Amyloid fibril length distribution quantified by atomic force microscopy single-particle image analysis

Amyloid fibrils are proteinaceous nano-scale linear aggregates. They are of key interest not only because of their association with numerous disorders, such as type II diabetes mellitus, Alzheimer's and Parkinson's diseases, but also because of their potential to become engineered high-performance nano-materials. Methods to characterise the length distribution of nano-scale linear aggregates such as amyloid fibrils are of paramount importance both in understanding the biological impact of these aggregates and in controlling their mechanical properties as potential nano-materials. Here, we present a new quantitative approach to the determination of the length distribution of amyloid fibrils using tapping-mode atomic force microscopy. The method described employs single-particle image analysis corrected for the length-dependent bias that is a common problem associated with surface-based imaging techniques. Applying this method, we provide a detailed characterisation of the length distribution of samples containing long-straight fibrils formed in vitro from β2-microglobulin. The results suggest that the Weibull distribution is a suitable model in describing fibril length distributions, and reveal that fibril fragmentation is an important process even under unagitated conditions. These results demonstrate the significance of quantitative length distribution measurements in providing important new information regarding amyloid assembly

Prescribing practices of primary-care veterinary practitioners in dogs diagnosed with bacterial pyoderma

Concern has been raised regarding the potential contributions of veterinary antimicrobial use to increasing levels of resistance in bacteria critically important to human health. Canine pyoderma is a frequent, often recurrent diagnosis in pet dogs, usually attributable to secondary bacterial infection of the skin. Lesions can range in severity based on the location, total area and depth of tissue affected and antimicrobial therapy is recommended for resolution. This study aimed to describe patient signalment, disease characteristics and treatment prescribed in a large number of UK, primary-care canine pyoderma cases and to estimate pyoderma prevalence in the UK vet-visiting canine population

Systematics of collective correlation energies from self-consistent mean-field calculations

The collective ground-state correlations stemming from low-lying quadrupole excitations are computed microscopically. To that end, the self-consistent mean-field model is employed on the basis of the Skyrme-Hartre-Fock (SHF) functional augmented by BCS pairing. The microscopic-macroscopic mapping is achieved by quadrupole-constrained mean-field calculations which are processed further in the generator-coordinate method (GCM) at the level of the Gaussian overlap approximation (GOA). We study the correlation effects on energy, charge radii, and surface thickness for a great variety of semi-magic nuclei. A key issue is to work out the influence of variations of the SHF functional. We find that collective ground-state correlations (GSC) are robust under change of nuclear bulk properties (e.g., effective mass, symmetry energy) or of spin-orbit coupling. Some dependence on the pairing strength is observed. This, however, does not change the general conclusion that collective GSC obey a general pattern and that their magnitudes are rather independent of the actual SHF parameters.Comment: 13 pages, 13 figure

Nuclear starburst-driven evolution of the central region in NGC 6764

We study the CO and the radiocontinuum emission in an active galaxy to analyze the interplay between the central activity and the molecular gas. We present new high-resolution observations of the CO(1-0) and CO(2-1) emission lines, and 3.5 cm and 20 cm radio continuum emission in the central region of the LINER/starburst galaxy NGC 6764. The galaxy has an outflow morphology in radio continuum, spatially coincident with the CO and H$\alpha$ emission, and centered slightly off the radio continuum peak at the LINER nucleus. The total molecular gas mass in the center is about 7x10^8 \msun, using a CO luminosity to total molecular gas conversion factor that is three times lower than the standard one. CO(1-0) emission is found near the boundaries of the radio continuum emission cone. The outflow has a projected expansion velocity of 25 km/s relative to the systemic velocity of NGC6764. About 4x 10^6 \msun of molecular gas is detected in the outflow. The approximate location (~1 kpc) of the dynamical inner Lindblad resonance has been derived from the rotation curve. The peak of the CO emission is slightly (< 200 pc) offset from the peak of the radio continuum. The molecular gas has most likely been ejected by the stellar winds from the recent starburst, but the CO line ratios show indication of an interaction with the AGN. The energy released by the nuclear starburst is sufficient to explain the observed outflow, even if the data cannot exclude the AGN from being the major energy source. Comparison of the outflow with hydrodynamical simulations suggests that the nuclear starburst is 3--7 Myr old and the bubble-like outflow is still confined and not freely expanding.Comment: Accepted for publication in A&

Population genomics of a predatory mammal reveals patterns of decline and impacts of exposure to toxic toads

