Four outbreaks of norovirus gastroenteritis after consuming raspberries, Sweden, June-August 2006.
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Adult↗
Biomedical subjects
M Olsson
Publications and source records attributed to M Olsson.
Functional connection between p53 and caspase-2 is essential for apoptosis induced by DNA damage.
Recent findings have established caspase-2 as an important apical regulator in apoptotic pathways leading from DNA damage to release of mitochondrial cytochrome c and subsequent activation of effector caspases. Yet, the molecular map connecting the embarking stimuli of genotoxic stress with caspase-2 activation remains to be elucidated. Here, we address the question of potential caspase-2 regulators by examining 5-fluorouracil (5-FU)-induced apoptosis in wild-type and p53-deficient human colon carcinoma cells. Apoptosis was observed only in p53(+/+) cells and was preceded by caspase-2 activation. Hence, although no direct interaction between p53 and caspase-2 was observed in the cell system used, our data clearly demonstrate that a functional connection between these two proteins is essential for initiation of the 5-FU-induced apoptotic process. Proposed mediators of caspase-2 activation include PIDDosome complex proteins PIDD and RAIDD. Surprisingly, the presence of a complex encompassing at least RAIDD, PIDD and caspase-2 was verified in both p53(+/+) and p53(-/-) cells, also in the absence of 5-FU treatment. Thus, our results confirm the participation of PIDD and RAIDD in PIDDosome complex formation but question their role as sole mediators of caspase-2 activation. This assumption was further supported by siRNA transfections targeting PIDD or RAIDD. In conclusion, our findings support the hypothesis of p53 as an upstream regulator of caspase activity and provide data concerning caspase-2 processing mechanisms. As suppression of caspase-2 expression in 5-FU-treated cells also affects the level of the p53 protein, possibilities of a reciprocal interaction between these proteins are discussed.
Apoptosis↗
Target cell CD47 regulates macrophage activation and erythrophagocytosis.
The ubiquitously expressed cell surface glycoprotein CD47 (integrin-associated protein, IAP) was originally identified as a regulator of integrin-dependent leukocyte responses to extracellular matrix proteins. However, it has been shown that CD47 has several important functions in addition to regulating integrin activation. Extensive studies in murine systems have shown that CD47 on erythrocytes and other cells can function as a regulator of target cell phagocytosis, by binding to the inhibitory receptor SIRPalpha on macrophages. In this way, macrophages are less likely to phagocytose an autoimmune sensitized cell with CD47 on its surface than a CD47-deficient cell where this inhibitory mechanism will not be engaged. The CD47-SIRPalpha interaction seems to be important in limiting destruction of host cells in experimental models of autoimmune diseases like autoimmune hemolytic anemia (AIHA) or immune thrombocytopenia, where macrophages destroy antibody or complement opsonized cells.
Anemia, Hemolytic, Autoimmune↗
Linkage disequilibrium and haplotype blocks in the MHC vary in an HLA haplotype specific manner assessed mainly by DRB1*03 and DRB1*04 haplotypes.
First generation linkage disequilibrium (LD) and haplotype maps of the human major histocompatibility complex (MHC) have been generated in order to aid the unraveling of the numerous disease predisposing genes in this region by offering a first set of haplotype tagSNPs. Several parameters, like the population studied, the marker map used, the density of polymorphisms and the applied algorithm, are influencing the appearance of haplotype blocks and selection of tags. The MHC comprises a limited number of ancestral, conserved haplotypes. We address the impact of the underlying HLA haplotypes on the LD patterns, haplotype blocks and tag selection throughout the entire extended MHC (xMHC) by studying DR-DQ haplotypes, mainly those carrying DRB1*03 and DRB1*04 alleles. We observed significantly different degree and extent of LD calculated on different HLA backgrounds, as well as variation in the size and boundaries of the defined haplotype and tags selected. Our results demonstrate that the underlying ancestral HLA haplotypic architecture is yet another parameter to take into consideration when constructing LD maps of the xMHC. This may be essential for mapping of disease susceptibility genes since many diseases are associated with and map on particular HLA haplotypes.
Chromosome Mapping↗
Increased expression of aquaporin 3 in atopic eczema.
