Epidemiological, clinical, outcome and antibiotic susceptibility differences between PVL positive and PVL negative Staphylococcus aureus infections in Western Australia: A case control study

Background: Panton Valentine Leukocidin (PVL) has been associated with invasive Staphylococcus aureus soft tissue and pneumonic infections. Methods: From September 2007 to January 2009 at Royal Perth Hospital we tested for the PVL gene in S. aureus isolates from an invasive site, a suspected PVL-related soft tissue infection and all MRSA isolates. We could access medical records for 141 PVL positive (PVL + ve) infections and compared these to a control group comprised of 148 PVL negative (PVL-ve) infections. Results: In the PVL + ve group 62 isolates were MRSA (48 were ST93-MRSA-IV) and 79 isolates were methicillin-sensitive S. aureus, and in the PVL-ve group 56 were MRSA (50 were WA-MRSA strains) and 92 were methicillin-sensitive S. aureus. We found the presence of PVL to be significantly associated with younger age, aboriginality, intravenous drug use, community acquisition, shorter length of hospital stay and lower mortality at 1 year. Overall PVL + ve infections more often required surgical intervention (73.0% versus 44.6%, p < 0.001) and were less often polymicrobial (8.5% versus 41.2%, p < 0.001). PVL + ve isolates were more often susceptible to clindamycin (87.9% versus 73.0%, p = 0.002). Conclusions: This study demonstrates that PVL + ve infections are associated with a distinct clinical picture, predominantly pyogenic skin and soft tissue infections often requiring surgery, disproportionately affecting patients who are younger, indigenous or with fewer health-care risk factors

Evidence for plunging river plume deposits in the Pahrump Hills member of the Murray formation, Gale crater, Mars

Recent robotic missions to Mars have offered new insights into the extent, diversity and habitability of the Martian sedimentary rock record. Since the Curiosity rover landed in Gale crater in August 2012, the Mars Science Laboratory Science Team has explored the origins and habitability of ancient fluvial, deltaic, lacustrine and aeolian deposits preserved within the crater. This study describes the sedimentology of a ca 13 m thick succession named the Pahrump Hills member of the Murray formation, the first thick fine‐grained deposit discovered in situ on Mars. This work evaluates the depositional processes responsible for its formation and reconstructs its palaeoenvironmental setting. The Pahrump Hills succession can be sub‐divided into four distinct sedimentary facies: (i) thinly laminated mudstone; (ii) low‐angle cross‐stratified mudstone; (iii) cross‐stratified sandstone; and (iv) thickly laminated mudstone–sandstone. The very fine grain size of the mudstone facies and abundant millimetre‐scale and sub‐millimetre‐scale laminations exhibiting quasi‐uniform thickness throughout the Pahrump Hills succession are most consistent with lacustrine deposition. Low‐angle geometric discordances in the mudstone facies are interpreted as ‘scour and drape’ structures and suggest the action of currents, such as those associated with hyperpycnal river‐generated plumes plunging into a lake. Observation of an overall upward coarsening in grain size and thickening of laminae throughout the Pahrump Hills succession is consistent with deposition from basinward progradation of a fluvial‐deltaic system derived from the northern crater rim into the Gale crater lake. Palaeohydraulic modelling constrains the salinity of the ancient lake in Gale crater: assuming river sediment concentrations typical of floods on Earth, plunging river plumes and sedimentary structures like those observed at Pahrump Hills would have required lake densities near freshwater to form. The depositional model for the Pahrump Hills member presented here implies the presence of an ancient sustained, habitable freshwater lake in Gale crater for at least ca 103 to 107 Earth years

The long and the short of it: Mechanisms of synchronous and compensatory dynamics across temporal scales

Synchronous dynamics (fluctuations that occur in unison) are universal phenomena with widespread implications for ecological stability. Synchronous dynamics can amplify the destabilizing effect of environmental variability on ecosystem functions such as productivity, whereas the inverse, compensatory dynamics, can stabilize function. Here we combine simulation and empirical analyses to elucidate mechanisms that underlie patterns of synchronous versus compensatory dynamics. In both simulated and empirical communities, we show that synchronous and compensatory dynamics are not mutually exclusive but instead can vary by timescale. Our simulations identify multiple mechanisms that can generate timescale-specific patterns, including different environmental drivers, diverse life histories, dispersal, and non-stationary dynamics. We find that traditional metrics for quantifying synchronous dynamics are often biased toward long-term drivers and may miss the importance of short-term drivers. Our findings indicate key mechanisms to consider when assessing synchronous versus compensatory dynamics and our approach provides a pathway for disentangling these dynamics in natural systems

