953 resultados para Surrogate Host
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It has been widely thought that measuring the misalignment angle between the orbital plane of a transiting exoplanet and the spin of its host star was a good discriminator between different migration processes for hot-Jupiters. Specifically, well-aligned hot-Jupiter systems (as measured by the Rossiter-McLaughlin effect) were thought to have formed via migration through interaction with a viscous disc, while misaligned systems were thought to have undergone a more violent dynamical history. These conclusions were based on the assumption that the planet-forming disc was well-aligned with the host star. Recent work by a number of authors has challenged this assumption by proposing mechanisms that act to drive the star-disc interaction out of alignment during the pre-main-sequence phase. We have estimated the stellar rotation axis of a sample of stars which host spatially resolved debris discs. Comparison of our derived stellar rotation axis inclination angles with the geometrically measured debris-disc inclinations shows no evidence for a misalignment between the two.
Ecological dynamics of extinct species in empty habitat networks. 2. The role of host plant dynamics
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This paper explores the relative effects of host plant dynamics and butterfly-related parameters on butterfly persistence. It considers an empty habitat network where a rare butterfly (Cupido minimus) became extinct in 1939 in part of its historical range in north Wales, UK. Surviving populations of the butterfly in southern Britain were visited to assess use of its host plant (Anthyllis vulneraria) in order to calibrate habitat suitability and carrying capacity in the empty network in north Wales. These data were used to deduce that only a portion ( similar to 19%) of the host plant network from north Wales was likely to be highly suitable for oviposition. Nonetheless, roughly 65,460 eggs (3273 adult equivalents) could be expected to be laid in north Wales, were the empty network to be populated at the same levels as observed on comparable plants in surviving populations elsewhere. Simulated metapopulations of C. minimus in the empty network revealed that time to extinction and patch occupancy were significantly influenced by carrying capacity, butterfly mean dispersal distance and environmental stochasticity, although for most reasonable parameter values, the model system persisted. Simulation outputs differed greatly when host plant dynamics was incorporated into the modelled butterfly dynamics. Cupido minimus usually went extinct when host plant were at low densities. In these simulations host plant dynamics appeared to be the most important determinant of the butterfly's regional extirpation. Modelling the outcome of a reintroduction programme to C. minimus variation at high quality locations, revealed that 65% of systems survived at least 100 years. Given the current amount of resources of the north Wales landscape, the persistence of C. minimus under a realistic reintroduction programme has a good chance of being successful, if carried out in conjunction with a host plant management programme.
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BACKGROUND: The liver fluke Fasciola hepatica is a major pathogen of livestock worldwide, causing huge economic losses to agriculture, as well as 2.4 million human infections annually.
RESULTS: Here we provide a draft genome for F. hepatica, which we find to be among the largest known pathogen genomes at 1.3 Gb. This size cannot be explained by genome duplication or expansion of a single repeat element, and remains a paradox given the burden it may impose on egg production necessary to transmit infection. Despite the potential for inbreeding by facultative self-fertilisation, substantial levels of polymorphism were found, which highlights the evolutionary potential for rapid adaptation to changes in host availability, climate change or to drug or vaccine interventions. Non-synonymous polymorphisms were elevated in genes shared with parasitic taxa, which may be particularly relevant for the ability of the parasite to adapt to a broad range of definitive mammalian and intermediate molluscan hosts. Large-scale transcriptional changes, particularly within expanded protease and tubulin families, were found as the parasite migrated from the gut, across the peritoneum and through the liver to mature in the bile ducts. We identify novel members of anti-oxidant and detoxification pathways and defined their differential expression through infection, which may explain the stage-specific efficacy of different anthelmintic drugs.
CONCLUSIONS: The genome analysis described here provides new insights into the evolution of this important pathogen, its adaptation to the host environment and external selection pressures. This analysis also provides a platform for research into novel drugs and vaccines.
