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The shared functions of the skull are thought to result in common evolutionary patterns in mammalian cranial shape. Craniofacial evolutionary allometry (CREA) is a particularly prominent pattern where larger species display proportionally elongate facial skeletons and smaller braincases. It was recently proposed that CREA arises from biomechanical effects of cranial scaling when diets are similar. Thus, deviations from CREA should occur with changes in cranial biomechanics, for example due to dietary change. Here, we test this using 3D geometric morphometric analysis in a dataset of Australian murine crania, which are highly allometric. We contrast allometric and non‐allometric variation in the cranium by comparing evolutionary mode, allometry, ordinations, as well as allometry, integration, and modularity in functional modules. We found evidence of stabilising selection in allometry‐containing and size‐free shape, and substantial non‐allometric variation aligned with dietary specialisation in parallel with CREA. Integration among cranial modules was higher, and modularity lower, with size included, but integration between rostrum and cranial vault, which are involved in the CREA pattern, dropped dramatically after size removal. Our results thus support the hypothesis that CREA is a composite arising from selection on cranial function, with substantial non‐allometric shape variation occurring alongside CREA where dietary specialisation impacts selection on gnawing function. This emphasises the need to research mammalian cranial evolution in the context of allometric and non‐allometric selection on biomechanical function. [ABSTRACT FROM AUTHOR]

The mammalian cranium (skull without lower jaw) is representative of mammalian diversity and is thus of particular interest to mammalian biologists across disciplines. One widely retrieved pattern accompanying mammalian cranial diversification is referred to as 'craniofacial evolutionary allometry' (CREA). This posits that adults of larger species, in a group of closely related mammals, tend to have relatively longer faces and smaller braincases. However, no process has been officially suggested to explain this pattern, there are many apparent exceptions, and its predictions potentially conflict with well‐established biomechanical principles. Understanding the mechanisms behind CREA and causes for deviations from the pattern therefore has tremendous potential to explain allometry and diversification of the mammalian cranium. Here, we propose an amended framework to characterise the CREA pattern more clearly, in that 'longer faces' can arise through several kinds of evolutionary change, including elongation of the rostrum, retraction of the jaw muscles, or a more narrow or shallow skull, which all result in a generalised gracilisation of the facial skeleton with increased size. We define a standardised workflow to test for the presence of the pattern, using allometric shape predictions derived from geometric morphometrics analysis, and apply this to 22 mammalian families including marsupials, rabbits, rodents, bats, carnivores, antelopes, and whales. Our results show that increasing facial gracility with size is common, but not necessarily as ubiquitous as previously suggested. To address the mechanistic basis for this variation, we then review cranial adaptations for harder biting. These dictate that a more gracile cranium in larger species must represent a structural sacrifice in the ability to produce or withstand harder bites, relative to size. This leads us to propose that facial gracilisation in larger species is often a product of bite force allometry and phylogenetic niche conservatism, where more closely related species tend to exhibit more similar feeding ecology and biting behaviours and, therefore, absolute (size‐independent) bite force requirements. Since larger species can produce the same absolute bite forces as smaller species with less effort, we propose that relaxed bite force demands can permit facial gracility in response to bone optimisation and alternative selection pressures. Thus, mammalian facial scaling represents an adaptive by‐product of the shifting importance of selective pressures occurring with increased size. A reverse pattern of facial 'shortening' can accordingly also be found, and is retrieved in several cases here, where larger species incorporate novel feeding behaviours involving greater bite forces. We discuss multiple exceptions to a bite force‐mediated influence on facial proportions across mammals which lead us to argue that ecomorphological specialisation of the cranium is likely to be the primary driver of facial scaling patterns, with some developmental constraints as possible secondary factors. A potential for larger species to have a wider range of cranial functions when less constrained by bite force demands might also explain why selection for larger sizes seems to be prevalent in some mammalian clades. The interplay between adaptation and constraint across size ranges thus presents an interesting consideration for a mechanistically grounded investigation of mammalian cranial allometry. [ABSTRACT FROM AUTHOR]

Abstract The shared functions of the skull are thought to result in common evolutionary patterns in mammalian cranial shape. Craniofacial evolutionary allometry (CREA) is a particularly prominent pattern where larger species display proportionally elongate facial skeletons and smaller braincases. It was recently proposed that CREA arises from biomechanical effects of cranial scaling when diets are similar. Thus, deviations from CREA should occur with changes in cranial biomechanics, for example due to dietary change. Here, we test this using 3D geometric morphometric analysis in a dataset of Australian murine crania, which are highly allometric. We contrast allometric and non‐allometric variation in the cranium by comparing evolutionary mode, allometry, ordinations, as well as allometry, integration, and modularity in functional modules. We found evidence of stabilising selection in allometry‐containing and size‐free shape, and substantial non‐allometric variation aligned with dietary specialisation in parallel with CREA. Integration among cranial modules was higher, and modularity lower, with size included, but integration between rostrum and cranial vault, which are involved in the CREA pattern, dropped dramatically after size removal. Our results thus support the hypothesis that CREA is a composite arising from selection on cranial function, with substantial non‐allometric shape variation occurring alongside CREA where dietary specialisation impacts selection on gnawing function. This emphasises the need to research mammalian cranial evolution in the context of allometric and non‐allometric selection on biomechanical function.

The exopolysaccharide galactosaminogalactan (GAG) contributes to biofilm formation and virulence in the pathogenic fungus Aspergillus fumigatus. Increasing evidence indicates that GAG production is inversely linked with asexual development. However, the mechanisms underlying this regulatory relationship are unclear. In this study, we found that the dysfunction of CreA, a conserved transcription factor involved in carbon catabolite repression in many fungal species, causes abnormal asexual development (conidiation) under liquid‐submerged culture conditions specifically in the presence of glucose. The loss of creA decreased GAG production independent of carbon sources. Furthermore, CreA contributed to asexual development and GAG production via distinct pathways. CreA promoted A. fumigatus GAG production by positively regulating GAG biosynthetic genes (uge3 and agd3). CreA suppressed asexual development in glucose liquid‐submerged culture conditions via central conidiation genes (brlA, abaA, and wetA) and their upstream activators (flbC and flbD). Restoration of brlA expression to the wild‐type level by flbC or flbD deletion abolished the abnormal submerged conidiation in the creA null mutant but did not restore GAG production. The C‐terminal region of CreA was crucial for the suppression of asexual development, and the repressive domain contributed to GAG production. Overall, CreA is involved in GAG production and asexual development in an inverse manner. [ABSTRACT FROM AUTHOR]

