1,168 research outputs found
Heparan sulphate mediates swine vesicular disease virus attachment to the host cell
Heparan sulphate (HS) has been found to serve as receptor for initial cell binding of numerous viruses. Different glycosaminoglycans (GAGs), including heparin and HS, were analysed for their ability to bind swine vesicular disease virus (SVDV), a picornavirus with close homology to human coxsackie B5 virus. Binding of SVDV was established by heparin-affinity chromatography. In addition, infection of IB-RS-2 epithelial porcine cells was inhibited by treating the virus with soluble HS, heparin, and chondroitin sulphate B (CS-B), as well as by enzymic digestion of cell surface GAGs. Analysis of the infection course showed that SVDV uses cellular HS for its binding to the cell surface and that this interaction occurs during attachment of the virus, prior to its internalization into the cell. Sequence analysis of SVDV variants selected for their lack of sensitivity to heparin inhibition in vitro led to the identification of two residues (A2135V and 11 266K) potentially involved in heparin/HS interaction. The location of these residues in a three-dimensional model shows that they are clustered in a well-exposed region of the capsid, providing a physical mechanism that could account for the heparin-binding phenotype
Detecting the direction of a signal on high-dimensional spheres: Non-null and Le Cam optimality results
We consider one of the most important problems in directional statistics,
namely the problem of testing the null hypothesis that the spike direction
of a Fisher-von Mises-Langevin distribution on the -dimensional
unit hypersphere is equal to a given direction . After a reduction
through invariance arguments, we derive local asymptotic normality (LAN)
results in a general high-dimensional framework where the dimension goes
to infinity at an arbitrary rate with the sample size , and where the
concentration behaves in a completely free way with , which
offers a spectrum of problems ranging from arbitrarily easy to arbitrarily
challenging ones. We identify various asymptotic regimes, depending on the
convergence/divergence properties of , that yield different
contiguity rates and different limiting experiments. In each regime, we derive
Le Cam optimal tests under specified and we compute, from the Le Cam
third lemma, asymptotic powers of the classical Watson test under contiguous
alternatives. We further establish LAN results with respect to both spike
direction and concentration, which allows us to discuss optimality also under
unspecified . To investigate the non-null behavior of the Watson test
outside the parametric framework above, we derive its local asymptotic powers
through martingale CLTs in the broader, semiparametric, model of rotationally
symmetric distributions. A Monte Carlo study shows that the finite-sample
behaviors of the various tests remarkably agree with our asymptotic results.Comment: 47 pages, 4 figure
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Fast continuous alcohol amination employing a hydrogen borrowing protocol
A continuous flow method for the direct conversion of alcohols to amines via a hydrogen borrowing approach is reported.The authors are grateful to Eli Lilly & Co. (RL) and the EPSRC (SVL, grants EP/K009494/1, EP/M004120/1 and EP/K039520/1) for financial support. This work was supported by Eli Lilly & Co. through the Lilly Research Award Program (LRAP)
Connection Between Type A and E Factorizations and Construction of Satellite Algebras
Recently, we introduced a new class of symmetry algebras, called satellite
algebras, which connect with one another wavefunctions belonging to different
potentials of a given family, and corresponding to different energy
eigenvalues. Here the role of the factorization method in the construction of
such algebras is investigated. A general procedure for determining an so(2,2)
or so(2,1) satellite algebra for all the Hamiltonians that admit a type E
factorization is proposed. Such a procedure is based on the known relationship
between type A and E factorizations, combined with an algebraization similar to
that used in the construction of potential algebras. It is illustrated with the
examples of the generalized Morse potential, the Rosen-Morse potential, the
Kepler problem in a space of constant negative curvature, and, in each case,
the conserved quantity is identified. It should be stressed that the method
proposed is fairly general since the other factorization types may be
considered as limiting cases of type A or E factorizations.Comment: 20 pages, LaTeX, no figure, to be published in J. Phys.
Mangroves enhance the biomass of coral reef fish communities in the Caribbean
Mangrove forests are one of the world's most threatened tropical ecosystems with global loss exceeding 35% (ref. 1). Juvenile coral reef fish often inhabit mangroves, but the importance of these nurseries to reef fish population dynamics has not been quantified. Indeed, mangroves might be expected to have negligible influence on reef fish communities: juvenile fish can inhabit alternative habitats and fish populations may be regulated by other limiting factors such as larval supply or fishing. Here we show that mangroves are unexpectedly important, serving as an intermediate nursery habitat that may increase the survivorship of young fish. Mangroves in the Caribbean strongly influence the community structure of fish on neighbouring coral reefs. In addition, the biomass of several commercially important species is more than doubled when adult habitat is connected to mangroves. The largest herbivorous fish in the Atlantic, Scarus guacamaia, has a functional dependency on mangroves and has suffered local extinction after mangrove removal. Current rates of mangrove deforestation are likely to have severe deleterious consequences for the ecosystem function, fisheries productivity and resilience of reefs. Conservation efforts should protect connected corridors of mangroves, seagrass beds and coral reefs
Development of the preterm gut microbiome in twins at risk of necrotising enterocolitis and sepsis
The preterm gut microbiome is a complex dynamic community influenced by genetic and environmental factors and is implicated in the pathogenesis of necrotising enterocolitis (NEC) and sepsis. We aimed to explore the longitudinal development of the gut microbiome in preterm twins to determine how shared environmental and genetic factors may influence temporal changes and compared this to the expressed breast milk (EBM) microbiome. Stool samples (n = 173) from 27 infants (12 twin pairs and 1 triplet set) and EBM (n = 18) from 4 mothers were collected longitudinally. All samples underwent PCR-DGGE (denaturing gradient gel electrophoresis) analysis and a selected subset underwent 454 pyrosequencing. Stool and EBM shared a core microbiome dominated by Enterobacteriaceae, Enterococcaceae, and Staphylococcaceae. The gut microbiome showed greater similarity between siblings compared to unrelated individuals. Pyrosequencing revealed a reduction in diversity and increasing dominance of Escherichia sp. preceding NEC that was not observed in the healthy twin. Antibiotic treatment had a substantial effect on the gut microbiome, reducing Escherichia sp. and increasing other Enterobacteriaceae.
