Peptidylarginine Deiminase (PAD) and Post-Translational Protein Deimination-Novel Insights into Alveolata Metabolism, Epigenetic Regulation and Host-Pathogen Interactions.

The alveolates (Superphylum Alveolata) comprise a group of primarily single-celled eukaryotes that have adopted extremely diverse modes of nutrition, such as predation, photoautotrophy and parasitism. The alveolates consists of several major phyla including the apicomplexans, a large group of unicellular, spore forming obligate intracellular parasites, and chromerids, which are believed to be the phototrophic ancestors of the parasitic apicomplexans. Molecular pathways involved in Alveolata host-pathogen interactions, epigenetic regulation and metabolism in parasite development remain to be fully understood. Peptidylarginine deiminases (PADs) are a phylogenetically conserved enzyme family which causes post-translational protein deimination, affecting protein function through the conversion of arginine to citrulline in a wide range of target proteins, contributing to protein moonlighting in physiological and pathological processes. The identification of deiminated protein targets in alveolate parasites may therefore provide novel insight into pathogen survival and host-pathogen interactions. The current study assessed PAD homologues and deiminated protein profiles of two alveolate parasites, Piridium sociabile (Chromerida) and Merocystis kathae (Apicomplexa). Histological analysis verified strong cytoplasmic PAD expression in both Alveolates, detected deiminated proteins in nuclear and cytoplasmic compartments of the alveolate parasites and verified the presence of citrullinated histone H3 in Alveolata nucleus, indicating roles in epigenetic regulation. Histone H3 citrullination was also found significantly elevated in the host tissue, indicative of neutrophil extracellular trap formation, a host-defence mechanism against a range of pathogens, particularly those that are too large for phagocytosis. Proteomic analysis of deiminated proteins from both Alveolata identified GO and KEGG pathways strongly relating to metabolic and genetic regulation, with some species-specific differences between the apicomplexan and the chromerid. Our findings provide novel insights into roles for the conserved PAD/ADI enzyme family in the regulation of metabolic and epigenetic pathways in alveolate parasites, possibly also relating to their life cycle and host-pathogen interactions.

Is an Apicomplexan Parasite Responsible for the Collapse of the Iceland Scallop (Chlamys islandica) Stock?

Due to the total and unexpected collapse of the Iceland scallop, Chlamys islandica, stocks around Iceland during the 2000s, a commercial fishing ban has been imposed on this valuable resource since 2003. Following the initial identification of an apicomplexan parasite in the scallops, a long-term surveillance program was established to evaluate the effect of the parasite on the population. The infections were highly prevalent in all shell sizes throughout the study. However, the parasite only impacts mature scallops where they cause severe macroscopic changes, characterized by an extensively diminished and abnormally coloured adductor muscle. A highly significant relationship was observed between infection intensity and gonad and adductor muscle indices. The first four years of the study, were characterized by high infection intensity and very poor condition of the adductor muscle and gonads, whilst during subsequent years, infections gradually decreased and the condition of the scallops improved. Histopathological changes were restricted to the presence of apicomplexan zoites which were widely distributed, causing varying degrees of pathology in all organs. In heavy infections, muscular and connective tissues were totally necrotized, destroying significant parts of numerous organs, especially the adductor muscle, digestive gland and gonads. The progression of the disease was in good synchrony with the mortality rates and the subsequent decline observed in the scallop stock and recruitment indices. Our findings strongly suggest that the apicomplexan parasite played a major role in the collapse of the Iceland scallop stock in Breidafjordur. In addition to causing mortality, the infections significantly impact gonad development which contributes further to the collapse of the stock in the form of lower larval recruitment. Furthermore, compelling evidence exists that this apicomplexan pathogen is causing serious disease outbreaks in other scallop populations. Similar abnormal adductor muscles and the parasite itself have been identified or observed in association with other mass mortality events in several different scallop species and commercial stocks in the northern hemisphere.

Smoking during pregnancy: childbirth and health study in primary care in Iceland.

OBJECTIVE: To study the prevalence and possible predictors for smoking during pregnancy in Iceland. DESIGN: A cross-sectional study. SETTING: Twenty-six primary health care centres in Iceland 2009-2010. SUBJECTS. Women attending antenatal care in the 11th-16th week of pregnancy were invited to participate by convenient consecutive manner, stratified according to residency. A total of 1111 women provided data in this first phase of the cohort study. MAIN OUTCOME MEASURES: Smoking habits before and during early pregnancy were assessed with a postal questionnaire, which also included questions about socio-demographic background, physical and emotional well-being, and use of medications. RESULTS: The prevalence of smoking prior to pregnancy was 20% (223/1111). During early pregnancy, it was 5% (53/1111). In comparison with women who stopped smoking during early pregnancy, those who continued to smoke had on average a significantly lower level of education, had smoked more cigarettes per day before pregnancy, and were more likely to use nicotine replacement therapy in addition to smoking during pregnancy. A higher number of cigarettes consumed per day before pregnancy and a lower level of education were the strongest predictors for continued smoking during pregnancy. CONCLUSION: The majority of Icelandic women who smoke stop when they become pregnant, and the prevalence of smoking during pregnancy in Iceland is still about 5%. Our results indicate stronger nicotine dependence in women who do not stop smoking during pregnancy. Awareness of this can help general practitioners (GPs) and others providing antenatal care to approach these women with more insight and empathy, which might theoretically help them to quit.

Blood pressure in children and target-organ damage later in life.

The aim of this study was to examine the association between blood pressure (BP) in children and adolescents and cardiovascular and renal disease in adulthood. This was a retrospective study on patients <18 years of age with an elective admission to Landspitali University Hospital in Reykjavik, Iceland, between 1950 and 1967. We recorded baseline variables including BP and invited all patients for a follow-up visit in 2008 for repeat studies. We used chi(2), Fisher's exact test, and logistic regression to examine the association between BP in childhood and outcome variables at follow-up. We identified 126 individuals (54 men) for the study. The median age (range) at childhood admission was 15 (10-17) years and the median BP was 125/80 mmHg. Median age at follow-up was 58 (42-68) years, follow-up time 43 (25-52) years, and median BP 133/75 mmHg. Eleven had died (five men) and 49 had been diagnosed with hypertension (23 men) and 12 with coronary artery disease (ten men). There was a significant correlation between the diagnosis of coronary artery disease at follow-up and childhood systolic BP (odds ratio = 1.052; P = 0.03) as well as systolic BP >/= 95th percentile (P = 0.03). Our results suggest that elevated childhood systolic BP may increase the risk of coronary artery disease in adult life. The sample size is a limiting factor, and the study should be carried out in a larger population.