Carbon catabolite repression enables fungi to utilize the most favourable carbon source in the environment, and is mediated by a key regulator, CreA, in most fungi. CreA-mediated regulation has mainly been studied at high monosaccharide concentrations, an uncommon situation in most natural biotopes. In nature, many fungi rely on plant biomass as their major carbon source by producing enzymes to degrade plant cell wall polysaccharides into metabolizable sugars. To determine the role of CreA when fungi grow in more natural conditions and in particular with respect to degradation and conversion of plant cell walls, we compared transcriptomes of a creA deletion and reference strain of the ascomycete Aspergillus niger during growth on sugar beet pulp and wheat bran. Transcriptomics, extracellular sugar concentrations and growth profiling of A. niger on a variety of carbon sources, revealed that also under conditions with low concentrations of free monosaccharides, CreA has a major effect on gene expression in a strong time and substrate composition dependent manner. In addition, we compared the CreA regulon from five fungi during their growth on crude plant biomass or cellulose. It showed that CreA commonly regulated genes related to carbon metabolism, sugar transport and plant cell wall degrading enzymes across different species. We therefore conclude that CreA has a crucial role for fungi also in adapting to low sugar concentrations as occurring in their natural biotopes, which is supported by the presence of CreA orthologs in nearly all fungi.

A 3 years old, 40.8 kg, intact male American Bully, diagnosed with acute kidney injury in a private clinic in Serbia was referred for hemodialysis therapy. The dog was presented with the following symptoms: lethargy, appetite loss, vomiting, diarrhea, weight loss, dehydration (8-10%, Considerable loss of skin turgor), rectal temperature of 38.8oC and dry mucous membranes. Arterial blood pressure was elevated 218-220 mmHg systolic, using Doppler method. The biochemistry revealed elevated ALT 191 (RR: 10-118 U/L), AMY 1390 (RR: 200-1200 U/L), BUN 94 (RR: 7-25 mg/dL), CREA 3.6 (RR: 0.4-1.2 mg/dL), PHOS 9.8 (RR: 2.9-6.6 mg/dL), GLU 121 (RR: 60-110 mg/dL), K 3.3 (RR: 3.4-5.6 mmol/L). Urine analysis was performed with UPC 0.2-0.5 (borderline proteinuric), pH 5.5, microalbumin >25 mg/L, creatinine >26.4 mmol/L. The infestation with Leishmania infantum was confirmed using quantitative PCR. The patient was stabilized using fluid therapy and parenteral feeding. Hemodialysis was decided as an extracorporeal replacement therapy for sustaining renal function. A central venous catheter was placed under a light sedation with oxygen therapy. Hemodialysis was performed for three times in a period of 11 days. A key treatment for acute kidney injury in canine patients is represented by intensive care, fluid therapy and hemodialysis therefore, the values were reduced in BUN from 94 mg/dL to 30 mg/dL and CRE from 3.6 mg/dL to 1.8 mg/dL. The BUN and CREA reached normal values 39 days after that the patient was discharged. [ABSTRACT FROM AUTHOR]

Copyright of Revista Interuniversitaria de Formación del Profesorado is the property of Asociacion Universitaria de Formacion del Profesorado (AUFOP) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The aim of this work is to show a work proposal that allows the development of creativity through the main theme: Portrait and Selfie. This study has been carried out in the subject of Art Education with pupils aged 11 to 12. Working on creativity and self-representation in pre-adolescence can be an interesting topic for their future development. Currently, there are not many quantitative studies on this subject. To this end, research was carried out in four groups, divided into two control subgroups and two experimental subgroups, in which the project was applied to check whether the proposed activities enhanced and developed the creativity of the subjects studied. The students had to complete a pre-test (TTCT) and a posttest (CREA). Comparing the results, it was found that there were non-significant improvements in the teams and unevenness in motivation towards the tests. This could be due to the small sample size, the low heterogeneity of the groups, the intervention implemented and the type of assessment carried out. [ABSTRACT FROM AUTHOR]

Carbon catabolite repression enables fungi to utilize the most favourable carbon source in the environment, and is mediated by a key regulator, CreA, in most fungi. CreA-mediated regulation has mainly been studied at high monosaccharide concentrations, an uncommon situation in most natural biotopes. In nature, many fungi rely on plant biomass as their major carbon source by producing enzymes to degrade plant cell wall polysaccharides into metabolizable sugars. To determine the role of CreA when fungi grow in more natural conditions and in particular with respect to degradation and conversion of plant cell walls, we compared transcriptomes of a creA deletion and reference strain of the ascomycete Aspergillus niger during growth on sugar beet pulp and wheat bran. Transcriptomics, extracellular sugar concentrations and growth profiling of A. niger on a variety of carbon sources, revealed that also under conditions with low concentrations of free monosaccharides, CreA has a major effect on gene expression in a strong time and substrate composition dependent manner. In addition, we compared the CreA regulon from five fungi during their growth on crude plant biomass or cellulose. It showed that CreA commonly regulated genes related to carbon metabolism, sugar transport and plant cell wall degrading enzymes across different species. We therefore conclude that CreA has a crucial role for fungi also in adapting to low sugar concentrations as occurring in their natural biotopes, which is supported by the presence of CreA orthologs in nearly all fungi.

