Cardiac 123I-MIBG normal uptake values are population-specific: Results from a cohort of controls over 60 years of age.

PURPOSE: Cardiac 123I-MIBG image interpretation is affected by population differences and technical factors. We recruited older adults without cognitive decline and compared their cardiac MIBG uptake with results from the literature. METHODS: Phantom calibration confirmed that cardiac uptake results from Japan could be applied to our center. We recruited 31 controls, 17 individuals with dementia with Lewy bodies (DLB) and 15 with Alzheimer's disease (AD). Images were acquired 20 minutes and four hours after injection using Siemens cameras with medium-energy low-penetration (MELP) collimators. Local normal heart-to-mediastinum (HMR) ratios were compared to Japanese results. RESULTS: Siemens gamma cameras with MELP collimators should give HMRs very close to the calibrated values used in Japan. However, our cut-offs with controls were lower at 2.07 for early and 1.86 for delayed images. Applying our lower cut-off to the dementia patients may increase the specificity of cardiac MIBG imaging for DLB diagnosis in a UK population without reducing sensitivity. CONCLUSIONS: Our local HMR cut-off values are lower than in Japan, higher than in a large US study but similar to those found in another UK center. UK centers using other cameras and collimators may need to use different cut-offs to apply our results.

The allocation of resources for animal health.

Economics is too important to be left to the experts. This paper is therefore mainly for animal health policy-makers who are not economists but want a better appreciation of how economics can contribute to resource allocation decisions. First, the methodology of economic analysis is outlined with the objective of dispelling criticisms of its simplifying assumption of rationality. Then, unusual in economics but more familiar to biological and veterinary scientists, the technical aspects of transforming resources into products are discussed. Economics' unique contribution is to establish criteria enabling society to obtain maximum value from the production and distribution of goods and services (products) from scarce resources. Animal disease reduces the efficiency of this process. Value is intangible, but people reveal how much they value (i.e. feel a want or need for) products by what they actually consume, in quality and quantity. Animal products, and so implicitly animals themselves, are an example. The strength of people's preferences is reflected both in the prices they pay for market goods and services, and by their political votes where markets do not exist. Importantly, there is a difference between financial value (what the consumer pays for a good or service) and economic value (the maximum amount of money they would be prepared to pay for it). Allocating resources for animal health creates both costs and benefits, financial and economic. Moreover, costs and benefits are both private and social because of externalities, a major consideration in infectious diseases. Where production decisions with animal health implications are made exclusively for private benefit, government has a role in providing incentives for animal sectors to act in ways that result in socially efficient outcomes.

L'économie est trop importante pour être laissée entre les seules mains des experts. C'est pourquoi cet article s'adresse principalement aux responsables des politiques de santé animale qui ne sont pas économistes mais qui souhaitent néanmoins évaluer l'apport de l'économie aux décisions relatives à l'affectation des ressources. L'auteur commence par rappeler la méthodologie de l'analyse économique afin de réfuter les critiques sur le caractère supposément simplificateur du postulat de rationalité. Il examine ensuite les aspects techniques liés à la transformation de ressources en produits, concept familier pour les biologistes et les chercheurs en médecine vétérinaire mais moins courant chez les économistes. La véritable contribution de l'économie consiste à déterminer les critères qui permettent à une société de valoriser le plus possible la production et la distribution de biens et de services (produits) à partir de ressources limitées. Les maladies animales compromettent l'efficacité de ce processus. La valeur est intangible par nature mais les individus expriment la valeur qu'ils attachent à un produit (c'est-à-dire le désir ou le besoin qu'ils ont de ce produit) à travers leur consommation, au plan qualitatif et quantitatif. Les produits d'origine animale et partant, implicitement, les animaux eux-mêmes illustrent parfaitement ce phénomène. L'influence des préférences des individus se manifeste par le prix qu'ils sont disposés à payer pour les biens et les services pour lesquels il existe un marché, et par le vote politique pour tout ce qui est extérieur au marché. La distinction entre la valeur financière (prix payé par le consommateur pour un bien ou un service) et la valeur économique (le montant le plus élevé qu'il serait disposé à payer pour ce même bien ou service) est un aspect important. Les ressources allouées à la santé animale génèrent à la fois des coûts et des bénéfices, financiers et économiques. De plus, du fait des externalités, ces coûts et bénéfices sont de nature tant privée que sociale, facteur essentiel à prendre en compte pour les maladies infectieuses. Dans les situations où les décisions en matière de production animale obéissent aux seuls impératifs du profit privé, sans tenir compte des répercussions sur la santé animale, les gouvernements ont un rôle incitatif à jouer pour que le secteur de l'élevage infléchisse son action en vue de résultats efficients pour la société.

