Mimesis en Aristóteles : Reconsideración de su significado y su función en el Corpus Aristotelicum

El punto de partida de la presente investigación sobre el significado y la función que la mimesis tiene en el pensamiento de Aristóteles está dado por la adopción de una perspectiva de estudio 'amplia', i.e. no restringida a la esfera de las artes miméticas y que atienda al vasto y diverso registro de usos del vocabulario mimético atestiguado en el Corpus Aristotelicum. La exégesis contemporánea -paradigmáticamente representada por Halliwell (2002)- acuerda en recortar la superficie textual de investigación al dominio de la Poética (especialmente, al de sus tres primeros capítulos) y en menor medida, al libro VIII de la Política. Aún cuando es innegable el valor que la Poética tiene en la reconstrucción de la significación aristotélica de mimesis, la consideración de otras obras y otros pasajes en los que el filósofo recurre al empleo de este vocabulario, v.gr. H.A., Mete., Phys., Met., permite comprender el lugar destacado que Aristóteles le otorga a la habilidad y a las artes miméticas en el marco general de su pensamiento. La reevaluación general del significado de esta familia de palabras en el Corpus se organiza en dos partes principales. La primera está dedicada al análisis de la habilidad y de las artes miméticas como formas de aprendizaje a partir de los empleos atestiguados en Poética y en Política VII-VIII. A pesar de no ofrecer en la Poética ni en ninguna otra parte del Corpus una definición del término, el análisis realizado en el primer capítulo de la tesis sobre los principales usos del vocabulario mimético en dicha obra, i.e. capítulos 1-3, 4, 9, 24 y 25, revela que la habilidad y las artes miméticas, en cuanto que derivan de ella, constituyen para Aristóteles formas más o menos complejas de aprendizaje por medio de la identificación de semejanzas. En el segundo capítulo se examina el valor pedagógico que en los dos últimos libros de la Política Aristóteles le reconoce a la mimesis, y la singularidad que le atribuye a la mimesis musical entre las artes miméticas. El carácter antropológico de la mimesis como habilidad primaria de adquisición de conocimientos, ligada al deseo humano de conocer, permite explicar la función ético-política que le otorga a la música y de manera plausible, a las restantes artes miméticas en el programa educativo utópico del Estado ideal. La segunda parte está consagrada a investigar el empleo del vocabulario mimético en el resto del Corpus, i.e. aquellos usos no referidos a las artes miméticas y que permiten esclarecer la significación general de este concepto, y comprender mejor su empleo en relación a ese grupo de artes. En el tercer capítulo se consideran diversos pasajes que revelan el valor didáctico y heurístico que dicho vocabulario tiene en el ámbito de la investigación natural. El cuarto capítulo responde a la exigencia metodológica según la cual, es preciso comprender la mimesis aristotélica a la luz de su historia efectual. El principio conforme al cual las artes imitan a la naturaleza ha sido el eje de la recepción de la mimesis aristotélica hasta el siglo XIX. Completamente ajeno al interés primariamente estético de la exégesis actual, el principio es visto como una amenaza que atenta contra la singularidad del arte. A pesar de esta actitud generalizada por parte de los estudios histórico-sistemáticos contemporáneos se rescata el valor de este principio pues, si bien es cierto que fue formulado por Aristóteles en relación a todas las artes (miméticas y no-miméticas), su aplicación al primer grupo permite elucidar cuál es la función de ellas respecto al fin que la naturaleza ha establecido para el hombre. Finalmente, el apéndice está dedicado a la consideración de la innegable actualidad que la mimesis aristotélica tiene en la reflexión filosófica sistemática sobre el arte.

