Genetic Variation in Spatio-Temporal Confined USA300 Community-Associated MRSA Isolates: A Shift from Clonal Dispersion to Genetic Evolution?

NTRODUCTION: Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) are increasingly isolated, with USA300-0114 being the predominant clone in the USA. Comparative whole genome sequencing of USA300 isolates collected in 2002, 2003 and 2005 showed a limited number of single nucleotide polymorphisms and regions of difference. This suggests that USA300 has undergone rapid clonal expansion without great genomic diversification. However, whole genome comparison of CA-MRSA has been limited to isolates belonging to USA300. The aim of this study was to compare the genetic repertoire of different CA-MRSA clones with that of HA-MRSA from the USA and Europe through comparative genomic hybridization (CGH) to identify genetic clues that may explain the successful and rapid emergence of CA-MRSA. MATERIALS AND METHODS: Hierarchical clustering based on CGH of 48 MRSA isolates from the community and nosocomial infections from Europe and the USA revealed dispersed clustering of the 19 CA-MRSA isolates. This means that these 19 CA-MRSA isolates do not share a unique genetic make-up. Only the PVL genes were commonly present in all CA-MRSA isolates. However, 10 genes were variably present among 14 USA300 isolates. Most of these genes were present on mobile elements. CONCLUSION: The genetic variation present among the 14 USA300 isolates is remarkable considering the fact that the isolates were recovered within one month and originated from a confined geographic area, suggesting continuous evolution of this clone

Window screening, ceilings and closed eaves as sustainable ways to control malaria in Dar es Salaam, Tanzania.

BACKGROUND\ud \ud Malaria transmission in Africa occurs predominantly inside houses where the primary vectors prefer to feed. Human preference and investment in blocking of specific entry points for mosquitoes into houses was evaluated and compared with known entry point preferences of the mosquitoes themselves.\ud \ud METHODS\ud \ud Cross-sectional household surveys were conducted in urban Dar es Salaam, Tanzania to estimate usage levels of available options for house proofing against mosquito entry, namely window screens, ceilings and blocking of eaves. These surveys also enabled evaluation of household expenditure on screens and ceilings and the motivation behind their installation.\ud \ud RESULTS\ud \ud Over three quarters (82.8%) of the 579 houses surveyed in Dar es Salaam had window screens, while almost half (48.9%) had ceilings. Prevention of mosquito entry was cited as a reason for installation of window screens and ceilings by 91.4% (394/431) and 55.7% (127/228) of respondents, respectively, but prevention of malaria was rarely cited (4.3%, 22/508). The median cost of window screens was between US $21-30 while that of ceilings was between US$301-400. The market value of insecticide-treated nets, window screening and ceilings currently in use in the city was estimated as 2, 5 and 42 million US$. More than three quarters of the respondents that lacked them said it was too expensive to install ceilings (82.2%) or window screens (75.5%).\ud \ud CONCLUSION\ud \ud High coverage and spending on screens and ceilings implies that these techniques are highly acceptable and excellent uptake can be achieved in urban settings like Dar es Salaam. Effective models for promotion and subsidization should be developed and evaluated, particularly for installation of ceilings that prevent entry via the eaves, which are the most important entry point for mosquitoes that cause malaria, a variety of neglected tropical diseases and the nuisance which motivates uptake

Harbouring public good mutants within a pathogen population can increase both fitness and virulence

This is the final version of the article. Available from the publisher via the DOI in this record.Existing theory, empirical, clinical and field research all predict that reducing the virulence of individuals within a pathogen population will reduce the overall virulence, rendering disease less severe. Here, we show that this seemingly successful disease management strategy can fail with devastating consequences for infected hosts. We deploy cooperation theory and a novel synthetic system involving the rice blast fungus Magnaporthe oryzae. In vivo infections of rice demonstrate that M. oryzae virulence is enhanced, quite paradoxically, when a public good mutant is present in a population of high-virulence pathogens. We reason that during infection, the fungus engages in multiple cooperative acts to exploit host resources. We establish a multi-trait cooperation model which suggests that the observed failure of the virulence reduction strategy is caused by the interference between different social traits. Multi-trait cooperative interactions are widespread, so we caution against the indiscriminant application of anti-virulence therapy as a disease-management strategy.Natural Environment Research Council NE/E013007/3Natural Environment Research Council Doctoral training grantEngineering and Physical Sciences Research Council Doctoral training grant studentshipEuropean Research Council no. 294702 GENBLASTEuropean Research Council no. 647292 MathModEx

