RNA-seq transcriptional profiling of peripheral blood leukocytes from cattle infected with Mycobacterium bovis

Bovine tuberculosis, caused by infection with Mycobacterium bovis, is a major endemic disease affecting cattle populations worldwide, despite the implementation of stringent surveillance and control programs in many countries. The development of high-throughput functional genomics technologies, including gene expression microarrays and RNA-sequencing (RNA-seq), has enabled detailed analysis of the host transcriptome to M. bovis infection, particularly at the macrophage and peripheral blood level. In the present study, we have analyzed the peripheral blood leukocyte (PBL) transcriptome of eight natural M. bovis-infected and eight age- and sex-matched non-infected control Holstein-Friesian animals using RNA-seq. In addition, we compared gene expression profiles generated using RNA-seq with those previously generated using the high-density Affymetrix(®) GeneChip(®) Bovine Genome Array platform from the same PBL-extracted RNA. A total of 3,250 differentially expressed (DE) annotated genes were detected in the M. bovis-infected samples relative to the controls (adjusted P-value ≤0.05), with the number of genes displaying decreased relative expression (1,671) exceeding those with increased relative expression (1,579). Ingenuity(®) Systems Pathway Analysis (IPA) of all DE genes revealed enrichment for genes with immune function. Notably, transcriptional suppression was observed among several of the top-ranking canonical pathways including Leukocyte Extravasation Signaling. Comparative platform analysis demonstrated that RNA-seq detected a larger number of annotated DE genes (3,250) relative to the microarray (1,398), of which 917 genes were common to both technologies and displayed the same direction of expression. Finally, we show that RNA-seq had an increased dynamic range compared to the microarray for estimating differential gene expression

Surface energy and stability of stress-driven discommensurate surface structures

A method is presented to obtain {\it ab initio} upper and lower bounds to surface energies of stress-driven discommensurate surface structures, possibly non-periodic or exhibiting very large unit cells. The instability of the stressed, commensurate parent of the discommensurate structure sets an upper bound to its surface energy; a lower bound is defined by the surface energy of an ideally commensurate but laterally strained hypothetical surface system. The surface energies of the phases of the Si(111):Ga and Ge(111):Ga systems and the energies of the discommensurations are determined within $\pm 0.2$ eV.Comment: 4 pages RevTeX. 2 Figures not included. Ask for a hard copy (through regular mail) to [email protected]

Sommerfeld enhancement from Goldstone pseudo-scalar exchange

We point out that the exchange of a Goldstone pseudo-scalar can provide an enhancement in the dark matter annihilation rate capable of explaining the excess flux seen in high energy cosmic ray data. The mechanism of enhancement involves the coupling of s and d waves through the tensor force that is very strong and, in fact, singular at short distances. The results indicate that large enhancements require some amount of fine tuning. We also discuss the enhancement due to other singular attractive potentials, such as WIMP models with a permanent electric dipole.Comment: 14 pages, 4 figures, v2 includes contact informatio

Discovery of Highly Obscured Galaxies in the Zone of Avoidance

We report the discovery of twenty-five previously unknown galaxies in the Zone of Avoidance. Our systematic search for extended extra-galactic sources in the GLIMPSE and MIPSGAL mid-infrared surveys of the Galactic plane has revealed two overdensities of these sources, located around l ~ 47 and 55 degrees and |b| less than 1 degree in the Sagitta-Aquila region. These overdensities are consistent with the local large-scale structure found at similar Galactic longitude and extending from |b| ~ 4 to 40 degrees. We show that the infrared spectral energy distribution of these sources is indeed consistent with those of normal galaxies. Photometric estimates of their redshift indicate that the majority of these galaxies are found in the redshift range z = 0.01 - 0.05, with one source located at z = 0.07. Comparison with known sources in the local Universe reveals that these galaxies are located at similar overdensities in redshift space. These new galaxies are the first evidence of a bridge linking the large-scale structure between both sides of the Galactic plane at very low Galactic latitude and clearly demonstrate the feasibility of detecting galaxies in the Zone of Avoidance using mid-to-far infrared surveys.Comment: Accepted for publication in the Astronomical Journal, 28 pages, 5 tables, 11 figure

Rational Design, Synthesis, and Biological Evaluation of Progesterone-Modified MRI Contrast Agents

