Phosphonopeptides Revisited, in an Era of Increasing Antimicrobial Resistance

Given the increase in resistance to antibacterial agents, there is an urgent need for the development of new agents with novel modes of action. As an interim solution, it is also prudent to reinvestigate old or abandoned antibacterial compounds to assess their efficacy in the context of widespread resistance to conventional agents. In the 1970s, much work was performed on the development of peptide mimetics, exemplified by the phosphonopeptide, alafosfalin. We investigated the activity of alafosfalin, di-alanyl fosfalin and β-chloro-L-alanyl-β-chloro-L-alanine against 297 bacterial isolates, including carbapenemase-producing Enterobacterales (CPE) (n = 128), methicillin-resistant Staphylococcus aureus (MRSA) (n = 37) and glycopeptide-resistant enterococci (GRE) (n = 43). The interaction of alafosfalin with meropenem was also examined against 20 isolates of CPE. The MIC50 and MIC90 of alafosfalin for CPE were 1 mg/L and 4 mg/L, respectively and alafosfalin acted synergistically when combined with meropenem against 16 of 20 isolates of CPE. Di-alanyl fosfalin showed potent activity against glycopeptide-resistant isolates of Enterococcus faecalis (MIC90; 0.5 mg/L) and Enterococcus faecium (MIC90; 2 mg/L). Alafosfalin was only moderately active against MRSA (MIC90; 8 mg/L), whereas β-chloro-L-alanyl-β-chloro-L-alanine was slightly more active (MIC90; 4 mg/L). This study shows that phosphonopeptides, including alafosfalin, may have a therapeutic role to play in an era of increasing antibacterial resistance

Virus evolution in Wolbachia-infected Drosophila

Wolbachia, a common vertically transmitted symbiont, can protect insects against viral infection and prevent mosquitoes from transmitting viral pathogens. For this reason, Wolbachia-infected mosquitoes are being released to prevent the transmission of dengue and other arboviruses. An important question for the long-term success of these programmes is whether viruses can evolve to escape the antiviral effects of Wolbachia. We have found that Wolbachia altered the outcome of competition between strains of the DCV virus in Drosophila. However, Wolbachia still effectively blocked the virus genotypes that were favoured in the presence of the symbiont. We conclude that Wolbachia did cause an evolutionary response in viruses, but this has little or no impact on the effectiveness of virus blocking

Virus evolution in Wolbachia-infected Drosophila

Wolbachia, a common vertically transmitted symbiont, can protect insects against viral infection and prevent mosquitoes from transmitting viral pathogens. For this reason, Wolbachia-infected mosquitoes are being released to prevent the transmission of dengue and other arboviruses. An important question for the long-term success of these programmes is whether viruses can evolve to escape the antiviral effects of Wolbachia. We have found that Wolbachia altered the outcome of competition between strains of the DCV virus in Drosophila. However, Wolbachia still effectively blocked the virus genotypes that were favoured in the presence of the symbiont. We conclude that Wolbachia did cause an evolutionary response in viruses, but this has little or no impact on the effectiveness of virus blocking

18-month hydration of a low-pH cement for geological disposal of radioactive waste: The Cebama reference cement

Low-pH cements are candidate materials for use in the construction of geological disposal facilities for the long-term management of nuclear waste. Since these facilities will operate over long time scales, the changes in mineralogy and microstructure require evaluation as a function of time. As a first step towards this understanding, the hydration of a standardised low-pH cement paste, known as the Cebama reference cement, was investigated over an 18-month period. Characterisation was performed at 28 days of curing, at 20 °C and 40 °C, and novel synchrotron radiation X-ray diffraction experiments were performed, in-situ, from 90 min to 18 months of curing. Concurrent solid state 29Si and 27Al MAS NMR data were acquired for parallel samples to quantify the extent of cement hydration and the composition and mean chain length of the predominant calcium aluminosilicate hydrate (C-(A)-S-H) reaction product. After 18 months, cement clinker phases were still present, highlighting the slow hydration kinetics of this low-pH cement. The data presented provide a benchmark for ongoing and future studies of low-pH cements in geological disposal environments, over extended time scales

Combined Use of Mycobacterium tuberculosis-Specific CD4 and CD8 T-Cell Responses Is a Powerful Diagnostic Tool of Active Tuberculosis.

Immune-based assays are promising tools to help to formulate diagnosis of active tuberculosis. A multiparameter flow cytometry assay assessing T-cell responses specific to Mycobacterium tuberculosis and the combination of both CD4 and CD8 T-cell responses accurately discriminated between active tuberculosis and latent infection

Freshwater fish introductions in mediterranean-climate regions: are there commonalities in the conservation problem?

