North American Hard Yellow Liver Disease: An Old Problem Readdressed

Hard yellow liver disease or fatty cirrhosis periodically affects cattle, sheep, goats, pronghorn antelope (Antilocapra americana) and whitetail deer (Odocoileus virginianus texanus) within several Texas counties in the United States. Clinically it presents as chronic liver disease with progressive hepatic necrosis and fibrosis, icterus and liver failure. The damaged livers are yellow and many have multiple firm, often gritty foci that are scattered throughout all lobes. Early investigations included feeding studies using potential toxic plants, climate and forage studies, infectious disease surveys and various mycotoxin studies and analyses. None have definitively reproduced the disease or identified the inciting cause. However, the problem continues and recent outbreaks have allowed the collection of additional frozen tissues, and numerous paraffin tissue blocks and slides for additional studies. The objectives for this work are to evaluate and compare the microscopic changes, special histochemical studies, microbial and fungal surveys and chemical assays for dehyro-pyrrolizidine alkaloid (DHPA) metabolites of these additional cases with historical reports. These bovine livers had a spectrum of lesions including lipid degeneration and necrosis, eosinophilic granulomatous hepatitis, focal follicular lymphoid proliferation and chronic fibrosing hepatitis with dystrophic mineralization. No pyrrolizidine alkaloid metabolites were detected in any of the livers and select special stains did not reveal any fungal, bacterial or parasitic etiologies. The lack of findings and mixed histologic presentation suggest that this syndrome is a collection of chronic diseases probably of various etiologies. Earlier animal surveillance work is needed in endemic areas to better understand the etiology and pathogenesis of this syndrome

A high resolution RH map of the bovine major histocompatibility complex

<p>Abstract</p> <p>Background</p> <p>The cattle MHC is termed the bovine leukocyte antigen (BoLA) and, along with the MHCs of other ruminants, is unique in its genomic organization. Consequently, correct and reliable gene maps and sequence information are critical to the study of the BoLA region. The bovine genome sequencing project has produced two assemblies (Btau_3.1 and 4.0) that differ substantially from each other and from conventional gene maps in the BoLA region. To independently compare the accuracies of the different sequence assemblies, we have generated a high resolution map of BoLA using a 12,000_radradiation hybrid panel. Seventy-seven unique sequence tagged site (STS) markers chosen at approximately 50 kb intervals from the Btau 2.0 assembly and spanning the IIa-III-I and IIb regions of the bovine MHC were mapped on a 12,000_radbovine radiation hybrid (RH) panel to evaluate the different assemblies of the bovine genome sequence.</p> <p>Results</p> <p>Analysis of the data generated a high resolution RH map of BoLA that was significantly different from the Btau_3.1 assembly of the bovine genome but in good agreement with the Btau_4.0 assembly. Of the few discordancies between the RH map and Btau_4.0, most could be attributed to closely spaced markers that could not be precisely ordered in the RH panel. One probable incorrectly-assembled sequence and three missing sequences were noted in the Btau_4.0 assembly. The RH map of BoLA is also highly concordant with the sequence-based map of HLA (NCBI build 36) when reordered to account for the ancestral inversion in the ruminant MHC.</p> <p>Conclusion</p> <p>These results strongly suggest that studies using Btau_3.1 for analyses of the BoLA region should be reevaluated in light of the Btau_4.0 assembly and indicate that additional research is needed to produce a complete assembly of the BoLA genomic sequences.</p

Understanding the UK hospital supply chain in an era of patient choice

Author Posting © Westburn Publishers Ltd, 2011. This is a post-peer-review, pre-copy-edit version of an article which has been published in its definitive form in the Journal of Marketing Management, and has been posted by permission of Westburn Publishers Ltd for personal use, not for redistribution. The article was published in Journal of Marketing Management, 27(3-4), 401 - 423, doi:10.1080/0267257X.2011.547084 http://dx.doi.org/10.1080/0267257X.2011.547084The purpose of this paper is to investigate the UK hospital supply chain in light of recent government policy reform where patients will have, inter alia, greater choice of hospital for elective surgery. Subsequently, the hospital system should become far more competitive with supply chains having to react to these changes as patient demand becomes less predictable. Using a qualitative case study methodology, hospital managers are interviewed on a range of issues. Views on the development of the hospital supply chain in different phases are derived, and are used to develop a map of the current hospital chain. The findings show hospital managers anticipating some significant changes to the hospital supply chain and its workings as Patient Choice expands. The research also maps the various aspects of the hospital supply chain as it moves through different operational phases and highlights underlying challenges and complexities. The hospital supply chain, as discussed and mapped in this research, is original work given there are no examples in the literature that provide holistic representations of hospital activity. At the end, specific recommendations are provided that will be of interest to service to managers, researchers, and policymakers