The black koji mold, Aspergillus luchuensis , which belongs to Aspergillus section Nigri , is used for the production of traditional Japanese spirits (shochu) mainly in the southern districts of Japan. This mold is known to produce amylolytic enzymes essential for shochu production; however, mechanisms regulating amylolytic gene expression in A. luchuensis have not been studied in as much detail as those in the yellow koji mold, Aspergillus oryzae. Here, we examined the gene expression profiles of deletion mutants of transcription factors orthologous to A. oryzae AmyR and CreA in A. luchuensis. A. luchuensis produces acid-unstable (AmyA) and acid-stable (AsaA) α-amylases. AmyA production and amyA gene expression were not influenced by amyR or creA deletion, indicating that amyA was constitutively expressed. In contrast, asaA gene expression was significantly down- and upregulated upon deletion of amyR and creA , respectively. Furthermore, the glaA and agdA genes (encoding glucoamylase and α-glucosidase, respectively) showed expression profiles similar to those of asaA. Thus, genes that play pivotal roles in starch saccharification, asaA , glaA , and agdA , were found to be regulated by AmyR and CreA. Moreover, despite previous reports on AsaA being only produced in solid-state culture, deletion of the ortholog of A. oryzae flbC, which is involved in the expression of the solid-state culture-specific genes, did not affect AsaA α-amylase activity, suggesting that FlbC was not associated with asaA expression. [ABSTRACT FROM AUTHOR]

Objective: With the aim to decipher the mechanisms involved in the transcriptional regulation of feruloyl esterase encoded by faeB, a genetic screen was performed to isolate A. niger mutants displaying inducer-independent expression from the faeB promoter. Result: PfaeB-amdS and PfaeB-lux dual reporter strains were constructed and used to isolate trans-acting mutants in which the expression of both reporters was increased, based on the ability to grow on acetamide plates and higher luciferase activity, respectively. The genetic screen on the non-inducing carbon source D-fructose yielded in total 111 trans-acting mutants. The genome of one of the mutants was sequenced and revealed several SNPs, including a point mutation in the creA gene encoding a transcription factor known to be involved in carbon catabolite repression. Subsequently, all mutants were analyzed for defects in carbon catabolite repression by determining sensitivity towards allyl alcohol. All except four of the 111 mutants were sensitive to allyl alcohol, indicating that the vast majority of the mutants are defective in carbon catabolite repression. The creA gene of 32 allyl alcohol sensitive mutants was sequenced and 27 of them indeed contained a mutation in the creA gene. Targeted deletion of creA in the reporter strain confirmed that the loss of CreA results in constitutive expression from the faeB promoter. Conclusion: Loss of function of CreA leads to low but inducer-independent expression from the faeB promoter in A. niger. [ABSTRACT FROM AUTHOR]

We decide to start this article with the narrative of Laura Ruiz-Eugenio due to the coincidence that in 1999, the year in which the first issue of the Journal of Educational Science was published, she graduated in Social Education and began to collaborate in CREA´s researches. We include at the end, the story of Nerea Gutierrez as one of the researchers who more recently has been linked to the line of research on educational actions evidence-based.

This study aimed to determine the effectiveness of guanidinoacetic acid (GAA) with or without methionine (Met) compared to creatine (CREA) at enhancing duck’s performance, restoring tissue CREA and improving meat quality. Mulard ducklings (n = 250) were randomly assigned to control (without additives), or control plus CREA, GAA, GAA + 0.2%Met (GAAMet0.2) or GAA + 0.4%Met (GAAMet0.4) groups in a completely random experimental design. Dietary supplementation of CREA or GAA significantly increased (P

Los cambios de escala de los procesos políticos-económicos impuestos por la globalización orientan cada vez más, en Europa, Asia y América Latina, las prácticas de la planificación territorial hacia la implementación de estrategias de desarrollo regional y sub-regional. La “regionalización” es un tema pendiente en la agenda política del Ecuador, y no obstante la actual Constitución establece que el país se organiza territorialmente en regiones, provincias, cantones y parroquias rurales, el desarrollo equitativo, la autonomía y la descentralización de los distintos niveles de gobierno siguen siendo objetivos a alcanzar. Este artículo respalda este debate indagando sobre el enfoque espacial y las visiones territoriales que entre 1952 y 1982 orientaron las propuestas de regionalización en el Ecuador. A tal propósito se analizan valiosos documentos inéditos (estudios, planes y proyectos) realizados por la JUNAPLA y el CREA: únicos ensayos de Planificación Regional realizados en el país, de manera particular en la Región Centro-Sur.

This study aimed to determine the effectiveness of guanidinoacetic acid (GAA) with or without methionine (Met) compared to creatine (CREA) at enhancing duck's performance, restoring tissue CREA and improving meat quality. Mulard ducklings (n = 250) were randomly assigned to control (without additives), or control plus CREA, GAA, GAA + 0.2%Met (GAAMet0.2) or GAA + 0.4%Met (GAAMet0.4) groups in a completely random experimental design. Dietary supplementation of CREA or GAA significantly increased (P < 0.05) overall weight gain and improved feed:gain ratio. Supplementation of GAA (especially GAAMet0.4 group) significantly increased (P < 0.05) carcass and breast yield. Meat pH values were higher (P < 0.05) with dietary GAA + Met or CREA. Providing of dietary GAA + Met led to higher levels of plasma CREA than dietary CREA itself. The molecular investigation indicated that dietary CREA or GAA with Met enhanced the gene expression of hepatic insulin-like growth factor-1, growth hormone and muscle myogenin. Finally, dietary GAA + Met was superior to CREA in improving duck's performance based on molecular markers related to growth (IGF-1 and growth hormone) and myogenesis (upregulating myogenin and downregulating myostatin). Although, dietary GAA + Met enhanced muscle's CREA loading than CREA, the long-term GAA supplementation in ducks may induce methyl-groups shortage for protein synthesis, this was resolved with Met addition in our study. [ABSTRACT FROM AUTHOR]

As a C2H2 type zinc finger transcription factor, CreA is the key in Carbon Catabolism Repression (CCR) pathway, which negatively regulates the genes in carbon sources utilization. As conidiation in filamentous fungi is affected by nutritional conditions, CreA may contribute to fungal conidiation, which has been well studied in filamentous fungi, especially Aspergillus spp., but researches on entomopathogenic fungi are not enough. In this study, we found a homologous gene MaCreA in Metarhizium acridum, and the MaCreA deletion strain showed delayed conidiation, significant decrease in conidial yield, and 96.88% lower conidial production, when compared with the wild-type strain, and the normal conidiation and microcycle conidiation pattern shift was blocked. RT-qPCR showed that the transcription levels of the genes FlbD and LaeA (related to asexual development) were significantly altered, and those of most of the conidiation-related genes were higher in ΔMaCreA strain. The results of RNA-Seq revealed that MaCreA regulated the two conidiation patterns by mediating genes related to cell cycle, cell division, cell wall, and cell polarity. In conclusion, CreA, as a core regulatory gene in conidiation, provides new insight into the mechanism of conidiation in entomopathogenic fungi.