Aim To compare patterns and drivers of freshwater fish introductions across five climatically similar regions and evaluate similarities and differences in the nonnative species introduced. Location Five mediterranean-climate regions: California (USA), central Chile, south-western Australia, the Iberian peninsula (Spain and Portugal) and the south-western Cape (South Africa). Methods Species presence–absence for native and non-native fishes were collated across the regions, and patterns of faunal change were examined using univariate and multivariate statistical approaches. Taxonomic patterns in freshwater fish introductions were evaluated by comparing the number of species introduced by order to the numbers expected from binomial probabilities. Factors influencing multiple introductions of freshwater fish species in mediterranean regions were determined using generalized linear modelling. Results High levels of endemism (70–90%) were revealed for south-western Cape, south-western Australia and Chile. Despite their high rates of endemism, all regions currently have more non-native species than endemic species. Taxonomic selection was found for five orders, although this was only significant for Salmoniformes across regions. The average increase in regional compositional similarity of fish faunas resulting from non-native fish introductions was 8.0%. Important factors predicting multiple introductions of a species include previous introduction success and mean latitude of its distribution Main conclusions The mediterranean-climate regions of the world, separated by vast distances, originally had a few fish species in common but are now more similar, owing to species introductions, illustrating the extent and importance of taxonomic homogenization. Introductions are largely driven by taxonomically biased human interests in recreational fisheries, aquaculture and ornamental pet species.Centre of Excellence for Invasion Biolog

Взаємозв’язок великих кондратьєвських циклів розвитку економіки і системних світових конфліктів

Однією з найважливіших проблем, що постала перед сучасною наукою у зв’язку із стрімким розгортанням глобальної економічної кризи, загостренням світових конфліктів, є вироблення науково обґрунтованих «метричних» експрес прогнозів розвитку суспільства на ближчу і далеку перспективу

Some life-history parameters of the non-native amphipod Platorchestia platensis (Talitridae) in a warm temperate South African estuary

Density, population structure, growth, mortality and aspects of reproduction of the non-native amphipod Platorchestia platensis were studied for 20 consecutive months (October 2008 to May 2010) in the supralittoral wrack of the Knysna Estuary, South Africa. Amphipod density varied over the sampling period with the lowest numbers recorded in summer (January and February). Ovigerous females with embryos, and juveniles were found in most months with peaks in recruitment found in both April and October, suggesting that in Knysna this species is a biannual breeder. Average female size was significantly greater in winter, with larger females tending to brood more embryos. The largest adults (13.5 mm total length) were always male although the monthly sex ratio was nearly always female biased. Growth rate estimated from a cohort analysis was about 1 mm per month and monthly survival about 69%. The ability to reproduce all year round may be one reason why this introduced species has become established within this warm temperate estuary

The induction of behavioural sensitization is associated with cocaine-induced structural plasticity in the core (but not shell) of the nucleus accumbens

Repeated exposure to cocaine increases the density of dendritic spines on medium spiny neurons in the nucleus accumbens (Acb) and pyramidal cells in the medial prefrontal cortex (mPFC). To determine if this is associated with the development of psychomotor sensitization, rats were given daily i.p. injections of 15 mg/kg of cocaine (or saline) for 8 days, either in their home cage (which failed to induce significant psychomotor sensitization) or in a distinct and relatively novel test cage (which induced robust psychomotor sensitization). Their brains were obtained 2 weeks after the last injection and processed for Golgi–Cox staining. In the Acb core (AcbC) cocaine treatment increased spine density only in the group that developed psychomotor sensitization (i.e. in the Novel but not Home group), and there was a significant positive correlation between the degree of psychomotor sensitization and spine density. In the Acb shell (AcbS) cocaine increased spine density to the same extent in both groups; i.e. independent of psychomotor sensitization. In the mPFC cocaine increased spine density in both groups, but to a significantly greater extent in the Novel group. Furthermore, when rats were treated at Home with a higher dose of cocaine (30 mg/kg), cocaine now induced psychomotor sensitization in this context, and also increased spine density in the AcbC. Thus, the context in which cocaine is experienced influences its ability to reorganize patterns of synaptic connectivity in the Acb and mPFC, and the induction of psychomotor sensitization is associated with structural plasticity in the AcbC and mPFC, but not the AcbS.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73532/1/j.1460-9568.2004.03612.x.pd

A First Search for coincident Gravitational Waves and High Energy Neutrinos using LIGO, Virgo and ANTARES data from 2007

We present the results of the first search for gravitational wave bursts associated with high energy neutrinos. Together, these messengers could reveal new, hidden sources that are not observed by conventional photon astronomy, particularly at high energy. Our search uses neutrinos detected by the underwater neutrino telescope ANTARES in its 5 line configuration during the period January - September 2007, which coincided with the fifth and first science runs of LIGO and Virgo, respectively. The LIGO-Virgo data were analysed for candidate gravitational-wave signals coincident in time and direction with the neutrino events. No significant coincident events were observed. We place limits on the density of joint high energy neutrino - gravitational wave emission events in the local universe, and compare them with densities of merger and core-collapse events.Comment: 19 pages, 8 figures, science summary page at http://www.ligo.org/science/Publication-S5LV_ANTARES/index.php. Public access area to figures, tables at https://dcc.ligo.org/cgi-bin/DocDB/ShowDocument?docid=p120000