This study demonstrates related preterm twins share similar gut microbiome development, even within the complex environment of neonatal intensive care. This is likely a result of shared genetic and immunomodulatory factors as well as exposure to the same maternal microbiome during birth, skin contact and exposure to EBM. Environmental factors including antibiotic exposure and feeding are additional significant determinants of community structure, regardless of host genetics
Social interaction, noise and antibiotic-mediated switches in the intestinal microbiota
The intestinal microbiota plays important roles in digestion and resistance
against entero-pathogens. As with other ecosystems, its species composition is
resilient against small disturbances but strong perturbations such as
antibiotics can affect the consortium dramatically. Antibiotic cessation does
not necessarily restore pre-treatment conditions and disturbed microbiota are
often susceptible to pathogen invasion. Here we propose a mathematical model to
explain how antibiotic-mediated switches in the microbiota composition can
result from simple social interactions between antibiotic-tolerant and
antibiotic-sensitive bacterial groups. We build a two-species (e.g. two
functional-groups) model and identify regions of domination by
antibiotic-sensitive or antibiotic-tolerant bacteria, as well as a region of
multistability where domination by either group is possible. Using a new
framework that we derived from statistical physics, we calculate the duration
of each microbiota composition state. This is shown to depend on the balance
between random fluctuations in the bacterial densities and the strength of
microbial interactions. The singular value decomposition of recent metagenomic
data confirms our assumption of grouping microbes as antibiotic-tolerant or
antibiotic-sensitive in response to a single antibiotic. Our methodology can be
extended to multiple bacterial groups and thus it provides an ecological
formalism to help interpret the present surge in microbiome data.Comment: 20 pages, 5 figures accepted for publication in Plos Comp Bio.
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Transglucosidase improves the gut microbiota profile of type 2 diabetes mellitus patients: a randomized double-blind, placebo-controlled study
The <i>N</i>-myristoylome of <i>Trypanosoma cruzi</i>
Protein N-myristoylation is catalysed by N-myristoyltransferase (NMT), an essential and druggable target in Trypanosoma cruzi, the causative agent of Chagas’ disease. Here we have employed whole cell labelling with azidomyristic acid and click chemistry to identify N-myristoylated proteins in different life cycle stages of the parasite. Only minor differences in fluorescent-labelling were observed between the dividing forms (the insect epimastigote and mammalian amastigote stages) and the non-dividing trypomastigote stage. Using a combination of label-free and stable isotope labelling of cells in culture (SILAC) based proteomic strategies in the presence and absence of the NMT inhibitor DDD85646, we identified 56 proteins enriched in at least two out of the three experimental approaches. Of these, 6 were likely to be false positives, with the remaining 50 commencing with amino acids MG at the N-terminus in one or more of the T. cruzi genomes. Most of these are proteins of unknown function (32), with the remainder (18) implicated in a diverse range of critical cellular and metabolic functions such as intracellular transport, cell signalling and protein turnover. In summary, we have established that 0.43–0.46% of the proteome is N-myristoylated in T. cruzi approaching that of other eukaryotic organisms (0.5–1.7%)
Ovine pedomics : the first study of the ovine foot 16S rRNA-based microbiome
We report the first study of the bacterial microbiome of ovine interdigital skin based on 16S rRNA by pyrosequencing and conventional cloning with Sanger-sequencing. Three flocks were selected, one a flock with no signs of footrot or interdigital dermatitis, a second flock with interdigital dermatitis alone and a third flock with both interdigital dermatitis and footrot. The sheep were classified as having either healthy interdigital skin (H), interdigital dermatitis (ID) or virulent footrot (VFR). The ovine interdigital skin bacterial community varied significantly by flock and clinical condition. The diversity and richness of operational taxonomic units was greater in tissue from sheep with ID than H or VFR affected sheep. Actinobacteria, Bacteriodetes, Firmicutes and Proteobacteria were the most abundant phyla comprising 25 genera. Peptostreptococcus, Corynebacterium and Staphylococcus were associated with H, ID and VFR respectively. Sequences of Dichelobacter nodosus, the causal agent of ovine footrot, were not amplified due to mismatches in the 16S rRNA universal forward primer (27F). A specific real time PCR assay was used to demonstrate the presence of D. nodosus which was detected in all samples including the flock with no signs of ID or VFR. Sheep with ID had significantly higher numbers of D. nodosus (104-109 cells/g tissue) than those with H or VFR feet
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