Mimesis en Aristóteles : Reconsideración de su significado y su función en el Corpus Aristotelicum

El punto de partida de la presente investigación sobre el significado y la función que la mimesis tiene en el pensamiento de Aristóteles está dado por la adopción de una perspectiva de estudio 'amplia', i.e. no restringida a la esfera de las artes miméticas y que atienda al vasto y diverso registro de usos del vocabulario mimético atestiguado en el Corpus Aristotelicum. La exégesis contemporánea -paradigmáticamente representada por Halliwell (2002)- acuerda en recortar la superficie textual de investigación al dominio de la Poética (especialmente, al de sus tres primeros capítulos) y en menor medida, al libro VIII de la Política. Aún cuando es innegable el valor que la Poética tiene en la reconstrucción de la significación aristotélica de mimesis, la consideración de otras obras y otros pasajes en los que el filósofo recurre al empleo de este vocabulario, v.gr. H.A., Mete., Phys., Met., permite comprender el lugar destacado que Aristóteles le otorga a la habilidad y a las artes miméticas en el marco general de su pensamiento. La reevaluación general del significado de esta familia de palabras en el Corpus se organiza en dos partes principales. La primera está dedicada al análisis de la habilidad y de las artes miméticas como formas de aprendizaje a partir de los empleos atestiguados en Poética y en Política VII-VIII. A pesar de no ofrecer en la Poética ni en ninguna otra parte del Corpus una definición del término, el análisis realizado en el primer capítulo de la tesis sobre los principales usos del vocabulario mimético en dicha obra, i.e. capítulos 1-3, 4, 9, 24 y 25, revela que la habilidad y las artes miméticas, en cuanto que derivan de ella, constituyen para Aristóteles formas más o menos complejas de aprendizaje por medio de la identificación de semejanzas. En el segundo capítulo se examina el valor pedagógico que en los dos últimos libros de la Política Aristóteles le reconoce a la mimesis, y la singularidad que le atribuye a la mimesis musical entre las artes miméticas. El carácter antropológico de la mimesis como habilidad primaria de adquisición de conocimientos, ligada al deseo humano de conocer, permite explicar la función ético-política que le otorga a la música y de manera plausible, a las restantes artes miméticas en el programa educativo utópico del Estado ideal. La segunda parte está consagrada a investigar el empleo del vocabulario mimético en el resto del Corpus, i.e. aquellos usos no referidos a las artes miméticas y que permiten esclarecer la significación general de este concepto, y comprender mejor su empleo en relación a ese grupo de artes. En el tercer capítulo se consideran diversos pasajes que revelan el valor didáctico y heurístico que dicho vocabulario tiene en el ámbito de la investigación natural. El cuarto capítulo responde a la exigencia metodológica según la cual, es preciso comprender la mimesis aristotélica a la luz de su historia efectual. El principio conforme al cual las artes imitan a la naturaleza ha sido el eje de la recepción de la mimesis aristotélica hasta el siglo XIX. Completamente ajeno al interés primariamente estético de la exégesis actual, el principio es visto como una amenaza que atenta contra la singularidad del arte. A pesar de esta actitud generalizada por parte de los estudios histórico-sistemáticos contemporáneos se rescata el valor de este principio pues, si bien es cierto que fue formulado por Aristóteles en relación a todas las artes (miméticas y no-miméticas), su aplicación al primer grupo permite elucidar cuál es la función de ellas respecto al fin que la naturaleza ha establecido para el hombre. Finalmente, el apéndice está dedicado a la consideración de la innegable actualidad que la mimesis aristotélica tiene en la reflexión filosófica sistemática sobre el arte.

Executive Managers in Peru's Family Businesses

As in many other developing countries, family businesses are major players in the Peruvian economy. Despite their growth into large-scale groups spanning a wide range of businesses, the owner families still have strong control over their ownership and management. However, Peru's liberal economic reforms in the 1990s brought intense competition into the national market. Not only have these family businesses been forced to compete against large-scale foreign capital that entered the national market through the privatization of state enterprises, but also against cheap goods imported from foreign countries. In order to compete, family businesses have had to move beyond the limited human resources available within the family. The advancement within owner families of new generations with better education and training together with the promotion to top managerial positions of professional salaried managers from outside the family are some of the measures owner families are taking to overcome their human resource limitations.

