Differences in genotype and virulence among four multidrug-resistant Streptococcus pneumoniae isolates belonging to the PMEN1 clone

We report on the comparative genomics and characterization of the virulence phenotypes of four S. pneumoniae strains that belong to the multidrug resistant clone PMEN1 (Spain(23F) ST81). Strains SV35-T23 and SV36-T3 were recovered in 1996 from the nasopharynx of patients at an AIDS hospice in New York. Strain SV36-T3 expressed capsule type 3 which is unusual for this clone and represents the product of an in vivo capsular switch event. A third PMEN1 isolate - PN4595-T23 - was recovered in 1996 from the nasopharynx of a child attending day care in Portugal, and a fourth strain - ATCC700669 - was originally isolated from a patient with pneumococcal disease in Spain in 1984. We compared the genomes among four PMEN1 strains and 47 previously sequenced pneumococcal isolates for gene possession differences and allelic variations within core genes. In contrast to the 47 strains - representing a variety of clonal types - the four PMEN1 strains grouped closely together, demonstrating high genomic conservation within this lineage relative to the rest of the species. In the four PMEN1 strains allelic and gene possession differences were clustered into 18 genomic regions including the capsule, the blp bacteriocins, erythromycin resistance, the MM1-2008 prophage and multiple cell wall anchored proteins. In spite of their genomic similarity, the high resolution chinchilla model was able to detect variations in virulence properties of the PMEN1 strains highlighting how small genic or allelic variation can lead to significant changes in pathogenicity and making this set of strains ideal for the identification of novel virulence determinants.     

Human remains from the Pleistocene-Holocene transition of southwest China suggest a complex evolutionary history for East Asians

Background

Later Pleistocene human evolution in East Asia remains poorly understood owing to a scarcity of well described, reliably classified and accurately dated fossils. Southwest China has been identified from genetic research as a hotspot of human diversity, containing ancient mtDNA and Y-DNA lineages, and has yielded a number of human remains thought to derive from Pleistocene deposits. We have prepared, reconstructed, described and dated a new partial skull from a consolidated sediment block collected in 1979 from the site of Longlin Cave (Guangxi Province). We also undertook new excavations at Maludong (Yunnan Province) to clarify the stratigraphy and dating of a large sample of mostly undescribed human remains from the site.

Methodology/Principal Findings

We undertook a detailed comparison of cranial, including a virtual endocast for the Maludong calotte, mandibular and dental remains from these two localities. Both samples probably derive from the same population, exhibiting an unusual mixture of modern human traits, characters probably plesiomorphic for later Homo, and some unusual features. We dated charcoal with AMS radiocarbon dating and speleothem with the Uranium-series technique and the results show both samples to be from the Pleistocene-Holocene transition: ∼14.3-11.5 ka.

Conclusions/Significance

Our analysis suggests two plausible explanations for the morphology sampled at Longlin Cave and Maludong. First, it may represent a late-surviving archaic population, perhaps paralleling the situation seen in North Africa as indicated by remains from Dar-es-Soltane and Temara, and maybe also in southern China at Zhirendong. Alternatively, East Asia may have been colonised during multiple waves during the Pleistocene, with the Longlin-Maludong morphology possibly reflecting deep population substructure in Africa prior to modern humans dispersing into Eurasia.     

Climate change and the potential distribution of an invasive shrub, Lantana camara L

The threat posed by invasive species, in particular weeds, to biodiversity may be exacerbated by climate change. Lantana camara L. (lantana) is a woody shrub that is highly invasive in many countries of the world. It has a profound economic and environmental impact worldwide, including Australia. Knowledge of the likely potential distribution of this invasive species under current and future climate will be useful in planning better strategies to manage the invasion. A process-oriented niche model of L. camara was developed using CLIMEX to estimate its potential distribution under current and future climate scenarios. The model was calibrated using data from several knowledge domains, including phenological observations and geographic distribution records. The potential distribution of lantana under historical climate exceeded the current distribution in some areas of the world, notably Africa and Asia. Under future scenarios, the climatically suitable areas for L. camara globally were projected to contract. However, some areas were identified in North Africa, Europe and Australia that may become climatically suitable under future climates. In South Africa and China, its potential distribution could expand further inland. These results can inform strategic planning by biosecurity agencies, identifying areas to target for eradication or containment. Distribution maps of risk of potential invasion can be useful tools in public awareness campaigns, especially in countries that have been identified as becoming climatically suitable for L. camara under the future climate scenarios.     

