Selected polymorphisms in sex hormone-related genes, circulating sex hormones and risk of endometrial cancer

Background: The role of estrogen and progesterone in the development of endometrial cancer is well documented. Few studies have examined the association of genetic variants in sex hormone-related genes with endometrial cancer risk. Methods: We conducted a case-control study nested within three cohorts to examine the association of endometrial cancer risk with polymorphisms in hormone-related genes among 391 cases (92% postmenopausal at diagnosis) and 712 individually-matched controls. We also examined the association of these polymorphisms with circulating levels of sex hormones and SHBG in a cross-sectional analysis including 596 healthy postmenopausal women at blood donation (controls from this nested case-control study and from a nested case-control study of breast cancer in one of the three cohorts). Results: Adjusting for endometrial cancer risk factors, the A allele of rs4775936 in CYP19 was significantly associated (OR(per allele)=1.22, 95% CI=1.01-1.47, p(trend)=0.04), while the T allele of rs10046 was marginally associated with increased risk of endometrial cancer (OR(per allele)=1.20, 95% CI=0.99-1.45, p(trend)=0.06). PGR rs1042838 was also marginally associated with risk (OR(per allele)=1.25, 95% CI=0.96-1.61, p(trend)=0.09). No significant association was found for the other polymorphisms, i.e. CYP1B1 rs1800440 and rs1056836, UGT1A1 rs8175347, SHBG rs6259 and ESR1 rs2234693. Rs8175347 was significantly associated with postmenopausal levels of estradiol, free estradiol and estrone and rs6259 with SHBG and estradiol. Conclusion: Our findings support an association between genetic variants in CYP19, and possibly PGR, and risk of endometrial cancer.     

Fatty acid composition of different serum phospholipids in men and women

1. Eight young healthy persons, four men and four women, were maintained for a total of 2 months on a diet in which 40%, 16% and 44% of the total calories were present as fats, proteins and carbohydrates respectively. The ratio of complex to simple carbohydrates in the diet was 1:4. 2. The fatty acids of serum kephalins, lecithins, lysolecithins and sphingomyelins were determined by gas-liquid column chromatography. 3. Lysolecithins in both men and women had the highest content of saturated acids, followed by sphingomyelins, lecithins and kephalins in that order. The degrees of saturation and of polyunsaturation of the fatty acids in the different phospholipid fractions were significantly different, except for the differences in the polyunsaturation of the kephalins and lecithins. 4. No sex difference was found in the fatty acid composition of the different phospholipids.     

Studies on the activation of purified mitochondrial ATPase by phospholipids

1. An ATPase which is activated by phospholipids and inhibited by oligomycin, has been purified from beef heart submitochondrial particles using affinity chromatography. Phospholipid and detergent are removed by washing the enzyme with a solution of serum albumin while it is attached to the biospecific adsorbent.

2. The ATPase is activated up to 18-fold by lysolecithin and to a smaller extent by cardiolipin, phosphatidylinositol and phosphatidylethanolamine. The amount required of each of these phospholipids to give half-maximal activation is apparently inversely related to the number of fatty acid chains in the lipid. Lecithin, which is a poor activator of the ATPase, competitively inhibits the activation by cardiolipin.

3. The activation of the ATPase consists of an increase in both the maximal velocity of the reaction and the affinity for substrate ATP. The pH optimum of the reaction is not influenced by the charge of the lipid.

4. Arrhenius plots of ATPase activated with lysolecithin show a transition to a higher activation energy at temperatures below 19 °C. The sensitivity of the lysolecithin-activated enzyme to oligomycin is markedly reduced below the same temperature. With cardiolipin the transition is observed at 13 °C.

5. ADP, Mg²⁺ and to a smaller extent ATP, Mg²⁺ enhance the activation of ATPase by suboptimal amounts of phospholipid.     

Fine-scale distribution of the epiphytic lichen Usnea longissima on two even-aged neighbouring Picea abies trees

Abstract. Two neighbouring even-aged 130-yr old Picea abies trees in a homogeneous stand can differ substantially with respect to their epiphytic vegetation. Sampled branches from the canopy of one tree harboured 781 specimens of the old forest lichen Usnea longissima of which only 50 could be seen from the ground, whereas no U. longissima were found on its nearest neighbour. Usnea longissima was most abundant on branch tips in lower parts of the canopy on branch segments having the highest biomass of other alectorioid species. Trees with and without U. longissima showed a different pattern in their mineral composition, suggesting that a tree-specific difference in nutritional status might contribute to explain the patchy distribution of this lichen within seemingly homogeneous stands.     

MtDNA Sequences Support Monophyly of Hemispingus Tanagers

Tanagers of the genus Hemispingus comprise an array of 12 recognized species of rather dull-colored tanagers restricted to Andean forests. Four of these species are polytypic, with as many as seven subspecies recognized for H. superciliaris. Taxonomic relationships within this group, and with similar-looking Basileuterus warblers, have been confusing and not well understood. We used partial DNA sequences of the mitochondrial ND2 gene and a set of morphological characters to study their phylogenetic relationships. Our molecular dataset strongly supports the monophyly of Hemispingus (including the warbler-like species and the finch-like H. rufosuperciliaris) compared to other nine-primaried oscines (Ramphocelus, Chlorospingus, Atlapetes/Buarremon, Basileuterus) and indicates either that Atlapetes/Buarremon could be tanagers or that Chlorospingus could be finches. We propose a phylogeny containing three major clades: mostly greenish eye-browed birds (trifasciatus, atropileus, auricularis, calophrys), mostly gray warbler-like birds (superciliaris, verticalis, xanthophthalmus), and mostly ochraceous birds (rufosuperciliaris and goeringi, piurae, frontalis, melanotis). The relationships among these three clades are left unresolved. We suggest species status for H. auricularis and H. piurae. Our molecular data suggest that most of the diversity in Hemispingus tanagers predates the period of marked ecoclimatic fluctuations in the upper Pleistocene.     