Transcription factors of the bzip factors of the BZIP family affecting arabidopsis thaliana germination sensu stricto

During seed germination, the endosperm cell walls (CWs) suffer an important weakening process mainly driven by hydrolytic enzymes, such are endo-?- mannanases (MAN; EC. 3.2.1.78) that catalyze the cleavage of ?1?4 bonds in the mannan-polymers. In Arabidopsis thaliana seeds, endo-?-mannanase activity increases during seed imbibition, decreasing after radicle emergence1. AtMAN7 is the most highly expressed MAN gene in seeds upon germination and their transcripts are restricted to the micropylar endosperm and to the radicle tip just before radicle emergence. Mutants with a T-DNA insertion in this gene (K.O. MAN7) have a slower germination rate than the wild type (t50=34 h versus t50=25 h). To gain insight into the transcriptional regulation of the AtMAN7 gene, a bioinformatic search for conserved non-coding cis-elements (phylogenetic shadowing) within the Brassicaceae orthologous MAN7 gene promoters has been done and these conserved motives have been used as baits to look for their interacting transcription factors (TFs), using as a prey an arrayed yeast library of circa 1,200 TFs from A. thaliana. The basic leucine zipper AtbZIP44, but not its closely related ortholog AtbZIP11, has been thus identified and its regulatory function upon AtMAN7 during seed germination validated by different molecular and physiological techniques, such are RT-qPCR analyses, mRNA Fluorescence in situ Hybridization (FISH) experiments, and by the establishment of the germination kinetics of both over-expression (oex) lines and TDNA insertion mutants in AtbZIP44. The transcriptional combinatorial network through which AtbZIP44 regulates AtMAN7 gene expression during seed germination has been further explored through protein-protein interactions between AtbZIP44 and other bZIP members. In such a way, AtbZIP9 has been identified by yeast two-hybrid experiments and its physiological implication in the control of AtMAN7 expression similarly established.

The role of enzyme distortion in the single displacement mechanism of family 19 chitinases

By using molecular dynamics simulations, we have examined the binding of a hexaNAG substrate and two potential hydrolysis intermediates (an oxazoline ion and an oxocarbenium ion) to a family 19 barley chitinase. We find the hexaNAG substrate binds with all sugars in a chair conformation, unlike the family 18 chitinase which causes substrate distortion. Glu 67 is in a position to protonate the anomeric oxygen linking sugar residues D and E whereas Asn 199 serves to hydrogen bond with the C2′ N-acetyl group of sugar D, thus preventing the formation of an oxazoline ion intermediate. In addition, Glu 89 is part of a flexible loop region allowing a conformational change to occur within the active site to bring the oxocarbenium ion intermediate and Glu 89 closer by 4–5 Å. A hydrolysis product with inversion of the anomeric configuration occurs because of nucleophilic attack by a water molecule that is coordinated by Glu 89 and Ser 120. Issues important for the design of inhibitors specific to family 19 chitinases over family 18 chitinases also are discussed.

Free recombination within Helicobacter pylori

Sequences of three gene fragments (flaA, flaB, and vacA) from Helicobacter pylori strains isolated from patients in Germany, Canada, and South Africa were analyzed for diversity and for linkage equilibrium by using the Homoplasy Test and compatibility matrices. Horizontal genetic exchange in H. pylori is so frequent that different loci and polymorphisms within each locus are all at linkage equilibrium. These results indicate that H. pylori is panmictic. Comparisons with sequences from Escherichia coli, Neisseria meningitidis, and Drosophila melanogaster showed that recombination in H. pylori was much more frequent than in other species. In contrast, when multiple family members infected with H. pylori were investigated, some strains were indistinguishable at all three loci. Thus, H. pylori is clonal over short time periods after natural transmission.