Leaf-applied sodium chloride promotes cadmium accumulation in durum wheat grain

Cadmium (Cd) accumulation in durum wheat grain is a growing concern. Among the factors affecting Cd accumulation in plants, soil chloride (Cl) concentration plays a critical role. The effect of leaf NaCl application on grain Cd was studied in greenhouse-grown durum wheat (Triticum turgidum L. durum, cv. Balcali-2000) by immersing (10 s) intact flag leaves into Cd and/or NaCl-containing solutions for 14 times during heading and dough stages. Immersing flag leaves in solutions containing increasing amount of Cd resulted in substantial increases in grain Cd concentration. Adding NaCl alone or in combination with the Cd-containing immersion solution promoted accumulation of Cd in the grains, by up to 41%. In contrast, Zn concentrations of grains were not affected or even decreased by the NaCl treatments. This is likely due to the effect of Cl complexing Cd and reducing positive charge on the metal ion, an effect that is much smaller for Zn. Charge reduction or removal (CdCl2 0 species) would increase the diffusivity/lipophilicity of Cd and enhance its capability to penetrate the leaf epidermis and across membranes. Of even more significance to human health was the ability of Cl alone to penetrate leaf tissue and mobilize and enhance shoot Cd transfer to grains, yet reducing or not affecting Zn transfer

P-rex1 cooperates with PDGFRβ to drive cellular migration in 3D microenvironments

Expression of the Rac-guanine nucleotide exchange factor (RacGEF), P-Rex1 is a key determinant of progression to metastasis in a number of human cancers. In accordance with this proposed role in cancer cell invasion and metastasis, we find that ectopic expression of P-Rex1 in an immortalised human fibroblast cell line is sufficient to drive multiple migratory and invasive phenotypes. The invasive phenotype is greatly enhanced by the presence of a gradient of serum or platelet-derived growth factor, and is dependent upon the expression of functional PDGF receptor β. Consistently, the invasiveness of WM852 melanoma cells, which endogenously express P-Rex1 and PDGFRβ, is opposed by siRNA of either of these proteins. Furthermore, the current model of P-Rex1 activation is advanced through demonstration of P-Rex1 and PDGFRβ as components of the same macromolecular complex. These data suggest that P-Rex1 has an influence on physiological migratory processes, such as invasion of cancer cells, both through effects upon classical Rac1-driven motility and a novel association with RTK signalling complexes

Antimicrobial activity and brine shrimp toxicity of extracts of Terminalia brownii roots and stem

BACKGROUND: Ternimalia brownii Fresen (Combretaceae) is widely used in traditional medicine to treat bacterial, fungal and viral infections. There is a need to evaluate extracts of this plant in order to provide scientific proof for it's wide application in traditional medicine system. METHODS: Extraction of stem bark, wood and whole roots of T. brownii using solvents of increasing polarity, namely, Pet ether, dichloromethane, dichloromethane: methanol (1:1), methanol and aqua, respectively, afforded dry extracts. The extracts were tested for antifungal and antibacterial activity and for brine shrimp toxicity test. RESULTS: Extracts of the stem bark, wood and whole roots of T. brownii exhibited antibacterial activity against standard strains of Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Salmonella typhi, and Bacillus anthracis and the fungi, Candida albicans and Cryptococcus neoformans. Aqueous extracts exhibited the strongest activity against both bacteria and fungi. Extracts of the roots and stem bark exhibited relatively mild cytotoxic activity against brine shrimp larvae with LC(50 )values ranging from 113.75–4356.76 and 36.12–1458.81 μg/ml, respectively. The stem wood extracts exhibited the highest toxicity against the shrimps (LC(50 )values 2.58–14.88 μg/ml), while that of cyclophosphamide, a standard anticancer drug, was 16.33 (10.60–25.15) μg/ml. CONCLUSION: These test results support traditional medicinal use of, especially, aqueous extracts for the treatment of conditions such as diarrhea, and gonorrhea. The brine shrimp results depict the general trend among plants of the genus Terminalia, which are known to contain cytotoxic compounds such as hydrolysable tannins. These results warrant follow-up through bioassay-directed isolation of the active principles