SummaryA series of contrast agents for magnetic resonance imaging (MRI) aimed at noninvasively determining the hormone receptor status of cancer in vitro was developed. These MRI contrast agents were prepared by conjugating progesterone to clinically used Gd(III) chelates. These agents exhibited higher progesterone receptor binding affinities in the nanomolar range and intracellular accumulation. High logP values of the modified compounds suggested that the lipophilicity of the steroid conjugates may have contributed to membrane permeability. Synchrotron radiation X-ray fluorescence microscopy and magnetic resonance images revealed that the synthesized conjugates showed the greatest cellular accumulation and significant increase in relaxivity in vitro compared to the previously developed steroid-modified agent. Transcriptional assays using the progesterone response element linked to luciferase indicated that the contrast agents entered the cell, interacted with the biological target, and drove specific progesterone-mediated transcription

A Steroid-Conjugated Contrast Agent for Magnetic Resonance Imaging of Cell Signaling

We have synthesized the first steroid hormone−MR contrast agent conjugate designed to track the cell signaling process upon binding to a gene switch system. The derivative has a high relaxivity and when tested in vitro is active as a progesterone antagonist (RU-486). By combining a transcriptional system and a noninvasive imaging technology, such as MRI, it would be a powerful tool to research the cell signaling pathway in vivo

Etched distributed Bragg reflectors as three-dimensional photonic crystals: photonic bands and density of states

The photonic band dispersion and density of states (DOS) are calculated for the three-dimensional (3D) hexagonal structure corresponding to a distributed Bragg reflector patterned with a 2D triangular lattice of circular holes. Results for the Si/SiO$_2$ and GaAs/AlGaAs systems determine the optimal parameters for which a gap in the 2D plane occurs and overlaps the 1D gap of the multilayer. The DOS is considerably reduced in correspondence with the overlap of 2D and 1D gaps. Also, the local density of states (i.e., the DOS weighted with the squared electric field at a given point) has strong variations depending on the position. Both results imply substantial changes of spontaneous emission rates and patterns for a local emitter embedded in the structure and make this system attractive for the fabrication of a 3D photonic crystal with controlled radiative properties.Comment: 8 pages, 5 figures; to appear in Phys. Rev.

What is Socialism Today? Conceptions of a Cooperative Economy

Socialism is back on the political agenda in the United States. Politicians and some economists who identify as socialists, however, do not discuss property relations, a topic that was central in the intellectual history of socialism, but rather limit themselves to advocacy of economic reforms, funded through taxation, that would tilt the income distribution in favor of the disadvantaged in society. In the absence of a more precise discussion of property relations, the presumption must be that ownership of firms would remain private or corporate with privately owned shares. This formula is identified with the Nordic and other western European social democracies. In this article, I propose several variants of socialism, which are characterized by different kinds of property relation in the ownership of society’s firms. In addition to varying property relations, I include as part of socialism a conception of what it means for a socialist society to possess a cooperative ethos, in place of the individualistic ethos of capitalist society. Differences in ethea are modeled as differences in the manner in which economic agents optimize. With an individualistic ethos, economic agents optimize in the manner of John Nash, while under a cooperative ethos, many optimize in the manner of Immanuel Kant. It is shown that Kantian optimization can decentralize resource allocation in ways that neatly separate issues of income distribution from those of efficiency. In particular, remuneration of labor and capital contributions to production need no longer be linked to marginal-product pricing of these factors, as is the key to efficiency with capitalist property relations. I present simulations of socialist income distributions, and offer some tentative conclusions concerning how we should conceive of socialism today

The development and use of Actiphage® to detect viable mycobacteria from bovine tuberculosis and Johne’s disease-infected animals

Here, we describe the development of a method that exploits bacteriophage D29 as a lysis agent for efficient DNA extraction from low numbers of mycobacterial cells. This method (Actiphage®) used in combination with PCR achieved rapid and sensitive (LOD ≤ 10 cell ml−1) detection and identification of viable, pathogenic mycobacteria in blood samples within 6 h. We demonstrate that mycobacteriophage D29 can be used to detect a range of mycobacteria from clinical blood samples including both Mycobacterium tuberculosis complex and Mycobacterium avium subsp. paratuberculosis without the need for culture and confirms our earlier observations that a low‐level bacteraemia is associated with these infections in cattle. In a study of M. bovis‐infected cattle (n = 41), the sensitivity of the Actiphage® method was 95 % (95 % CI; 0.84–0.99) and specificity was 100 % (95% CI; 0.92–1). We further used Actiphage® to demonstrate viable Mycobacterium avium subsp. paratuberculosis is present in the blood of Johne’s infected cattle. This method provides a revolutionary new tool for the study of infections caused by these difficult to grow pathogens