RESUMO
Over 5000 years ago, a man climbed up to the icy heights of the glacier in South Tyrol, Italy and died. He was found by accident in 1991, with his clothes and equipment, mummified and frozen: an archaeological sensation and a unique snapshot of a Copper Age man. For several years highly specialised research teams have examined the mummy and all accompanying items. This paper describes how fur and leather clothes of the iceman could have been tanned. Details of the analytical tests undertaken on the 5000 year old leather samples and what they revealed are presented.
Assuntos
Arqueologia/métodos , Vestuário/história , Curtume/história , Curtume/métodos , Cromatografia Gasosa-Espectrometria de Massas , História Antiga , Humanos , Masculino , Múmias/patologia , Espectrofotometria Atômica , Espectrofotometria InfravermelhoRESUMO
Careful regulation of mRNA half-lives is a fundamental mechanism allowing cells to quickly respond to changing environmental conditions. The mRNA-binding Hu proteins are important for stabilization of short-lived mRNAs. Here we describe the identification and mechanistic characterization of the first low-molecular-weight inhibitors for Hu protein R (HuR) from microbial broths (Actinomyces sp.): dehydromutactin (1), MS-444 (2) and okicenone (3). These compounds interfere with HuR RNA binding, HuR trafficking, cytokine expression and T-cell activation. A mathematical and experimental analysis of the compounds' mode of action suggests that HuR homodimerizes before RNA binding and that the compounds interfere with the formation of HuR dimers. Our results demonstrate the chemical drugability of HuR; to our knowledge HuR is the first example of a drugable protein within the Hu family. MS-444, dehydromutactin and okicenone may become valuable tools for studying HuR function. An assessment of HuR inhibition as a central node in malignant processes might open up new conceptual routes toward combatting cancer.