BACKGROUND: Dry skin in atopic eczema depends on increased water loss. The mechanisms behind this are poorly understood. The aim of this work was to identify genes that may contribute to water loss in eczema. METHODS: Affymetrix DNA microarrays U133A were used to analyse gene expression in skin biopsies from 10 patients with atopic eczema and 10 healthy controls. RESULTS: DNA microarray analysis showed up-regulation of 262 genes and down-regulation of 129 genes in atopic eczema. The known functions of these genes were analysed using Gene Ontology to identify genes that could contribute to increased water loss. This led to identification of aquaporin 3 (AQP3), which has a key role in hydrating healthy epidermis. Increased expression of AQP3 was found in eczema compared with healthy skin. This was confirmed with real-time polymerase chain reaction (P<0.001). In healthy skin, epidermal AQP3 immunoreactivity was weak and mainly found in the stratum basale. A gradient was formed with decreasing AQP3 staining in the lower layers of the stratum spinosum. By contrast, in acute and chronic atopic eczema strong AQP3 staining was found in both the stratum basale and the stratum spinosum. CONCLUSIONS: Aquaporin 3 is the predominant aquaporin in human skin. Increased expression and altered cellular distribution of AQP3 is found in eczema and this may contribute to water loss.
Adult↗
Chronically administered islet amyloid polypeptide in rats serves as an adiposity inhibitor and regulates energy homeostasis.
AIMS/HYPOTHESIS: Islet amyloid polypeptide (IAPP) reduces food intake and body weight in laboratory animals. In addition, IAPP appears to regulate nutrient metabolism. In the present studies, we investigated the effect of chronic IAPP treatment on different aspects of energy homeostasis. METHODS: IAPP was infused (25 pmol/kg/min) from subcutaneous osmotic pumps for 2-7 days. Rats in 2 saline-infused control groups were fed ad libitum (AF) or pair-fed (PF) against the IAPP-treated rats. RESULTS: As expected, the IAPP infusion reduced food intake and body weight gain. In addition, the IAPP treatment decreased the epididymal fat pad (vs. PF rats, p < 0.05) and lowered circulating levels of triglycerides (vs. PF rats, p < 0.05), free fatty acids (vs. PF rats, p < 0.05), leptin (vs. both AF and PF rats, p < 0.05) and insulin (vs. AF rats, p < 0.05). In contrast, glucose and protein metabolism in the IAPP-treated rats was largely unchanged, as shown in results regarding serum glucose, glucose transport in skeletal muscle, blood urea nitrogen, and glycogen and protein content in the liver and in skeletal muscle. CONCLUSION/INTERPRETATION: In summary, chronic IAPP exposure led to a changed lipid metabolism, which was characterized by decreased adiposity, hypolipidemia and hypoleptinemia, and to unchanged glucose and protein homeostasis. These results were similar to those seen in rodents during chronic exposure to another satiety/adiposity regulator, leptin. In conclusion, chronically administered IAPP plays a role as a satiety and adiposity signal in rats, and helps regulate energy homeostasis.
Adipose Tissue↗
Polybrominated diphenyl ethers (PBDEs) and their methoxylated derivatives in pike from Swedish waters with emphasis on temporal trends, 1967-2000.
Temporal trends of five tetra- to hexabromodiphenyl ethers [BDE47, BDE99, BDE100, BDE153 and BDE154) and two methoxy-tetraBDEs [6-methoxy-2,2',4,4'- tetraBDE (6-MeO-BDE47) and 2'-methoxy-2,3',4,5'- tetraBDE (2'-MeO-BDE68)] in pike from Lake Bolmen for the years 1967-2000, are presented. All BDE congeners show increasing trends up to the mid-1980s (Sigma5PBDE from 60 to 1600 pg/g wet weight in 1989, i.e. a more than 25-fold increase), and then decrease or level off. The decreasing trends of PBDEs after the 1980s were considerably slower in the present study than was found in a study of an environmental matrix from the Baltic Proper covering the same time period. This difference suggests local sources near Lake Bolmen. The MeO-BDEs show initially decreasing concentrations, which for 6-MeO-BDE47 continues until the early 1990s. The concentrations of 6-MeO-BDE47 in herring from five locations along the Swedish coast increased from south to north in the Baltic Sea. No correlation between the concentrations of the BDE congeners and the MeO-BDEs was observed, indicating sources other than PBDEs for these compounds. The presence of MeO-BDEs in fish from lakes with different characteristics suggests a natural production not favoured by eutrophication, or dependent on sampling season and geographical location.