An ancient family of human endogenous retroviruses encodes a functional homolog of the HIV-1 Rev protein

The human endogenous retrovirus K (HERV-K) family of endogenous retroviruses consists of ≈50 proviral copies per haploid human genome. Herein, the HERV-Ks are shown to encode a sequence-specific nuclear RNA export factor, termed K-Rev, that is functionally analogous to the HIV-1 Rev protein. Like HIV-1 Rev, K-Rev binds to both the Crm1 nuclear export factor and to a cis-acting viral RNA target to activate nuclear export of unspliced RNAs. Surprisingly, this HERV-K RNA sequence, which is encoded within the HERV-K long terminal repeat, is also recognized by HIV-1 Rev. These data provide surprising evidence for an evolutionary link between HIV-1 and a group of endogenous retroviruses that first entered the human genome ≈30 million years ago.

Mapping regions containing binding residues within functional domains of Plasmodium vivax and Plasmodium knowlesi erythrocyte-binding proteins

Invasion of erythrocytes by malaria parasites is mediated by specific molecular interactions. Whereas Plasmodium vivax and Plasmodium knowlesi use the Duffy blood group antigen, Plasmodium falciparum uses sialic acid residues of glycophorin A as receptors to invade human erythrocytes. P. knowlesi uses the Duffy antigen as well as other receptors to invade rhesus erythrocytes by multiple pathways. Parasite ligands that bind these receptors belong to a family of erythrocyte-binding proteins (EBP). The EBP family includes the P. vivax and P. knowlesi Duffy-binding proteins, P. knowlesi β and γ proteins, which bind alternate receptors on rhesus erythrocytes, and P. falciparum erythrocyte-binding antigen (EBA-175), which binds sialic acid residues of human glycophorin A. Binding domains of each EBP lie in a conserved N-terminal cysteine-rich region, region II, which contains around 330 amino acids with 12 to 14 conserved cysteines. Regions containing binding residues have now been mapped within P. vivax and P. knowlesi β region II. Chimeric domains containing P. vivax region II sequences fused to P. knowlesi β region II sequences were expressed on the surface of COS cells and tested for binding to erythrocytes. Binding residues of P. vivax region II lie in a 170-aa stretch between cysteines 4 and 7, and binding residues of P. knowlesi β region II lie in a 53-aa stretch between cysteines 4 and 5. Mapping regions responsible for receptor recognition is an important step toward understanding the structural basis for the interaction of these parasite ligands with host receptors.

A family of membrane-embedded metalloproteases involved in regulated proteolysis of membrane-associated transcription factors

We present evidence that the sporulation protein SpoIVFB of Bacillus subtilis is a member of a newly recognized family of metalloproteases that have catalytic centers adjacent to or within the membrane. SpoIVFB is required for converting the membrane-associated precursor protein, pro-σK, to the mature and active transcription factor σK by proteolytic removal of an N-terminal extension of 20 amino acids. SpoIVFB and other family members share the conserved sequence HEXXH, a hallmark of metalloproteases, as well as a second conserved motif NPDG, which is unique to the family. Both motifs, which are expected to form the catalytic center of the protease, overlap hydrophobic segments that are predicted to be separate transmembrane domains. The only other characterized member of this family of membrane-embedded metalloproteases is the mammalian Site-2 protease (S2P), which is required for the intramembrane cleavage of the eukaryotic transcription factor sterol regulatory element binding protein (SREBP). We report that amino acid substitutions in the two conserved motifs of SpoIVFB impair pro-σK processing and σK-directed gene expression during sporulation. These results and those from a similar analysis of S2P support the interpretation that both proteins are founding members of a family of metalloproteases involved in the activation of membrane-associated transcription factors. Thus, the pathways that govern the activation of the prokaryotic transcription factor pro-σK and the mammalian transcription factor SREBP not only are analogous but also use processing enzymes with strikingly homologous features.