Air–liquid interface cultures enhance the oxygen supply and trigger the structural and functional differentiation of intestinal porcine epithelial cells (IPEC)

The specific function of the epithelium as critical barrier between the intestinal lumen and the organism’s internal microenvironment is reflected by permanent maintenance of intercellular junctions and cellular polarity. The intestinal epithelial cells are responsible for absorption of nutritional components, facing mechanical stress and a changing oxygen supplementation via blood stream. Oxygen itself can regulate the barrier and the absorptive function of the epithelium. Therefore, we compared the dish cell culture, the transwell-like membrane culture and the oxygen enriched air–liquid interface (ALI) culture. We demonstrated strong influence of the different culture conditions on morphology and function of intestinal porcine epithelial cell lines in vitro. ALI culture resulted in a significant increase in cell number, epithelial cell layer thickness and expression as well as apical localisation of the microvilli-associated protein villin. Remarkable similarities regarding the morphological parameters were observed between ALI cultures and intestinal epithelial cells in vivo. Furthermore, the functional analysis of protein uptake and degradation by the epithelial cells demonstrated the necessity of sufficient oxygen supply as achieved in ALI cultures. Our study is the first report providing marked evidence that optimised oxygen supply using ALI cultures directly affects the morphological differentiation and functional properties of intestinal epithelial cells in vitro

Glycerol Monolaurate and Dodecylglycerol Effects on Staphylococcus aureus and Toxic Shock Syndrome Toxin-1 In Vitro and In Vivo

BACKGROUND:Glycerol monolaurate (GML), a 12 carbon fatty acid monoester, inhibits Staphylococcus aureus growth and exotoxin production, but is degraded by S. aureus lipase. Therefore, dodecylglycerol (DDG), a 12 carbon fatty acid monoether, was compared in vitro and in vivo to GML for its effects on S. aureus growth, exotoxin production, and stability. METHODOLOGY/PRINCIPAL FINDINGS:Antimicrobial effects of GML and DDG (0 to 500 microg/ml) on 54 clinical isolates of S. aureus, including pulsed-field gel electrophoresis (PFGE) types USA200, USA300, and USA400, were determined in vitro. A rabbit Wiffle ball infection model assessed GML and DDG (1 mg/ml instilled into the Wiffle ball every other day) effects on S. aureus (MN8) growth (inoculum 3x10(8) CFU/ml), toxic shock syndrome toxin-1 (TSST-1) production, tumor necrosis factor-alpha (TNF-alpha) concentrations and mortality over 7 days. DDG (50 and 100 microg/ml) inhibited S. aureus growth in vitro more effectively than GML (p<0.01) and was stable to lipase degradation. Unlike GML, DDG inhibition of TSST-1 was dependent on S. aureus growth. GML-treated (4 of 5; 80%) and DDG-treated rabbits (2 of 5; 40%) survived after 7 days. Control rabbits (5 of 5; 100%) succumbed by day 4. GML suppressed TNF-alpha at the infection site on day 7; however, DDG did not (<10 ng/ml versus 80 ng/ml, respectively). CONCLUSIONS/SIGNIFICANCE:These data suggest that DDG was stable to S. aureus lipase and inhibited S. aureus growth at lower concentrations than GML in vitro. However, in vivo GML was more effective than DDG by reducing mortality, and suppressing TNF-alpha, S. aureus growth and exotoxin production, which may reduce toxic shock syndrome. GML is proposed as a more effective anti-staphylococcal topical anti-infective candidate than DDG, despite its potential degradation by S. aureus lipase

Phosphorus dynamics in a tropical forest soil restored after strip mining

Background and aims We hypothesized that successful early ecosystem and soil development in these P-deficient soil materials will initially depend on effective re-establishment of P storage and cycling through organic matter. This hypothesis was tested in a 26-year chronosequence of seven lightly fertilized, oxidic soil materials restored to eucalypt forest communities after bauxite mining. Methods Total P (Pt) status, Hedley P fractions and partial chemical speciation (NaOH-EDTA extraction and analysed using solution 31P NMR spectroscopy) were determined in the restored soils. Results Concentrations of Pt and most Hedley fractions changed with restoration period, declined with depth and were strongly positively correlated with C and N concentrations. Biological P dominated the Labile and Intermediate P fractions while Long-term P was dominantly inorganic. Organic P concentrations in NaOH-EDTA extracts and their chemical natures were similar in restored and unburned native forest sites. Phosphomonoesters were the dominant class of organic P. Conclusions Surprisingly rapid P accretion and fractional changes occurred over 26 years, largely in the surface soils and closely associated with organic matter status. Alkaline hydrolysis products of phosphodiesters and pyrophosphate indicated the importance of microbial P cycling. The important consequences for long-term ecosystem development and biological diversity require further study