La economía es demasiado importante para abandonarla a los expertos. Por ello este artículo va dirigido sobre todo a los planificadores de políticas zoosanitarias que no son economistas pero desean tener una idea más clara de cómo puede ayudar la economía a tomar decisiones sobre la asignación de los recursos. Ante todo el autor presenta sucintamente la metodología del análisis económico, a fin de refutar las críticas que achacan una excesiva simplificación al postulado de la racionalidad. Después aborda algo inusual en economía, pero más familiar para biólogos y veterinarios: los aspectos técnicos de la transformación de los recursos en productos. La singular aportación de la economía estriba en definir criterios que permiten a la sociedad extraer el máximo «valor¼ de la producción y distribución de bienes y servicios (productos) a partir de recursos escasos. Las enfermedades animales restan eficiencia a este proceso. El «valor¼ es algo intangible, pero las personas revelan cuánto valoran un producto (es decir, hasta qué punto sienten que lo desean o lo necesitan) por lo que en la práctica consumen, tanto cualitativa como cuantitativamente. Los productos animales, y por ende, implícitamente, los propios animales, son ejemplo de ello. La fuerza de las preferencias de la gente se manifiesta en el precio que paga por bienes y servicios, cuando hay un mercado para ellos, o por su voto político, cuando no lo hay. Es importante señalar que hay una diferencia entre el valor monetario (lo que pagan los consumidores por un bien o servicio) y el valor económico (la cantidad máxima de dinero que estarían dispuestos a pagar por él). La forma en que se distribuyen los recursos en sanidad animal genera costos y beneficios, tanto monetarios como económicos. Además, esos costos y beneficios son tanto privados como sociales debido a la existencia de externalidades, factor este de gran importancia en el caso de las enfermedades infecciosas. Allí donde las decisiones de producción que tienen consecuencias zoosanitarias se rijan únicamente por el criterio del beneficio privado, las administraciones públicas deben cumplir la función de ofrecer incentivos a los sectores ligados a la producción animal para que su proceder se traduzca en resultados socialmente eficientes.

The sensory shark: high-quality morphological, genomic and transcriptomic data for the small-spotted catshark Scyliorhinus canicula reveal the molecular bases of sensory organ evolution in jawed vertebrates.

Cartilaginous fishes (chimaeras and elasmobranchs -sharks, skates and rays) hold a key phylogenetic position to explore the origin and diversifications of jawed vertebrates. Here, we report and integrate reference genomic, transcriptomic and morphological data in the small-spotted catshark Scyliorhinus canicula to shed light on the evolution of sensory organs. We first characterise general aspects of the catshark genome, confirming the high conservation of genome organisation across cartilaginous fishes, and investigate population genomic signatures. Taking advantage of a dense sampling of transcriptomic data, we also identify gene signatures for all major organs, including chondrichthyan specializations, and evaluate expression diversifications between paralogs within major gene families involved in sensory functions. Finally, we combine these data with 3D synchrotron imaging and in situ gene expression analyses to explore chondrichthyan-specific traits and more general evolutionary trends of sensory systems. This approach brings to light, among others, novel markers of the ampullae of Lorenzini electro-sensory cells, a duplication hotspot for crystallin genes conserved in jawed vertebrates, and a new metazoan clade of the Transient-receptor potential (TRP) family. These resources and results, obtained in an experimentally tractable chondrichthyan model, open new avenues to integrate multiomics analyses for the study of elasmobranchs and jawed vertebrates.

Economic principles for resource allocation decisions at national level to mitigate the effects of disease in farm animal populations.

