones/diagnóstico , Femenino , Humanos , Masculino , Trastornos de la Personalidad/psicología , Inventario de Personalidad
17.
Proc Natl Acad Sci U S A ; 116(51): 25614-25623, 2019 12 17.
Artículo en Inglés | MEDLINE | ID: mdl-31801877

RESUMEN

Nonribosomal peptide synthetases (NRPSs) generate the core peptide scaffolds of many natural products. These include small cyclic dipeptides such as the insect feeding deterrent peramine, which is a pyrrolopyrazine (PPZ) produced by grass-endophytic Epichloë fungi. Biosynthesis of peramine is catalyzed by the 2-module NRPS, PpzA-1, which has a C-terminal reductase (R) domain that is required for reductive release and cyclization of the NRPS-tethered dipeptidyl-thioester intermediate. However, some PpzA variants lack this R domain due to insertion of a transposable element into the 3' end of ppzA We demonstrate here that these truncated PpzA variants utilize nonenzymatic cyclization of the dipeptidyl thioester to a 2,5-diketopiperazine (DKP) to synthesize a range of novel PPZ products. Truncation of the R domain is sufficient to subfunctionalize PpzA-1 into a dedicated DKP synthetase, exemplified by the truncated variant, PpzA-2, which has also evolved altered substrate specificity and reduced N-methyltransferase activity relative to PpzA-1. Further allelic diversity has been generated by recombination-mediated domain shuffling between ppzA-1 and ppzA-2, resulting in the ppzA-3 and ppzA-4 alleles, each of which encodes synthesis of a unique PPZ metabolite. This research establishes that efficient NRPS-catalyzed DKP biosynthesis can occur in vivo through nonenzymatic dipeptidyl cyclization and presents a remarkably clean example of NRPS evolution through recombinant exchange of functionally divergent domains. This work highlights that allelic variants of a single NRPS can result in a surprising level of secondary metabolite diversity comparable to that observed for some gene clusters.


Asunto(s)
Péptido Sintasas , Pirazinas , Ciclización/genética , Barajamiento de ADN , Dicetopiperazinas/química , Epichloe/enzimología , Epichloe/genética , Proteínas Fúngicas/química , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Péptido Sintasas/química , Péptido Sintasas/genética , Péptido Sintasas/metabolismo , Pirazinas/química , Pirazinas/metabolismo , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo
18.
Mol Microbiol ; 112(3): 837-853, 2019 09.
Artículo en Inglés | MEDLINE | ID: mdl-31165508

RESUMEN

Studies on the regulation of fungal secondary metabolism highlight the importance of histone H3K4 methylation regulators Set1, CclA (Ash2) and KdmB (KDM5), but it remains unclear whether these proteins act by direct modulation of H3K4me3 at the target genes. In filamentous fungi, secondary metabolite genes are frequently located near telomeres, a site where H3K4 methylation is thought to have a repressive role. Here we analyzed the role of CclA, KdmB and H3K4me3 in regulating the subtelomeric EAS and LTM cluster genes in Epichloë festucae. Depletion of H3K4me3 correlated with transcriptional activation of these genes in ΔcclA, similarly enrichment of H3K4me3 correlated with transcriptional repression of the genes in ΔkdmB which was accompanied by significant reduction in the levels of the agriculturally undesirable lolitrems. These transcriptional changes could only be explained by the alterations in H3K4me3 and not in the subtelomerically-important marks H3K9me3/K27me3. However, H3K4me3 changes in both mutants were not confined to these regions but occurred genome-wide, and at other subtelomeric loci there were inconsistent correlations between H3K4me3 enrichment and gene repression. Our study suggests that CclA and KdmB are crucial regulators of secondary metabolite genes, but these proteins likely act via means independent to, or in conjunction with the H3K4me3 mark.


Asunto(s)
Epichloe/metabolismo , Proteínas Fúngicas/metabolismo , Regulación Fúngica de la Expresión Génica , Histonas/metabolismo , Epichloe/genética , Proteínas Fúngicas/genética , Genoma Fúngico , Histonas/genética , Mutación , Metabolismo Secundario
19.
Mol Plant Pathol ; 20(7): 961-975, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-31008572

RESUMEN

Epichloë festucae is an endophytic fungus that forms a mutualistic symbiotic association with the grass host Lolium perenne. Endophytic hyphae exit the host by an appressorium-like structure known as an expressorium. In plant-pathogenic fungi, the tetraspanin Pls1 and the NADPH oxidase component Nox2 are required for appressorium development. Previously we showed that the homologue of Nox2, NoxB, is required for E. festucae expressorium development and establishment of a mutualistic symbiotic interaction with the grass host. Here we used a reverse genetics approach to functionally characterize the role of the E. festucae homologue of Pls1, PlsA. The morphology and growth of ΔplsA in axenic culture was comparable to wild-type. The tiller length of plants infected with ΔplsA was significantly reduced. Hyphae of ΔplsA had a proliferative pattern of growth within the leaves of L. perenne with increased colonization of the intercellular spaces and the vascular bundles. The ΔplsA mutant was also defective in expressorium development although the phenotype was not as severe as for ΔnoxB, highlighting potentially distinct roles for PlsA and NoxB in signalling through the NoxB complex. Hyphae of ΔplsA proliferate below the cuticle surface but still occasionally form an expressorium-like structure that enables the mutant hyphae to exit the leaf to grow on the surface. These expressoria still form a septin ring-like structure at the point of cuticle exit as found in the wild-type strain. These results establish that E. festucae PlsA has an important, but distinct, role to NoxB in expressorium development and plant symbiosis.


Asunto(s)
Epichloe/metabolismo , Proteínas Fúngicas/química , Proteínas Fúngicas/metabolismo , Hifa/crecimiento & desarrollo , Lolium/microbiología , Homología de Secuencia de Aminoácido , Simbiosis , Tetraspaninas/metabolismo , Epichloe/crecimiento & desarrollo , Epichloe/ultraestructura , Eliminación de Gen , Hifa/metabolismo , Procesamiento de Imagen Asistido por Computador , Lolium/ultraestructura , Fenotipo
20.
Front Psychol ; 10: 467, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30914993

RESUMEN

While there is a growing literature on "dark traits" (i.e., socially aversive traits), there has been a lack of integration with the burgeoning research literature on positive traits and fulfilling and growth-oriented outcomes in life. To help move the field toward greater integration, we contrasted the nomological network of the Dark Triad (a well-studied cluster of socially aversive traits) with the nomological network of the Light Triad, measured by the 12-item Light Triad Scale (LTS). The LTS is a first draft measure of a loving and beneficent orientation toward others ("everyday saints") that consists of three facets: Kantianism (treating people as ends unto themselves), Humanism (valuing the dignity and worth of each individual), and Faith in Humanity (believing in the fundamental goodness of humans). Across four demographically diverse samples (N = 1,518), the LTS demonstrated excellent reliability and validity, predicting life satisfaction and a wide range of growth-oriented and self-transcendent outcomes above and beyond existing measures of personality. In contrast, the Dark Triad was negatively associated with life satisfaction and growth-oriented outcomes, and showed stronger linkages to selfish, exploitative, aggressive, and socially aversive outcomes. This exploratory study of the contrasting nomological networks of the Light vs. Dark Triad provides several ways forward for more principled and data driven approaches to explore both the malevolent and beneficent sides of human nature.

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