ABSTRACT In filamentous fungi, an important kinase responsible for adaptation to changes in available nutrients is cyclic AMP (cAMP)-dependent protein kinase (protein kinase A [PKA]). This kinase has been well characterized at a molecular level, but its systemic action and direct/indirect targets are generally not well understood in filamentous fungi. In this work, we used a pkaA deletion strain (ΔpkaA) to identify Aspergillus nidulans proteins for which phosphorylation is dependent (either directly or indirectly) on PKA. A combination of phosphoproteomic and transcriptomic analyses revealed both direct and indirect targets of PKA and provided a global perspective on its function. One of these targets was the transcription factor CreA, the main repressor responsible for carbon catabolite repression (CCR). In the ΔpkaA strain, we identified a previously unreported phosphosite in CreA, S319, which (based on motif analysis) appears to be a direct target of Stk22 kinase (AN5728). Upon replacement of CreA S319 with an alanine (i.e., phosphonull mutant), the dynamics of CreA import to the nucleus are affected. Collectively, this work provides a global overview of PKA function while also providing novel insight regarding significance of a specific PKA-mediated phosphorylation event. IMPORTANCE The cyclic AMP (cAMP)-dependent protein kinase A (PKA) signaling pathway is well conserved across eukaryotes, and previous work has shown that it plays an important role in regulating development, growth, and virulence in a number of fungi. PKA is activated in response to extracellular nutrients and acts to regulate metabolism and growth. While a number of components in the PKA pathway have been defined in filamentous fungi, current understanding does not provide a global perspective on PKA function. Thus, this work is significant in that it comprehensively identifies proteins and functional pathways regulated by PKA in a model filamentous fungus. This information enhances our understanding of PKA action and may provide information on how to manipulate it for specific purposes.

Carbon catabolite repression (CCR) is a global regulatory mechanism that allows organisms to preferentially utilize a preferred carbon source (usually glucose) by suppressing the expression of genes associated with the utilization of nonpreferred carbon sources. Aspergillus is a large genus of filamentous fungi, some species of which have been used as microbial cell factories for the production of organic acids, industrial enzymes, pharmaceuticals, and other fermented products due to their safety, substrate convenience, and well-established post-translational modifications. Many recent studies have verified that CCR-related genetic alterations can boost the yield of various carbohydrate-active enzymes (CAZymes), even under CCR conditions. Based on these findings, we emphasize that appropriate regulation of the CCR pathway, especially the expression of the key transcription factor CreA gene, has great potential for further expanding the application of Aspergillus cell factories to develop strains for industrial CAZymes production. Further, the genetically modified CCR strains (chassis hosts) can also be used for the production of other useful natural products and recombinant proteins, among others. We here review the regulatory mechanisms of CCR in Aspergillus and its direct application in enzyme production, as well as its potential application in organic acid and pharmaceutical production to illustrate the effects of CCR on Aspergillus cell factories., (© 2024 Wiley-VCH GmbH.)

As a C2H2 type zinc finger transcription factor, CreA is the key in Carbon Catabolism Repression (CCR) pathway, which negatively regulates the genes in carbon sources utilization. As conidiation in filamentous fungi is affected by nutritional conditions, CreA may contribute to fungal conidiation, which has been well studied in filamentous fungi, especially Aspergillus spp., but researches on entomopathogenic fungi are not enough. In this study, we found a homologous gene MaCreA in Metarhizium acridum , and the MaCreA deletion strain showed delayed conidiation, significant decrease in conidial yield, and 96.88% lower conidial production, when compared with the wild-type strain, and the normal conidiation and microcycle conidiation pattern shift was blocked. RT-qPCR showed that the transcription levels of the genes FlbD and LaeA (related to asexual development) were significantly altered, and those of most of the conidiation-related genes were higher in Δ MaCreA strain. The results of RNA-Seq revealed that MaCreA regulated the two conidiation patterns by mediating genes related to cell cycle, cell division, cell wall, and cell polarity. In conclusion, CreA , as a core regulatory gene in conidiation, provides new insight into the mechanism of conidiation in entomopathogenic fungi. [ABSTRACT FROM AUTHOR]

The AraR transcription factor of Aspergillus niger encodes a Zn(II)2Cys6 transcription factor required for the induction of genes encoding arabinolytic enzymes. One of the target genes of AraR is abfA, encoding an arabinofuranosidase. The expression of abfA as well as other L-arabinose-induced genes in A. niger requires the presence of L-arabinose or its derivative L-arabitol as an inducer to activate AraR-dependant gene expression. In this study, mutants were isolated that express L-arabinose-induced genes independently of the presence of an inducer under derepressing conditions. To obtain these mutants, a reporter strain was constructed in a ΔcreA background containing the L-arabinose-responsive promoter (PabfA) fused to the acetamidase (amdS) gene. Spores of the ΔcreA PabfA-amdS reporter strain were UV-mutagenized and mutants were obtained by their ability to grow on acetamide without the presence of inducer. From a total of 164 mutants, 15 mutants were identified to contain transacting mutations resulting in high arabinofuranosidase activity in the medium after growth under non-inducing conditions. Sequencing of the araR gene of the 15 constitutive mutants revealed that 14 mutants carried a mutation in AraR. Some mutations were found more than once and in total nine different point mutations were identified in AraR. The AraRN806I point mutation was reintroduced into a parental strain and confirmed that this point mutation leads to inducer-independent expression of AraR target genes. The inducer independent of L-arabinose-induced genes in the AraRN806I mutant was found to be sensitive to carbon catabolite repression, indicating that the CreA-mediated carbon catabolite repression is dominant over the AraRN806I mutant allele. These mutations in AraR provide new opportunities to improve arabinase production in industrial fungal strains. [ABSTRACT FROM AUTHOR]

