Age, parasites, and condition affect humoral immune response in tropical pythons

Mounting an immune response has been suggested to be physiologicallycostly because of metabolic requirements of immune cells specificallyand upregulation of the immune system in general. We investigatedsuch costs in free-living water pythons (Liasis fuscus), immunizedwith a harmless antigen, keyhole limpet hemocyanin. In the presentstudy, we analyze the independent effects of age, blood parasiteload, and body condition on the ability to mount a humoral immuneresponse (level of antibody production to novel antigens). Pythonhumoral immune response decreased with increasing body length/age,decreased with increasing blood parasite load, and decreasedwith declining body condition. The results suggest an energetictrade-off between immunocompetence and other energetically costlyprocesses.     

Amyloid-Precursor-Protein-Lowering Small Molecules for Disease Modifying Therapy of Alzheimer's Disease

Alzheimer''s disease (AD) is the most common form of dementia in the elderly with progressive cognitive decline and memory loss. According to the amyloid-hypothesis, AD is caused by generation and subsequent cerebral deposition of β-amyloid (Aβ). Aβ is generated through sequential cleavage of the transmembrane Amyloid-Precursor-Protein (APP) by two endoproteinases termed beta- and gamma-secretase. Increased APP-expression caused by APP gene dosage effects is a risk factor for the development of AD. Here we carried out a large scale screen for novel compounds aimed at decreasing APP-expression. For this we developed a screening system employing a cell culture model of AD. A total of 10,000 substances selected for their ability of drug-likeness and chemical diversity were tested for their potential to decrease APP-expression resulting in reduced Aβ-levels. Positive compounds were further evaluated for their effect at lower concentrations, absence of cytotoxicity and specificity. The six most promising compounds were characterized and structure function relationships were established. The novel compounds presented here provide valuable information for the development of causal therapies for AD.     

The DraC usher in Dr fimbriae biogenesis of uropathogenic E. coli Dr+ strains

Biogenesis of Dr fimbriae encoded by the dra gene cluster of uropathogenic Escherichia coli strains requires the chaperone-usher pathway. This secretion system is based on two non-structural assembly components, the DraB periplasmic chaperone and DraC outer-membrane usher. The DraB controls the folding of DraE subunits, and DraC forms the assembly and secretion platform for polymerization of subunits in linear fibers. In this study, mutagenesis of the DraC N-terminus was undertaken to select residues critical for Dr fimbriae bioassembly. The DraC-F4A, DraC-C64, DraC-C100A and DraC-W142A significantly reduced the adhesive ability of E. coli strains. The biological activity of the DraC mutants as a assembly platform for Dr fimbriae polymerization was verified by agglutination of human erythrocytes and adhesion to DAF localized at the surface of CHO-DAF⁺ and HeLa cells. The residue F4 of the DraC usher conserved among FGL and FGS chaperone-assembled adhesive organelles can be used to design pillicides blocking the biogenesis of Dr fimbriae. Because the draC and afaC-III genes share 100% identity the range of the virulence determinant inhibitors could also be extended to E. coli strains encoding afa-3 gene cluster. The investigations performed showed that the usher N-terminus plays an important role in biogenesis of complete fiber.     

Breast cancer: Actual methods of treatment and future trends

The recent ten to twenty years have seen a substantial progress in the diagnosis and treatment of breast cancer. A rapid development of various curative options has led to the improvement of treatment outcomes, while paying more and more attention to the aspects of quality of life and cosmetic effect. In our publication, we wish to outline certain trends in the development of modern treatment of breast cancer. Among topics discussed are new forms of molecular diagnostics, new approach to the idea of sentinel node biopsy, as well as new techniques for delivery of medical procedures, the increasing use of nomograms, progress in the techniques of breast conservative treatment, modern approach to occult breast lesions, the increasing use of neoadjuvant treatment and intraoperative radiotherapy.