The emerging role of interferon in human systemic lupus erythematosus.

Recent studies of patients with systemic lupus erythematosus, together with data from lupus-prone mice, suggest that inappropriate activation of type I interferon might have a role in disease pathogenesis. Serum levels of IFN-alpha are elevated in SLE patients, and gene expression profiling of peripheral blood cells shows that most lupus cases demonstrate an upregulation of IFN-responsive genes. Of interest, the IFN gene 'signature' correlates with more severe disease.

Advances in functional and structural MR image analysis and implementation as FSL.

The techniques available for the interrogation and analysis of neuroimaging data have a large influence in determining the flexibility, sensitivity, and scope of neuroimaging experiments. The development of such methodologies has allowed investigators to address scientific questions that could not previously be answered and, as such, has become an important research area in its own right. In this paper, we present a review of the research carried out by the Analysis Group at the Oxford Centre for Functional MRI of the Brain (FMRIB).

Changes in connectivity profiles define functionally distinct regions in human medial frontal cortex.

A fundamental issue in neuroscience is the relation between structure and function. However, gross landmarks do not correspond well to microstructural borders and cytoarchitecture cannot be visualized in a living brain used for functional studies. Here, we used diffusion-weighted and functional MRI to test structure-function relations directly.

Self-reported traffic density and atopic disease in children. Results of the ISAAC Phase III survey in Muenster, Germany.

Positive associations between traffic exposure and atopic respiratory disorders in children have been described in several studies. We analyzed data related to self-reported truck traffic density and several symptoms and diagnoses of asthma and hay fever (12-month wheezing and rhinitis symptoms, diagnoses of asthma and hay fever) from the ISAAC Phase III survey in Muenster, Germany, using core written and video questionnaires. Data were collected from representative school-based samples (n = 7345) of 6-7- and 13-14-yr-olds.

Genetic association of the R620W polymorphism of protein tyrosine phosphatase PTPN22 with human SLE.

We genotyped 525 independent North American white individuals with systemic lupus erythematosus (SLE) for the PTPN22 R620W polymorphism and compared the results with data generated from 1,961 white control individuals. The R620W SNP was associated with SLE (genotypic P=.00009), with estimated minor (T) allele frequencies of 12.

Functional-anatomical validation and individual variation of diffusion tractography-based segmentation of the human thalamus.

Parcellation of the human thalamus based on cortical connectivity information inferred from non-invasive diffusion-weighted images identifies sub-regions that we have proposed correspond to nuclei. Here we test the functional and anatomical validity of this proposal by comparing data from diffusion tractography, cytoarchitecture and functional imaging. We acquired diffusion imaging data in eleven healthy subjects and performed probabilistic tractography from voxels within the thalamus.

Keys to unlocking the mysteries of rheumatic autoimmune disease.

Autoimmune diseases are thought to affect between 14 million and 22 million people in this country. Despite decades of research, the underlying mechanisms of disease are poorly understood, diagnosis is often difficult, and therapies that minimize systemic side effects are lacking. Major advances in our understanding of human genetic variation and remarkable new technologies are paving the way for dramatically improving our fundamental knowledge of autoimmune diseases.

Expression levels for many genes in human peripheral blood cells are highly sensitive to ex vivo incubation.

Monitoring of gene and protein expression in peripheral blood cells has significant potential for improving the diagnosis and therapy of many human diseases. As genomic-scale microarray and proteomic technologies are applied to peripheral blood, it is important to consider the variables that may affect interpretation of data. Here we report experiments performed to identify genes that are particularly sensitive to ex vivo handling prior to RNA extraction for gene expression microarrays or quantitative real-time RT-PCR assays.

Single Logon: balancing security and healthcare productivity.

Mayo Single Logon (MSL) has faced the traditional dilemma that is painful to all IT organizations because it forces the tradeoff between user productivity and security. Recent regulatory initiatives, such as HIPAA, have caused the issue of security to take on more importance, forcing organizations to revisit the balance of security and productivity. MSL is a security application that brokers user credentials and facilitates desktop security.

Fatal acute lymphoblastic leukemia in mice transgenic for B cell-restricted bcl-xL and c-myc.

