Weather, Water Quality and Infectious Gastrointestinal Illness in Two Inuit Communities in Nunatsiavut, Canada: Potential Implications for Climate Change

Climate change is expected to cause changes in precipitation quantity, intensity, frequency and duration, which will subsequently alter environmental conditions and might increase the risk of waterborne disease. The objective of this study was to describe the seasonality of and explore associations between weather, water quality and occurrence of infectious gastrointestinal illnesses (IGI) in two communities in Nunatsiavut, Canada. Weather data were obtained from meteorological stations in Nain (2005–2008) and Rigolet (2008). Free-chlorine residual levels in drinking water were extracted from municipal records (2005–2008). Raw surface water was tested weekly for total coliform and E. coli counts. Daily counts of IGI-related clinic visits were obtained from health clinic registries (2005–2008). Analysis of weather and health variables included seasonal-trend decomposition procedures based on Loess. Multivariable zero-inflated Poisson regression was used to examine potential associations between weather events (considering 0–4 week lag periods) and IGI-related clinic visits. In Nain, water volume input (rainfall + snowmelt) peaked in spring and summer and was positively associated with levels of raw water bacteriological variables. The number of IGI-related clinic visits peaked in the summer and fall months. Significant positive associations were observed between high levels of water volume input 2 and 4 weeks prior, and IGI-related clinic visits (P < 0.05). This study is the first to systematically gather, analyse and compare baseline data on weather, water quality and health in Nunatsiavut, and illustrates the need for high quality temporal baseline information to allow for detection of future impacts of climate change on regional Inuit human and environmental health.     

Multilocus analyses of an Antarctic fish species flock (Teleostei, Notothenioidei, Trematominae): phylogenetic approach and test of the early-radiation event

Clades that have undergone episodes of rapid cladogenesis are challenging from a phylogenetic point of view. They are generally characterised by short or missing internal branches in phylogenetic trees and by conflicting topologies among individual gene trees. This may be the case of the subfamily Trematominae, a group of marine teleosts of coastal Antarctic waters, which is considered to have passed through a period of rapid diversification. Despite much phylogenetic attention, the relationships among Trematominae species remain unclear. In contrast to previous studies that were mostly based on concatenated datasets of mitochondrial and/or single nuclear loci, we applied various single-locus and multilocus phylogenetic approaches to sequences from 11 loci (eight nuclear) and we also used several methods to assess the hypothesis of a radiation event in Trematominae evolution. Diversification rate analyses support the hypothesis of a period of rapid diversification during Trematominae history and only a few nodes in the hypothetical species tree were consistently resolved with various phylogenetic methods. We detected significant discrepancies among trees from individual genes of these species, most probably resulting from incomplete lineage sorting, suggesting that concatenation of loci is not the most appropriate way to investigate Trematominae species interrelationships. These data also provide information about the possible effects of historic climate changes on the diversification rate of this group of fish.     

Evolutionary history of the Corallinales (Corallinophycidae, Rhodophyta) inferred from nuclear, plastidial and mitochondrial genomes

Systematics of the red algal order Corallinales has a long and convoluted history. In the present study, molecular approaches were used to assess the phylogenetic relationships based on the analyses of two datasets: a large dataset of SSU sequences including mainly sequences from GenBank; and a combined dataset including four molecular markers (two nuclear: SSU, LSU; one plastidial: psbA; and one mitochondrial: COI). Phylogenetic analyses of both datasets re-affirmed the monophyly of the Corallinales as well as the two families (Corallinaceae and Hapalidiaceae) currently recognized within the order. Three of the four subfamilies of the Corallinaceae (Corallinoideae, Lithophylloideae, Metagoniolithoideae) were also resolved as a monophyletic lineage whereas members of the Mastophoroideae were resolved as four distinct lineages. We therefore propose to restrict the Mastophoroideae to the genera Mastophora, Metamastophora, and possibly Lithoporella in the aim of rendering this subfamily monophyletic. In addition, our phylogenies resolved the genus Hydrolithon in two unrelated lineages, one containing the generitype Hydrolithon reinboldii and the second containing Hydrolithon onkodes, which used to be the generitype of the now defunct genus Porolithon. We therefore propose to resurrect the genus Porolithon for the second lineage encompassing those species with primarily monomerous thalli, and trichocyte arrangements in large pustulate horizontal rows. Moreover, our phylogenetic analyses revealed the presence of cryptic diversity in several taxa, shedding light on the need for further studies to better circumscribe species frontiers within the diverse order Corallinales, especially in the genera Mesophyllum and Neogoniolithon.     