Interaction analysis between HLA-DRB1 shared epitope alleles and MHC class II transactivator CIITA gene with regard to risk of rheumatoid arthritis

HLA-DRB1 shared epitope (SE) alleles are the strongest genetic determinants for autoantibody positive rheumatoid arthritis (RA). One of the key regulators in expression of HLA class II receptors is MHC class II transactivator (CIITA). A variant of the CIITA gene has been found to associate with inflammatory diseases.We wanted to explore whether the risk variant rs3087456 in the CIITA gene interacts with the HLA-DRB1 SE alleles regarding the risk of developing RA. We tested this hypothesis in a case-control study with 11767 individuals from four European Caucasian populations (6649 RA cases and 5118 controls).We found no significant additive interaction for risk alleles among Swedish Caucasians with RA (n = 3869, attributable proportion due to interaction (AP) = 0.2, 95%CI: −0.2–0.5) or when stratifying for anti-citrullinated protein antibodies (ACPA) presence (ACPA positive disease: n = 2945, AP = 0.3, 95%CI: −0.05–0.6, ACPA negative: n = 2268, AP = −0.2, 95%CI: −1.0–0.6). We further found no significant interaction between the main subgroups of SE alleles (DRB1*01, DRB1*04 or DRB1*10) and CIITA. Similar analysis of three independent RA cohorts from British, Dutch and Norwegian populations also indicated an absence of significant interaction between genetic variants in CIITA and SE alleles with regard to RA risk.Our data suggest that risk from the CIITA locus is independent of the major risk for RA from HLA-DRB1 SE alleles, given that no significant interaction between rs3087456 and SE alleles was observed. Since a biological link between products of these genes is evident, the genetic contribution from CIITA and class II antigens in the autoimmune process may involve additional unidentified factors.     

Can bison play a role in conserving habitat for endangered sandhills species in Canada?

Relative to their cultivated surroundings, sandhills of the Canadian prairies represent intact, heterogeneous ecosystems. These extensive tracts of sand dunes and native prairie are biodiversity hotspots, which act as refugia for a variety of specialized wildlife species. However, due to changes in climate and suppression of natural disturbance, the dunes have experienced drastic rates of stabilization over the past 200 years, such that the proportion of open sand in the region is currently less than 1%. This continuing trend is resulting in a gradual loss of sparsely vegetated, sandy habitat for many uncommon, specialist species, including a number that are considered to be at risk of extirpation or extinction by COSEWIC (Canada’s list agency). Without management to conserve active sandhill habitat the future long-term survival of rare and imperilled dune-dependent plants and animals is questionable. In this article we propose that the re-introduction of disturbance to southern Canadian prairie sandhills, specifically sandhill use by bison, might be effective in restoring and sustaining actively-eroding sandhill habitat to support some threatened and endangered species. We outline several lines of evidence (geological, geomorphological, archaeological, and historical accounts) indicating bison occupied sandhills and actively modified these ecosystems until European settlement of the prairies. We argue that bison were attracted to sandhills for a number of reasons, and that in great numbers they had considerable influence on sandhills ecosystem functions. Behaviours such as grazing, trailing, wallowing, horning, and trampling created a patchwork mosaic of disturbance effects. We hypothesize that it may be beneficial to reintroduce bison to sandhills ecosystems in the Canadian prairies to restore biodiversity at all levels.     

Impacts of Argentine ants on invertebrate communities with below-ground consequences

The Argentine ant, Linepithema humile (Mayr), is an invasive species that has been associated with various negative impacts in native communities around the world. These impacts, as for other invasive ants, are principally towards native ant species, and impacts on below-ground processes such as decomposition remain largely unexplored. We investigated the relationship between Argentine ants and invertebrate fauna, litter decomposition and soil microbial activity between paired invaded and uninvaded sites at two locations in Auckland, New Zealand, where there has been no research to date on their impacts. We examined the diversity and composition of invertebrate and microorganisms communities, and differences in soil and litter components. The composition of invertebrates (Order-level, ant and beetle species) was different between invaded and uninvaded sites, with fewer ants, isopods, amphipods, and fungus-feeding beetles at the invaded sites, whereas Collembola were more abundant at the invaded sites. There were significant differences in soil chemistry, including higher carbon and nitrogen microbial biomass at uninvaded sites. Several litter components were significantly different for Macropiper excelsum. The fibre content of litter was higher, and key nutrients (e.g. nitrogen) were lower, at invaded sites, indicating less breakdown of litter at invaded sites. A greater knowledge of the history of invasion at a site would clarify variation in the impacts of Argentine ants, but their persistence in the ground litter layer may have long-term implications for soil and plant health in native ecosystems.     

