A novel method of combining blood oxygenation and blood flow sensitive magnetic resonance imaging techniques to measure the cerebral blood flow and oxygen metabolism responses to an unknown neural stimulus.

Simultaneous implementation of magnetic resonance imaging methods for Arterial Spin Labeling (ASL) and Blood Oxygenation Level Dependent (BOLD) imaging makes it possible to quantitatively measure the changes in cerebral blood flow (CBF) and cerebral oxygen metabolism (CMRO(2)) that occur in response to neural stimuli. To date, however, the range of neural stimuli amenable to quantitative analysis is limited to those that may be presented in a simple block or event related design such that measurements may be repeated and averaged to improve precision. Here we examined the feasibility of using the relationship between cerebral blood flow and the BOLD signal to improve dynamic estimates of blood flow fluctuations as well as to estimate metabolic-hemodynamic coupling under conditions where a stimulus pattern is unknown. We found that by combining the information contained in simultaneously acquired BOLD and ASL signals through a method we term BOLD Constrained Perfusion (BCP) estimation, we could significantly improve the precision of our estimates of the hemodynamic response to a visual stimulus and, under the conditions of a calibrated BOLD experiment, accurately determine the ratio of the oxygen metabolic response to the hemodynamic response. Importantly we were able to accomplish this without utilizing a priori knowledge of the temporal nature of the neural stimulus, suggesting that BOLD Constrained Perfusion estimation may make it feasible to quantitatively study the cerebral metabolic and hemodynamic responses to more natural stimuli that cannot be easily repeated or averaged

Effects of deleting cannabinoid receptor-2 on mechanical and material properties of cortical and trabecular bone

Acknowledgements We thank Dr J.S. Gregory for assistance with Image J and Mr K. Mackenzie for assistance with Micro-CT analysis. Funding ABK was funded by a University of Aberdeen, Institute of Medical Sciences studentship and the Overseas Research Students Awards Scheme.Peer reviewedPublisher PD

Mechanical and material properties of cortical and trabecular bone from cannabinoid receptor-1-null (Cnr1-/-) mice

Funding ABK was funded by a studentship from the University of Aberdeen, Institute of Medical Sciences, and the Overseas Research Students Awards Scheme Acknowledgments We are grateful to Dr J.S. Gregory for assistance with Image J and Mr K. Mackenzie for assistance with Micro-CT analysis.Peer reviewedPostprin

Absolutely continuous spectrum for a random potential on a tree with strong transverse correlations and large weighted loops

We consider random Schr\"odinger operators on tree graphs and prove absolutely continuous spectrum at small disorder for two models. The first model is the usual binary tree with certain strongly correlated random potentials. These potentials are of interest since for complete correlation they exhibit localization at all disorders. In the second model we change the tree graph by adding all possible edges to the graph inside each sphere, with weights proportional to the number of points in the sphere.Comment: 25 pages, 4 figure

T1ρ-based fibril-reinforced poroviscoelastic constitutive relation of human articular cartilage using inverse finite element technology

BackgroundMapping of T1ρ relaxation time is a quantitative magnetic resonance (MR) method and is frequently used for analyzing microstructural and compositional changes in cartilage tissues. However, there is still a lack of study investigating the link between T1ρ relaxation time and a feasible constitutive relation of cartilage which can be used to model complicated mechanical behaviors of cartilage accurately and properly.MethodsThree-dimensional finite element (FE) models of ten in vitro human tibial cartilage samples were reconstructed such that each element was assigned by material-level parameters, which were determined by a corresponding T1ρ value from MR maps. A T1ρ-based fibril-reinforced poroviscoelastic (FRPE) constitutive relation for human cartilage was developed through an inverse FE optimization technique between the experimental and simulated indentations.ResultsA two-parameter exponential relationship was obtained between the T1ρ and the volume fraction of the hydrated solid matrix in the T1ρ-based FRPE constitutive relation. Compared with the common FRPE constitutive relation (i.e., without T1ρ), the T1ρ-based FRPE constitutive relation indicated similar indentation depth results but revealed some different local changes of the stress distribution in cartilages.ConclusionsOur results suggested that the T1ρ-based FRPE constitutive relation may improve the detection of changes in the heterogeneous, anisotropic, and nonlinear mechanical properties of human cartilage tissues associated with joint pathologies such as osteoarthritis (OA). Incorporating T1ρ relaxation time will provide a more precise assessment of human cartilage based on the individual in vivo MR quantification

Caenorhabditis elegans as a model system to identify therapeutics for alcohol use disorders