Animals↗
Intracerebroventricular administration of the angiotensin II receptor antagonist saralasin reduces respiratory rate and tidal volume variability in freely moving Wistar rats.
The possible importance of intra-individual variations in respiratory rate and tidal volume has recently gained interest in psychiatric research, as a result of the observations that patients with panic disorder or premenstrual dysphoric disorder display enhanced respiratory variability as compared to controls. Although the role of brain neurotransmitters in the regulation of breathing has been extensively studied, as yet data on the central regulation of respiratory variability is sparse. Prompted by previous studies indicating that angiotensin II (ANG II) may influence ventilation as well as anxiety, we have studied the effect of intracerebroventricular administration of an ANG II receptor antagonist, saralasin, on respiratory variability in unrestrained, freely moving male Wistar rats. Treatment with saralasin, 5 mug dissolved in 1 mul saline followed by 9 mul saline in each lateral cerebral ventricle, did not influence tidal volume, but markedly reduced tidal volume variability (p=0.0005), as compared to saline injections (10 mul). Respiratory rate was reduced by saralasin (p=0.02), and there was also a non-significant tendency for a reduction in respiratory rate variability. Both minute volume (p=0.005) and volume/10 s variability (p=0.0006) were reduced. It is suggested that ANG II in the brain of Wistar rats may regulate respiratory rate and tidal volume variability.
Angiotensin Receptor Antagonists↗
Pros and cons of microarray technology in allergy research.
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Computational Biology↗
Offspring-driven local dispersal in female sand lizards (Lacerta agilis).
We report on a field study in which determinants of female breeding dispersal (i.e. the shift in the mean home range coordinates between successive breeding events) was investigated. Offspring were released in full sib groups (or half sib ones if there was within-clutch multiple paternity) at a separation distance from the females that varied between 'families'. This allowed for analysis of 'offspring nearness' effects on maternal dispersal. When a female's offspring were released more closely to her, she responded with greater dispersal. Furthermore, when the data set was truncated at 100 m maternal-offspring separation distance at offspring release (because perception at longer distances is likely to be unrealistic), maternal dispersal resulted in greater separation distance between female and offspring in the following year. A corresponding analysis for juveniles revealed no effect of maternal nearness on offspring dispersal but identified a significant effect of clutch size, to our surprise with dispersal declining with increasing clutch size. We discuss this result in a context of the 'public information hypothesis' (reinterpreted for juveniles in a nonsocial foraging species), suggesting that conspecific abundance perhaps acts as an indicator of local habitat quality. Thus, our analysis suggests a microgeographic structuring of the adult female population driven by genetic factors, either through inbreeding avoidance, or from simply avoiding individuals with a similar genotype regardless of their pedigree relatedness, while a nongenetic factor seems more important in their offspring.
Animals↗
No evidence for genetic linkage between development of multiple sclerosis and components of the IFN system and the JAK-STAT pathway.
Multiple sclerosis (MS) is an inflammatory, demyelinating disease of the central nervous system (CNS). Several observations suggest that the interferon system may be of interest in the study of MS development To investigate whether polymorphism in components of the IFN system and the JAK-STAT pathway influence susceptibility to MS, we performed a linkage analysis between polymorphic loci in or close to the IFN gamma, IFN gamma receptor, IFN alpha/beta receptor, JAK 1, STAT 1 and STAT 3 genes in 27 Swedish families with at least two members having MS. Tests for transmission disequilibrium and nonparametric linkage analysis gave negative results. We found no evidence for linkage between MS and any of these loci.
Case-Control Studies↗
Simultaneous measurements of organic carbon mineralization and bacterial production in oxic and anoxic lake sediments.
Based on work in marine sediments it can be hypothesized that (i) overall OM mineralization depends on the enzymatic capacity and is largely independent from the energy yield, (ii) similar oxic and anoxic rates are expected for fresh OM, while oxic rates should be faster for old OM that is partially degraded or adsorbed to particles, and (iii) that the thermodynamic energy yield does not regulate mineralization, but primarily determines the energy fraction allocated to bacterial production (BP). We addressed these hypotheses by simultaneous measurements of mineralization rates (MR) and BP in sediments from a eutrophic lake, along with MR measurements in sediments of a dystrophic lake. Anoxic MR were 44 and 78% of oxic MR in the eutrophic and dystrophic lake, respectively, which was always higher than expected given the theoretical energy yields. The BP:MR ratio was 0.94 and 0.24 in the oxic and anoxic treatments, respectively, in accordance with the expected energy yields. Thus, the results support all three hypotheses above. We also critically discuss BP measurements in sediments and suggest that bacterial growth efficiency values from simultaneous MR and BP measurements can be used to evaluate the reliability of BP estimates.
