Highly Virulent Non-O157 Enterohemorrhagic Escherichia coli (EHEC) Serotypes Reflect Similar Phylogenetic Lineages,Providing New Insights into the Evolution of EHEC

Enterohemorrhagic Escherichia coli (EHEC) is the causative agent of bloody diarrhea and extraintestinal sequelae in humans, most importantly hemolytic-uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP). Besides the bacteriophage-encoded Shiga toxin gene (stx), EHEC harbors the locus of enterocyte effacement (LEE), which confers the ability to cause attaching and effacing lesions. Currently, the vast majority of EHEC infections are caused by strains belonging to five O serogroups (the “big five”), which, in addition to O157, the most important, comprise O26, O103, O111, and O145. We hypothesize that these four non-O157 EHEC serotypes differ in their phylogenies. To test this hypothesis, we used multilocus sequence typing (MLST) to analyze a large collection of 250 isolates of these four O serogroups, which were isolated from diseased as well as healthy humans and cattle between 1952 and 2009. The majority of the EHEC isolates of O serogroups O26 and O111 clustered into one sequence type complex, STC29. Isolates of O103 clustered mainly in STC20, and most isolates of O145 were found within STC32. In addition to these EHEC strains, STC29 also included stx-negative E. coli strains, termed atypical enteropathogenic E. coli (aEPEC), yet another intestinal pathogenic E. coli group. The finding that aEPEC and EHEC isolates of non-O157 O serogroups share the same phylogeny suggests an ongoing microevolutionary scenario in which the phage-encoded Shiga toxin gene stx is transferred between aEPEC and EHEC. As a consequence, aEPEC strains of STC29 can be regarded as post- or pre-EHEC isolates. Therefore, STC29 incorporates phylogenetic information useful for unraveling the evolution of EHEC.     

CTLA4 polymorphisms are associated with vitiligo, in patients with concomitant autoimmune diseases

The cytotoxic T lymphocyte antigen4 (CTLA4) gene plays a critical role in the control of T cell activation. The gene encodes a surface molecule with inhibitory effects on activated T cells. Several studies have disclosed an association between the previously known variants of the CTLA4 gene and autoimmune disorders, but no study has as yet found any definite association between vitiligo and the CTLA4 polymorphisms. A recent study identified new candidate susceptibility polymorphisms in this region, associated with differential gene splicing and thereby the relative abundance of soluble CTLA4. To assess these new polymorphisms in patients with vitiligo, we genotyped 100 vitiligo patients and 140 healthy controls from the UK, for these novel polymorphisms. No association was found in patients with isolated vitiligo, but a significant association was seen in patients with vitiligo and other autoimmune diseases. The results indicate that the polymorphisms in the CTLA4 gene region confer susceptibility to vitiligo when occurring together with other autoimmune diseases, but not in patients with isolated vitiligo. This raises the possibility that there are two distinct forms of vitiligo where only a subgroup of patients may have a disease caused by the autoimmune destruction of melanocytes.     

Mutagenicity and DNA repair of glycidamide-induced adducts in mammalian cells

Glycidamide (GA)-induced mutagenesis in mammalian cells is not very well understood. Here, we investigated mutagenicity and DNA repair of GA-induced adducts utilizing Chinese hamster cell lines deficient in base excision repair (BER), nucleotide excision repair (NER) or homologous recombination (HR) in comparison to parent wild-type cells. We used the DRAG assay in order to map pathways involved in the repair of GA-induced DNA lesions. This assay utilizes the principle that a DNA repair deficient cell line is expected to be affected in growth and/or survival more than a repair proficient cell. A significant induction of mutations by GA was detected in the hprt locus of wild-type cells but not in BER deficient cells. Cells deficient in HR or BER were three or five times, respectively, more sensitive to GA in terms of growth inhibition than were wild-type cells. The results obtained on the rate of incisions in BER and NER suggest that lesions induced by GA are repaired by short patch BER rather than long patch BER or NER. Furthermore, a large proportion of the GA-induced lesions gave rise to strand breaks that are repaired by a mechanism not involving PARP. It is suggested that these strand breaks, which might be the results from alkylation of the backbone phosphate, are misrepaired by HR during replication thereby leading to a clastogenic rather than a mutagenic pathway. The type of lesion responsible for the mutagenic effect of GA cannot be concluded from the results presented in this study.     

