Genome-Wide Linkage Analysis of Human Auditory Cortical Activation Suggests Distinct Loci on Chromosomes 2, 3, and 8

Neural processes are explored through macroscopic neuroimaging and microscopic molecular measures, but the two levels remain primarily detached. The identification of direct links between the levels would facilitate use of imaging signals as probes of genetic function and, vice versa, access to molecular correlates of imaging measures. Neuroimaging patterns have been mapped for a few isolated genes, chosen based on their connection with a clinical disorder. Here we propose an approach that allows an unrestricted discovery of the genetic basis of a neuroimaging phenotype in the normal human brain. The essential components are a subject population that is composed of relatives and selection of a neuroimaging phenotype that is reproducible within an individual and similar between relatives but markedly variable across a population. Our present combined magnetoencephalography and genome-wide linkage study in 212 healthy siblings demonstrates that auditory cortical activation strength is highly heritable and, specifically in the right hemisphere, regulated oligogenically with linkages to chromosomes 2q37, 3p12, and 8q24. The identified regions delimit as candidate genes TRAPPC9, operating in neuronal differentiation, and ROBO1, regulating projections of thalamocortical axons. Identification of normal genetic variation underlying neurophysiological phenotypes offers a non-invasive platform for an in-depth, concerted capitalization of molecular and neuroimaging levels in exploring neural function.Peer reviewe

The Baum-Connes Conjecture via Localisation of Categories

We redefine the Baum-Connes assembly map using simplicial approximation in the equivariant Kasparov category. This new interpretation is ideal for studying functorial properties and gives analogues of the assembly maps for all equivariant homology theories, not just for the K-theory of the crossed product. We extend many of the known techniques for proving the Baum-Connes conjecture to this more general setting

Equivariant Lefschetz maps for simplicial complexes and smooth manifolds

Let X be a locally compact space with a continuous proper action of a locally compact group G. Assuming that X satisfies a certain kind of duality in equivariant bivariant Kasparov theory, we can enrich the classical construction of Lefschetz numbers to equivariant K-homology classes. We compute the Lefschetz invariants for self-maps of finite-dimensional simplicial complexes and of self-maps of smooth manifolds. The resulting invariants are independent of the extra structure used to compute them. Since smooth manifolds can be triangulated, we get two formulas for the same Lefschetz invariant in these cases. The resulting identity is closely related to the equivariant Lefschetz Fixed Point Theorem of Luck and Rosenberg.Comment: Minor revisions, affecting some theorem number

Ramond-Ramond Fields, Fractional Branes and Orbifold Differential K-Theory

We study D-branes and Ramond-Ramond fields on global orbifolds of Type II string theory with vanishing H-flux using methods of equivariant K-theory and K-homology. We illustrate how Bredon equivariant cohomology naturally realizes stringy orbifold cohomology. We emphasize its role as the correct cohomological tool which captures known features of the low-energy effective field theory, and which provides new consistency conditions for fractional D-branes and Ramond-Ramond fields on orbifolds. We use an equivariant Chern character from equivariant K-theory to Bredon cohomology to define new Ramond-Ramond couplings of D-branes which generalize previous examples. We propose a definition for groups of differential characters associated to equivariant K-theory. We derive a Dirac quantization rule for Ramond-Ramond fluxes, and study flat Ramond-Ramond potentials on orbifolds.Comment: 46 pages; v2: typos correcte

MMP28 (epilysin) as a novel promoter of invasion and metastasis in gastric cancer

Background\ud The purpose of this study was to investigate invasion and metastasis related genes in gastric cancer.\ud \ud Methods\ud The transwell migration assay was used to select a highly invasive sub-line from minimally invasive parent gastric cancer cells, and gene expression was compared using a microarray. MMP28 upregulation was confirmed using qRT-PCR. MMP28 immunohistochemistry was performed in normal and gastric cancer specimens. Invasiveness and tumor formation of stable cells overexpressing MMP28 were tested in vitro and in vivo.\ud \ud Results\ud MMP28 was overexpressed in the highly invasive sub-cell line. Immunohistochemistry revealed MMP28 expression was markedly increased in gastric carcinoma relative to normal epithelia, and was significantly associated with depth of tumor invasion, lymph node metastasis and poorer overall survival. Ectopic expression of MMP28 indicated MMP28 promoted tumor cell invasion in vitro and increased gastric carcinoma metastasis in vivo.\ud \ud Conclusions\ud This study indicates MMP28 is frequently overexpressed during progression of gastric carcinoma, and contributes to tumor cell invasion and metastasis. MMP28 may be a novel therapeutic target for prevention and treatment of metastases in gastric cancer

