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Vacuolar Ca2+-ATPases in Plants. Regulation by calmodulin binding to a N-terminal autoinhibitory domain.

The calcium ion (Ca2+) is essential for all plant and animal life. One important function of Ca2+ is as a second messenger in the responses of the cell to environmental and hormonal signals as well as in some intrinsic developmental processes. The intracellular concentration of Ca2+ must be strictly regulated, since a high concentration of free cytosolic Ca2+ is toxic. All eukaryotic cells carry c

A Biopsychosocial Approach to the Onset of Childhood Diabetes

This thesis is a part of a prospective multi-centre study concerning psychosocial aspects of importance for the onset and course of insulin-dependent diabetes mellitus (IDDM). The investigated population was all children with onset of IDDM in the participating clinics during 1988 and 1989. Of 79 diseased children, 67 participated in the study. To each child a healthy control child was chosen, 61 a

The importance of major histocompatibility complex class II genes for the development of autoimmune inflammation

In this thesis the role of major histocompatibility complex (Mhc) class II molecules in development of autoimmune disease such as rheumatoid arthritis (RA), was studied. By combining an experimental model for RA, collagen type II induced arthritis (CIA), with molecular biology methods the importance of polymorphism in Mhc class II genes for disease development was investigated. The Mhc region con

Alternative NAD(P)H dehydrogenases in plant mitochondria - localisation, catalytic functions and physiological roles

In addition to complex I, the plant mitochondrial electron transport chain possesses several alternative NAD(P)H dehydrogenases, not present in animals. These enzymes allow nonenergy-conserving electron transfer from cytoplasmic and matrix NAD(P)H to ubiquinone. The mitochondrial inner membrane was permeabilised with a channel-forming antibiotic, alamethicin, and the activity of internal NADH deh

Involvement of Heparan Sulphate Biosynthesis and Turnover in Cell Proliferation. A Novel Role for Nitric Oxide in Recycling of Heparan Sulphate Proteoglycans.

The present investigation focuses on the role of HS metabolism in cell proliferation. The effect of the HS priming ß-D-xyloside, 2-(6-hydroxynaphthyl)-O-ß-D-xylopyranoside (Xyl-2-Nap-6-OH) on the proliferation of normal and transformed cells was studied. Xyl-2-Nap-6-OH inhibited growth of transformed cells to a significantly greater extent than normal cells. The growth inhibition exerted by the xy

Functionally-associated target antigens in cancer. Defined by human antibodies and small interfering RNAs.

Cancer is the collective name for diseases that have one thing in common ? uncontrolled cell growth. The increase in cancer cell proliferation eventually results in tumor formation and, in the worst case, metastatic spread to other organs. Common treatment modalities of cancer include chemotherapy and radiation therapy. However, these methods are associated with severe side effects as well as indu

Assessment of eosinophil degranulation in allergic diseases and experimental models

In allergic disorders, the eosinophilic granulocytes migrate to affected tissues and release granule proteins with cytotoxic, immunoregulatory, and remodeling-promoting properties. Given that degranulation is reflected by a loss in eosinophil granule density of living cells, or by cell membrane rupture and release of intact granules, these morphological changes may represent a biomarker of the all

Evolutionary and functional studies of protein H: a surface molecule of Streptococcus pyogenes

Several bacterial species express surface proteins with affinity for the Fc part of human IgG. This thesis describes evolutionary and functional studies of protein H, an IgGFc-binding surface protein of the human pathogen Streptococcus pyogenes. By using peptide mapping and NMR analysis the IgGFc-binding region of protein G, a surface protein of group C and G streptococci, was identified. Various

Resistance to activated protein C a novel risk factor for venous thrombosis

Activated protein C resistance (APC resistance) is the most common hereditary condition associated with venous thrombosis. The syndrome known as APC resistance is perfectly linked to a mutation in the gene coding coagulation FV (FV:Q506) mutation changing Arg 506 to Gln in the APC cleavage site. APC-resistance is associated with a hypercoagulable state and life-long increased risk of thrombosis. A

Protein folding variants, for better or for worse? The lesson learned from HAMLET.