This paper originated in a project to develop a practical, generic tool for the economic evaluation of surveillance for farm animal diseases at national level by a state veterinary service. Fundamental to that process is integration of epidemiological and economic perspectives. Using a generalized example of epidemic disease, we show that an epidemic curve maps into its economic equivalent, a disease mitigation function, that traces the relationship between value losses avoided and mitigation resources expended. Crucially, elementary economic principles show that mitigation, defined as loss reduction achieved by surveillance and intervention, must be explicitly conceptualized as a three-variable process, and the relative contributions of surveillance and intervention resources investigated with regard to the substitution possibilities between them. Modelling the resultant mitigation surfaces for different diseases should become a standard approach to animal health policy analysis for economic efficiency, a contribution to the evolving agenda for animal health economics research.

Identification of a role for a mouse sperm surface aldo-keto reductase (AKR1B7) and its human analogue in the detoxification of the reactive aldehyde, acrolein.

Mouse vas deferens protein (AKR1B7), a member of the aldo-keto reductase family, was purified to homogeneity. Antibodies raised to AKR1B7 revealed an aldo-keto reductase on the human sperm surface, while confocal microscopy experiments demonstrated that this enzyme covered the entire human sperm surface and was concentrated on the mid-piece. Further functional characterisation of a recombinant form of AKR1B7 showed that the likely role of AKR1B7 is the reduction of the reactive aldehyde, acrolein, a by-product of spermine catabolism in the reproductive tract. A similar acrolein detoxification activity was displayed by human sperm membrane extracts but was not present in seminal plasma. These results indicate that human sperm possess an aldo-keto reductase on their membrane surface and are thus enzymatically protected against reactive aldehyde species both in the male and female reproductive tract.

Genetics coupled to quantitative intact proteomics links heritable aphid and endosymbiont protein expression to circulative polerovirus transmission.

Yellow dwarf viruses in the family Luteoviridae, which are the causal agents of yellow dwarf disease in cereal crops, are each transmitted most efficiently by different species of aphids in a circulative manner that requires the virus to interact with a multitude of aphid proteins. Aphid proteins differentially expressed in F2 Schizaphis graminum genotypes segregating for the ability to transmit Cereal yellow dwarf virus-RPV (CYDV-RPV) were identified using two-dimensional difference gel electrophoresis (DIGE) coupled to either matrix-assisted laser desorption ionization-tandem mass spectrometry or online nanoscale liquid chromatography coupled to electrospray tandem mass spectrometry. A total of 50 protein spots, containing aphid proteins and proteins from the aphid's obligate and maternally inherited bacterial endosymbiont, Buchnera, were identified as differentially expressed between transmission-competent and refractive aphids. Surprisingly, in virus transmission-competent F2 genotypes, the isoelectric points of the Buchnera proteins did not match those in the maternal Buchnera proteome as expected, but instead they aligned with the Buchnera proteome of the transmission-competent paternal parent. Among the aphid proteins identified, many were involved in energy metabolism, membrane trafficking, lipid signaling, and the cytoskeleton. At least eight aphid proteins were expressed as heritable, isoelectric point isoform pairs, one derived from each parental lineage. In the F2 genotypes, the expression of aphid protein isoforms derived from the competent parental lineage aligned with the virus transmission phenotype with high precision. Thus, these isoforms are candidate biomarkers for CYDV-RPV transmission in S. graminum. Our combined genetic and DIGE approach also made it possible to predict where several of the proteins may be expressed in refractive aphids with different barriers to transmission. Twelve proteins were predicted to act in the hindgut of the aphid, while six proteins were predicted to be associated with the accessory salivary glands or hemolymph. Knowledge of the proteins that regulate virus transmission and their predicted locations will aid in understanding the biochemical mechanisms regulating circulative virus transmission in aphids, as well as in identifying new targets to block transmission.

The DNA sequence and biological annotation of human chromosome 1.

The reference sequence for each human chromosome provides the framework for understanding genome function, variation and evolution. Here we report the finished sequence and biological annotation of human chromosome 1. Chromosome 1 is gene-dense, with 3,141 genes and 991 pseudogenes, and many coding sequences overlap. Rearrangements and mutations of chromosome 1 are prevalent in cancer and many other diseases. Patterns of sequence variation reveal signals of recent selection in specific genes that may contribute to human fitness, and also in regions where no function is evident. Fine-scale recombination occurs in hotspots of varying intensity along the sequence, and is enriched near genes. These and other studies of human biology and disease encoded within chromosome 1 are made possible with the highly accurate annotated sequence, as part of the completed set of chromosome sequences that comprise the reference human genome.

