441 research outputs found
Do bioresorbable polyesters have antimicrobial properties?
Biodegradable and bioresorbable polyesters (BBPEs) are a widespread class of aliphatic polymers with a plethora of applications in the medical field. Some reports speculate that these polymers have intrinsic antibacterial activity as a consequence of their acidic degradation by-products. The release of organic acids as a result of the hydrolytic degradation of BBPEs in vivo and the resulting pH drop could be an effective inhibitor of the growth of pathogens in the local environment adjacent to BBPE-based devices. However, there is no clear and conclusive evidence in the literature concerning the antibacterial activity of BBPE to support or refute this hypothesis. In this communication we address this point through an assessment of the antibacterial properties of six well-established commercially available BBPEs. Agar diffusion assays and optical density measurements at 600 nm were performed on all the polymer samples to characterize the growth of bacteria and any potential inhibition over an incubation period of 24 h. The results indicated that BBPEs do not possess an intrinsic and immediate antibacterial activity, which is consistent with the clear mismatch between the time-scales for bacterial growth and the rate of degradation of the polyesters
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The stealth episome: suppression of gene expression on the excised genomic island PPHGI-1 from Pseudomonas syringae pv. phaseolicola
Pseudomonas syringae pv. phaseolicola is the causative agent of halo blight in the common bean, Phaseolus vulgaris. P. syringae pv. phaseolicola race 4 strain 1302A contains the avirulence gene avrPphB (syn. hopAR1), which resides on PPHGI-1, a 106 kb genomic island. Loss of PPHGI-1 from P. syringae pv. phaseolicola 1302A following exposure to the hypersensitive resistance response (HR) leads to the evolution of strains with altered virulence. Here we have used fluorescent protein reporter systems to gain insight into the mobility of PPHGI-1. Confocal imaging of dual-labelled P. syringae pv. phaseolicola 1302A strain, F532 (dsRFP in chromosome and eGFP in PPHGI-1), revealed loss of PPHGI-1::eGFP encoded fluorescence during plant infection and when grown in vitro on extracted leaf apoplastic fluids. Fluorescence-activated cell sorting (FACS) of fluorescent and non-fluorescent PPHGI-1::eGFP F532 populations showed that cells lost fluorescence not only when the GI was deleted, but also when it had excised and was present as a circular episome. In addition to reduced expression of eGFP, quantitative PCR on sub-populations separated by FACS showed that transcription of other genes on PPHGI-1 (avrPphB and xerC) was also greatly reduced in F532 cells harbouring the excised PPHGI-1::eGFP episome. Our results show how virulence determinants located on mobile pathogenicity islands may be hidden from detection by host surveillance systems through the suppression of gene expression in the episomal state
A Vast Thin Plane of Co-rotating Dwarf Galaxies Orbiting the Andromeda Galaxy
Dwarf satellite galaxies are thought to be the remnants of the population of
primordial structures that coalesced to form giant galaxies like the Milky Way.
An early analysis noted that dwarf galaxies may not be isotropically
distributed around our Galaxy, as several are correlated with streams of HI
emission, and possibly form co-planar groups. These suspicions are supported by
recent analyses, and it has been claimed that the apparently planar
distribution of satellites is not predicted within standard cosmology, and
cannot simply represent a memory of past coherent accretion. However, other
studies dispute this conclusion. Here we report the existence (99.998%
significance) of a planar sub-group of satellites in the Andromeda galaxy,
comprising approximately 50% of the population. The structure is vast: at least
400 kpc in diameter, but also extremely thin, with a perpendicular scatter
<14.1 kpc (99% confidence). Radial velocity measurements reveal that the
satellites in this structure have the same sense of rotation about their host.
