Breed-Specific Hematological Phenotypes in the Dog: A Natural Resource for the Genetic Dissection of Hematological Parameters in a Mammalian Species

Remarkably little has been published on hematological phenotypes of the domestic dog, the most polymorphic species on the planet. Information on the signalment and complete blood cell count of all dogs with normal red and white blood cell parameters judged by existing reference intervals was extracted from a veterinary database. Normal hematological profiles were available for 6046 dogs, 5447 of which also had machine platelet concentrations within the reference interval. Seventy-five pure breeds plus a mixed breed control group were represented by 10 or more dogs. All measured parameters except mean corpuscular hemoglobin concentration (MCHC) varied with age. Concentrations of white blood cells (WBCs), neutrophils, monocytes, lymphocytes, eosinophils and platelets, but not red blood cell parameters, all varied with sex. Neutering status had an impact on hemoglobin concentration, mean corpuscular hemoglobin (MCH), MCHC, and concentrations of WBCs, neutrophils, monocytes, lymphocytes and platelets. Principal component analysis of hematological data revealed 37 pure breeds with distinctive phenotypes. Furthermore, all hematological parameters except MCHC showed significant differences between specific individual breeds and the mixed breed group. Twenty-nine breeds had distinctive phenotypes when assessed in this way, of which 19 had already been identified by principal component analysis. Tentative breed-specific reference intervals were generated for breeds with a distinctive phenotype identified by comparative analysis. This study represents the first large-scale analysis of hematological phenotypes in the dog and underlines the important potential of this species in the elucidation of genetic determinants of hematological traits, triangulating phenotype, breed and genetic predisposition

Mutational analysis of Polycomb genes in solid tumours identifies <i>PHC3</i> amplification as a possible cancer-driving genetic alteration.

Background: Polycomb group genes (PcGs) are epigenetic effectors implicated in most cancer hallmarks. The mutational status of all PcGs has never been systematically assessed in solid tumours. Methods: We conducted a multi-step analysis on publically available databases and patient samples to identify somatic aberrations of PcGs. Results: Data from more than 1000 cancer patients show for the first time that the PcG member PHC3 is amplified in three epithelial neoplasms (rate: 8–35%). This aberration predicts poorer prognosis in lung and uterine carcinomas (Po0.01). Gene amplification correlates with mRNA overexpression (Po0.01), suggesting a functional role of this aberration. Conclusion: PHC3 amplification may emerge as a biomarker and potential therapeutic target in a relevant fraction of epithelial tumours

Phenoloxidase activity acts as a mosquito innate immune response against infection with semliki forest virus

Several components of the mosquito immune system including the RNA interference (RNAi), JAK/STAT, Toll and IMD pathways have previously been implicated in controlling arbovirus infections. In contrast, the role of the phenoloxidase (PO) cascade in mosquito antiviral immunity is unknown. Here we show that conditioned medium from the Aedes albopictus-derived U4.4 cell line contains a functional PO cascade, which is activated by the bacterium Escherichia coli and the arbovirus Semliki Forest virus (SFV) (Togaviridae; Alphavirus). Production of recombinant SFV expressing the PO cascade inhibitor Egf1.0 blocked PO activity in U4.4 cell- conditioned medium, which resulted in enhanced spread of SFV. Infection of adult female Aedes aegypti by feeding mosquitoes a bloodmeal containing Egf1.0-expressing SFV increased virus replication and mosquito mortality. Collectively, these results suggest the PO cascade of mosquitoes plays an important role in immune defence against arboviruses

Hypolithic and soil microbial community assembly along an aridity gradient in the Namib Desert

The Namib Dessert is considered the oldest desert in the world and hyperarid for the last 5 million years. However, the environmental buffering provided by quartz and other translucent rocks supports extensive hypolithic microbial communities. In this study, open soil and hypolithic microbial communities have been investigated along an East–West transect characterized by an inverse fog-rainfall gradient. Multivariate analysis showed that structurally different microbial communities occur in soil and in hypolithic zones. Using variation partitioning, we found that hypolithic communities exhibited a fog-related distribution as indicated by the significant East– West clustering. Sodium content was also an important environmental factor affecting the composition of both soil and hypolithic microbial communities. Finally, although null models for patterns in microbial communities were not supported by experimental data, the amount of unexplained variation (68–97 %) suggests that stochastic processes also play a role in the assembly of such communities in the Namib Desert.Web of Scienc

