Host Defense Properties of Collagen VI. A novel concept in connective tissue innate immunity.

Rapid and powerful host defense mechanisms are essential in order to overcome harmful actions of pathogenic bacteria. Antimicrobial peptides (AMPs) and proteins are vital effector molecules of the fast-acting innate immune system and exist virtually in all living organisms. They exert a broad spectrum of natural antibiotic activity, but also play important immunomodulatory functions in the host. During the past few decades, host defense molecules have gained remarkable attention as alternative treatments for bacterial infections due to the growing bacterial resistance to current antibiotics.This thesis sheds light on an intriguing and novel aspect of innate immunity in the context of connective tissues, where collagen VI emerges as a host defense molecule. Collagen VI is an extracellular matrix protein that forms complex microfibrillar networks in most connective tissues. The best studied form of collagen VI is a heterotrimer comprised of three α-chains, α1(VI), α2(VI) and α3(VI), where the majority of these α-chains are flanked by globular domains that share homology with von Willebrand factor type A (VWA) domains. The results presented in this thesis demonstrates that tissue-purified collagen VI exhibits a broad spectrum of antibacterial activity against Gram-positive and Gram-negative bacteria by disrupting the bacterial membranes and causing leakage of intracellular components, which subsequently leads to cell death. Interestingly, the expression of collagen VI was upregulated in the airways of chronic obstructive pulmonary disease (COPD) patients compared to healthy individuals. Upon airway epithelial damage in COPD, we found that collagen VI is exposed and serves both as an adhesive substrate and an antibacterial barrier for a number of pulmonary pathogens. In order to gain deeper insight into the antimicrobial nature of the collagen VI molecule, we identified and characterized cationic sequence motifs in the VWA domains of the α3(VI)-chain. These peptides showed a significant antibacterial activity against Gram-positive and Gram-negative bacteria in vitro and in vivo. Furthermore, some of them also displayed wound healing and anti-endotoxic properties in vitro.In conclusion, these data reveal for the first time in detail how extracellular matrix proteins, such as collagen VI, provide host defense mechanisms against bacterial infections in connective tissues. These findings also suggest a novel role for collagen VI-derived peptides in innate immunity and provide templates for the development of peptide-based antibacterial therapies

Integrity of Indigenous Knowledge Systems in Natural Resource Management: The Case of the Arid and Semi-Arid Baringo Herders of Kenya

Ineffective management of natural resources in arid and semi-arid lands (ASALs), resulting in resource depletion, rapid loss of biodiversity and environmental degradation, is of great concern globally. The Baringo herders in the ASALs of Kenya have been branded as perpetrators of this vice, with the blame placed particularly on their traditional livestock management, utilising indigenous knowledge systems (IKS). These IKS involve livestock mobility and maximisation, and have been regarded as being outdated and inefficient in meeting the challenges and demands for environmental conservation and sustainable management of the natural resources. A common reaction of the government has been to advocate modern interventions that are based on exogenous knowledge systems (EKS), involving sedentary livestock raising and destocking. These EKS are, however, not performing as well as expected, since they are not adapted to the ASALs ecological conditions and the herders\u27 socio-economic and cultural situations (Aboud et al 1997; Makenzi, 2003). This study empirically explored the above propositions, in order to test the integrity of the IKS, in relation to EKS and the herders\u27 levels of education

Barium modification of a high-silica zeolite for methanol conversion to light alkenes

High-silica zeolite (silicalite) was modified with Ba resulting in reduced acid strength of the catalyst and better performance when compared with ZSM-5 and fresh silicalite in converting MeOH to alkenes. Various concns. of Ba were ionexchanged and impregnated to achieve the optimum loading of the modifier. The fresh and the modified zeolites were fully characterized by x-ray diffraction, SEM, TGA, DTA, as well as by surface area, chem. and other analyses. Ba silicalite has a lowered coke deposition and an improved active life when ion exchanged. The reverse was obsd. in the case of impregnation

Therapeutic efficacy of chloroquine and sulfadoxine/pyrimethamine against Plasmodium falciparum infection in Somalia

Study on the therapeutic efficacy of treatments based on chloroquine and sulfadoxine/pyrimethamine in cases of malaria (Plasmodium falciparum) in Merka and Gabiley, Somalia.Daraasaad ku saabsan waxtarka ku daaweynta chloroquine iyo sulfadoxine/pyrimethamine cudurka duumada, degaannada soomaaliyeed ee Marka iyo Gabiley.Studio sull'efficacia terapeutica di trattamenti a base di clorochina e sulfadossina/pirimetamina nei casi di malaria (Plasmodium falciparum) a Merka e Gabiley, Somalia

Barium modification of a high-silica zeolite for methanol conversion to light alkenes

High-silica zeolite (silicalite) was modified with Ba resulting in reduced acid strength of the catalyst and better performance when compared with ZSM-5 and fresh silicalite in converting MeOH to alkenes. Various concns. of Ba were ionexchanged and impregnated to achieve the optimum loading of the modifier. The fresh and the modified zeolites were fully characterized by x-ray diffraction, SEM, TGA, DTA, as well as by surface area, chem. and other analyses. Ba silicalite has a lowered coke deposition and an improved active life when ion exchanged. The reverse was obsd. in the case of impregnation

Somalia: fragilidad y perspectivas de futuro

Este cuaderno contiene: "Introducción" "Prólogo" "De la unidad en 1960 a la desintegración: cronología de un Estado fallido" "Las migraciones en Somalia: mirando al pasado para comprender el presente" "Algunos datos sobre la cooperación internacional en Somalia" "Describir o prescribir: uso de la noción de Estado Fallido en las crisis somalíes""Los principios de la OCDE sobre intervención en Estados frágiles y su aplicación al caso de Somalia