This finding shows conclusively that substantial numbers of dwarf satellite
galaxies share the same dynamical orbital properties and direction of angular
momentum, a new insight for our understanding of the origin of these most dark
matter dominated of galaxies. Intriguingly, the plane we identify is
approximately aligned with the pole of the Milky Way's disk and is co-planar
with the Milky Way to Andromeda position vector. The existence of such
extensive coherent kinematic structures within the halos of massive galaxies is
a fact that must be explained within the framework of galaxy formation and
cosmology.Comment: Published in the 3rd Jan 2013 issue of Nature. 19 pages, 4 figures, 1
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Ammonia borane-polyethylene oxide composite materials for solid hydrogen storage (vol 3, pg 3683, 2015)
RNA Oxidation Adducts 8-OHG and 8-OHA Change with Aβ42 Levels in Late-Stage Alzheimer's Disease
While research supports amyloid-β (Aβ) as the etiologic agent of Alzheimer's disease (AD), the mechanism of action remains unclear. Evidence indicates that adducts of RNA caused by oxidation also represent an early phenomenon in AD. It is currently unknown what type of influence these two observations have on each other, if any. We quantified five RNA adducts by gas chromatography/mass spectroscopy across five brain regions from AD cases and age-matched controls. We then used a reductive directed analysis to compare the RNA adducts to common indices of AD neuropathology and various pools of Aβ. Using data from four disease-affected brain regions (Brodmann's Area 9, hippocampus, inferior parietal lobule, and the superior and middle temporal gyri), we found that the RNA adduct 8-hydroxyguanine (8-OHG) decreased, while 8-hydroxyadenine (8-OHA) increased in AD. The cerebellum, which is generally spared in AD, did not show disease related changes, and no RNA adducts correlated with the number of plaques or tangles. Multiple regression analysis revealed that SDS-soluble Aβ42 was the best predictor of changes in 8-OHG, while formic acid-soluble Aβ42 was the best predictor of changes in 8-OHA. This study indicates that although there is a connection between AD related neuropathology and RNA oxidation, this relationship is not straightforward
A Condensation-Ordering Mechanism in Nanoparticle-Catalyzed Peptide Aggregation
Nanoparticles introduced in living cells are capable of strongly promoting
the aggregation of peptides and proteins. We use here molecular dynamics
simulations to characterise in detail the process by which nanoparticle
surfaces catalyse the self- assembly of peptides into fibrillar structures. The
simulation of a system of hundreds of peptides over the millisecond timescale
enables us to show that the mechanism of aggregation involves a first phase in
which small structurally disordered oligomers assemble onto the nanoparticle
and a second phase in which they evolve into highly ordered beta-sheets as
their size increases
The Hubble Constant
I review the current state of determinations of the Hubble constant, which
gives the length scale of the Universe by relating the expansion velocity of
objects to their distance. There are two broad categories of measurements. The
first uses individual astrophysical objects which have some property that
allows their intrinsic luminosity or size to be determined, or allows the
determination of their distance by geometric means. The second category
comprises the use of all-sky cosmic microwave background, or correlations
between large samples of galaxies, to determine information about the geometry
of the Universe and hence the Hubble constant, typically in a combination with
other cosmological parameters. Many, but not all, object-based measurements
give values of around 72-74km/s/Mpc , with typical errors of 2-3km/s/Mpc.