Phylogenetics, species boundaries and timing of resource tracking in a highly specialized group of seed beetles (Coleoptera: Chrysomelidae: Bruchinae)

Though for a long time it was hypothesized that the extraordinary diversity of phytophagous insects was better explained by a synchronous pattern of co-diversification with plants, the results of recent studies have led to question this theory, suggesting that the diversification of insects occurred well after that of their hosts. In this study we address this issue by investigating the timing of diversification of a highly specialized group of seed beetles, which mostly feeds on legume plants from the tribe Indigofereae. To that purpose, a total of 130 specimens were sequenced for six genes and analyzed under a Bayesian phylogenetic framework. Based on the resulting trees we performed several analyses that allowed a better definition of the group boundaries and to investigate the status of several taxa through the use of molecular species delimitation analyses in combination with morphological evidences. In addition the evolution of host plant use was reconstructed and different molecular-dating approaches were carried out in order to assess the ages of several clades of interest. The resulting framework suggests a more ancient than previously thought origin for seed beetles, and a pattern of rapid host plant colonization. These findings call for further similar studies in other highly specialized groups of phytophagous insects.     

Mitochondrial inhibitory factor 1 (IF1) is present in human serum and is positively correlated with HDL-cholesterol

Background

Mitochondrial ATP synthase is expressed as a plasma membrane receptor for apolipoprotein A-I (apoA-I), the major protein component in High Density Lipoproteins (HDL). On hepatocytes, apoA-I binds to cell surface ATP synthase (namely ecto-F₁-ATPase) and stimulates its ATPase activity, generating extracellular ADP. This production of extracellular ADP activates a P2Y₁₃-mediated HDL endocytosis pathway. Conversely, exogenous IF1, classically known as a natural mitochondrial specific inhibitor of F₁-ATPase activity, inhibits ecto-F₁-ATPase activity and decreases HDL endocytosis by both human hepatocytes and perfused rat liver.

Methodology/Principal Findings

Since recent reports also described the presence of IF1 at the plasma membrane of different cell types, we investigated whether IF1 is present in the systemic circulation in humans. We first unambiguously detected IF1 in human serum by immunoprecipitation and mass spectrometry. We then set up a competitive ELISA assay in order to quantify its level in human serum. Analyses of IF1 levels in 100 normolipemic male subjects evidenced a normal distribution, with a median value of 0.49 µg/mL and a 95% confidence interval of 0.22–0.82 µg/mL. Correlations between IF1 levels and serum lipid levels demonstrated that serum IF1 levels are positively correlated with HDL-cholesterol and negatively with triglycerides (TG).

Conclusions/Significance

Altogether, these data support the view that, in humans, circulating IF1 might affect HDL levels by inhibiting hepatic HDL uptake and also impact TG metabolism.     

