Discovery of WRN inhibitor HRO761 with synthetic lethality in MSI cancers.

The Werner syndrome RecQ helicase WRN was identified as a synthetic lethal target in cancer cells with microsatellite instability (MSI) by several genetic screens. Despite advances in treatment with immune checkpoint inhibitors, there is an unmet need in the treatment of MSI cancers. Here we report the structural, biochemical, cellular and pharmacological characterization of the clinical-stage WRN helicase inhibitor HRO761, which was identified through an innovative hit-finding and lead-optimization strategy.

PAX8 and MECOM are interaction partners driving ovarian cancer.

The transcription factor PAX8 is critical for the development of the thyroid and urogenital system. Comprehensive genomic screens furthermore indicate an additional oncogenic role for PAX8 in renal and ovarian cancers. While a plethora of PAX8-regulated genes in different contexts have been proposed, we still lack a mechanistic understanding of how PAX8 engages molecular complexes to drive disease-relevant oncogenic transcriptional programs.

[Vaccination recommendations for health care workers in Austria].

In Austria the vaccination coverage among health care workers (HCW) - particularly among hospital personnel - is not sufficient. This is of specific concern, because not only the individual protection but also the prevention of disease transmission of vaccine preventable diseases between HCW and patients needs to be guaranteed. Particularly immunosuppressed patients, who are at higher risk for morbidity and mortality due to certain infections, but cannot be vaccination themselves, must be able to rely on herd protection, i.

Tick-borne encephalitis from eating goat cheese in a mountain region of Austria.

We report transmission of tick-borne encephalitis virus (TBEV) in July 2008 through nonpasteurized goat milk to 6 humans and 4 domestic pigs in an alpine pasture 1,500 m above sea level. This outbreak indicates the emergence of ticks and TBEV at increasing altitudes in central Europe and the efficiency of oral transmission of TBEV.

Measles outbreak linked to a minority group in Austria, 2008.

We report on a measles outbreak originating in an anthroposophic community in Austria, 2008. A total of 394 (94.9%) cases fulfilled the outbreak case definition including 168 cases affiliated to the anthroposophic community.

Vaccine strategies of meningococcal disease: results of a 10-year population-based study.

Unlabelled: Invasive meningococcal disease (IMD) is an important cause of morbidity and mortality in children and adults. This study was conducted to determine a possible increase in IMD in recent years with special interest focused on serogroup C disease. From January 1st 1993 to December 31st 2002, IMD was studied in one million residents of Austria.

Cellular characterisation of p53 mutants with a single missense mutation in the beta-strand 326-333 and correlation of their cellular activities with in vitro properties.

Recent evidence has shown that missense mutations in the p53 tetramerisation domain can inactivate the protein. However, most of these studies have been done only in vitro or concern proteins whose physico-chemical properties have not been fully investigated. Alanine mutants of the beta-strand 326-333 from the tetramerisation domain have been characterized in vitro and studied for their thermodynamic stability.

p53 mutants without a functional tetramerisation domain are not oncogenic.

p53 is altered in about 50 % of cancers. Most of the p53 mutants have lost the wild-type tumour suppressor activity but show oncogenic properties. The majority of the p53 alterations are missense mutations of residues located in its DNA binding domain (DBD).

[Cooperation in public health in the Bodensee district from the viewpoint of Vorarlberg].

Following a brief presentation of a few significant data and specifications in respect of the structure and organisation of the Austrian Public Health administration, general basic rules for across-the-border cooperation in the region of Lake Constance are outlined. The following subjects for such cooperation are listed: epidemiology and how to fight spring-summer meningoencephalitis, rabies, echinococcosis, AIDS/HIV. Other areas of cooperation are, for example.