Summary: Amongst the universal diseases affecting apples, blue mould caused by Penicillium expansum is a major concern, resulting in yield and quality losses as a result of the production of the mycotoxin patulin. Despite the characterization of the patulin biosynthetic gene cluster at both the molecular and chemical levels, the underlying regulation of patulin biosynthesis in P. expansum and the mechanisms of apple colonization remain largely obscure. Recent work has indicated that sucrose, a carbon catabolite repressive metabolite, is a critical factor in the regulation of patulin synthesis. Here, CreA, the global carbon catabolite regulator, was assessed for virulence both in vitro and in vivo. We showed that loss‐of‐function creA strains were nearly avirulent and did not produce patulin in apples. On the basis of RNA‐sequencing (RNA‐seq) analysis and physiological experimentation, these mutants were unable to successfully colonize apples for a multitude of potential mechanisms including, on the pathogen side, a decreased ability to produce proteolytic enzymes and to acidify the environment and impaired carbon/nitrogen metabolism and, on the host side, an increase in the oxidative defence pathways. Our study defines CreA and its downstream signalling pathways as promising targets for the development of strategies to fight against the development and virulence of this post‐harvest pathogen. [ABSTRACT FROM AUTHOR]

[Display omitted] • Transcriptional factor CreA negatively regulated potential xylose transporters DN7263 and DN7661 to inhibit xylose assimilation and lipid synthesis in Saitozyma podzolica zwy-2-3. • Overexpression of DN7263 and DN7661 and knockout CreA accelerated xylose utilization and promoted furfural tolerance. • DN7263 and DN7661 transporters alleviated the oxidative stress damage caused by furfural by reducing reactive oxygen species (ROS) production and accelerating ROS scavenging. • Δ CreA and OE:: DN7263 strains potentially develop to be the excellent robust chassis strain for industrial applications. Lignocellulose's hydrolysate, a significant renewable source, contains xylose and furfural, making it challenging for industrial production of oleaginous yeast. On xylose fermentation with furfural treatment, OE:: DN7263 and OE:: DN7661 increased lipid yield and furfural tolerance versus WT, while, which of OE:: CreA were decreased owing to CreA regulating DN7263 and DN7661 negatively. OE:: CreA generated reactive oxygen species (ROS) causing oxidative damage. OE:: DN7263 , OE:: DN7661 , and Δ CreA reduced furfural via NADH; while Δ CreA produced less ROS and OE:: DN7263 , and OE:: DN7661 scavenged ROS quickly, minimizing oxidative damage. Overall, CreA knockout increased DN7263 and DN7661 expression to facilitate xylose assimilation, enhancing NADH generation and ROS clearance. Finally, with mixed sugar fermentation, Δ CreA and OE:: DN7263 ′s biomass and lipid yield rose without furfural addition, while that of Δ CreA remained higher than WT after furfural treatment. These findings revealed how oleaginous yeast zwy-2–3 resisted furfural stress and indicated Δ CreA and OE:: DN7263 might develop into robust industrial chassis strains. [ABSTRACT FROM AUTHOR]

Carbon is one of the most important nutrients for the development and secondary metabolism in fungi. CreA is the major transcriptional factor mediating carbon catabolite repression, which is employed in the utilization of carbon sources. Aspergillus ochraceus contaminates various food and feed containing different carbon sources by producing ochratoxin A (OTA). However, little is known about the function of AoCreA in regulating the morphology and OTA production of A. ochraceus. To give an insight into the mechanism of the carbon sources regulating development of A. ochraceus and OTA production, we have identified AoCreA in A. ochraceus. The homologous recombination strategy was used to generate the AoCreA deletion mutant (ΔAoCreA). We have investigated the morphology and OTA production of the wild type (WT) and ΔAoCreA of A. ochraceus with media containing different carbon sources (glucose, fructose, maltose, D-xylose, D-mannose, acetate, D-galactose, D-mannitol and lactose). ΔAoCreA showed a significant growth and conidiation defect on all media as compared with WT. Glucose and maltose were the most inducing media for OTA production by A. ochraceus, followed by sucrose and the nutrient-rich Yeast Extract Sucrose (YES) and Potato Dextrose Agar (PDA). The deletion of AoCreA led to a drastic reduction of OTA production on all kinds of media except PDA, which was supported by the expression profile of OTA biosynthetic genes. Furthermore, infection studies of ΔAoCreA on oats and pears showed the involvement of AoCreA in the pathogenicity of A. ochraceus. Thus, these results suggest that AoCreA regulates morphological development and OTA biosynthesis in response to carbon sources in A. ochraceus.

ABSTRACT The attachment of one or more ubiquitin molecules by SCF (Skp–Cullin–F-box) complexes to protein substrates targets them for subsequent degradation by the 26S proteasome, allowing the control of numerous cellular processes. Glucose-mediated signaling and subsequent carbon catabolite repression (CCR) are processes relying on the functional regulation of target proteins, ultimately controlling the utilization of this carbon source. In the filamentous fungus Aspergillus nidulans, CCR is mediated by the transcription factor CreA, which modulates the expression of genes encoding biotechnologically relevant enzymes. Although CreA-mediated repression of target genes has been extensively studied, less is known about the regulatory pathways governing CCR and this work aimed at further unravelling these events. The Fbx23 F-box protein was identified as being involved in CCR and the Δfbx23 mutant presented impaired xylanase production under repressing (glucose) and derepressing (xylan) conditions. Mass spectrometry showed that Fbx23 is part of an SCF ubiquitin ligase complex that is bridged via the GskA protein kinase to the CreA-SsnF-RcoA repressor complex, resulting in the degradation of the latter under derepressing conditions. Upon the addition of glucose, CreA dissociates from the ubiquitin ligase complex and is transported into the nucleus. Furthermore, casein kinase is important for CreA function during glucose signaling, although the exact role of phosphorylation in CCR remains to be determined. In summary, this study unraveled novel mechanistic details underlying CreA-mediated CCR and provided a solid basis for studying additional factors involved in carbon source utilization which could prove useful for biotechnological applications. IMPORTANCE The production of biofuels from plant biomass has gained interest in recent years as an environmentally friendly alternative to production from petroleum-based energy sources. Filamentous fungi, which naturally thrive on decaying plant matter, are of particular interest for this process due to their ability to secrete enzymes required for the deconstruction of lignocellulosic material. A major drawback in fungal hydrolytic enzyme production is the repression of the corresponding genes in the presence of glucose, a process known as carbon catabolite repression (CCR). This report provides previously unknown mechanistic insights into CCR through elucidating part of the protein-protein interaction regulatory system that governs the CreA transcriptional regulator in the reference organism Aspergillus nidulans in the presence of glucose and the biotechnologically relevant plant polysaccharide xylan.

