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alpha-Lactalbumin unfolding is not sufficient to cause apoptosis, but is required for the conversion to HAMLET (human alpha-lactalbumin made lethal to tumor cells).

HAMLET (human -lactalbumin made lethal to tumor cells) is a complex of human -lactalbumin and oleic acid (C18:1:9 cis) that kills tumor cells by an apoptosis-like mechanism. Previous studies have shown that a conformational change is required to form HAMLET from -lactalbumin, and that a partially unfolded conformation is maintained in the HAMLET complex. This study examined if unfolding of -lactal

Mannan induces ROS-regulated, IL-17A-dependent psoriasis arthritis-like disease in mice.

Psoriasis (Ps) and psoriasis arthritis (PsA) are poorly understood common diseases, induced by unknown environmental factors, affecting skin and articular joints. A single i.p. exposure to mannan from Saccharomyces cerevisiae induced an acute inflammation in inbred mouse strains resembling human Ps and PsA-like disease, whereas multiple injections induced a relapsing disease. Exacerbation of disea

Galectins-1, -2 and -3 exhibit differential recognition of sialylated glycans and blood group antigens

Human galectins have functionally divergent roles, although most of the members of the galectin family bind weakly to the simple disaccharide lactose (Galss1-4Glc). To assess galectin-glycan interactions in more detail, we explored the binding of several important galectins (Gal-1, Gal-2, and Gal-3) on a glycan microarray containing hundreds of structurally diverse glycans. All three galectins exh

The social shaping of television in old age

Various studies have highlighted older persons' problems in potentially failing to keep pace with developments in information technology and the latest technologies that prevent physical and social loss. In contrast to such studies that treat users as static and technology as changing, it's important to understand the use of technology can change over time. For example, older persons have used tec

Structure-function analysis of HAMLET (human alpha-lactalbumin made lethal to tumor cells)

The human genome sequence encodes fewer proteins than expected, suggesting that one protein can have several functions and adjust their structure to meet different structural demands. Changes in tertiary structure have mostly been associated with disease and the most striking example is the prion protein, which changes from a mixed alpha-helical and beta-sheet conformation to the beta-sheet rich,

Apoptosis of Peripheral Blood Leukocytes in Systemic Lupus Erythematosus: Studies on Serum Induction and Complement-Dependent Clearance Mechanisms

Systemic lupus erythematosus (SLE) is an autoimmune disease involving many organ systems. The cause is not known, but a complex combination of environmental and genetic factors seems to be involved. In SLE upregulation of type I interferons, a hyperactive B-cell response, presence of autoantibodies against modified nuclear components, increased complement consumption, increased apoptosis and decre

Serological assessment for celiac disease in IgA deficient adults.

Selective immunoglobulin A deficiency is the most common primary immunodeficiency disorder that is strongly overrepresented among patients with celiac disease (CD). IgG antibodies against tissue transglutaminase (tTG) and deamidated gliadin peptides (DGP) serve as serological markers for CD in IgA deficient individuals, although the diagnostic value remains uncertain. The aim of this study was to

Genetic factors in childhood cancer. Associations between tumors in childhood and adulthood, and prevalence of germline TP53 mutations

Popular Abstract in Swedish Varje år insjuknar omkring 300 barn i cancer. Förbättrade behandlingsmetoder under de senaste decennierna har lett till att mer än tre av fyra barn idag faktiskt botas från sin sjukdom. Tyvärr drabbas en stor andel av de som överlever sin cancer av så kallade sena komplikationer till följd av den tuffa behandling de har utsatts för. Bland annat har man sett en livslång The etiology of childhood cancer is largely unknown. Approximately 1-10% of all childhood tumors are associated with known cancer predisposition syndromes. However, the contribution may be underestimated due to the failure to detect patients with genetic susceptibility for cancer when relying on known family pattern and anomalies. Growing evidence indicates that patients with genetic susceptibilit

The palaeolimnological record of regime shifts in lakes in response to climate change

Popular Abstract in Swedish Traditionellt sett har man tänkt sig att gradvisa förändringar i yttre miljöfaktorer leder till lika gradvisa ekosystemförändringar, men vi vet nu att ekosystem som utsätts för mänsklig påverkan eller klimatförändringar kan reagera kraftigt och abrupt genom att ett ekologiskt tröskelvärde överskrids varvid en förändring sker från en stabil ekologisk situation till en anRegime shifts in lake ecosystems can occur in response to both abrupt and continuous climate change, and the imprints they leave in palaeolimnological records allow us to investigate and better understand patterns and processes governing ecological changes on geological time scales. This thesis aims at investigating palaeolimnological records of regime shifts in lakes during the Holocene to explor

The Thrombin-Derived Host Defense Peptide GKY25 Inhibits Endotoxin-Induced Responses through Interactions with Lipopolysaccharide and Macrophages/Monocytes

Host defense peptides have recently gained much interest as novel anti-infectives owing to their ability to kill bacteria and simultaneously modulate host cell responses. The cationic host defense peptide GKY25 (GKYGFYTHVFRLKKWIQKVIDQFGE), derived from the C terminus of human thrombin, inhibits proinflammatory responses in vitro and in vivo, but the mode of action is unclear. In this study, we sho

alpha-Lactalbumin, Engineered to be Non-native and Inactive, Kills Tumor Cells when in Complex with Oleic Acid: A new biological function resulting from partial unfolding.

HAMLET (human alpha-lactalbumin made lethal to tumor cells) is a tumoricidal complex consisting of partially unfolded protein and fatty acid, and was first identified in casein fractions of human breast milk. The complex can be produced from its pure components through a modified chromatographic procedure where pre-applied oleic acid binds with partially-unfolded alpha-lactalbumin on the stationar