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Nontypable Haemophilus influenzae (NTHi) is a major cause of opportunistic respiratory tract disease, and initiates infection by colonizing the nasopharynx. Bacterial surface proteins play determining roles in the NTHi-airways interplay, but their specific and relative contribution to colonization and infection of the respiratory tract has not been addressed comprehensively. In this study, we focused on the ompP5 and hap genes, present in all H. influenzae genome sequenced isolates, and encoding the P5 and Hap surface proteins, respectively. We employed isogenic single and double mutants of the ompP5 and hap genes generated in the pathogenic strain NTHi375 to evaluate P5 and Hap contribution to biofilm growth under continuous flow, to NTHi adhesion, and invasion/phagocytosis on nasal, pharyngeal, bronchial, alveolar cultured epithelial cells and alveolar macrophages, and to NTHi murine pulmonary infection. We show that P5 is not required for bacterial biofilm growth, but it is involved in NTHi interplay with respiratory cells and in mouse lung infection. Mechanistically, P5NTHi375 is not a ligand for CEACAM1 or α5 integrin receptors. Hap involvement in NTHi375-host interaction was shown to be limited, despite promoting bacterial cell adhesion when expressed in H. influenzae RdKW20. We also show that Hap does not contribute to bacterial biofilm growth, and that its absence partially restores the deficiency in lung infection observed for the ΔompP5 mutant. Altogether, this work frames the relative importance of the P5 and Hap surface proteins in NTHi virulence.
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We describe a protocol for the generation and validation of bacteria microarrays and their application to the study of specific features of the pathogen's surface and interactions with host receptors. Bacteria were directly printed on nitrocellulose-coated glass slides, using either manual or robotic arrayers, and printing quality, immobilization efficiency and stability of the arrays were rigorously controlled by incorporating a fluorescent dye into the bacteria. A panel of wild type and mutant strains of the human pathogen Klebsiella pneumoniae, responsible for nosocomial and community-acquired infections, was selected as model bacteria, and SYTO-13 was used as dye. Fluorescence signals of the printed bacteria were found to exhibit a linear concentration-dependence in the range of 1 x 10(8) to 1 x 10(9) bacteria per ml. Similar results were obtained with Pseudomonas aeruginosa and Acinetobacter baumannii, two other human pathogens. Successful validation of the quality and applicability of the established microarrays was accomplished by testing the capacity of the bacteria array to detect recognition by anti-Klebsiella antibodies and by the complement subcomponent C1q, which binds K. pneumoniae in an antibody-independent manner. The biotin/AlexaFluor-647-streptavidin system was used for monitoring binding, yielding strain-and dose-dependent signals, distinctive for each protein. Furthermore, the potential of the bacteria microarray for investigating specific features, e.g. glycosylation patterns, of the cell surface was confirmed by examining the binding behaviour of a panel of plant lectins with diverse carbohydrate-binding specificities. This and other possible applications of the newly developed arrays, as e.g. screening/evaluation of compounds to identify inhibitors of host-pathogen interactions, make bacteria microarrays a useful and sensitive tool for both basic and applied research in microbiology, biomedicine and biotechnology.
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PURPOSE. Raman spectroscopy is an effective probe of advanced glycation end products (AGEs) in Bruch's membrane. However, because it is the outermost layer of the retina, this extracellular matrix is difficult to analyze in vivo with current technology. The sclera shares many compositional characteristics with Bruch's membrane, but it is much easier to access for in vivo Raman analysis. This study investigated whether sclera could act as a surrogate tissue for Raman-based investigation of pathogenic AGEs in Bruch's membrane.
METHODS. Human sclera and Bruch's membrane were dissected from postmortem eyes (n = 67) across a wide age range (33-92 years) and were probed by Raman spectroscopy. The biochemical composition, AGEs, and their age-related trends were determined from data reduction of the Raman spectra and compared for the two tissues.