Mammal declines across northern Australia are one of the major biodiversity loss events occurring globally. There has been no regional assessment of the implications of these species declines for genomic diversity. To address this, we conducted a species-wide assessment of genomic diversity in the northern quoll (Dasyurus hallucatus), an Endangered marsupial carnivore. We used next generation sequencing methods to genotype 10,191 single nucleotide polymorphisms (SNPs) in 352 individuals from across a 3220-km length of the continent, investigating patterns of population genomic structure and diversity, and identifying loci showing signals of putative selection. We found strong heterogeneity in the distribution of genomic diversity across the continent, characterized by (i) biogeographical barriers driving hierarchical population structure through long-term isolation, and (ii) severe reductions in diversity resulting from population declines, exacerbated by the spread of introduced toxic cane toads (Rhinella marina). These results warn of a large ongoing loss of genomic diversity and associated adaptive capacity as mammals decline across northern Australia. Encouragingly, populations of the northern quoll established on toad-free islands by translocations appear to have maintained most of the initial genomic diversity after 16 years. By mapping patterns of genomic diversity within and among populations, and investigating these patterns in the context of population declines, we can provide conservation managers with data critical to informed decision-making. This includes the identification of populations that are candidates for genetic management, the importance of remnant island and insurance/translocated populations for the conservation of genetic diversity, and the characterization of putative evolutionarily significant units

Antibody to the dendritic cell surface activation antigen CD83 prevents acute graft-versus-host disease

Allogeneic (allo) hematopoietic stem cell transplantation is an effective therapy for hematological malignancies but it is limited by acute graft-versus-host disease (GVHD). Dendritic cells (DC) play a major role in the allo T cell stimulation causing GVHD. Current immunosuppressive measures to control GVHD target T cells but compromise posttransplant immunity in the patient, particularly to cytomegalovirus (CMV) and residual malignant cells. We showed that treatment of allo mixed lymphocyte cultures with activated human DC-depleting CD83 antibody suppressed alloproliferation but preserved T cell numbers, including those specific for CMV. We also tested CD83 antibody in the human T cell–dependent peripheral blood mononuclear cell transplanted SCID (hu-SCID) mouse model of GVHD. We showed that this model requires human DC and that CD83 antibody treatment prevented GVHD but, unlike conventional immunosuppressants, did not prevent engraftment of human T cells, including cytotoxic T lymphocytes (CTL) responsive to viruses and malignant cells. Immunization of CD83 antibody-treated hu-SCID mice with irradiated human leukemic cell lines induced allo antileukemic CTL effectors in vivo that lysed 51Cr-labeled leukemic target cells in vitro without further stimulation. Antibodies that target activated DC are a promising new therapeutic approach to the control of GVHD

Mrk 609: resolving the circum-nuclear structure with near-infrared integral field spectroscopy

We present first results of near infrared J and H+K ESO-SINFONI integral field spectroscopy of the composite starburst/Seyfert 1.8 galaxy Mrk 609. The data were taken during the science verification period of SINFONI. We aim to investigate the morphology and excitation conditions within the central 2 kpc. Additional Nobeyama 45 m CO(1-0) data are presented, which we used to estimate the molecular gas mass. The source was selected from a sample of adaptive optics suitable, SDSS/ROSAT based, X-ray bright AGN with redshifts of 0.03 < z < 1. This sample allows for a detailed study of the NIR properties of the nuclear and host environments with high spectral and spatial resolution. Our NIR data reveal a complex emission-line morphology, possibly associated with a nuclear bar seen in the reconstructed continuum images. The detections of [SiVI] and a broad Pa alpha component are clear indicators for the presence of an accreting super-massive black hole at the center of Mrk 609. In agreement with previous observations we find that the circum-nuclear emission is not significantly extincted. The analysis of the high angular resolution rotational-vibrational molecular hydrogen and forbidden [FeII] emission reveals a LINER character of the nucleus. The large H_2 gas mass deduced from the CO(1-0) observation provides the fuel needed to feed the starburst and Seyfert activity in Mrk 609. High angular resolution imaging spectroscopy provides an ideal tool to resolve the nuclear and starburst contribution in active galaxies. We show that Mrk 609 exhibits LINER features, that appear to be hidden in larger aperture visible/NIR spectra.Comment: published by A&A, 19 pages, 16 figures, version with high resolution figures is available via http://www.ph1.uni-koeln.de/~zuther/mrk609.pd

Spirit, mind and body: the archaeology of monastic healing

Archaeology and material culture are used in this chapter to consider how monastic experience responded to illness, ageing and disability. The approach taken is influenced by the material study of religion, which interrogates how bodies and things engage to construct the sensory experience of religion, and by practice-based approaches in archaeology, which examine the active role of space and material culture in shaping religious agency and embodiment. The archaeology of monastic healing focuses on the full spectrum of healing technologies, from managing the body in order to prevent illness, through to the treatment of the sick and preparation of the corpse for burial

Capturing the complexity of first opinion small animal consultations using direct observation

Various different methods are currently being used to capture data from small animal consultations. The aim of this study was to develop a tool to record detailed data from consultations by direct observation. A second aim was to investigate the complexity of the consultation by examining the number of problems discussed per patient. A data collection tool was developed and used during direct observation of small animal consultations in eight practices. Data were recorded on consultation type, patient signalment and number of problems discussed. During 16?weeks of data collection, 1901 patients were presented. Up to eight problems were discussed for some patients; more problems were discussed during preventive medicine consultations than during first consultations (