Effects of genome-wide copy number variation on expression in mammalian cells

<p>Abstract</p> <p>Background</p> <p>There is only a limited understanding of the relation between copy number and expression for mammalian genes. We fine mapped <it>cis </it>and <it>trans </it>regulatory loci due to copy number change for essentially all genes using a human-hamster radiation hybrid (RH) panel. These loci are called copy number expression quantitative trait loci (ceQTLs).</p> <p>Results</p> <p>Unexpected findings from a previous study of a mouse-hamster RH panel were replicated. These findings included decreased expression as a result of increased copy number for 30% of genes and an attenuated relationship between expression and copy number on the X chromosome suggesting an <it>Xist </it>independent form of dosage compensation. In a separate glioblastoma dataset, we found conservation of genes in which dosage was negatively correlated with gene expression. These genes were enriched in signaling and receptor activities. The observation of attenuated X-linked gene expression in response to increased gene number was also replicated in the glioblastoma dataset. Of 523 gene deserts of size > 600 kb in the human RH panel, 325 contained <it>trans </it>ceQTLs with -log₁₀<it>P </it>> 4.1. Recently discovered genes, ultra conserved regions, noncoding RNAs and microRNAs explained only a small fraction of the results, suggesting a substantial portion of gene deserts harbor as yet unidentified functional elements.</p> <p>Conclusion</p> <p>Radiation hybrids are a useful tool for high resolution mapping of <it>cis </it>and <it>trans </it>loci capable of affecting gene expression due to copy number change. Analysis of two independent radiation hybrid panels show agreement in their findings and may serve as a discovery source for novel regulatory loci in noncoding regions of the genome.</p

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

TRY plant trait database – enhanced coverage and open access

Plant traits - the morphological, anatomical, physiological, biochemical and phenological characteristics of plants - determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait‐based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits - almost complete coverage for ‘plant growth form’. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait–environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

The impact of PICALM genetic variations on reserve capacity of posterior cingulate in AD continuum

Phosphatidylinositolbinding clathrin assembly protein (PICALM) gene is one novel genetic player associated with late-onset Alzheimer’s disease (LOAD), based on recent genome wide association studies (GWAS). However, how it affects AD occurrence is still unknown. Brain reserve hypothesis highlights the tolerant capacities of brain as a passive means to fight against neurodegenerations. Here, we took the baseline volume and/or thickness of LOAD-associated brain regions as proxies of brain reserve capacities and investigated whether PICALM genetic variations can influence the baseline reserve capacities and the longitudinal atrophy rate of these specific regions using data from Alzheimer’s Disease Neuroimaging Initiative (ADNI) dataset. In mixed population, we found that brain region significantly affected by PICALM genetic variations was majorly restricted to posterior cingulate. In sub-population analysis, we found that one PICALM variation (C allele of rs642949) was associated with larger baseline thickness of posterior cingulate in health. We found seven variations in health and two variations (rs543293 and rs592297) in individuals with mild cognitive impairment were associated with slower atrophy rate of posterior cingulate. Our study provided preliminary evidences supporting that PICALM variations render protections by facilitating reserve capacities of posterior cingulate in non-demented elderly

Brain multiplexes reveal morphological connectional biomarkers fingerprinting late brain dementia states

Accurate diagnosis of mild cognitive impairment (MCI) before conversion to Alzheimer’s disease (AD) is invaluable for patient treatment. Many works showed that MCI and AD affect functional and structural connections between brain regions as well as the shape of cortical regions. However, ‘shape connections’ between brain regions are rarely investigated -e.g., how morphological attributes such as cortical thickness and sulcal depth of a specific brain region change in relation to morphological attributes in other regions. To fill this gap, we unprecedentedly design morphological brain multiplexes for late MCI/AD classification. Specifically, we use structural T1-w MRI to define morphological brain networks, each quantifying similarity in morphology between different cortical regions for a specific cortical attribute. Then, we define a brain multiplex where each intra-layer represents the morphological connectivity network of a specific cortical attribute, and each inter-layer encodes the similarity between two consecutive intra-layers. A significant performance gain is achieved when using the multiplex architecture in comparison to other conventional network analysis architectures. We also leverage this architecture to discover morphological connectional biomarkers fingerprinting the difference between late MCI and AD stages, which included the right entorhinal cortex and right caudal middle frontal gyrus