Power training and postmenopausal hormone therapy affect transcriptional control of specific co-regulated gene clusters in skeletal muscle

At the moment, there is no clear molecular explanation for the steeper decline in muscle performance after menopause or the mechanisms of counteractive treatments. The goal of this genome-wide study was to identify the genes and gene clusters through which power training (PT) comprising jumping activities or estrogen containing hormone replacement therapy (HRT) may affect skeletal muscle properties after menopause. We used musculus vastus lateralis samples from early stage postmenopausal (50–57 years old) women participating in a yearlong randomized double-blind placebo-controlled trial with PT and HRT interventions. Using microarray platform with over 24,000 probes, we identified 665 differentially expressed genes. The hierarchical clustering method was used to assort the genes. Additionally, enrichment analysis of gene ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways was carried out to clarify whether assorted gene clusters are enriched with particular functional categories. The analysis revealed transcriptional regulation of 49 GO/KEGG categories. PT upregulated transcription in “response to contraction”—category revealing novel candidate genes for contraction-related regulation of muscle function while HRT upregulated gene expression related to functionality of mitochondria. Moreover, several functional categories tightly related to muscle energy metabolism, development, and function were affected regardless of the treatment. Our results emphasize that during the early stages of the postmenopause, muscle properties are under transcriptional modulation, which both PT and HRT partially counteract leading to preservation of muscle power and potentially reducing the risk for aging-related muscle weakness. More specifically, PT and HRT may function through improving energy metabolism, response to contraction as well as by preserving functionality of the mitochondria

The potential of antisense oligonucleotide therapies for inherited childhood lung diseases.

Antisense oligonucleotides are an emerging therapeutic option to treat diseases with known genetic origin. In the age of personalised medicines, antisense oligonucleotides can sometimes be designed to target and bypass or overcome a patient's genetic mutation, in particular those lesions that compromise normal pre-mRNA processing. Antisense oligonucleotides can alter gene expression through a variety of mechanisms as determined by the chemistry and antisense oligomer design. Through targeting the pre-mRNA, antisense oligonucleotides can alter splicing and induce a specific spliceoform or disrupt the reading frame, target an RNA transcript for degradation through RNaseH activation, block ribosome initiation of protein translation or disrupt miRNA function. The recent accelerated approval of eteplirsen (renamed Exondys 51™) by the Food and Drug Administration, for the treatment of Duchenne muscular dystrophy, and nusinersen, for the treatment of spinal muscular atrophy, herald a new and exciting era in splice-switching antisense oligonucleotide applications to treat inherited diseases. This review considers the potential of antisense oligonucleotides to treat inherited lung diseases of childhood with a focus on cystic fibrosis and disorders of surfactant protein metabolism

Ecological impacts of non-native Pacific oysters (Crassostrea gigas) and management measures for protected areas in Europe

Pacific oysters are now one of the most ‘globalised’ marine invertebrates. They dominate bivalve aquaculture production in many regions and wild populations are increasingly becoming established, with potential to displace native species and modify habitats and ecosystems. While some fishing communities may benefit from wild populations, there is now a tension between the continued production of Pacific oysters and risk to biodiversity, which is of particular concern within protected sites. The issue of the Pacific oyster therefore locates at the intersection between two policy areas: one concerning the conservation of protected habitats, the other relating to livelihoods and the socio-economics of coastal aquaculture and fishing communities. To help provide an informed basis for management decisions, we first summarise evidence for ecological impacts of wild Pacific oysters in representative coastal habitats. At local scales, it is clear that establishment of Pacific oysters can significantly alter diversity, community structure and ecosystem processes, with effects varying among habitats and locations and with the density of oysters. Less evidence is available to evaluate regional-scale impacts. A range of management measures have been applied to mitigate negative impacts of wild Pacific oysters and we develop recommendations which are consistent with the scientific evidence and believe compatible with multiple interests. We conclude that all stakeholders must engage in regional decision making to help minimise negative environmental impacts, and promote sustainable industry development