Bacterial Physiological Phenomena↗
Adult coeliac patients do tolerate large amounts of oats.
OBJECTIVE: The aim of the present study was to investigate whether adult patients with coeliac disease in remission could include large amounts of oats in their daily gluten-free diet for an extended period of time without adverse effects. DESIGN, SUBJECTS AND METHODS: Twenty adult coeliac patients in remission included large amounts of uncontaminated rolled oats in their daily diet for a prolonged period. The examinations, performed four times during the study period, included small bowel endoscopy with biopsies, blood samples (nutritional status, serological analysis), height and body weight, gastrointestinal symptoms and dietary records. Gastrointestinal symptoms and diet were also investigated through unannounced telephone interviews once a month during the study period. RESULTS: No adverse effects of a large intake of oats were seen in small bowel histology, serology nor in nutritional status in the 15 subjects who completed the whole study period. Two of the subjects dropped out because of gastrointestinal symptoms and three for non-medical reasons. The median intake of oats was 93 g/day and the compliance to the oat diet was found to be good. Examinations of the patients after drop-out did not show any deterioration in small bowel histology or nutritional status nor raised levels of antibodies. CONCLUSION: Results from this study indicate that adult patients with coeliac disease in remission can include large amounts of controlled wheat-free rolled oats for an extended period of time without adverse effects.
Adult↗
Family and population effects on disease resistance in a reptile.
Despite its importance in evolutionary biology, studies of the pattern of disease resistance in natural populations are rare. In this paper, we report patterns of infection of a viral eye disease in juvenile Swedish common lizards (Lacerta vivipara). Females were sampled at random from natural populations immediately prior to parturition with equal exposure of pathogens for all lizards once in captivity. No causative agents could be found that linked risk of disease to maternal/interfollicular transfer of pathogens. The results show that a major factor influencing offspring susceptibility is family identity, suggesting heritable variation in pathogen resistance. Our interpopulation comparison provides additional support for a link between genetics and disease resistance. Lizards in northern Sweden were not only more susceptible to the disease but were also more health compromised once infected, with relatively more reduced growth rate and increased mortality than lizards from the south. This scenario suggests that southern lizards have been under selection for resistance to this pathogen, whereas northern lizards have not, or at least not to the same degree. Thus, this study confirms the importance of genetic (family) effects on pathogen resistance with variation in this trait among natural populations.
Animals↗
When to be born? Prolonged pregnancy or incubation enhances locomotor performance in neonatal lizards (Scincidae).
The degree of offspring development at hatching (or birth) varies among species within most major vertebrate lineages; altricial vs. precocial birds offer the clearest example of a trade-off between early hatching and the degree of locomotor development of the hatchling. No such diversity has been reported for reptiles, but we suggest that natural selection may fine-tune the time of hatching (in oviparous species) or birth (in viviparous species) to optimize offspring phenotypes and hence, maximize fitness. This hypothesis predicts enhanced neonatal performance after more prolonged incubation or gestation, within as well as among populations. Both published and original data on Australian scincid lizards support this prediction. In a field study, viviparous alpine skinks (Niveoscincus microlepidotus) that gave birth later in the season had faster-running offspring, that had a higher probability of surviving through the first year of life. The enhanced performance and survival were not secondary results of larger offspring size. After controlling for effects of mean incubation temperature, prolonged development also correlated with enhanced locomotor performance in hatchlings from eggs of an oviparous skink (Bassiana duperreyi) incubated at warm temperatures (> 20 degrees C) but not at cooler temperatures (< 20 degrees C). We suggest that embryonic reptiles control their date of hatching or birth and thus, their stage of development at this critical life-history transition.
Adaptation, Physiological↗
Uses of pH electrodes in nuclear chemistry.