By varying its secondary or tertiary structure a single protein can attain new biological functions. The amyloid forming proteins are the best known examples where a change in conformation leads to the formation of amyloid fibrils that accumulate in tissues and cause disease. a-lactalbumin in contrast, is an example of a protein that acquires a beneficial function when the conformation is altered

Respiratory mechanics during mechanical ventilation in health and in disease

The elastic pressure-volume (Pel-V) curve of the respiratory system can be used as a guide for improved ventilator management. It may indicate risks of lung damage associated with collapse or overdistension of lung units. The work described in this thesis was aimed at developing methods for the determination and characterisation of the Pel-V curve under static and dynamic conditions and at a bette

Aspects of nutrition in geriatric patients - Especially dietary assessment, intake and requirements

The aim of this thesis was to develop and test the feasibility of a dietary record routine, where nursing staff assess the patient’s food and fluid intake based on standardised portion sizes and household measurements. The energy intake (EI) was studied with a dietary record in 61 geriatric patients. During the 6-month follow-up 11 patients died and an EI below median (1378 kcal) was associated w

On enchytraeids and naidids: Life history traits and responses to environmental stress

My thesis shows that enchytraeids and naidids are sensitive to various forms of environmental stress, which in combination with the wide distribution of both families make them highly suitable for use in risk assessment and soil monitoring. Enchytraeids were subject to chemical stress under both laboratory and field conditions. In laboratory experiments enchytraeids reacted to chemical stress with

Waterfowl in temperate eutrophic lakes - Interactions with macroinvertebrates, submerged vegetation and fish

The aim of this thesis was to explore some of the important links between waterfowl and the biota in shallow eutrophic lakes in temperate areas. Waterfowl depend on macroinvertebrates as sources of protein and calcium, which are essential for egg production and growth. Macroinvertebrates in turn depend on submerged vegetation for food and shelter. Increased density of vegetation thus leads to incr

Severe Head Injury. Evaluation of Acute Treatment and Rehabilitation

Mortality after severe head injury can be considerably reduce with a therapy using physiological principles for brain volume regulation and preserved microcirculation, with the main purpose of restricting the rise in ICP to reasonable levels simultaneously with preservation of adequate blood supply. This study shows that the ?Lund Concept? can reduce mortality in patients with severe traumatic bra

Assessment of Aerobic Capacity A Novel Rating Scale and Further Development of an Exercise Test including Analysis of Gas Exchange

Different methods are proposed to assess the aerobic capacity. A novel scale, rating of perceived capacity (RPC) based on metabolic equivalents (METs) from 1 to 20, is presented. Selected MET values are linked to physical activities. Comparison of the rating with an exercise test in a group of women revealed that a correction based on age more accurately predicted the maximal exercise capacity. An

U-Pb baddeleyite geochronology of Precambrian mafic dyke swarms and complexes in southern Africa - regional scale extensional events and the origin of the Bushveld Complex

Dolerite dykes are formed when iron- and magnesium-rich (mafic) mantle-derived magmas ascend through the lithosphere (upper part of the mantle) and crystallize as ‘hydro-fractures’ within the crust. Dykes may exist in great numbers to form dyke swarms (linear or radiating), which can be linked to time periods of continental break-up, or attempted break-up events, associated with voluminous volcani

Activating germline mutations in STAT3 cause early-onset multi-organ autoimmune disease.

Monogenic causes of autoimmunity provide key insights into the complex regulation of the immune system. We report a new monogenic cause of autoimmunity resulting from de novo germline activating STAT3 mutations in five individuals with a spectrum of early-onset autoimmune disease, including type 1 diabetes. These findings emphasize the critical role of STAT3 in autoimmune disease and contrast with