New World Bats Harbor Diverse Influenza A Viruses

Aquatic birds harbor diverse influenza A viruses and are a major viral reservoir in nature. The recent discovery of influenza viruses of a new H17N10 subtype in Central American fruit bats suggests that other New World species may similarly carry divergent influenza viruses. Using consensus degenerate RT-PCR, we identified a novel influenza A virus, designated as H18N11, in a flat-faced fruit bat (Artibeus planirostris) from Peru. Serologic studies with the recombinant H18 protein indicated that several Peruvian bat species were infected by this virus. Phylogenetic analyses demonstrate that, in some gene segments, New World bats harbor more influenza virus genetic diversity than all other mammalian and avian species combined, indicative of a long-standing host-virus association. Structural and functional analyses of the hemagglutinin and neuraminidase indicate that sialic acid is not a ligand for virus attachment nor a substrate for release, suggesting a unique mode of influenza A virus attachment and activation of membrane fusion for entry into host cells. Taken together, these findings indicate that bats constitute a potentially important and likely ancient reservoir for a diverse pool of influenza viruses.     

Drosophila S2 Cells Secrete Wingless on Exosome‐Like Vesicles but the Wingless Gradient Forms Independently of Exosomes

Wingless acts as a morphogen in Drosophila wing discs, where it specifies cell fates and controls growth several cell diameters away from its site of expression. Thus, despite being acylated and membrane associated, Wingless spreads in the extracellular space. Recent studies have focussed on identifying the route that Wingless follows in the secretory pathway and determining how it is packaged for release. We have found that, in medium conditioned by Wingless‐expressing Drosophila S2 cells, Wingless is present on exosome‐like vesicles and that this fraction activates signal transduction. Proteomic analysis shows that Wingless‐containing exosome‐like structures contain many Drosophila proteins that are homologous to mammalian exosome proteins. In addition, Evi, a multipass transmembrane protein, is also present on exosome‐like vesicles. Using these exosome markers and a cell‐based RNAi assay, we found that the small GTPase Rab11 contributes significantly to exosome production. This finding allows us to conclude from in vivo Rab11 knockdown experiments, that exosomes are unlikely to contribute to Wingless secretion and gradient formation in wing discs. Consistent with this conclusion, extracellularly tagged Evi expressed from a Bacterial Artificial Chromosome is not released from imaginal disc Wingless‐expressing cells.     

Etanercept may induce neurosarcoidosis in a patient treated for rheumatoid arthritis

Background

TNFα blockers have drastically improved rheumatoid arthritis prognosis by preventing joint destruction in DMARD resistant patients. Altering cytokine balance in immune diseases may expose to paradoxical adverse events.

Case presentation

We present the case of a 40-year-old woman, with a confirmed erosive and seropositive RA, successfully treated by TNFα blocker (etanercept) for seven years, and who developed a severe neurosarcoidosis. She had lymphocytic meningitis, bilateral peripheral facial paralysis and anosmia, associated with bilateral hilar lymph nodes, papilloedema, anterior uveitis and elevated serum angiotensin-converting enzyme level. Magnetic resonance imaging showed a bilateral thickening of the Gasser’s ganglia walls and enhanced signal of the vestibulocochlear, the facial and the proximal portion of trijeminal nerves.

Conclusion

This case raised the issue of the imputability of etanercept in the development of neurosarcoidosis. Neurological symptoms onset in patients on TNFα blockers should lead to exclude infections, induced lupus but also paradoxical neurosarcoidosis.

     

Source pools and disharmony of the world's island floras

Island disharmony refers to the biased representation of higher taxa on islands compared to their mainland source regions and represents a central concept in island biology. Here, we develop a generalizable framework for approximating these source regions and conduct the first global assessment of island disharmony and its underlying drivers. We compiled vascular plant species lists for 178 oceanic islands and 735 mainland regions. Using mainland data only, we modelled species turnover as a function of environmental and geographic distance and predicted the proportion of shared species between each island and mainland region. We then quantified the over‐ or under‐representation of families on individual islands (representational disharmony) by contrasting the observed number of species against a null model of random colonization from the mainland source pool, and analysed the effects of six family‐level functional traits on the resulting measure. Furthermore, we aggregated the values of representational disharmony per island to characterize overall taxonomic bias of a given flora (compositional disharmony), and analysed this second measure as a function of four island biogeographical variables. Our results indicate considerable variation in representational disharmony both within and among plant families. Examples of generally over‐represented families include Urticaceae, Convolvulaceae and almost all pteridophyte families. Other families such as Asteraceae and Orchidaceae were generally under‐represented, with local peaks of over‐representation in known radiation hotspots. Abiotic pollination and a lack of dispersal specialization were most strongly associated with an insular over‐representation of families, whereas other family‐level traits showed minor effects. With respect to compositional disharmony, large, high‐elevation islands tended to have the most disharmonic floras. Our results provide important insights into the taxon‐ and island‐specific drivers of disharmony. The proposed framework allows overcoming the limitations of previous approaches and provides a quantitative basis for incorporating functional and phylogenetic approaches into future studies of island disharmony.     