Premature Adult Death in Individuals Born Preterm: A Sibling Comparison in a Prospective Nationwide Follow-Up Study

BackgroundClose to one in ten individuals worldwide is born preterm, and it is important to understand patterns of long-term health and mortality in this group. This study assesses the relationship between gestational age at birth and early adult mortality both in a nationwide population and within sibships. The study adds to existing knowledge by addressing selected causes of death and by assessing the role of genetic and environmental factors shared by siblings.MethodsStudy population was all Norwegian men and women born from 1967 to 1997 followed using nation-wide registry linkage for mortality through 2011 when they were between 15 and 45 years of age. Analyses were performed within maternal sibships to reduce variation in unobserved genetic and environmental factors shared by siblings. Specific outcomes were all-cause mortality and mortality from cardiovascular diseases, cancer and external causes including accidents, suicides and drug abuse/overdoses.ResultsCompared with a sibling born in week 37–41, preterm siblings born before 34 weeks gestation had 50% increased mortality from all causes (adjusted Hazard Ratio (aHR) 1.54, 95% confidence interval (CI) 1.17, 2.03). The corresponding estimate for the entire population was 1.27 (95% CI 1.09, 1.47). The majority of deaths (65%) were from external causes and the corresponding risk estimates for these deaths were 1.52 (95% CI 1.08, 2.14) in the sibships and 1.20 (95% CI 1.01, 1.43) in the population.ConclusionPreterm birth before week 34 was associated with increased mortality between 15 and 45 years of age. The results suggest that increased premature adult mortality in this group is related to external causes of death and that the increased risks are unlikely to be explained by factors shared by siblings.     

Calcium content of crustacean zooplankton and its potential role in species distribution

SUMMARY 1. The occurrence and species composition of crustacean zooplankton in Norwegian lakes was related to ambient Ca concentrations, pH, total phosphorus and chlorophyll a , and to the presence/absence of other zooplankters and a planktivorous fish (roach: Rutilus rutilus ).
2. Ambient Ca concentrations appeared to influence the distribution of Daphnia species: Daphnia longispina often occurred in Ca-rich lakes with low fish-predation pressure while the smaller Daphnia cristata often occurred in opposite conditions.
3. Body Ca contents were measured in zooplankters from a wide range of localities, to examine Ca requirements and thus the potential for Ca-limitation of common species.
4. All Daphnia species had relatively high specific Ca contents [ranging from 0.8 to 4.4% Ca dry weight (DW)⁻¹] compared with other cladocerans and also copepods (ranging from 0.1 to 0.4% Ca DW⁻¹). Within the Daphnia genus, the specific Ca content increased with increasing body size of the species, and thus the large-bodied species had especially high Ca demands.
5. Because of their high Ca demands, species of Daphnia could be competitively disadvantaged in softwater lakes relative to less Ca-demanding species.     

The costs of moulting in Daphnia; mineral regulation of carbon budgets

1. Zooplankton differ in their elemental contents. For the essential elements calcium (Ca) and phosphorus (P), Daphnia spp. have particularly high contents, and thus high demands, compared with other cladocera and copepods.
2. There are recent indications that the growth of zooplankton, notably Daphnia , may be directly constrained by the availability of P and Ca.
3. Major pools of P and Ca are associated with the carapace, and the moulting process represents a constant drain of these elements, as well as carbon (C), from the animals.
4. The demands for P and Ca for moulting may pose constraints on the carbon accumulation in the animals, and thus the extensive needs for these elements may translate into a total loss of C transported in the pelagic food web.
5. While the costs of moulting are substantial for the zooplankton, the export of minerals bound in the moult will play only a minor role for the epilimnetic element budgets in most lakes.
     