The "regionalization" is a pending issue of Ecuador's political agenda, well the equitable development, the autonomy and the decentralization of the different government levels continue being objective to achieve. This article endorses this debate through a historical-critical and interdisciplinary discussion over the institutionalization and evolution of the National Planning in Ecuador (1952-1982) and the "physicist" and "regional" approaches of the National Development Plans. For this purpose, are analyzed studies, schemes and plans, elaborated by national, international and regional developmet entities: proposals that will be formulated in supporting Center-South Region develompment and partially implemented at the microregional scale. [ABSTRACT FROM AUTHOR]

Carbon catabolite repression (CCR) is a very important mechanism employed in the utilization of carbon as an energy source, required for the regulation of growth, development and secondary metabolite production in fungi. Despite the wide study of this mechanism in fungi, little is known about the major CCR gene creA in A. flavus . Hence, we report identification of A. flavus carbon catabolite repression gene creA , which is responsible for the repression of secondary carbon sources. Gene deletion and over-expression was employed to explicate the role of creA in the morphology, pathogenicity, and secondary metabolite production in A. flavus . We investigated these factors using three carbon sources including glucose, sucrose and maltose. Gene deletion mutant (Δ creA ) had a significant growth defect on complete medium and minimal medium containing maltose. Conidia production in Δ creA was significantly impaired irrespective of the carbon source available, while sclerotia production was significantly increased, compared to wild type (WT) and over-expression strain (OE:: creA ). Importantly, Δ creA produced insignificant amount of aflatoxin in complete medium, and its ability to colonize hosts was also impaired. Concisely, we showed that creA played an important role in the morphology, pathogenicity and secondary metabolite production of A. flavus . [ABSTRACT FROM AUTHOR]

Carbon Catabolite Repression (CCR) has fascinated scientists and researchers around the globe for the past few decades. This important mechanism allows preferential utilization of an energy-efficient and readily available carbon source over relatively less easily accessible carbon sources. This mechanism helps microorganisms to obtain maximum amount of glucose in order to keep pace with their metabolism. Microorganisms assimilate glucose and highly favorable sugars before switching to less-favored sources of carbon such as organic acids and alcohols. In CCR of filamentous fungi, CreA acts as a transcription factor, which is regulated to some extent by ubiquitination. CreD-HulA ubiquitination ligase complex helps in CreA ubiquitination, while CreB-CreC deubiquitination (DUB) complex removes ubiquitin from CreA, which causes its activation. CCR of fungi also involves some very crucial elements such as Hexokinases, cAMP, Protein Kinase (PKA), Ras proteins, G protein-coupled receptor (GPCR), Adenylate cyclase, RcoA and SnfA. Thorough study of molecular mechanism of CCR is important for understanding growth, conidiation, virulence and survival of filamentous fungi. This review is a comprehensive revision of the regulation of CCR in filamentous fungi as well as an updated summary of key regulators, regulation of different CCR-dependent mechanisms and its impact on various physical characteristics of filamentous fungi. [ABSTRACT FROM AUTHOR]

The role of the transcription factor creA-mediating carbon catabolite repression in Trichoderma orientalis EU7-22 was investigated for cellulase and hemicellulase production. The binary vector pUR5750G/ creA:: hph was constructed to knock out creA by homologous integration, generating the Δ creA mutant Trichoderma orientalis CF1D. For strain CF1D, the filter paper activities (FPA), endoglucanase activities (CMC), cellobiohydrolase activity(CBH), β-glucosidase activity (BG), xylanase activity (XYN), and extracellular protein concentration were 1.45-, 1.15-, 1.71-, 2.51-, 2.72, and 1.95-fold higher in inducing medium and were 6.41-, 7.50-, 10.27-, 11.79-, 9.25-, and 3.77-fold higher in glucose repressing medium, respectively, than those in the parent strain after 4 days. SDS-PAGE demonstrated that the extracellular proteins were largely secreted in the mutant CF1D. Quantitative reverse-transcription polymerase chain reaction indicated that the expressions of cbh1, cbh2, eg1, eg2, bgl1, xyn1, and xyn2 were significantly increasing for the mutant CF1D not only in the inducing medium but also in the repressing medium. Those results indicated that creA was a valid target gene in strain engineering for improved enzyme production in T. orientalis. [ABSTRACT FROM AUTHOR]

Aureobasidium melanogenum P16 is a high pullulan-producing yeast. However, glucose repression on its pullulan biosynthesis must be relieved. After the gene encoding a glucose repressor was cloned, characterized and analyzed, it was found that the repressor belonged to one member of the CreA in filamentous fungi, not to one member of the Mig1 in yeasts. After the CREA gene was fully removed from the yeast strain P16, the glucose repression in the disruptant DG41 was relieved. At the same time, the pullulan production by the disruptant DG41 was enhanced compared to that by its wild-type strain P16, and the transcriptional levels of the gene encoding a glucosyltransferase, three genes encoding glucose transporters, the gene encoding a 6-P-glucose kinase and the genes encoding α-amylase, glucoamylase and pullulanase in the disruptant DG41 were also promoted. However, the transcriptional levels of the genes encoding the CreA and another two glucose transporters were greatly reduced. During the 10-liter fermentation, the disruptant DG41 produced 64.93 ± 1.33 g/l pullulan from 120 g/l of glucose, while its wild-type strain P16 produced only 52.0 ± 1.95 g/l pullulan within 132 h. After the CREA gene was complemented in the disruptant D373, the pullulan production by the transformant BC4 was greatly reduced compared to that by its wild-type strain P16, and the transcriptional levels of the many genes in the transformant BC4 were also decreased. All the results confirmed that the CreA played an important role in the regulation of pullulan biosynthesis in A. melanogenum P16, and that glucose derepression on pullulan biosynthesis could improve pullulan production from glucose. This study opened the possibility for improving the industrial production of this exopolysaccharide by genetic engineering. [ABSTRACT FROM AUTHOR]