Alcohol use disorders (AUDs) cause serious problems in society and few effective treatments are available. Caenorhabditis elegans (C. elegans) is an excellent invertebrate model to study the neurobiological basis of human behavior with a conserved, fully tractable genome, and a short generation time for fast generation of data at a fraction of the cost of other organisms. C. elegans demonstrate movement toward, and concentration-dependent self-exposure to various psychoactive drugs. The discovery of opioid receptors in C. elegans provided the impetus to test the hypothesis that C. elegans may be used as a medications screen to identify new AUD treatments. We tested the effects of naltrexone, an opioid antagonist and effective treatment for AUDs, on EtOH preference in C. elegans. Six-well agar test plates were prepared with EtOH placed in a target zone on one side and water in the opposite target zone of each well. Worms were treated with naltrexone before EtOH preference testing and then placed in the center of each well. Wild-type worms exhibited a concentration-dependent preference for 50, 70 and 95% EtOH. Naltrexone blocked acute EtOH preference, but had no effect on attraction to food or benzaldehyde in wild-type worms. Npr-17 opioid receptor knockout mutants did not display a preference for EtOH. In contrast, npr-17 opioid receptor rescue mutants exhibited significant EtOH preference behavior, which was attenuated by naltrexone. Chronic EtOH exposure induced treatment resistance and compulsive-like behavior. These data indicate that C. elegans can serve as a model system to identify compounds to treat AUDs

The Divine Clockwork: Bohr's correspondence principle and Nelson's stochastic mechanics for the atomic elliptic state

We consider the Bohr correspondence limit of the Schrodinger wave function for an atomic elliptic state. We analyse this limit in the context of Nelson's stochastic mechanics, exposing an underlying deterministic dynamical system in which trajectories converge to Keplerian motion on an ellipse. This solves the long standing problem of obtaining Kepler's laws of planetary motion in a quantum mechanical setting. In this quantum mechanical setting, local mild instabilities occur in the Kelperian orbit for eccentricities greater than 1/\sqrt{2} which do not occur classically.Comment: 42 pages, 18 figures, with typos corrected, updated abstract and updated section 6.

Developing a biodiversity-based indicator for large-scale environmental assessment: a case study of proposed shale gas extraction sites in Britain

1. Environmental impact assessments are important tools for predicting the consequences of development and changes in land use. These assessments generally use a small subset of total biodiversity – typically rare and threatened species and habitats – as indicators of ecological status. However, these indicators do not necessarily reflect changes in the many more widespread (but increasingly threatened) species, which are important for ecosystem functions. In addition, assessment of threatened species through field surveys is time-consuming and expensive and, therefore, only possible at small spatial scales. In contrast, planning changes in land use over large spatial scales (e.g. national infrastructure projects) require assessment and prioritization of biodiversity over large spatial extents. 2. Here, we provide a method for the assessment of biodiversity, which takes account of species diversity across larger spatial scales, based on occurrence records from 5553 species across 11 taxonomic groups. We compare the efficacy of the biodiversity-based indicator we developed against one based on threatened species only and then use it to consider spatial and temporal patterns in ecological status across Great Britain. Finally, we develop a case study to investigate biodiversity status in regions proposed for shale gas extraction in Great Britain. 3. Our results show a strong relationship between the ecological status of areas defined by all biodiversity versus only threatened species, although they also demonstrate that significant exceptions do exist where threatened species do not always accurately indicate the ecological status of wider biodiversity. 4. Spatial and temporal analyses show large variation in ecological status across Great Britain both within the area made available for shale gas licensing and within individual environmental zones. In total, however, 63% of hectads across Britain have suffered a net reduction in our biodiversity-based indicator since 1970. 5. Synthesis and applications. We provide a method and develop a biodiversity-based indicator for the assessment and prioritization of biodiversity at large spatial scales. We highlight the potential applications of this approach for the prioritization of areas that would benefit from conservation and restoration. We also emphasize the danger of insufficient consideration of more widespread species and not just rare and threatened species and habitats as indicators of ecological status when prioritizing large-scale national infrastructure projects. Our method should be a useful tool to complement existing environmental impact assessment methods

Method for RNA extraction and transcriptomic analysis of single fungal spores

Transcriptomic analysis of single cells has been increasingly in demand in recent years, thanks to technological and methodological advances as well as growing recognition of the importance of individuals in biological systems. However, the majority of these studies have been performed in mammalian cells, due to their ease of lysis and high RNA content. No single cell transcriptomic analysis has yet been applied to microbial spores, even though it is known that heterogeneity at the phenotype level exists among individual spores. Transcriptomic analysis of single spores is challenging, in part due to the physically robust nature of the spore wall. This precludes the use of methods commonly used for mammalian cells. Here, we describe a simple method for extraction and amplification of transcripts from single fungal conidia (asexual spores), and its application in single-cell transcriptomics studies. The method can also be used for studies of small numbers of fungal conidia, which may be necessary in the case of limited sample availability, low-abundance transcripts or interest in small subpopulations of conidia.• The method allows detection of transcripts from single conidia of Aspergillus niger• The method allows detection of genomic DNA from single conidia of Aspergillus nige