Nature of the Earth's earliest crust from hafnium isotopes in single detrital zircons

Continental crust forms from, and thus chemically depletes, the Earth's mantle. Evidence that the Earth's mantle was already chemically depleted by melting before the formation of today's oldest surviving crust has been presented in the form of Sm-Nd isotope studies of 3.8-4.0 billion years old rocks from Greenland(1-5) and Canada(5-7). But this interpretation has been questioned because of the possibility that subsequent perturbations may have re-equilibrated the neodymium-isotope compositions of these rocks(8). Independent and more robust evidence for the origin of the earliest crust and depletion of the Archaean mantle can potentially be provided by hafnium-isotope compositions of zircon, a mineral whose age can be precisely determined by U-Pb dating, and which can survive metamorphisms(4). But the amounts of hafnium in single zircon grains are too small for the isotopic composition to be precisely analysed by conventional methods. Here we report hafnium-isotope data, obtained using the new technique of multiple-collector plasma-source mass spectrometry(9), for 37 individual grains of the oldest known terrestrial zircons (from the Narryer Gneiss Complex, Australia, with U-Pb ages of up to 4.14 Gyr (refs 10-13)). We find that none of the grains has a depleted mantle signature, but that many were derived from a source with a hafnium-isotope composition similar to that of chondritic meteorites. Furthermore, more than half of the analysed grains seem to have formed by remelting of significantly older crust, indicating that crustal preservation and subsequent reworking might have been important processes from earliest times.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62681/1/399252a0.pd

The Spin Structure of the Nucleon

We present an overview of recent experimental and theoretical advances in our understanding of the spin structure of protons and neutrons.Comment: 84 pages, 29 figure

Attitudes and Practices Among Internists Concerning Genetic Testing

Many questions remain concerning whether, when, and how physicians order genetic tests, and what factors are involved in their decisions. We surveyed 220 internists from two academic medical centers about their utilization of genetic testing. Rates of genetic utilizations varied widely by disease. Respondents were most likely to have ordered tests for Factor V Leiden (16.8 %), followed by Breast/Ovarian Cancer (15.0 %). In the past 6 months, 65 % had counseled patients on genetic issues, 44 % had ordered genetic tests, 38.5 % had referred patients to a genetic counselor or geneticist, and 27.5 % had received ads from commercial labs for genetic testing. Only 4.5 % had tried to hide or disguise genetic information, and <2 % have had patients report genetic discrimination. Only 53.4 % knew of a geneticist/genetic counselor to whom to refer patients. Most rated their knowledge as very/somewhat poor concerning genetics (73.7 %) and guidelines for genetic testing (87.1 %). Most felt needs for more training on when to order tests (79 %), and how to counsel patients (82 %), interpret results (77.3 %), and maintain privacy (80.6 %). Physicians were more likely to have ordered a genetic test if patients inquired about genetic testing (p  < .001), and if physicians had a geneticist/genetic counselor to whom to refer patients (p  < .002), had referred patients to a geneticist/genetic counselor in the past 6 months, had more comfort counseling patients about testing (p  < .019), counseled patients about genetics, larger practices (p  < .032), fewer African‐American patients (p  < .027), and patients who had reported genetic discrimination (p  < .044). In a multiple logistic regression, ordering a genetic test was associated with patients inquiring about testing, having referred patients to a geneticist/genetic counselor and knowing how to order tests. These data suggest that physicians recognize their knowledge deficits, and are interested in training. These findings have important implications for future medical practice, research, and education

Application of chemometric analysis to infrared spectroscopy for the identification of wood origin

Chemical characteristics of wood are used in this study for plant taxonomy classification based on the current Angiosperm Phylogeny Group classification (APG III System) for the division, class and subclass of woody plants. Infrared spectra contain information about the molecular structure and intermolecular interactions among the components in wood but the understanding of this information requires multivariate techniques for the analysis of highly dense datasets. This article is written with the purposes of specifying the chemical differences among taxonomic groups, and predicting the taxa of unknown samples with a mathematical model. Principal component analysis, t-test, stepwise discriminant analysis and linear discriminant analysis, were some of the chosen multivariate techniques. A procedure to determine the division, class, subclass and order of unknown samples was built with promising implications for future applications of Fourier Transform Infrared spectroscopy in wood taxonomy classification