RESULTS. Raman microscopy demonstrated that Bruch's membrane and sclera are composed of a similar range of biomolecules but with distinct relative quantities, such as in the heme/collagen and the elastin/collagen ratios. Both tissues accumulated AGEs, and these correlated with chronological age (R(2) = 0.824 and R(2) = 0.717 for sclera and Bruch's membrane, respectively). The sclera accumulated AGE adducts at a lower rate than Bruch's membrane, and the models of overall age-related changes exhibited a lower rate (one-fourth that of Bruch's membrane) but a significant increase with age (P <0.05).
CONCLUSIONS. The results suggest that the sclera is a viable surrogate marker for estimating AGE accumulation in Bruch's membrane and for reliably predicting chronological age. These findings also suggest that sclera could be a useful target tissue for future patient-based, Raman spectroscopy studies. (Invest Ophthalmol Vis Sci 2011;52:1593-1598) DOI:10.1167/iovs.10-6554
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In COPD inflammation driven by exposure to tobacco smoke results in impaired innate immunity in the airway and ultimately to lung injury and remodeling. To understand the biological processes involved in host interactions with cigarette derived toxins submerged epithelial cell culture is widely accepted as a model for primary human airway epithelial cell culture research. Primary nasal and bronchial epithelial cells can also be cultured in air-liquid interface (ALI) models. ALI and submerged culture models have their individual merits, and the decision to use either technique should primarily be determined primarily by the research hypothesis.
Cigarette smoke has gaseous and particulate matter, the latter constituent primarily represented in cigarette smoke extract (CSE). Although not ideal in order to facilitate our understanding of the responses of epithelial cells to cigarette smoke, CSE still has scientific merit in airway cell biology research. Using this model, it has been possible to demonstrate differences in levels of tight junction disruption after CSE exposure along with varied vulnerability to the toxic effects of CSE in cell cultures derived from COPD and control study groups.
Primary nasal epithelial cells (PNECs) have been used as an alternative to bronchial epithelial cells (PBECs). However, at least in subjects with COPD, PNECs cannot consistently substitute for PBECs. Although airway epithelial cells from patients with COPD exhibit a constitutional pro-inflammatory phenotype, these cells have a diminished inflammatory response to CSE exposure. COPD epithelial cells have an increased susceptibility to undergo apoptosis, and have reduced levels of Toll-like receptor-4 expression after CSE exposure, both of which may account for the reduced inflammatory response observed in this group.
The use of CSE in both submerged and ALI epithelial cultures has extended our understanding of the cellular mechanisms that are important in COPD, and helped to unravel important pathways which may be of relevance in its pathogenesis.
Hydrogen-Poor Superluminous Supernovae and Long-Duration Gamma-Ray Bursts Have Similar Host Galaxies
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We present optical spectroscopy and optical/near-IR photometry of 31 host galaxies of hydrogen-poor superluminous supernovae (SLSNe), including 15 events from the Pan-STARRS1 Medium Deep Survey. Our sample spans the redshift range 0.1 ≲ z ≲ 1.6, and is the first comprehensive host galaxy study of this specific subclass of cosmic explosions. Combining the multi-band photometry and emission-line measurements, we determine the luminosities, stellar masses, star formation rates, and metallicities. We find that, as a whole, the hosts of SLSNe are a low-luminosity (〈MB 〉 ≈ -17.3 mag), low stellar mass (〈M〉 ≈ 2 × 108 M⊙) population, with a high median specific star formation rate (〈sSFR〉 ≈ 2 Gyr-1). The median metallicity of our spectroscopic sample is low, 12 + log (O/H) ≈ 8.35 ≈ 0.45 Z⊙, although at least one host galaxy has solar metallicity. The host galaxies of H-poor SLSNe are statistically distinct from the hosts of GOODS core-collapse SNe (which cover a similar redshift range), but resemble the host galaxies of long-duration gamma-ray bursts (LGRBs) in terms of stellar mass, SFR, sSFR, and metallicity. This result indicates that the environmental causes leading to massive stars forming either SLSNe or LGRBs are similar, and in particular that SLSNe are more effectively formed in low metallicity environments. We speculate that the key ingredient is large core angular momentum, leading to a rapidly spinning magnetar in SLSNe and an accreting black hole in LGRBs.