NQO1-dependent redox cycling of idebenone: effects on cellular redox potential and energy levels

Short-chain quinones are described as potent antioxidants and in the case of idebenone have already been under clinical investigation for the treatment of neuromuscular disorders. Due to their analogy to coenzyme Q10 (CoQ10), a long-chain quinone, they are widely regarded as a substitute for CoQ10. However, apart from their antioxidant function, this provides no clear rationale for their use in disorders with normal CoQ10 levels. Using recombinant NAD(P)H:quinone oxidoreductase (NQO) enzymes, we observed that contrary to CoQ10 short-chain quinones such as idebenone are good substrates for both NQO1 and NQO2. Furthermore, the reduction of short-chain quinones by NQOs enabled an antimycin A-sensitive transfer of electrons from cytosolic NAD(P)H to the mitochondrial respiratory chain in both human hepatoma cells (HepG2) and freshly isolated mouse hepatocytes. Consistent with the substrate selectivity of NQOs, both idebenone and CoQ1, but not CoQ10, partially restored cellular ATP levels under conditions of impaired complex I function. The observed cytosolic-mitochondrial shuttling of idebenone and CoQ1 was also associated with reduced lactate production by cybrid cells from mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) patients. Thus, the observed activities separate the effectiveness of short-chain quinones from the related long-chain CoQ10 and provide the rationale for the use of short-chain quinones such as idebenone for the treatment of mitochondrial disorders.     

Tumor-associated macrophages (TAMs) form an interconnected cellular supportive network in anaplastic thyroid carcinoma

Background

A relationship between the increased density of tumor-associated macrophages (TAMs) and decreased survival was recently reported in thyroid cancer patients. Among these tumors, anaplastic thyroid cancer (ATC) is one of the most aggressive solid tumors in humans. TAMs (type M2) have been recognized as promoting tumor growth. The purpose of our study was to analyze with immunohistochemistry the presence of TAMs in a series of 27 ATC.

Methodology/Principal Findings

Several macrophages markers such as NADPH oxidase complex NOX2-p22phox, CD163 and CD 68 were used. Immunostainings showed that TAMs represent more than 50% of nucleated cells in all ATCs. Moreover, these markers allowed the identification of elongated thin ramified cytoplasmic extensions, bestowing a “microglia-like” appearance on these cells which we termed “Ramified TAMs” (RTAMs). In contrast, cancer cells were totally negative. Cellular stroma was highly simplified since apart from cancer cells and blood vessels, RTAMs were the only other cellular component. RTAMs were evenly distributed and intermingled with cancer cells, and were in direct contact with other RTAMs via their ramifications. Moreover, RTAMs displayed strong immunostaining for connexin Cx43. Long chains of interconnected RTAMs arose from perivascular clusters and were dispersed within the tumor parenchyma. When expressed, the glucose transporter Glut1 was found in RTAMs and blood vessels, but rarely in cancer cells.

Conclusion

ATCs display a very dense network of interconnected RTAMs in direct contact with intermingled cancer cells. To our knowledge this is the first time that such a network is described in a malignant tumor. This network was found in all our studied cases and appeared specific to ATC, since it was not found in differentiated thyroid cancers specimens. Taken together, these results suggest that RTAMs network is directly related to the aggressiveness of the disease via metabolic and trophic functions which remain to be determined.     

Assembly of the mariner Mos1 synaptic complex

The mobility of transposable elements via a cut-and-paste mechanism depends on the elaboration of a nucleoprotein complex known as the synaptic complex. We show here that the Mos1 synaptic complex consists of the two inverted terminal repeats of the element brought together by a transposase tetramer and is designated paired-end complex 2 (PEC2). The assembly of PEC2 requires the formation of a simpler complex, containing one terminal repeat and two transposase molecules and designated single-end complex 2 (SEC2). In light of the formation of SEC2 and PEC2, we demonstrate the presence of two binding sites for the transposase within a single terminal repeat. We have found that the sequence of the Mos1 inverted terminal repeats contains overlapping palindromic and mirror motifs, which could account for the binding of two transposase molecules "side by side" on the same inverted terminal repeat. We provide data indicating that the Mos1 transposase dimer is formed within a single terminal repeat through a cooperative pathway. Finally, the concept of a tetrameric synaptic complex may simply account for the inability of a single mariner transposase molecule to interact at the same time with two kinds of DNA: the inverted repeat and the target DNA.