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Resumen: Nietzsche considera, al igual que Kant, que la sumisión a tutores y prejuicios restringe el ejercicio del pensar. Sin embargo, cree necesario extender la crítica hasta los valores morales. La emancipación que promueve Kant no es realizable a menos que se someta a crítica la moral occidental. Someterla a examen es preguntar por el origen del valor de la moral. En este artículo se revisa el modo en que la emancipación tiene lugar en la crítica de los valores. Se propone que el ejercicio de la crítica permite el fortalecimiento y desarrollo del espíritu humano, pues da lugar a una ruptura con valores y principios heredados. El espíritu es apertura y transformación, y se debilita y petrifica si se le constriñe a un conjunto fijo de principios. Dicha ruptura crea las condiciones necesarias para el crecimiento y ampliación del espíritu. El proceso de emancipación conlleva una serie de transfiguraciones del espíritu que se experimenta como un extrañamiento ante los valores tradicionales. Este extrañamiento es afín al sentimiento de lo siniestro (Umheimlich). // // Abstract: Nietzsche considers, like Kant, that submission to tutors and prejudices restricts the exercise of thinking. However, he also believes it necessary to extend the critique to moral values. The emancipation that Kant promotes is not achievable unless Western morality is subjected to criticism. To subject it to examination is to ask about the origin of the value of morality. This article reviews the way in which emancipation takes place in the critique of values. It is proposed that the exercise of critique allows for the strengthening and development of the human spirit, as it results in a rupture with inherited values and principles. The spirit is openness and transformation, and it weakens and dies if it is constrained to a fixed set of principles. Such a rupture creates the neces-sary conditions for the growth of the spirit. The process of emancipation entails a series of transfigurations of the spirit that is experienced as an estrangement from traditional values. This estrangement is akin to the feeling of the sinister (Umheimlich). //

Gadamer argumenta contra la lectura moderna del prejuicio que éste no es mera fuente de error sino ante todo posibilidad de experimentar la verdad. A pesar de la rehabilitación hermenéutica del prejuicio, lo cierto es que éste puede conducirnos tanto a la verdad como al error. Por esta razón, es necesario distinguir los presupuestos que nos llevan a la comprensión de aquellos que nos conducen al malentendido. A esta exigencia metodológica Gadamer la caracteriza como la “verdadera cuestión crítica de la hermenéutica”. En este texto se muestra que existe una tensión fundamental en Verdad y método entre la rehabilitación ontológica del prejuicio y la exigencia epistemológica de diferenciar los prejuicios legítimos de los ilegítimos. Gadamer holds against the modern reading of prejudice, which conceives it as a mere source of error, that it is above all a form of experiencing truth. Hermeneutics shows that prejudice conditions understanding. Despite this defense, it is the case that assumptions can equally lead to understanding or misunderstanding. For this reason, Gadamer argues that it is necessary to distinguish between productive and unproductive prejudices. This methodological task is known as “question of critique in hermeneutics”. In this article it is argued that these two different forms of understanding prejudice bring about an essential tension in Gadamer’shermeneuctics.

Reseña crítica en torno al libro La interpretación estética como experiencia del arte, de Mónica Uribe.

Heidegger formula una de las tesis filosóficas más radicales del siglo XX: la distinción puntual entre los estudios sobre lo óntico y los análisis ontológicos. Este planteamiento da lugar a la escisión fundamental entre la epistemología, cuyo tema es el ser-objeto, y la hermenéutica ontológica, que analiza el carácter de ser del existir. Uno de los intentos más notables por poner en juego estas dos posturas tan distanciadas se encuentra en la filosofía gadameriana, la cual se caracteriza por sostener que la comprensión verdadera acontece bajo la forma del diálogo. Este trabajo revisa si el esfuerzo gadameriano por aproximar la epistemología a la ontología tiene lugar bajo la forma del diálogo hermenéutico. Heidegger formulates one of the most radical theses in the philosophy of the twenty century: the distinction between the studies on specific entities and those on Being itself (ontology). This thesis shows the essential difference between epistemology and ontological hermeneutics, since the first deals with objectivity, while the second worries about Being. Gadamer’s philosophy, which holds that true understanding takes place dialogically, represents one of the most important efforts to draw near these two divorced positions. This paper analyzes in what sense Gadamer’s attempt to confront ontology with epistemology takes place dialogically.

Abstract Background Genome-wide association studies (GWAS) have identified genetic variants linked to fat metabolism and related traits, but rarely pinpoint causative variants. This limitation arises from GWAS not considering functional implications of noncoding variants that can affect transcription factor binding and potentially regulate gene expression. The aim of this study is to investigate a candidate noncoding functional variant within a genetic locus flagged by a GWAS SNP associated with non-alcoholic fatty liver disease (NAFLD), a condition characterized by liver fat accumulation in non-alcohol consumers. Methods CRISPR-Cas9 gene editing in HepG2 cells was used to modify the regulatory element containing the candidate functional variant linked to NAFLD. Global gene expression in mutant cells was assessed through RT-qPCR and targeted transcriptomics. A phenotypic assay measured lipid droplet accumulation in the CRISPR-Cas9 mutants. Results The candidate functional variant, rs2294510, closely linked to the NAFLD-associated GWAS SNP rs11206226, resided in a regulatory element within the DIO1 gene's promoter region. Altering this element resulted in changes in transcription factor binding sites and differential expression of candidate target genes like DIO1, TMEM59, DHCR24, and LDLRAD1, potentially influencing the NAFLD phenotype. Mutant HepG2 cells exhibited increased lipid accumulation, a hallmark of NAFLD, along with reduced LDL-C, HDL-C and elevated triglycerides. Conclusions This comprehensive approach, that combines genome editing, transcriptomics, and phenotypic assays identified the DIO1 promoter region as a potential enhancer. Its activity could regulate multiple genes involved in the NAFLD phenotype or contribute to defining a polygenic risk score for enhanced risk assessment in NAFLD patients.

Abstract Background Genome-wide association studies (GWAS) of diseases and traits have found associations to gene regions but not the functional SNP or the gene mediating the effect. Difference in gene regulatory signals can be detected using chromatin immunoprecipitation and next-gen sequencing (ChIP-seq) of transcription factors or histone modifications by aligning reads to known polymorphisms in individual genomes. The aim was to identify such regulatory elements in the human liver to understand the genetics behind type 2 diabetes and metabolic diseases. Methods The genome of liver tissue was sequenced using 10X Genomics technology to call polymorphic positions. Using ChIP-seq for two histone modifications, H3K4me3 and H3K27ac, and the transcription factor CTCF, and our established bioinformatics pipeline, we detected sites with significant difference in signal between the alleles. Results We detected 2329 allele-specific SNPs (AS-SNPs) including 25 associated to GWAS SNPs linked to liver biology, e.g., 4 AS-SNPs at two type 2 diabetes loci. Two hundred ninety-two AS-SNPs were associated to liver gene expression in GTEx, and 134 AS-SNPs were located on 166 candidate functional motifs and most of them in EGR1-binding sites. Conclusions This study provides a valuable collection of candidate liver regulatory elements for further experimental validation.