Genetic variability within the innate immune system influences personality traits in women

Raised levels of inflammation markers have been associated with several mental disorders; however, studies regarding the relationship between inflammation or the immune system and various aspects of human behaviour are not numerous. The aim of the present study was to investigate whether an association exists between personality traits and two single nucleotide polymorphisms located in genes that are associated with the innate immune system. The studied population consisted of 42-year-old women recruited from the population registry that had been assessed by means of Karolinska Scales of Personality, a self-reported inventory. The first polymorphism, +1444C>T (rs1130864), is located in the gene coding for C-reactive protein (CRP), a marker of low-grade inflammation. The T-allele has previously been suggested to be linked to raised serum levels of CRP. The second polymorphism, Y402H (1277T>C, rs1061170), is located in the gene coding for complement factor H, an important regulator of the complement system. The C-allele has consistently been associated with age-related macular degeneration. While the +1444T allele was associated with higher scores in the personality traits impulsiveness, monotony avoidance and social desirability, the 1277C polymorphism was associated with higher scores in verbal aggression and lower scores in social desirability. In conclusion, the associations between the personality traits and the studied polymorphisms further support the possible influence of the immune system on mental functions.     

The Future of the Oceans Past: Towards a Global Marine Historical Research Initiative

Historical research is playing an increasingly important role in marine sciences. Historical data are also used in policy making and marine resource management, and have helped to address the issue of shifting baselines for numerous species and ecosystems. Although many important research questions still remain unanswered, tremendous developments in conceptual and methodological approaches are expected to contribute to a comprehensive understanding of the global history of human interactions with life in the seas. Based on our experiences and knowledge from the “History of Marine Animal Populations” project, this paper identifies the emerging research topics for future historical marine research. It elaborates on concepts and tools which are expected to play a major role in answering these questions, and identifies geographical regions which deserve future attention from marine environmental historians and historical ecologists.     

Dose-response relationship for parathyroid adenoma after exposure to ionizing radiation in infancy

Several authors have suggested that there is an excess risk of hyperparathyroidism, adenomas or hyperplasia after exposure to ionizing radiation. There is still, however, some uncertainty about this association, because these diseases are often asymptomatic and escape clinical detection if not specially searched for. This study is based on a pooled Swedish cohort of 27,925 persons with skin hemangiomas. The majority received radiation treatment in infancy between 1920 and 1965 in Stockholm and Gothenburg. The mean age at treatment was 6 months and the median thyroid dose was 0.20 Gy (range 0-28.5 Gy). Record linkage with the Swedish Cancer Register for the period 1958-1997 gave 43 cases of parathyroid adenoma in the cohort. Analyses of excess relative risk (ERR) models were performed using Poisson regression methods. Clinical records were scrutinized to determine if the childhood radiation exposure was known (biased cases) at the time of diagnosis. Seven of the cases of parathyroid adenoma were classified as biased cases. The standardized incidence ratio (SIR) was 2.10 (95% confidence interval 1.52-2.82) when all cases were included and 1.76 (95% CI 1.23-2.43) with the biased cases excluded. A linear dose-response model with stratification for sex fitted the data best. The ERR per gray was 3.84 (95% CI 1.56-8.99) with all cases and 1.56 (95% CI 0.36-4.45) with the biased cases excluded. There was a significant difference in the ERR per gray between the two subcohorts, probably because of different diagnostic activity in the regions. Our findings confirm that there is a dose-response relationship for radiation-induced parathyroid adenomas.     

Evaluation of different domain-based methods in protein interaction prediction

Protein-protein interactions (PPIs) play an important role in many biological functions. PPIs typically involve binding between domains, the basic units of protein folding, evolution and function. Identifying domain-domain interactions (DDIs) would aid understanding PPI networks. Recently, many computational methods aimed to infer DDIs from databases of interacting proteins and subsequently used the inferred DDIs to predict new PPIs. We attempt to describe systematically current domain-based approaches including the association method, maximum likelihood estimation and parsimonious explanation method. The performance of these methods at inferring DDIs and predicting PPIs was evaluated comparatively. We observe that each method generates artefacts in certain situations and discuss biases in the available benchmark sets.     

SLC26A9 is expressed in gastric surface epithelial cells, mediates Cl-/HCO3- exchange, and is inhibited by NH4+

HCO3- secretion by gastric mucous cells is essential for protection against acidic injury and peptic ulcer. Herein we report the identification of an apical HCO3- transporter in gastric surface epithelial cells. Northern hybridization and RT-PCR demonstrate the expression of this transporter, also known as SLC26A9, in mouse and rat stomach and trachea (but not kidney). In situ hybridization in mouse stomach showed abundant expression of SLC26A9 in surface epithelial cells with apical localization on immunofluorescence labeling. Functional studies in HEK-293 cells demonstrated that SLC26A9 mediates Cl-/HCO3- exchange and is also capable of Cl--independent HCO3- extrusion. Unlike other anion exchangers or transport proteins reported to date, SLC26A9 activity is inhibited by ammonium (NH4+). The inhibitory effect of NH4+ on gastric HCO3- secretion was also indicated by reduced gastric juxtamucosal pH (pHjm) in rat stomach in vivo. This report is the first to describe the inhibition of HCO3- transport in vitro and the reduction of pHjm in stomach in vivo by NH4+. Given its critical localization on the apical membrane of surface epithelial cells, its ability to transport HCO3-, and its inhibition by NH4+, we propose that SLC26A9 mediates HCO3- secretion in surface epithelial cells and is essential for protection against acidic injury in the stomach. Disease states that are associated with increased ammonia (NH3)/NH4+ generation (e.g., Helicobacter pylori) may impair gastric HCO3- secretion and therefore predispose patients to peptic ulcer by inhibiting SLC26A9.     

Solid phase synthesis of diamides as potential bone resorption inhibitors

Unsymmetrical diamide libraries have been prepared by a general and versatile solid phase route, using diacid templates in combination with aromatic and aliphatic amines chosen with the help of statistical experimental design. The compounds were tested as potential inhibitors of osteoclast vacuolar ATPase.