This is in mild discrepancy with CMB-based measurements, in particular those
from the Planck satellite, which give values of 67-68km/s/Mpc and typical
errors of 1-2km/s/Mpc. The size of the remaining systematics indicate that
accuracy rather than precision is the remaining problem in a good determination
of the Hubble constant. Whether a discrepancy exists, and whether new physics
is needed to resolve it, depends on details of the systematics of the
object-based methods, and also on the assumptions about other cosmological
parameters and which datasets are combined in the case of the all-sky methods.Comment: Extensively revised and updated since the 2007 version: accepted by
Living Reviews in Relativity as a major (2014) update of LRR 10, 4, 200
Structure and Molecular Evolution of CDGSH Iron-Sulfur Domains
The recently discovered CDGSH iron-sulfur domains (CISDs) are classified into seven major types with a wide distribution throughout the three domains of life. The type 1 protein mitoNEET has been shown to fold into a dimer with the signature CDGSH motif binding to a [2Fe-2S] cluster. However, the structures of all other types of CISDs were unknown. Here we report the crystal structures of type 3, 4, and 6 CISDs determined at 1.5 Å, 1.8 Å and 1.15 Å resolution, respectively. The type 3 and 4 CISD each contain one CDGSH motif and adopt a dimeric structure. Although similar to each other, the two structures have permutated topologies, and both are distinct from the type 1 structure. The type 6 CISD contains tandem CDGSH motifs and adopts a monomeric structure with an internal pseudo dyad symmetry. All currently known CISD structures share dual iron-sulfur binding modules and a β-sandwich for either intermolecular or intramolecular dimerization. The iron-sulfur binding module, the β-strand N-terminal to the module and a proline motif are conserved among different type structures, but the dimerization module and the interface and orientation between the two iron-sulfur binding modules are divergent. Sequence analysis further shows resemblance between CISD types 4 and 7 and between 1 and 2. Our findings suggest that all CISDs share common ancestry and diverged into three primary folds with a characteristic phylogenetic distribution: a eukaryote-specific fold adopted by types 1 and 2 proteins, a prokaryote-specific fold adopted by types 3, 4 and 7 proteins, and a tandem-motif fold adopted by types 5 and 6 proteins. Our comprehensive structural, sequential and phylogenetic analysis provides significant insight into the assembly principles and evolutionary relationship of CISDs
Adherence to isoniazid preventive therapy in Indonesian children: A quantitative and qualitative investigation
<p>Abstract</p> <p>Background</p> <p>It is recommended that young child contacts of sputum smear positive tuberculosis cases receive isoniazid preventive therapy (IPT) but reported adherence is low and risk factors for poor adherence in children are largely unknown.</p> <p>Methods</p> <p>We prospectively determined rates of IPT adherence in children < 5 yrs in an Indonesian lung clinic. Possible risk factors for poor adherence, defined as ≤3 months prescription collection, were calculated using logistic regression. To further investigate adherence barriers in-depth interviews were conducted with caregivers of children with good and poor adherence.</p> <p>Results</p> <p>Eighty-two children eligible for IPT were included, 61 (74.4%) of which had poor adherence. High transport costs (OR 3.3, 95% CI 1.1-10.2) and medication costs (OR 20.0, 95% CI 2.7-414.5) were significantly associated with poor adherence in univariate analysis. Access, medication barriers, disease and health service experience and caregiver TB and IPT knowledge and beliefs were found to be important determinants of adherence in qualitative analysis.</p> <p>Conclusion</p> <p>Adherence to IPT in this setting in Indonesia is extremely low and may result from a combination of financial, knowledge, health service and medication related barriers. Successful reduction of childhood TB urgently requires evidence-based interventions that address poor adherence to IPT.</p
Origin of micro-scale heterogeneity in polymerisation of photo-activated resin composites
Photo-activated resin composites are widely used in industry and medicine. Despite extensive chemical characterisation, the micro-scale pattern of resin matrix reactive group conversion between filler particles is not fully understood. Using an advanced synchrotron-based wide-field IR imaging system and state-of-the-art Mie scattering corrections, we observe how the presence of monodispersed silica filler particles in a methacrylate based resin reduces local conversion and chemical bond strain in the polymer phase. Here we show that heterogeneity originates from a lower converted and reduced bond strain boundary layer encapsulating each particle, whilst at larger inter-particulate distances light attenuation and monomer mobility predominantly influence conversion. Increased conversion corresponds to greater bond strain, however, strain generation appears sensitive to differences in conversion rate and implies subtle distinctions in the final polymer structure. We expect these findings to inform current predictive models of mechanical behaviour in polymer-composite materials, particularly at the resin-filler interface
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