The effects of low dose parathyroid hormone on lumbar vertebrae in a rat model for chronic alcohol abuse.

UNLABELLED: This study evaluated the hypothesis that increased bone marrow adipogenesis is coupled to decreased bone formation in rats consuming alcohol. Parathyroid hormone (PTH) increased bone formation but had no effect on marrow adiposity. We conclude that increased adiposity does not prevent the bone anabolic response to PTH. INTRODUCTION: Alcoholism results in decreased bone formation and increased bone marrow adiposity. The present study tested the hypothesis that these reciprocal changes are coupled by evaluating the effect of intermittent PTH on bone formation and bone marrow adiposity in a rat model for chronic alcohol abuse. METHODS: Three-month-old male Sprague Dawley rats (n = 10-11/group) were fed the Lieber-DeCarli liquid diet with 35% of the calories derived from ethanol. Control rats were pair-fed an isocaloric alcohol-free diet. The rats were administered low dose PTH (1 µg/kg/day sc, 5 d/week) or vehicle for 6 weeks. Cancellous bone architecture in lumbar vertebrae was evaluated by micro-computed tomography followed by histomorphometric assessment of bone formation and marrow adiposity. RESULTS: Alcohol increased bone marrow adiposity but reduced bone formation. The latter was due to decreases in mineralizing perimeter/bone perimeter, a surrogate measure of osteoblast number, and mineral apposition rate, a measure of osteoblast activity. PTH increased bone formation by increasing mineralizing perimeter/bone perimeter. In contrast, PTH had no effect on mineral apposition rate or bone marrow adiposity. Interactions between alcohol consumption and PTH treatment were not detected for any endpoints evaluated. CONCLUSIONS: PTH treatment blunted the decrease in mineralizing perimeter/bone perimeter in alcohol-fed rats but was ineffective in preventing the increase in bone marrow adiposity. These findings suggest that the alcohol-induced increase in adipocytes is not directly responsible for the accompanying reduction in bone formation.

Evaluation of enrichment media for improved PCR-based detection of V. cholerae and V. vulnificus from estuarine water and plankton.

AIMS: Pathogenic Vibrio spp., including V. cholerae and V. vulnificus, are commonly found along the estuaries of the south-east United States; however, it is often difficult to recover these species directly from environmental samples. Pre-enrichment assays are commonly used to improve the detection of pathogenic vibrios from environmental sources. Here, we evaluated a novel enrichment procedure using freshly collected and autoclaved natural estuarine water amended with 1% peptone (designated as estuarine peptone water, EPW) and compared it to traditional alkaline peptone water (APW) for detection by PCR of V. cholerae and V. vulnificus. METHODS AND RESULTS: Of the 50 samples collected in total, V. cholerae DNA was detected in APW 10% of the time and in EPW 40% of the time. Likewise, the cholera toxin gene (ctxA) was detected in 4 vs 18% of the samples using APW and EPW, respectively. Conversely, APW showed improved recovery for V. vulnificus relative to EPW with respective detection frequencies of 46 and 20%. Results showed similar patterns across different sample types (water and plankton). CONCLUSIONS: While enrichment in traditional APW was adequate for the recovery of Vibrio vulnificius, use of sterile estuarine water amended with peptone significantly improved the detection of V. cholerae and the virulence gene ctxA from estuarine sources.

Ensembl 2009.

The Ensembl project (http://www.ensembl.org) is a comprehensive genome information system featuring an integrated set of genome annotation, databases, and other information for chordate, selected model organism and disease vector genomes. As of release 51 (November 2008), Ensembl fully supports 45 species, and three additional species have preliminary support. New species in the past year include orangutan and six additional low coverage mammalian genomes. Major additions and improvements to Ensembl since our previous report include a major redesign of our website; generation of multiple genome alignments and ancestral sequences using the new Enredo-Pecan-Ortheus pipeline and development of our software infrastructure, particularly to support the Ensembl Genomes project (http://www.ensemblgenomes.org/).

DNA sequence and analysis of human chromosome 9.