Seed contamination with polyketide mycotoxins such as sterigmatocystin (ST) produced by Aspergilli is a worldwide issue. The ST biosynthetic pathway is well-characterized in A. nidulans, but regulatory aspects related to the carbon source are still enigmatic. This is particularly true for lactose, inasmuch as some ST production mutant strains still synthesize ST on lactose but not on other carbon substrates. Here, kinetic data revealed that on D-glucose, ST forms only after the sugar is depleted from the medium, while on lactose, ST appears when most of the carbon source is still available. Biomass-specified ST production on lactose was significantly higher than on D-glucose, suggesting that ST formation may either be mediated by a carbon catabolite regulatory mechanism, or induced by low specific growth rates attainable on lactose. These hypotheses were tested by D-glucose limited chemostat-type continuous fermentations. No ST formed at a high growth rate, while a low growth rate led to the formation of 0.4 mg·L-1 ST. Similar results were obtained with a CreA mutant strain. We concluded that low specific growth rates may be the primary cause of mid-growth ST formation on lactose in A. nidulans, and that carbon utilization rates likely play a general regulatory role during biosynthesis. [ABSTRACT FROM AUTHOR]

Fusarium avenaceum is a widespread pathogen of important crops in the temperate climate zones that can produce many bioactive secondary metabolites, including moniliformin, fusarin C, antibiotic Y, 2-amino-14,16-dimethyloctadecan-3-ol (2-AOD-3-ol), chlamydosporol, aurofusarin and enniatins. Here, we examine the production of these secondary metabolites in response to cultivation on different carbon sources in order to gain insight into the regulation and production of secondary metabolites in F. avenaceum. Seven monosaccharides (arabinose, xylose, fructose, sorbose, galactose, mannose, glucose), five disaccharides (cellobiose, lactose, maltose, sucrose and trehalose) and three polysaccharides (dextrin, inulin and xylan) were used as substrates. Three F. avenaceum strains were used in the experiments. These were all able to grow and produce aurofusarin on the tested carbon sources. Moniliformin and enniatins were produced on all carbon types, except on lactose, which suggest a common conserved regulation mechanism. Differences in the strains was observed for production of fusarin C, 2-AOD-3-ol, chlamydosporol and antibiotic Y, which suggests that carbon source plays a role in the regulation of their biosynthesis.

Se analiza el planteamiento teórico, desarrollo metodológico y aproximación a unos primeros resultados de un proyecto de investigación aplicada, financiado por el Ministerio de Educación, para la propuesta de un modelo de indicadores competenciales de alfabetización en información en bibliotecas escolares. A partir de la consideración de la alfabetización en información como competencia para conocer y saber en red y la biblioteca escolar como Centro de Recursos para la Enseñanza y el Aprendizaje (CREA), se plantean, siguiendo propuestas ya enunciadas, como objetivos el diseño de indicadores cualitativos para medir el progreso y la calidad de programas de alfabetización en información para bibliotecas escolares. Se presenta la formulación del modelo de indicadores, categorizado en destrezas, habilidades y competencias, plasmado luego en un cuestionario-tipo según niveles educativos y sobre unos recursos digitales seleccionados, que fue pre-testado para su aplicación en Asturias, Navarra y Madrid. Se describe su aplicación en las tres comunidades, la naturaleza de las cuestiones, el procesamiento de datos y una aproximación a un primer análisis interpretativo por niveles educativos. Se aborda, finalmente, la argumentación de unas primeras conclusiones a modo de desarrollos futuros del proyecto y recomendaciones para el desarrollo de la Sociedad del conocimiento, a partir de un eficaz plan de programas de alfabetización en información desde bibliotecas escolares transformadas en CREA.

Aflatoxin biosynthesis is correlated with oxidative stress and is proposed to function as a secondary defense mechanism to redundant intracellular reactive oxygen species (ROS). We find that the antioxidant gallic acid inhibits aflatoxin formation and growth in Aspergillus flavus in a dose-dependent manner. Global expression analysis (RNA-Seq) of gallic acid-treated A. flavus showed that 0.8% (w/v) gallic acid revealed two possible routes of aflatoxin inhibition. Gallic acid significantly inhibited the expression of farB, encoding a transcription factor that participates in peroxisomal fatty acid β-oxidation, a fundamental contributor to aflatoxin production. Secondly, the carbon repression regulator encoding gene, creA, was significantly down regulated by gallic acid treatment. CreA is necessary for aflatoxin synthesis, and aflatoxin biosynthesis genes were significantly downregulated in ∆creA mutants. In addition, the results of antioxidant enzyme activities and the lipid oxidation levels coupled with RNA-Seq data of antioxidant genes indicated that gallic acid may reduce oxidative stress through the glutathione- and thioredoxin-dependent systems in A. flavus.

This paper aims to show some of the advantages of and the need for using corpora for exploring and assessing Anglicisms in contemporary Spanish. In order to do this a case study is presented: the adverb dramáticamente, as it is taking on the new sense ‘espectacularmente’ under the influence of English dramatically. The presence of this adverb with this new sense in contemporary Spanish is explored and supported with the data found in CORDE and CREA, the two corpora of the Royal Spanish Academy. Since the paper also seeks to show in what ways the Spanish lexicon is being influenced by English, evidence from two major English corpora, the BNC and the COCA, will be used.Este artículo pretende mostrar las ventajas y la necesidad del uso de corpus electrónicos para explorar y evaluar la presencia de anglicismos en español contemporáneo. Para ello se analiza el caso del adverbio dramáticamente, que está desarrollando un nuevo sentido por influencia del inglés dramatically. La presencia de dramáticamente usado con este nuevo sentido en español contemporáneo se explora, apoya y documenta con los datos obtenidos del CORDE y el CREA, los corpus de la Real Academia Española. Puesto que el fin del trabajo es en última instancia demostrar de manera empírica la influencia del inglés en el léxico español, se utilizan también dos corpus de inglés, el BNC y el COCA.