The determination and definition of pH is a controversial subject in many areas in chemistry. For these reasons the International Union of Pure and Applied Chemistry (IUPAC) has developed recommendations for pH measurement. These recommendations are currently (winter 2001) under revision - there will be increased emphasis on traceability of uncertainties in pH measurement. Here we describe how glass electrodes designed for measurement of pH are used in nuclear chemistry. The use of pH electrodes is then related to the IUPAC recommendations. In applied chemistry, e.g. nuclear chemistry, a pH is not sought as often as a hydrogen ion concentration or a simple equilibrium point during a titration. Ionic strengths are, moreover, often above the range in which the IUPAC recommendations apply. In these instances uncertainties must be assessed individually.
Journal Article↗
Global distribution of halogenated dimethyl bipyrroles in marine mammal blubber.
Four halogenated dimethyl bipyrroles (HDBPs), hypothesized to be naturally produced, were quantitated in marine mammal blubber from a number of species obtained from various locations worldwide. HDBPs were found in samples from all locations studied. Concentrations of total HDBPs (SigmaHDBPs) ranged from 0.4 ng/g lipid weight in ringed seals (Phoca hispida) from the White Sea to 2,540 ng/g lipid weight in Dall's porpoise (Phocoenoides dalli) from the northwestern North Pacific Ocean. At their highest levels, SigmaHDBPs made up 11% of the total quantitated organohalogen body burden of adult male Dall's porpoises. In two beluga (Delphinapterus leucas) data subsets, it was found that males contained significantly higher concentrations of SigmaHDBPs than females. No significant effects of age or sex on SigmaHDBPs were observed in harbor seal (Phoca vitulina) and bowhead whale (Balaena mysticetus) data subsets. The geographical distribution of concentrations did not resemble that of the ubiquitous anthropogenic organohalogen, polychlorinated biphenyl congener CB-153. Higher concentrations of HDBPs and different patterns of congeners were observed in samples from Pacific as opposed to non-Pacific Ocean influenced environments. Concentrations of HDBPs in beluga from the Arctic and St. Lawrence River were similar. Their high abundance in north Pacific Ocean biota and widespread occurrence suggest that HDBPs undergo extensive transport from a source located primarily in the Pacific Ocean. Evidence from HDBP congener patterns indicates that both ocean currents and atmospheric transport likely play a role in the movement of HDBPs. These results imply that HDBPs and anthropogenic organohalogens have different sources and support the natural production hypothesis.
Adipose Tissue↗
HLA in coeliac disease families: a novel test of risk modification by the 'other' haplotype when at least one DQA1*05-DQB1*02 haplotype is carried.
Predisposition to coeliac disease (CD) involves HLA genes. We investigated whether any haplotypes modify risk when carried trans to a known high-risk haplotype, DQA1*05-DQB1*02. Earlier attempts to rank levels of risk contributed by the 'other' haplotype were burdened by use of case-control populations; haplotype frequencies were estimated and homozygosity was only presumed. In contrast, exact haplotypes can be determined and allele transmission can be traced in families. A similar study in narcolepsy reported strata of different degrees of predisposition, attributable to the 'other' haplotype. A gene dosage effect similar to that described for DQB1*02 in CD, has also been reported in narcolepsy. We genotyped 439 simplex/multiplex trios for DQA1 and DQB1. We designed a new statistic to test risk modulation by the trans haplotype, even if the affected offspring was homozygous. We tested for significant deviation in transmission of the 'other' haplotype, i.e., modification of DQA1*05-DQB1*02 risk. We also addressed the proposed difference in risk, between DQA1*05-DQB1*02 homozygotes and DQA1*05-DQB1*02/DQA1*0201-DQB1*02 heterozygotes, reported in Southern Europe. We confirmed a DQB1*02 gene dosage effect. However, no haplotypes were found to modify risk when carried trans to DQA1*05-DQB1*02, except DQA1*05-DQB1*02 and DQA1*0201-DQB1*02 which were already known. We did not find credible evidence for a difference in risk conferred by DQA1*05-DQB1*02 and DQA1*0201-DQB1*02, when carried with DQA1*05-DQB1*02. The new test, which directly inspects haplotype transmissions rather than estimated haplotype frequencies, was used to demonstrate that the 'other' haplotype (except DQA1*05-DQB1*02 and DQA1*0201-DQB1*02) does not modify risk conferred by DQA1*05-DQB1*02. The test is applicable to other diseases.
Celiac Disease↗