Sapwood and heartwood affect differentially bacterial and fungal community structure and successional dynamics during Quercus petraea decomposition

In forests, bacteria and fungi are key players in wood degradation. Still, studies focusing on bacterial and fungal successions during the decomposition process depending on the wood types (i.e. sapwood and heartwood) remain scarce. This study aimed to understand the effect of wood type on the dynamics of microbial ecological guilds in wood decomposition. Using Illumina metabarcoding, bacterial and fungal communities were monitored every 3 months for 3 years from Quercus petraea wood discs placed on forest soil. Wood density and microbial enzymes involved in biopolymer degradation were measured. We observed rapid changes in the bacterial and fungal communities and microbial ecological guilds associated with wood decomposition throughout the experiment. Bacterial and fungal succession dynamics were very contrasted between sapwood and heartwood. The initial microbial communities were quickly replaced by new bacterial and fungal assemblages in the sapwood. Conversely, some initial functional guilds (i.e. endophytes and yeasts) persisted all along the experiment in heartwood and finally became dominant, possibly limiting the development of saprotrophic fungi. Our data also suggested a significant role of bacteria in nitrogen cycle during wood decomposition.     

Targeted analysis of nucleotide and copy number variation by exon capture in allotetraploid wheat genome

Background  

The ability of grass species to adapt to various habitats is attributed to the dynamic nature of their genomes, which have been shaped by multiple rounds of ancient and recent polyploidization. To gain a better understanding of the nature and extent of variation in functionally relevant regions of a polyploid genome, we developed a sequence capture assay to compare exonic sequences of allotetraploid wheat accessions.     

Venation networks and the origin of the leaf economics spectrum

The leaf economics spectrum describes biome-invariant scaling functions for leaf functional traits that relate to global primary productivity and nutrient cycling. Here, we develop a comprehensive framework for the origin of this leaf economics spectrum based on venation-mediated economic strategies. We define a standardized set of traits - density, distance and loopiness - that provides a common language for the study of venation. We develop a novel quantitative model that uses these venation traits to model leaf-level physiology, and show that selection to optimize the venation network predicts the mean global trait-trait scaling relationships across 2548 species. Furthermore, using empirical venation data for 25 plant species, we test our model by predicting four key leaf functional traits related to leaf economics: net carbon assimilation rate, life span, leaf mass per area ratio and nitrogen content. Together, these results indicate that selection on venation geometry is a fundamental basis for understanding the diversity of leaf form and function, and the carbon balance of leaves. The model and associated predictions have broad implications for integrating venation network geometry with pattern and process in ecophysiology, ecology and palaeobotany.     

Randomized trial of safety and effectiveness of chlorproguanil-dapsone and lumefantrine-artemether for uncomplicated malaria in children in the Gambia

Background

Chlorproguanil-dapsone (Lapdap), developed as a low-cost antimalarial, was withdrawn in 2008 after concerns about safety in G6PD deficient patients. This trial was conducted in 2004 to evaluate the safety and effectiveness of CD and comparison with artemether-lumefantrine (AL) under conditions of routine use in G6PD normal and G6PD deficient patients with uncomplicated malaria in The Gambia. We also examined the effects of a common genetic variant that affects chlorproguanil metabolism on risk of treatment failure.

Methods

1238 children aged 6 months to 10 years with uncomplicated malaria were randomized to receive CD or artemether-lumefantrine (AL) and followed for 28 days. The first dose was supervised, subsequent doses given unsupervised at home. G6PD genotype was determined to assess the interaction between treatment and G6PD status in their effects on anaemia. The main endpoints were clinical treatment failure by day 28, incidence of severe anaemia (Hb<5 g/dL), and haemoglobin concentration on day 3.