Human MMP28 expression is unresponsive to inflammatory stimuli and does not correlate to the grade of intervertebral disc degeneration

BACKGROUND: MMP28 (epilysin) is a recently discovered member of the MMP (matrix metalloproteinase) family that is, amongst others, expressed in osteoarthritic cartilage and intervertebral disc (IVD) tissue. In this study the hypothesis that increased expression of MMP28 correlates with higher grades of degeneration and is stimulated by the presence of proinflammatory molecules was tested. Gene expression levels of MMP28 were investigated in traumatic and degenerative human IVD tissue and correlated to the type of disease and the degree of degeneration (Thompson grade). Quantification of MMP28 gene expression in human IVD tissue or in isolated cells after stimulation with the inflammatory mediators lipopolysaccharide (LPS), interleukin (IL)-1β, tumor necrosis factor (TNF)-α or the histondeacetylase inhibitor trichostatin A was performed by real-time RT PCR. RESULTS: While MMP28 expression was increased in individual cases with trauma or disc degeneration, there was no significant correlation between the grade of disease and MMP28 expression. Stimulation with LPS, IL-1β, TNF-α or trichostatin A did not alter MMP28 gene expression at any investigated time point or any concentration. CONCLUSIONS: Our results demonstrate that gene expression of MMP28 in the IVD is not regulated by inflammatory mechanisms, is donor-dependent and cannot be positively or negatively linked to the grade of degeneration and only weakly to the occurrence of trauma. New hypotheses and future studies are needed to find the role of MMP28 in the intervertebral disc

Persistent psychogenic déjà vu: a case report

Introduction: Déjà vu is typically a transient mental state in which a novel experience feels highly familiar. Although extensively studied in relation to temporal lobe epilepsy as part of simple partial seizures, déjà vu has been less studied in other clinical populations. A recent review of temporal lobe epilepsy suggested a possible link between clinical levels of anxiety and debilitating déjà vu, indicating further research is required. Here, for the first time in the literature, we present a case study of a young man with anxiety and depersonalisation who reported experiencing persistent and debilitating déjà vu. This report therefore adds to the limited literature on the relationship between anxiety and déjà vu. Case presentation: A 23-year-old White British man presented with a form of persistent déjà vu in 2010, approximately 3 years since symptom onset. He reported a history of anxiety and experiencing feelings of depersonalisation. Neurological assessment (electroencephalogram and magnetic resonance imaging) did not indicate any abnormalities. We assessed his recognition memory with a task used in patients with dementia who report similar experiences but lack awareness of their falseness. Conclusions: Our case' s memory performance was more conservative than controls but did not indicate a memory deficit. Unlike other patients with chronic déjà vu (for example, in dementia), he is fully aware of the false nature of his déjà vu and this presumably leads to his intact recognition memory performance. We suggest that his persistent déjà vu is psychogenic and conclude that déjà vu should be further studied in psychiatric disorders.</p

A field assessment of the value of steady shape hydraulic tomography for characterization of aquifer heterogeneities

This is the published version. Copyright American Geophysical Union[1] Hydraulic tomography is a promising approach for obtaining information on variations in hydraulic conductivity on the scale of relevance for contaminant transport investigations. This approach involves performing a series of pumping tests in a format similar to tomography. We present a field-scale assessment of hydraulic tomography in a porous aquifer, with an emphasis on the steady shape analysis methodology. The hydraulic conductivity (K) estimates from steady shape and transient analyses of the tomographic data compare well with those from a tracer test and direct-push permeameter tests, providing a field validation of the method. Zonations based on equal-thickness layers and cross-hole radar surveys are used to regularize the inverse problem. The results indicate that the radar surveys provide some useful information regarding the geometry of the K field. The steady shape analysis provides results similar to the transient analysis at a fraction of the computational burden. This study clearly demonstrates the advantages of hydraulic tomography over conventional pumping tests, which provide only large-scale averages, and small-scale hydraulic tests (e.g., slug tests), which cannot assess strata connectivity and may fail to sample the most important pathways or barriers to flow