A family of phase-variable restriction enzymes with differing specificities generated by high-frequency gene rearrangements

The hsd genes of Mycoplasma pulmonis encode restriction and modification enzymes exhibiting a high degree of sequence similarity to the type I enzymes of enteric bacteria. The S subunits of type I systems dictate the DNA sequence specificity of the holoenzyme and are required for both the restriction and the modification reactions. The M. pulmonis chromosome has two hsd loci, both of which contain two hsdS genes each and are complex, site-specific DNA inversion systems. Embedded within the coding region of each hsdS gene are a minimum of three sites at which DNA inversions occur to generate extensive amino acid sequence variations in the predicted S subunits. We show that the polymorphic hsdS genes produced by gene rearrangement encode a family of functional S subunits with differing DNA sequence specificities. In addition to creating polymorphisms in hsdS sequences, DNA inversions regulate the phase-variable production of restriction activity because the other genes required for restriction activity (hsdR and hsdM) are expressed only from loci that are oriented appropriately in the chromosome relative to the hsd promoter. These data cast doubt on the prevailing paradigms that restriction systems are either selfish or function to confer protection from invasion by foreign DNA.

Ultrastructural localization of zinc transporter-3 (ZnT-3) to synaptic vesicle membranes within mossy fiber boutons in the hippocampus of mouse and monkey

Zinc transporter-3 (ZnT-3), a member of a growing family of mammalian zinc transporters, is expressed in regions of the brain that are rich in histochemically reactive zinc (as revealed by the Timm’s stain), including entorhinal cortex, amygdala, and hippocampus. ZnT-3 protein is most abundant in the zinc-enriched mossy fibers that project from the dentate granule cells to hilar and CA3 pyramidal neurons. We show here by electron microscopy that ZnT-3 decorates the membranes of all clear, small, round synaptic vesicles (SVs) in the mossy fiber boutons of both mouse and monkey. Furthermore, up to 60–80% of these SVs contain Timm’s-stainable zinc. The coincidence of ZnT-3 on the membranes of SVs that accumulate zinc, and its homology with known zinc transporters, suggest that ZnT-3 is responsible for the transport of zinc into SVs, and hence for the ability of these neurons to release zinc upon excitation.

RacF1, a Novel Member of the Rho Protein Family in Dictyostelium discoideum, Associates Transiently with Cell Contact Areas, Macropinosomes, and Phagosomes

Using a PCR approach we have isolated racF1, a novel member of the Rho family in Dictyostelium. The racF1 gene encodes a protein of 193 amino acids and is constitutively expressed throughout the Dictyostelium life cycle. Highest identity (94%) was found to a RacF2 isoform, to Dictyostelium Rac1A, Rac1B, and Rac1C (70%), and to Rac proteins of animal species (64–69%). To investigate the role of RacF1 in cytoskeleton-dependent processes, we have fused it at its amino-terminus with green fluorescent protein (GFP) and studied the dynamics of subcellular redistribution using a confocal laser scanning microscope and a double-view microscope system. GFP–RacF1 was homogeneously distributed in the cytosol and accumulated at the plasma membrane, especially at regions of transient intercellular contacts. GFP–RacF1 also localized transiently to macropinosomes and phagocytic cups and was gradually released within <1 min after formation of the endocytic vesicle or the phagosome, respectively. On stimulation with cAMP, no enrichment of GFP–RacF1 was observed in leading fronts, from which it was found to be initially excluded. Cell lines were obtained using homologous recombination that expressed a truncated racF1 gene lacking sequences encoding the carboxyl-terminal region responsible for membrane targeting. These cells displayed normal phagocytosis, endocytosis, and exocytosis rates. Our results suggest that RacF1 associates with dynamic structures that are formed during pinocytosis and phagocytosis. Although RacF1 appears not to be essential, it might act in concert and/or share functions with other members of the Rho family in the regulation of a subset of cytoskeletal rearrangements that are required for these processes.