Findings

One third of patients treated with AL, and 6% of patients treated with CD, did not complete their course of medication. 18% (109/595) of children treated with CD and 6.1% (36/587) with AL required rescue medication within 4 weeks, risk difference 12% (95%CI 8.9%–16%). 23 children developed severe anaemia (17 (2.9%) treated with CD and 6 (1.0%) with AL, risk difference 1.8%, 95%CI 0.3%–3.4%, P = 0.02). Haemoglobin concentration on day 3 was lower among children treated with CD than AL (difference 0.43 g/dL, 95% CI 0.24 to 0.62), and within the CD group was lower among those children who had higher parasite density at enrolment. Only 17 out of 1069 children who were typed were G6PD A- deficient, of these 2/9 treated with CD and 1/8 treated with AL developed severe anaemia. 5/9 treated with CD had a fall of 2 g/dL or more in haemoglobin concentration by day 3.

Interpretation

AL was well tolerated and highly effective and when given under operational conditions despite poor adherence to the six-dose regimen. There were more cases of severe malaria and anaemia after CD treatment although G6PD deficiency was uncommon.

Trial Registration

Clinicaltrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00118794","term_id":"NCT00118794"}}NCT00118794     

Rodent abundance dynamics and leptospirosis carriage in an area of hyper-endemicity in New Caledonia

Background

Widespread but particularly incident in the tropics, leptospirosis is transmitted to humans directly or indirectly by virtually any Mammal species. However, rodents are recognized as the most important reservoir. In endemic regions, seasonal outbreaks are observed during hot rainy periods. In such regions, hot spots can be evidenced, where leptospirosis is “hyper-endemic”, its incidence reaching 500 annual cases per 100,000. A better knowledge of how rodent populations and their Leptospira prevalence respond to seasonal and meteorological fluctuations might help implement relevant control measures.

Methodology/Principal Findings

In two tribes in New Caledonia with hyper-endemic leptospirosis, rodent abundance and Leptospira prevalence was studied twice a year, in hot and cool seasons for two consecutive years. Highly contrasted meteorological situations, particularly rainfall intensities, were noted between the two hot seasons studied. Our results show that during a hot and rainy period, both the rodent populations and their Leptospira carriage were higher. This pattern was more salient in commensal rodents than in the sylvatic rats.

Conclusions/Significance

The dynamics of rodents and their Leptospira carriage changed during the survey, probably under the influence of meteorology. Rodents were both more numerous and more frequently carrying (therefore disseminating) leptospires during a hot rainy period, also corresponding to a flooding period with higher risks of human exposure to waters and watered soils. The outbreaks of leptospirosis in hyper-endemic areas could arise from meteorological conditions leading to both an increased risk of exposure of humans and an increased volume of the rodent reservoir. Rodent control measures would therefore be most effective during cool and dry seasons, when rodent populations and leptospirosis incidence are low.     

Interleukin 12B (IL12B) genetic variation and pulmonary tuberculosis: a study of cohorts from The Gambia, Guinea-Bissau, United States and Argentina

We examined whether polymorphisms in interleukin-12B (IL12B) associate with susceptibility to pulmonary tuberculosis (PTB) in two West African populations (from The Gambia and Guinea-Bissau) and in two independent populations from North and South America. Nine polymorphisms (seven SNPs, one insertion/deletion, one microsatellite) were analyzed in 321 PTB cases and 346 controls from Guinea-Bissau and 280 PTB cases and 286 controls from The Gambia. For replication we studied 281 case and 179 control African-American samples and 221 cases and 144 controls of European ancestry from the US and Argentina. First-stage single locus analyses revealed signals of association at IL12B 3′ UTR SNP rs3212227 (unadjusted allelic p = 0.04; additive genotypic p = 0.05, OR = 0.78, 95% CI [0.61–0.99]) in Guinea-Bissau and rs11574790 (unadjusted allelic p = 0.05; additive genotypic p = 0.05, OR = 0.76, 95% CI [0.58–1.00]) in The Gambia. Association of rs3212227 was then replicated in African-Americans (rs3212227 allelic p = 0.002; additive genotypic p = 0.05, OR = 0.78, 95% CI [0.61–1.00]); most importantly, in the African-American cohort, multiple significant signals of association (seven of the nine polymorphisms tested) were detected throughout the gene. These data suggest that genetic variation in IL12B, a highly relevant candidate gene, is a risk factor for PTB in populations of African ancestry, although further studies will be required to confirm this association and identify the precise mechanism underlying it.