The Impact of Escaped Farmed Atlantic Salmon (Salmo salar L.) on Catch Statistics in Scotland

In Scotland and elsewhere, there are concerns that escaped farmed Atlantic salmon (Salmo salar L.) may impact on wild salmon stocks. Potential detrimental effects could arise through disease spread, competition, or inter-breeding. We investigated whether there is evidence of a direct effect of recorded salmon escape events on wild stocks in Scotland using anglers' counts of caught salmon (classified as wild or farmed) and sea trout (Salmo trutta L.). This tests specifically whether documented escape events can be associated with reduced or elevated escapes detected in the catch over a five-year time window, after accounting for overall variation between areas and years. Alternate model frameworks were somewhat inconsistent, however no robust association was found between documented escape events and higher proportion of farm-origin salmon in anglers' catch, nor with overall catch size. A weak positive correlation was found between local escapes and subsequent sea trout catch. This is in the opposite direction to what would be expected if salmon escapes negatively affected wild fish numbers. Our approach specifically investigated documented escape events, contrasting with earlier studies examining potentially wider effects of salmon farming on wild catch size. This approach is more conservative, but alleviates some potential sources of confounding, which are always of concern in observational studies. Successful analysis of anglers' reports of escaped farmed salmon requires high data quality, particularly since reports of farmed salmon are a relatively rare event in the Scottish data. Therefore, as part of our analysis, we reviewed studies of potential sensitivity and specificity of determination of farmed origin. Specificity estimates are generally high in the literature, making an analysis of the form we have performed feasible.     

Common pathogenic effects of missense mutations in the P-type ATPase ATP13A2 (PARK9) associated with early-onset parkinsonism

Mutations in the ATP13A2 gene (PARK9) cause autosomal recessive, juvenile-onset Kufor-Rakeb syndrome (KRS), a neurodegenerative disease characterized by parkinsonism. KRS mutations produce truncated forms of ATP13A2 with impaired protein stability resulting in a loss-of-function. Recently, homozygous and heterozygous missense mutations in ATP13A2 have been identified in subjects with early-onset parkinsonism. The mechanism(s) by which missense mutations potentially cause parkinsonism are not understood at present. Here, we demonstrate that homozygous F182L, G504R and G877R missense mutations commonly impair the protein stability of ATP13A2 leading to its enhanced degradation by the proteasome. ATP13A2 normally localizes to endosomal and lysosomal membranes in neurons and the F182L and G504R mutations disrupt this vesicular localization and promote the mislocalization of ATP13A2 to the endoplasmic reticulum. Heterozygous T12M, G533R and A746T mutations do not obviously alter protein stability or subcellular localization but instead impair the ATPase activity of microsomal ATP13A2 whereas homozygous missense mutations disrupt the microsomal localization of ATP13A2. The overexpression of ATP13A2 missense mutants in SH-SY5Y neural cells does not compromise cellular viability suggesting that these mutant proteins lack intrinsic toxicity. However, the overexpression of wild-type ATP13A2 may impair neuronal integrity as it causes a trend of reduced neurite outgrowth of primary cortical neurons, whereas the majority of disease-associated missense mutations lack this ability. Finally, ATP13A2 overexpression sensitizes cortical neurons to neurite shortening induced by exposure to cadmium or nickel ions, supporting a functional interaction between ATP13A2 and heavy metals in post-mitotic neurons, whereas missense mutations influence this sensitizing effect. Collectively, our study provides support for common loss-of-function effects of homozygous and heterozygous missense mutations in ATP13A2 associated with early-onset forms of parkinsonism.     

Predicting the benefits of banana bunchy top virus exclusion from commercial plantations in australia

Benefit cost analysis is a tried and tested analytical framework that can clearly communicate likely net changes in producer welfare from investment decisions to diverse stakeholder audiences. However, in a plant biosecurity context, it is often difficult to predict policy benefits over time due to complex biophysical interactions between invasive species, their hosts, and the environment. In this paper, we demonstrate how a break-even style benefit cost analysis remains highly relevant to biosecurity decision-makers using the example of banana bunchy top virus, a plant pathogen targeted for eradication from banana growing regions of Australia. We develop an analytical approach using a stratified diffusion spread model to simulate the likely benefits of exclusion of this virus from commercial banana plantations over time relative to a nil management scenario in which no surveillance or containment activities take place. Using Monte Carlo simulation to generate a range of possible future incursion scenarios, we predict the exclusion benefits of the disease will avoid Aus$15.9-27.0 million in annual losses for the banana industry. For these exclusion benefits to be reduced to zero would require a bunchy top re-establishment event in commercial banana plantations three years in every four. Sensitivity analysis indicates that exclusion benefits can be greatly enhanced through improvements in disease surveillance and incursion response.