A Role for Tlg1p in the Transport of Proteins within the Golgi Apparatus of Saccharomyces cerevisiae

Members of the syntaxin protein family participate in the docking–fusion step of several intracellular vesicular transport events. Tlg1p has been identified as a nonessential protein required for efficient endocytosis as well as the maintenance of normal levels of trans-Golgi network proteins. In this study we independently describe Tlg1p as an essential protein required for cell viability. Depletion of Tlg1p in vivo causes a defect in the transport of the vacuolar protein carboxypeptidase Y through the early Golgi. Temperature-sensitive (ts) mutants of Tlg1p also accumulate the endoplasmic reticulum/cis-Golgi form of carboxypeptidase Y at the nonpermissive temperature (38°C) and exhibit underglycosylation of secreted invertase. Overexpression of Tlg1p complements the growth defect of vti1-11 at the nonpermissive temperature, whereas incomplete complementation was observed with vti1-1, further suggesting a role for Tlg1p in the Golgi apparatus. Overexpression of Sed5p decreases the viability of tlg1 ts mutants compared with wild-type cells, suggesting that tlg1 ts mutants are more susceptible to elevated levels of Sed5p. Tlg1p is able to bind His6-tagged Sec17p (yeast α-SNAP) in a dose-dependent manner and enters into a SNARE complex with Vti1p, Tlg2p, and Vps45p. Morphological analyses by electron microscopy reveal that cells depleted of Tlg1p or tlg1 ts mutants incubated at the restrictive temperature accumulate 40- to 50-nm vesicles and experience fragmentation of the vacuole.

Cloning, expression, and genetic mapping of Sema W, a member of the semaphorin family

The semaphorins comprise a large family of membrane-bound and secreted proteins, some of which have been shown to function in axon guidance. We have cloned a transmembrane semaphorin, Sema W, that belongs to the class IV subgroup of the semaphorin family. The mouse and rat forms of Sema W show 97% amino acid sequence identity with each other, and each shows about 91% identity with the human form. The gene for Sema W is divided into 15 exons, up to 4 of which are absent in the human cDNAs that we sequenced. Unlike many other semaphorins, Sema W is expressed at low levels in the developing embryo but was found to be expressed at high levels in the adult central nervous system and lung. Functional studies with purified membrane fractions from COS7 cells transfected with a Sema W expression plasmid showed that Sema W has growth-cone collapse activity against retinal ganglion-cell axons, indicating that vertebrate transmembrane semaphorins, like secreted semaphorins, can collapse growth cones. Genetic mapping of human SEMAW with human/hamster radiation hybrids localized the gene to chromosome 2p13. Genetic mapping of mouse Semaw with mouse/hamster radiation hybrids localized the gene to chromosome 6, and physical mapping placed the gene on bacteria artificial chromosomes carrying microsatellite markers D6Mit70 and D6Mit189. This localization places Semaw within the locus for motor neuron degeneration 2, making it an attractive candidate gene for this disease.

Dynamic regulation of neuronal NO synthase transcription by calcium influx through a CREB family transcription factor-dependent mechanism

Neuronal nitric oxide (NO) synthase (nNOS) is dynamically regulated in response to a variety of physiologic and pathologic stimuli. Although the dynamic regulation of nNOS is well established, the molecular mechanisms by which such diverse stimuli regulate nNOS expression have not yet been identified. We describe experiments demonstrating that Ca2+ entry through voltage-sensitive Ca2+ channels regulates nNOS expression through alternate promoter usage in cortical neurons and that nNOS exon 2 contains the regulatory sequences that respond to Ca2+. Deletion and mutational analysis of the nNOS exon 2 promoter reveals two critical cAMP/Ca2+ response elements (CREs) that are immediately upstream of the transcription start site. CREB binds to the CREs within the nNOS gene. Mutation of the nNOS CREs as well as blockade of CREB function results in a dramatic loss of nNOS transcription. These findings suggest that nNOS is a Ca2+-regulated gene through the interactions of CREB on the CREs within the nNOS exon 2 promoter and that these interactions are likely to be centrally involved in the regulation of nNOS in response to neuronal injury and activity-dependent plasticity.