Chromosome 9 is highly structurally polymorphic. It contains the largest autosomal block of heterochromatin, which is heteromorphic in 6-8% of humans, whereas pericentric inversions occur in more than 1% of the population. The finished euchromatic sequence of chromosome 9 comprises 109,044,351 base pairs and represents >99.6% of the region. Analysis of the sequence reveals many intra- and interchromosomal duplications, including segmental duplications adjacent to both the centromere and the large heterochromatic block. We have annotated 1,149 genes, including genes implicated in male-to-female sex reversal, cancer and neurodegenerative disease, and 426 pseudogenes. The chromosome contains the largest interferon gene cluster in the human genome. There is also a region of exceptionally high gene and G + C content including genes paralogous to those in the major histocompatibility complex. We have also detected recently duplicated genes that exhibit different rates of sequence divergence, presumably reflecting natural selection.

The DNA sequence and comparative analysis of human chromosome 10.

The finished sequence of human chromosome 10 comprises a total of 131,666,441 base pairs. It represents 99.4% of the euchromatic DNA and includes one megabase of heterochromatic sequence within the pericentromeric region of the short and long arm of the chromosome. Sequence annotation revealed 1,357 genes, of which 816 are protein coding, and 430 are pseudogenes. We observed widespread occurrence of overlapping coding genes (either strand) and identified 67 antisense transcripts. Our analysis suggests that both inter- and intrachromosomal segmental duplications have impacted on the gene count on chromosome 10. Multispecies comparative analysis indicated that we can readily annotate the protein-coding genes with current resources. We estimate that over 95% of all coding exons were identified in this study. Assessment of single base changes between the human chromosome 10 and chimpanzee sequence revealed nonsense mutations in only 21 coding genes with respect to the human sequence.

The DNA sequence and analysis of human chromosome 13.

Chromosome 13 is the largest acrocentric human chromosome. It carries genes involved in cancer including the breast cancer type 2 (BRCA2) and retinoblastoma (RB1) genes, is frequently rearranged in B-cell chronic lymphocytic leukaemia, and contains the DAOA locus associated with bipolar disorder and schizophrenia. We describe completion and analysis of 95.5 megabases (Mb) of sequence from chromosome 13, which contains 633 genes and 296 pseudogenes. We estimate that more than 95.4% of the protein-coding genes of this chromosome have been identified, on the basis of comparison with other vertebrate genome sequences. Additionally, 105 putative non-coding RNA genes were found. Chromosome 13 has one of the lowest gene densities (6.5 genes per Mb) among human chromosomes, and contains a central region of 38 Mb where the gene density drops to only 3.1 genes per Mb.

The vertebrate genome annotation (Vega) database.

The Vertebrate Genome Annotation (Vega) database (http://vega.sanger.ac.uk) was first made public in 2004 and has been designed to view manual annotation of human, mouse and zebrafish genomic sequences produced at the Wellcome Trust Sanger Institute. Since its initial release, the number of human annotated loci has more than doubled to close to 33 000 and now contains comprehensive annotation on 20 of the 24 human chromosomes, four whole mouse chromosomes and around 40% of the zebrafish Danio rerio genome. In addition, we offer manual annotation of a number of haplotype regions in mouse and human and regions of comparative interest in pig and dog that are unique to Vega.

Ensembl 2008.

The Ensembl project (http://www.ensembl.org) is a comprehensive genome information system featuring an integrated set of genome annotation, databases and other information for chordate and selected model organism and disease vector genomes. As of release 47 (October 2007), Ensembl fully supports 35 species, with preliminary support for six additional species. New species in the past year include platypus and horse. Major additions and improvements to Ensembl since our previous report include extensive support for functional genomics data in the form of a specialized functional genomics database, genome-wide maps of protein-DNA interactions and the Ensembl regulatory build; support for customization of the Ensembl web interface through the addition of user accounts and user groups; and increased support for genome resequencing. We have also introduced new comparative genomics-based data mining options and report on the continued development of our software infrastructure.

Alcohol alters whole body composition, inhibits bone formation, and increases bone marrow adiposity in rats.

