Comparative transcriptomics of stickleback immune gene responses upon infection by two helminth parasites, Diplostomum pseudospathaceum and Schistocephalus solidus

Immune systems of vertebrates are much more diverse than previously thought, in particular at the base of the vertebrate clade. RNA-seq was used to describe in detail the transcriptomic response of stickleback hosts to infection by two helminth parasites, the trematode . Diplostomum pseudospathaceum (2 genotypes plus a genotype mix) and the cestode . Schistocephalus solidus. Based on a global transcription profiling, we present immune genes that are active during chronic or multiple repeated infection. We found that the transcription profiles of . D. pseudospathaceum genotypes were as divergent as those of the two parasite species. When comparing the host immune response, only 5 immune genes were consistently upregulated upon infection by both species. These genes indicated a role for enhanced toll like receptor (TLR) activity (CTSK, CYP27B1) and an associated positive regulation of macrophages (CYP27B1, THBS1) for general helminth defense. We interpret the largely differentiated gene expression response among parasite species as general redundancy of the vertebrate immune system, which was also visible in genotype-specific responses among the different . D. . pseudospathaceum infections. The present study provides the first evidence that IL4-mediated activation of T-helper lymphocyte cells is also important in anti-helminthic immune responses of teleost fish

Green's Functions and Non-Singlet Glueballs on Deformed Conifolds

We study the Laplacian on Stenzel spaces (generalized deformed conifolds), which are tangent bundles of spheres endowed with Ricci flat metrics. The (2d-2)-dimensional Stenzel space has SO(d) symmetry and can be embedded in C^d through the equation \sum_{i = 1}^d {z_i^2} = \epsilon^2. We discuss the Green's function with a source at a point on the S^{d-1} zero section of TS^{d-1}. Its calculation is complicated by mixing between different harmonics with the same SO(d) quantum numbers due to the explicit breaking by the \epsilon-deformation of the U(1) symmetry that rotates z_i by a phase. A similar mixing affects the spectrum of normal modes of warped deformed conifolds that appear in gauge/gravity duality. We solve the mixing problem numerically to determine certain bound state spectra in various representations of SO(d) for the d=4 and d=5 examples.Comment: 52 pages, 3 figure

Holographic Walking from Tachyon DBI

We use holography to study Conformal Phase Transitions, which are believed to be realized in four dimensional QCD and play an important role in walking technicolor models of electroweak symmetry breaking. At strong coupling they can be modeled by the non-linear dynamics of a tachyonic scalar field with mass close to the Breitenlohner-Freedman bound in anti de Sitter spacetime. Taking the action for this field to have a Tachyon-Dirac-Born-Infeld form gives rise to models that resemble hard and soft wall AdS/QCD, with a dynamically generated wall. For hard wall models, the highly excited spectrum has the KK form m_n ~ n; in the soft wall case we exhibit potentials with m_n ~ n^\alpha, 0<\alpha\leq1/2. We investigate the finite temperature phase structure and find first or second order symmetry restoration transitions, depending on the behavior of the potential near the origin of field space.Comment: 48 pages; v2: references adde

Specific Gene Expression Responses to Parasite Genotypes Reveal Redundancy of Innate Immunity in Vertebrates

Vertebrate innate immunity is the first line of defense against an invading pathogen and has long been assumed to be largely unspecific with respect to parasite/pathogen species. However, recent phenotypic evidence suggests that immunogenetic variation, i.e. allelic variability in genes associated with the immune system, results in host-parasite genotype-by-genotype interactions and thus specific innate immune responses. Immunogenetic variation is common in all vertebrate taxa and this reflects an effective immunological function in complex environments. However, the underlying variability in host gene expression patterns as response of innate immunity to within-species genetic diversity of macroparasites in vertebrates is unknown. We hypothesized that intra-specific variation among parasite genotypes must be reflected in host gene expression patterns. Here we used high-throughput RNA-sequencing to examine the effect of parasite genotypes on gene expression patterns of a vertebrate host, the three-spined stickleback (Gasterosteus aculeatus). By infecting naïve fish with distinct trematode genotypes of the species Diplostomum pseudospathaceum we show that gene activity of innate immunity in three-spined sticklebacks depended on the identity of an infecting macroparasite genotype. In addition to a suite of genes indicative for a general response against the trematode we also find parasite-strain specific gene expression, in particular in the complement system genes, despite similar infection rates of single clone treatments. The observed discrepancy between infection rates and gene expression indicates the presence of alternative pathways which execute similar functions. This suggests that the innate immune system can induce redundant responses specific to parasite genotypes

Designer receptors show role for ventral pallidum input to ventral tegmental area in cocaine seeking.

The ventral pallidum is centrally positioned within mesocorticolimbic reward circuits, and its dense projection to the ventral tegmental area (VTA) regulates neuronal activity there. However, the ventral pallidum is a heterogeneous structure, and how this complexity affects its role within wider reward circuits is unclear. We found that projections to VTA from the rostral ventral pallidum (RVP), but not the caudal ventral pallidum (CVP), were robustly Fos activated during cue-induced reinstatement of cocaine seeking--a rat model of relapse in addiction. Moreover, designer receptor-mediated transient inactivation of RVP neurons, their terminals in VTA or functional connectivity between RVP and VTA dopamine neurons blocked the ability of drug-associated cues (but not a cocaine prime) to reinstate cocaine seeking. In contrast, CVP neuronal inhibition blocked cocaine-primed, but not cue-induced, reinstatement. This double dissociation in ventral pallidum subregional roles in drug seeking is likely to be important for understanding the mesocorticolimbic circuits underlying reward seeking and addiction

Nanotools for Neuroscience and Brain Activity Mapping

Neuroscience is at a crossroads. Great effort is being invested into deciphering specific neural interactions and circuits. At the same time, there exist few general theories or principles that explain brain function. We attribute this disparity, in part, to limitations in current methodologies. Traditional neurophysiological approaches record the activities of one neuron or a few neurons at a time. Neurochemical approaches focus on single neurotransmitters. Yet, there is an increasing realization that neural circuits operate at emergent levels, where the interactions between hundreds or thousands of neurons, utilizing multiple chemical transmitters, generate functional states. Brains function at the nanoscale, so tools to study brains must ultimately operate at this scale, as well. Nanoscience and nanotechnology are poised to provide a rich toolkit of novel methods to explore brain function by enabling simultaneous measurement and manipulation of activity of thousands or even millions of neurons. We and others refer to this goal as the Brain Activity Mapping Project. In this Nano Focus, we discuss how recent developments in nanoscale analysis tools and in the design and synthesis of nanomaterials have generated optical, electrical, and chemical methods that can readily be adapted for use in neuroscience. These approaches represent exciting areas of technical development and research. Moreover, unique opportunities exist for nanoscientists, nanotechnologists, and other physical scientists and engineers to contribute to tackling the challenging problems involved in understanding the fundamentals of brain function