Milan Kundera et la littérature mondiale

« Les littératures nationales ne signifient plus grand-chose aujourd’hui. Nous entrons dans l’ère de la littérature mondiale et il appartient à chacun de nous de hâter cette évolution » (Goethe). Milan Kundera, écrivain natif de Moravie ayant émigré en France en 1975, reprend à son compte cet idéal formulé en 1827 par Goethe et le réactive : selon lui, en effet, le seul contexte où peuvent véritablement se révéler le sens et la valeur d’une œuvre est le grand contexte de l’histoire supranationale. Dans cet espace de diversité où l’œuvre n’est pas soutenue par son prestige national, mais par son originalité, un roman tchèque (littérature d’une petite nation) aussi bien qu’un roman français (littérature d’une grande nation) peut trouver sa place. Comment faire une histoire de la littérature mondiale sans la présenter comme une juxtaposition d’histoires littéraires nationales ? C’est la question à laquelle cette conférence s’efforcera de répondre en s’appuyant sur les réflexions culturelles aussi bien que politiques de Milan Kundera.

Exil, espace et frontières dans l'oeuvre de Milan Kundera

Milan Kundera emigrierte 1975 nach Frankreich. Der Zeitpunkt seiner Emigration trifft mit jenem zusammen, in dem sich in seiner Arbeit Überlegungen zu Exil, Grenzen und Raum entwickeln. In seinen politischen Schriften hebt er die Veränderung der europäischen Grenzen nach dem Zweiten Weltkrieg hervor sowie den Umstand, dass sich die Tschechoslowakei und Zentraleuropa in der Sowjetunion im „Exil“ befinden. In seinen Exilromanen bewegen sich die Figuren zwischen heimischem und exilischem Raum, und diese territoriale Grenzüberschreitung wird systematisch von einem metaphysischen Grenzübergang begleitet. Schliesslich zeigt Kundera in seinen Erwägungen zur Literatur, dass literarische Werke, um in ihrer ganzen Vielfalt berücksichtigt zu werden, in anderen Kulturräumen als ihrem eigenen zirkulieren müssen. Diese „Reise“ durch Kunderas Werk wird uns denn auch dazu bringen, über mögliche paradigmatische Figuren des zeitgenössischen Exils nachzudenken.

Common CFTR haplotypes and susceptibility to chronic pancreatitis and congenital bilateral absence of the vas deferens

CFTR mutations enhance susceptibility for idiopathic chronic pancreatitis (ICP) and congenital bilateral absence of the vas deferens (CBAVD); however, it is unknown why CFTR heterozygotes are at increased disease risk. We recently showed that common CFTR variants are associated with aberrantly spliced transcripts. Here, we genotyped for common CFTR variants and tested for associations in two ICP (ICP-A: 126 patients, 319 controls; ICP-B: 666 patients, 1,181 controls) and a CBAVD population (305 patients, 319 controls). Haplotype H10 (TG11-T7-470V) conferred protection (ICP-A: OR 0.19, P<0.0001; ICP-B: OR 0.78, P = 0.06; CBAVD OR 0.08, P<0.001), whereas haplotype H3 (TG10-T7-470M) increased disease risk (ICP-A: OR 8.34, P = 0.003; ICP-B: OR 1.88, P = 0.007; CBAVD: OR 5.67, P = 0.01). The risk of heterozygous CFTR mutations carriers for ICP (OR 2.44, P<0.001) and CBAVD (OR 14.73, P<0.001) was fully abrogated by the H10/H10 genotype. Similarly, ICP risk of heterozygous p.Asn34Ser SPINK1 mutation carriers (OR 10.34, P<0.001) was compensated by H10/H10. Thus, common CFTR haplotypes modulate ICP and CBAVD susceptibility alone and in heterozygous CFTR and p.Asn34Ser mutation carriers. Determination of these haplotypes helps to stratify carriers into high- and low-risk subjects, providing helpful information for genetic counseling.

A degradation-sensitive anionic trypsinogen (PRSS2) variant protects against chronic pancreatitis

Chronic pancreatitis is a common inflammatory disease of the pancreas. Mutations in the genes encoding cationic trypsinogen (PRSS1) and the pancreatic secretory trypsin inhibitor (SPINK1) are associated with chronic pancreatitis. Because increased proteolytic activity owing to mutated PRSS1 enhances the risk for chronic pancreatitis, mutations in the gene encoding anionic trypsinogen (PRSS2) may also predispose to disease. Here we analyzed PRSS2 in individuals with chronic pancreatitis and controls and found, to our surprise, that a variant of codon 191 (G191R) is overrepresented in control subjects: G191R was present in 220/6,459 (3.4%) controls but in only 32/2,466 (1.3%) affected individuals (odds ratio 0.37; P = 1.1 x 10(-8)). Upon activation by enterokinase or trypsin, purified recombinant G191R protein showed a complete loss of trypsin activity owing to the introduction of a new tryptic cleavage site that renders the enzyme hypersensitive to autocatalytic proteolysis. In conclusion, the G191R variant of PRSS2 mitigates intrapancreatic trypsin activity and thereby protects against chronic pancreatitis.

Do common genetic variants in endotoxin signaling pathway contribute to predisposition to alcoholic liver cirrhosis?

BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta), produced by endotoxin-activated Kupffer cells, play a key role in the pathogenesis of alcoholic liver cirrhosis (ALC). Alleles TNFA -238A, IL1B -31T and variant IL1RN*2 of repeat polymorphism in the gene encoding the IL-1 receptor antagonist increase production of TNF-alpha and IL-1beta, respectively. Alleles CD14 -159T, TLR4 c.896G and TLR4 c.1196T modify activation of Kupffer cells by endotoxin. We confirmed the published associations between these common variants and genetic predisposition to ALC by means of a large case-control association study conducted on two Central European populations. METHODS: The study population comprised a Czech sample of 198 ALC patients and 370 controls (MONICA project), and a German sample of 173 ALC patients and 331 controls (KORA-Augsburg), and 109 heavy drinkers without liver disease. RESULTS: Single locus analysis revealed no significant difference between patients and controls in all tested loci. Diplotype [IL1RN 2/ 2; IL1B -31T+] was associated with increased risk of ALC in the pilot study, but not in the validation samples. CONCLUSIONS: Although cytokine mediated immune reactions play a role in the pathogenesis of ALC, hereditary susceptibility caused by variants in the corresponding genes is low in Central European populations.