Do Cadmium, Lead, and Aluminum in Drinking Water Increase the Risk of Hip Fractures? A NOREPOS Study

The aim of this study was to investigate relations between cadmium, lead, and aluminum in municipality drinking water and the incidence of hip fractures in the Norwegian population. A trace metals survey in 566 waterworks was linked geographically to hip fractures from hospitals throughout the country (1994–2000). In all those supplied from these waterworks, 5,438 men and 13,629 women aged 50–85 years suffered a hip fracture. Poisson regression models were fitted, adjusting for age, region of residence, urbanization, and type of water source as well as other possibly bone-related water quality factors. Effect modification by background variables and interactions between water quality factors were examined (correcting for false discovery rate). Men exposed to a relatively high concentration of cadmium (IRR?=?1.10; 95 % CI 1.01, 1.20) had an increased risk of fracture. The association between relatively high lead and hip fracture risk was significant in the oldest age group (66–85 years) for both men (IRR?=?1.11; 95 % CI 1.02, 1.21) and women (IRR?=?1.10; 95 % CI 1.04, 1.16). Effect modification by degree of urbanization on hip fracture risk in men was also found for all three metals: cadmium, lead, and aluminum. In summary, a relatively high concentration of cadmium, lead, and aluminum measured in drinking water increased the risk of hip fractures, but the associations depended on gender, age, and urbanization degree. This study could help in elucidating the complex effects on bone health by risk factors found in the environment.     

Filtration and respiration of the deep living bivalve Acesta excavata (J.C. Fabricius, 1779) (Bivalvia; Limidae)

Here we report the first study of clearance rate and respiration rate of a deep living bivalve, Acesta excavata (J.C. Fabricius, 1779) (Mollusca: Limidae). We found that A. excavata had extreme values both for clearance and respiration rates compared to other bivalves. It has the second largest clearance rate ever reported, 13.36 l h^− 1 g^− 1, and the second lowest value of respiration rate, 0.12 ml O₂ h^− 1 g^− 1. The gill area of 7063 mm² g^− 1 is one of the largest found in bivalves so far. We suggest that these values indicate a physiological adaptation to the low and irregular food supply in the deep sea rather that a specific adaptation to depth.     

Paradoxical redistribution of pulmonary blood flow in prone and supine humans exposed to hypergravity.

We hypothesized that exposure to hypergravity in the supine and prone postures causes a redistribution of pulmonary blood flow to dependent lung regions. Four normal subjects were exposed to hypergravity by use of a human centrifuge. Regional lung perfusion was estimated by single-photon-emission computed tomography (SPECT) after administration of (99m)Tc-labeled albumin macroaggregates during normal and three times normal gravity conditions in the supine and prone postures. All images were obtained during normal gravity. Exposure to hypergravity caused a redistribution of blood flow from dependent to nondependent lung regions in all subjects in both postures. We speculate that this unexpected and paradoxical redistribution is a consequence of airway closure in dependent lung regions causing alveolar hypoxia and hypoxic vasoconstriction. Alternatively, increased vascular resistance in dependent lung regions is caused by distortion of lung parenchyma. The redistribution of blood flow is likely to attenuate rather than contribute to the arterial desaturation caused by hypergravity.     

Calanoid copepods from South Georgia,with special reference to size dimorphism within the genus Pseudoboeckella

Summary Three species of calanoid copepods, Boeckella michaelseni, Parabroteas sarsii and Pseudoboeckella poppei were recorded from 6 freshwater localities in the Husvik area, South Georgia. Of the latter species two distinct size morphs occurred, with no overlap in size even in closely situated populations. The large morph was recorded in lakes, the small was found in ponds. The small morph did not coexist with the large predatory P. sarsii, and we suggest predation pressure from this species as the major cause for the observed distribution of these morphs. The pronounced size segregation as well as small morphological dissimilarities suggest that these morphs are reproductively isolated. While the large morphotype corresponds to that of P. poppei, the taxonomic affinities of the small morph are uncertain.