The morphological development of fungi is a complex process and is often coupled with secondary metabolite production. In this study, we assessed the function of putative methyltransferase LaeA and transcription factor CreA in controlling asexual development and secondary metabolic gene cluster expression in Penicillium oxalicum . The deletion of laeA (Δ laeA ) impaired the conidiation in P. oxalicum , with a downregulated expression of brlA . Overexpression of P . oxalicum brlA in Δ laeA could upregulate brlA and abaA remarkably, but could not rescue the conidiation defect; therefore, brlA and abaA expression were necessary but not sufficient for conidiation. Deletion of creA in Δ laeA background (Δ laeA Δ creA ) blocked conidiation with a white fluffy phenotype. Nutrient-rich medium could not rescue developmental defects in Δ laeA Δ creA mutant but could rescue defects in Δ laeA . Expression of 10 genes, namely, albA / wA , abrB / yA , arpA , aygA , arpA-like , arpB , arpB-like , rodA , rodA-like , and rodB , for pigmentation and spore wall protein genes was silenced in Δ laeA Δ creA , whereas only six of them were downregulated in Δ laeA . Among the 28 secondary metabolism gene clusters in P. oxalicum , four secondary metabolism gene clusters were silenced in Δ laeA and two were also silenced in Δ brlA mutant. A total of 10 physically linked and coregulated genes were distributed over five chromosomes in Δ laeA . Six of these genes were located in subtelomeric regions, thus demonstrating a positional bias for LaeA-regulated clusters toward subtelomeric regions. All of silenced clusters located in subtelomeric regions were derepressed in Δ laeA Δ creA , hence showing that lack of CreA could remediate the repression of gene clusters in Δ laeA background. Results show that both putative methyltransferase LaeA and transcription factor CreA are necessary for proper asexual development and controlling secondary metabolic gene cluster expression. [ABSTRACT FROM AUTHOR]

The ascomycete fungus Mycosphaerella graminicola (synonym Zymoseptoria tritici) is an important pathogen of wheat causing economically significant losses. The primary nutritional mode of this fungus is thought to be hemibiotrophic. This pathogenic lifestyle is associated w ith an early biotrophic stage of nutrient uptake followed by a necrotrophic stage aided possibly by production of a toxin or reactive oxygen species (ROS). In many other fungi, the genes CREA and AREA are important during the biotrophic stage of infection, while the NOXa gene product is important during necrotrophic growth. To test the hypothesis that these genes are important for pathogenicity of M. graminicola, we employed an over-expression strategy for the selected target genes CREA, AREA, and NOXa, which might function as regulators of nutrient acquisition or ROS generation. Increased expressions of CREA, AREA, and NOXa in M. graminicola were confirmed via quantitative real-time PCR and strains were subsequently assayed for pathogenicity. Among them, the NOXa over-expression strain, N02, resulted in significantly increased virulence. Moreover, instead of the usual filamentous growth, we observed a predominance of yeast-like growth of N02 which was correlated with ROS production. Our data indicate that ROS generation via NOXa is important to pathogenicity as well as development in M. graminicola. [ABSTRACT FROM AUTHOR]

Background: Transcription of genes coding for xylanolytic and cellulolytic enzymes in Aspergillus niger is controlled by the transactivator XlnR. In this work we analyse and model the transcription dynamics in the XlnR regulon from time-course data of the messenger RNA levels for some XlnR target genes, obtained by reverse transcription quantitative PCR (RT-qPCR). Induction of transcription was achieved using low (1 mM) and high (50 mM) concentrations of D-xylose (Xyl). We investigated the wild type strain (Wt) and a mutant strain with partial loss-of-function of the carbon catabolite repressor CreA (Mt). Results: An improved kinetic differential equation model based on two antagonistic Hill functions was proposed, and fitted to the time-course RT-qPCR data from the Wt and the Mt by numerical optimization of the parameters. We show that perturbing the XlnR regulon with Xyl in low and high concentrations results in different expression levels and transcription dynamics of the target genes. At least four distinct transcription profiles were observed, particularly for the usage of 50 mM Xyl. Higher transcript levels were observed for some genes after induction with 1 mM rather than 50 mM Xyl, especially in the Mt. Grouping the expression profiles of the investigated genes has improved our understanding of induction by Xyl and the according regulatory role of CreA. Conclusions: The model explains for the higher expression levels at 1 mM versus 50 mM in both Wt and Mt. It does not yet fully encapsulate the effect of partial loss-of-function of CreA in the Mt. Themodel describes the dynamics in most of the data and elucidates the time-dynamics of the two major regulatory mechanisms: i) the activation by XlnR, and ii) the carbon catabolite repression by CreA. [ABSTRACT FROM AUTHOR]

Aspergillus niger is an important industrial fungus expressing a broad spectrum of pectinolytic genes. The main constituent of pectin, polygalacturonic acid (PGA), is degraded into galacturonic acid (GA) by the combined activity of endo- and exo-polygalacturonases some of which are specifically induced by GA. The regulatory mechanisms that control the expression of genes encoding PGA-degrading enzymes are not well understood. Based on available genome-wide expression profiles from literature, we selected five genes that were specifically induced by GA. These genes include three exo-polygalacturonases ( pgaX , pgxB and pgxC ), a GA transporter ( gatA ), and an intracellular enzyme involved in GA metabolism ( gaaB ). These five genes contain a conserved motif (5′-TCCNCCAAT-3′) in their promoter regions, which we named GARE (galacturonic acid-responsive element). Promoter deletion studies and site-directed mutagenesis of the conserved motif of the pgaX gene showed that the conserved element is required for GA-mediated induction. A set of promoter reporter strains was constructed by fusing the promoter region of the five above-mentioned genes to the amdS reporter gene. Expression of the amdS gene is quantitatively correlated with ability to utilise acetamide as an N-source, hence higher expression of amdS improves growth of the strain on acetamide and therefore can be used as an in vivo reporter for gene expression. Growth analysis of the reporter strains indicated that four genes ( pgaX , pgxB , pgxC , and gatA ) are specifically induced by GA. The in vivo promoter reporter strains were also used to monitor carbon catabolite repression control. Except for gaaB , all promoter–reporter genes analysed were repressed by glucose in a glucose concentration-dependent way. Interestingly, the strength of glucose repression was different for the tested promoters. CreA is important in mediating carbon catabolite repression as deletion of the creA gene in the reporter strains abolished carbon catabolite repression for most promoters. Interestingly, the pgxC promoter was still repressed by glucose even in the creA null background, suggesting a role for alternative repression mechanisms. Finally, we showed that low concentrations of GA are required to induce gene expression of pgaX , pgxB , and pgxC even under derepressing conditions. The results obtained are consistent with a model in which a GA-specific transcription factor is activated by GA or a GA-derivative, which binds to the conserved motif, possibly in combination with the HAP-complex, to drive GA-specific gene expression. [ABSTRACT FROM AUTHOR]