Treatment outcomes for 618 women with gestational trophoblastic tumours following a molar pregnancy at the Charing Cross Hospital, 2000-2009

BACKGROUND: Post-molar pregnancy gestational trophoblastic tumours (GTT) have been curable with chemotherapy treatment for over 50 years. Because of the rarity of the diagnosis, detailed structured information on prognosis, treatment escalations and outcome is limited. METHODS: We have reviewed the demographics, prognostic variables, treatment course and clinical outcomes for the post-mole GTT patients treated at Charing Cross Hospital between 2000 and 2009. RESULTS: Of the 618 women studied, 547 had a diagnosis of complete mole, 13 complete mole with a twin conception and 58 partial moles. At the commencement of treatment, 94% of patients were in the FIGO low-risk group (score 0–6). For patients treated with single-agent methotrexate, the primary cure rate ranged from 75% for a FIGO score of 0–1 through to 31% for those with a FIGO score of 6. CONCLUSION: In the setting of a formal follow-up programme, the expected cure rate for GTT after a molar pregnancy should be 100%. Prompt treatment and diagnosis should limit the exposure of most patients to combination chemotherapy. Because of the post-treatment relapse rate of 3% post-chemotherapy, hCG monitoring should be performed routinely

Geographic Coincidence of Increased Malaria Transmission Hazard and Vulnerability Occurring at the Periphery of two Tanzanian Villages.

The goal of malaria elimination necessitates an improved understanding of any fine-scale geographic variations in transmission risk so that complementary vector control tools can be integrated into current vector control programmes as supplementary measures that are spatially targeted to maximize impact upon residual transmission. This study examines the distribution of host-seeking malaria vectors at households within two villages in rural Tanzania. Host-seeking mosquitoes were sampled from 72 randomly selected households in two villages on a monthly basis throughout 2008 using CDC light-traps placed beside occupied nets. Spatial autocorrelation in the dataset was examined using the Moran's I statistic and the location of any clusters was identified using the Getis-Ord Gi* statistic. Statistical associations between the household characteristics and clusters of mosquitoes were assessed using a generalized linear model for each species. For both Anopheles gambiae sensu lato and Anopheles funestus, the density of host-seeking females was spatially autocorrelated, or clustered. For both species, houses with low densities were clustered in the semi-urban village centre while houses with high densities were clustered in the periphery of the villages. Clusters of houses with low or high densities of An. gambiae s.l. were influenced by the number of residents in nearby houses. The occurrence of high-density clusters of An. gambiae s.l. was associated with lower elevations while An. funestus was also associated with higher elevations. Distance from the village centre was also positively correlated with the number of household occupants and having houses constructed with open eaves. The results of the current study highlight that complementary vector control tools could be most effectively targeted to the periphery of villages where the households potentially have a higher hazard (mosquito densities) and vulnerability (open eaves and larger households) to malaria infection

Enhanced cosmic-ray flux toward zeta Persei inferred from laboratory study of H3+ - e- recombination rate

The H3+ molecular ion plays a fundamental role in interstellar chemistry, as it initiates a network of chemical reactions that produce many interstellar molecules. In dense clouds, the H3+ abundance is understood using a simple chemical model, from which observations of H3+ yield valuable estimates of cloud path length, density, and temperature. On the other hand, observations of diffuse clouds have suggested that H3+ is considerably more abundant than expected from the chemical models. However, diffuse cloud models have been hampered by the uncertain values of three key parameters: the rate of H3+ destruction by electrons, the electron fraction, and the cosmic-ray ionisation rate. Here we report a direct experimental measurement of the H3+ destruction rate under nearly interstellar conditions. We also report the observation of H3+ in a diffuse cloud (towards zeta Persei) where the electron fraction is already known. Taken together, these results allow us to derive the value of the third uncertain model parameter: we find that the cosmic-ray ionisation rate in this sightline is forty times faster than previously assumed. If such a high cosmic-ray flux is indeed ubiquitous in diffuse clouds, the discrepancy between chemical models and the previous observations of H3+ can be resolved.Comment: 6 pages, Nature, in pres