UNLABELLED: Chronic alcohol abuse is a risk factor for osteoporosis and sarcopenia, but the long-term effects of alcohol on the immature musculoskeletal system are less clear. The present investigation in growing rats was designed to determine the effects of alcohol consumption on body composition, muscle mass, and bone mass, architecture, and turnover. INTRODUCTION: Few studies have focused on the long-term effects of drinking on bone and muscle during skeletal maturation. METHODS: Alcohol was included in the diet of 4-week-old male Sprague-Dawley rats (35% caloric intake) for 3 months. The controls were fed an isocaloric alcohol-free liquid diet ad libitum. A second study was performed in which the controls were pair-fed to the alcohol-fed animals. RESULTS: Compared to ad libitum-fed age-matched controls, alcohol-fed rats weighed less and had lower lean mass, fat mass, and percent body fat. In addition, they had lower slow- and fast-twitch muscle mass, lower total body bone mineral content and bone mineral density, and lower cancellous bone volume in the lumbar vertebra and proximal tibia. The effects of alcohol consumption on body composition were reduced when compared to the pair-fed control diet, indicating that caloric restriction was a comorbidity factor. In contrast, the effects of alcohol to decrease bone formation and serum leptin and IGF-I levels and to increase bone marrow adiposity appeared independent of caloric restriction. CONCLUSIONS: The skeletal abnormalities in growing alcohol-fed rats were due to a combination of effects specific to alcohol consumption and alcohol-induced caloric restriction.

Ensembl 2007.

The Ensembl (http://www.ensembl.org/) project provides a comprehensive and integrated source of annotation of chordate genome sequences. Over the past year the number of genomes available from Ensembl has increased from 15 to 33, with the addition of sites for the mammalian genomes of elephant, rabbit, armadillo, tenrec, platypus, pig, cat, bush baby, common shrew, microbat and european hedgehog; the fish genomes of stickleback and medaka and the second example of the genomes of the sea squirt (Ciona savignyi) and the mosquito (Aedes aegypti). Some of the major features added during the year include the first complete gene sets for genomes with low-sequence coverage, the introduction of new strain variation data and the introduction of new orthology/paralog annotations based on gene trees.

Ensembl 2006.

The Ensembl (http://www.ensembl.org/) project provides a comprehensive and integrated source of annotation of large genome sequences. Over the last year the number of genomes available from the Ensembl site has increased from 4 to 19, with the addition of the mammalian genomes of Rhesus macaque and Opossum, the chordate genome of Ciona intestinalis and the import and integration of the yeast genome. The year has also seen extensive improvements to both data analysis and presentation, with the introduction of a redesigned website, the addition of RNA gene and regulatory annotation and substantial improvements to the integration of human genome variation data.

CUS2, a yeast homolog of human Tat-SF1, rescues function of misfolded U2 through an unusual RNA recognition motif.

A screen for suppressors of a U2 snRNA mutation identified CUS2, an atypical member of the RNA recognition motif (RRM) family of RNA binding proteins. CUS2 protein is associated with U2 RNA in splicing extracts and interacts with PRP11, a subunit of the conserved splicing factor SF3a. Absence of CUS2 renders certain U2 RNA folding mutants lethal, arguing that a normal activity of CUS2 is to help refold U2 into a structure favorable for its binding to SF3b and SF3a prior to spliceosome assembly. Both CUS2 function in vivo and the in vitro RNA binding activity of CUS2 are disrupted by mutation of the first RRM, suggesting that rescue of misfolded U2 involves the direct binding of CUS2. Human Tat-SF1, reported to stimulate Tat-specific, transactivating region-dependent human immunodeficiency virus transcription in vitro, is structurally similar to CUS2. Anti-Tat-SF1 antibodies coimmunoprecipitate SF3a66 (SAP62), the human homolog of PRP11, suggesting that Tat-SF1 has a parallel function in splicing in human cells.

Ensembl 2005.

The Ensembl (http://www.ensembl.org/) project provides a comprehensive and integrated source of annotation of large genome sequences. Over the last year the number of genomes available from the Ensembl site has increased by 7 to 16, with the addition of the six vertebrate genomes of chimpanzee, dog, cow, chicken, tetraodon and frog and the insect genome of honeybee. The majority have been annotated automatically using the Ensembl gene build system, showing its flexibility to reliably annotate a wide variety of genomes. With the increased number of vertebrate genomes, the comparative analysis provided to users has been greatly improved, with new website interfaces allowing annotation of different genomes to be directly compared. The Ensembl software system is being increasingly widely reused in different projects showing the benefits of a completely open approach to software development and distribution.