Salmonellae interplay with host cells

Salmonellae are important causes of enteric diseases in all vertebrates. Characterization of the molecular mechanisms that underpin the interactions of salmonellae with their animal hosts has advanced greatly over the past decade, mainly through the study of Salmonella enterica serovar Typhimurium in tissue culture and animal models of infection. Knowledge of these bacterial processes and host responses has painted a dynamic and complex picture of the interaction between salmonellae and animal cells. This Review focuses on the molecular mechanisms of these host-pathogen interactions, in terms of their context, significance and future perspectives.     

A high‐throughput FTIR spectroscopy approach to assess adaptive variation in the chemical composition of pollen

The two factors defining male reproductive success in plants are pollen quantity and quality, but our knowledge about the importance of pollen quality is limited due to methodological constraints. Pollen quality in terms of chemical composition may be either genetically fixed for high performance independent of environmental conditions, or it may be plastic to maximize reproductive output under different environmental conditions. In this study, we validated a new approach for studying the role of chemical composition of pollen in adaptation to local climate. The approach is based on high‐throughput Fourier infrared (FTIR) characterization and biochemical interpretation of pollen chemical composition in response to environmental conditions. The study covered three grass species, Poa alpina, Anthoxanthum odoratum, and Festuca ovina. For each species, plants were grown from seeds of three populations with wide geographic and climate variation. Each individual plant was divided into four genetically identical clones which were grown in different controlled environments (high and low levels of temperature and nutrients). In total, 389 samples were measured using a high‐throughput FTIR spectrometer. The biochemical fingerprints of pollen were species and population specific, and plastic in response to different environmental conditions. The response was most pronounced for temperature, influencing the levels of proteins, lipids, and carbohydrates in pollen of all species. Furthermore, there is considerable variation in plasticity of the chemical composition of pollen among species and populations. The use of high‐throughput FTIR spectroscopy provides fast, cheap, and simple assessment of the chemical composition of pollen. In combination with controlled‐condition growth experiments and multivariate analyses, FTIR spectroscopy opens up for studies of the adaptive role of pollen that until now has been difficult with available methodology. The approach can easily be extended to other species and environmental conditions and has the potential to significantly increase our understanding of plant male function.     

A method to find tissue-specific novel sites of selective adenosine deamination

Site-selective adenosine (A) to inosine (I) RNA editing by the ADAR enzymes has been found in a variety of metazoan from fly to human. Here we describe a method to detect novel site-selective A to I editing that can be used on various tissues as well as species. We have shown previously that there is a preference for ADAR2-binding to selectively edited sites over non-specific interactions with random sequences of double-stranded RNA. The method utilizes immunoprecipitation (IP) of intrinsic RNA–protein complexes to extract substrates subjected to site-selective editing in vivo, in combination with microarray analyses of the captured RNAs. We show that known single sites of A to I editing can be detected after IP using an antibody against the ADAR2 protein. The RNA substrates were verified by RT–PCR, RNase protection and microarray. Using this method it is possible to uniquely identify novel single sites of selective A to I editing.     

Continuous weak-affinity immunosensing

A multitude of weak biological interactions, either working alone or in concert, occur frequently throughout biological systems. We have used this natural feature of readily reversible interactions as the basis for continuous immunosensing. In a model system, a set of weak monoclonal antibodies directed towards a carbohydrate epitope was studied with the aid of surface plasmon resonance. Because the system requires no regeneration, it can be used as a truly on-line immunosensing device. This principle should have wide application in all areas where there is a need for the continuous evaluation of a molecule.     

A lectin immunosensor technique for determination of alpha(1)-acid glycoprotein fucosylation

The fucosylation of alpha(1)-acid glycoprotein (AGP), an acute-phase protein, is known to change in association with inflammatory diseases. Thus, fucosylation of AGP could be a potential diagnostic or prognostic marker. The change in fucosylation has previously been investigated using crossed affinoimmunoelectrophoresis, high-pH anion-exchange chromatography, and lectin ELISA. This study describes a surface plasmon resonance-based affinity biosensor assay for quantification of the fucosylation of AGP. Diluted EDTA plasma or serum was injected directly in a BIACORE 2000 biosensor. AGP was captured on the sensor surface using immobilized antibodies and a fucose-binding lectin from Aleuria aurentia was then used for the detection of fucosylation. The feature of the biosensor makes it possible to determine both the amount of bound AGP and the amount of bound lectin. Using a calibration curve it was possible to obtain a fucosylation ratio that was independent of AGP concentration. The assay was validated against a lectin ELISA and used to follow inflammation in patients with severe burns.