Expression of the c-myc gene is frequently dysregulated in malignant tumors and translocations of c-myc into the Ig H chain locus are associated with Burkitt's-type lymphoma. There is indirect evidence that bcl-x, an anti-apoptotic member of the bcl-2 gene family, may also contribute to a variety of B lymphoid tumors. In this study, we show that mice transgenic for both B cell-restricted c-myc and bcl-x(L) developed aggressive, acute leukemias expressing early B lineage and stem cell surface markers.

Predictors of health care utilization of children with asthma in the community.

The aim of this study was to assess the pattern of use of health care services among children with asthma symptoms within the community, and assess groups at increased risk of emergency department (ED) visits or hospital admissions (HA). Using International Study of Asthma and Allergies in Childhood phase II protocol, information about asthma management and utilization of health care services was collected by parental questionnaire in a community-based random sample of 5-7- and 9-11-year-old children (n = 11,094) in Dresden and Munich. Only 11.

Constrained linear basis sets for HRF modelling using Variational Bayes.

FMRI modelling requires flexible haemodynamic response function (HRF) modelling, with the HRF being allowed to vary spatially and between subjects. To achieve this flexibility, voxelwise parameterised HRFs have been proposed; however, inference on such models is very slow. An alternative approach is to use basis functions allowing inference to proceed in the more manageable General Linear Model (GLM) framework.

Multilevel linear modelling for FMRI group analysis using Bayesian inference.

Functional magnetic resonance imaging studies often involve the acquisition of data from multiple sessions and/or multiple subjects. A hierarchical approach can be taken to modelling such data with a general linear model (GLM) at each level of the hierarchy introducing different random effects variance components. Inferring on these models is nontrivial with frequentist solutions being unavailable.

The use of microarrays to study autoimmunity.

As with the development of any novel and potentially powerful technology, the prospect of revealing new information that may dramatically change our understanding of biological processes can generate much excitement. Such is true for the emerging genomic approaches that make possible high-density assays using microarray platforms. Indeed, it is difficult, if not impossible, to imagine any area of biology that could not be affected by the wide range of potential applications of microarray technology.

Functional asymmetry for auditory processing in human primary auditory cortex.

Structural asymmetries in the supratemporal plane of the human brain are often cited as the anatomical basis for the lateralization of language predominantly to the left hemisphere. However, similar asymmetries are found for structures mediating earlier events in the auditory processing stream, suggesting that functional lateralization may occur even at the level of primary auditory cortex. We tested this hypothesis using functional magnetic resonance imaging to evaluate human auditory cortex responses to monaurally presented tones.

Characterization and propagation of uncertainty in diffusion-weighted MR imaging.

A fully probabilistic framework is presented for estimating local probability density functions on parameters of interest in a model of diffusion. This technique is applied to the estimation of parameters in the diffusion tensor model, and also to a simple partial volume model of diffusion. In both cases the parameters of interest include parameters defining local fiber direction.

Working Pasteur's Quadrant: harnessing science and action for community change.

Community psychology in general and the field of prevention in particular has unquestioningly accepted the assumption that the research process should proceed in a linear fashion from a search for basic knowledge to application in the community context. This ignores the compelling insight offered by Stokes (1997) that the drive for new knowledge and the pursuit of application can be combined in a single effort. If research in community psychology pursues the drive for application without an equal commitment to the development of knowledge about underlying community processes of social cooperation and change, it will become a field less capable of innovative and enduring contributions to community well-being and effectiveness Opportunities abound in community psychology for the simultaneous pursuit of new knowledge and more effective practice.

Late immature B cells (IgMhighIgDneg) undergo a light chain receptor editing response to soluble self-antigen.

Receptor editing is an important mechanism to modify the Ag specificity of newly developing B cells that are reactive with self-Ags. Previous studies have suggested that late immature B cells, bearing high levels of IgM on their cell surface, are unable to initiate receptor editing and instead are deleted by apoptosis. Using the hen egg lysozyme transgenic system, we show that IgM(high) late-immature B cells are fully capable of receptor editing to soluble self-Ag.

Are asthma and allergies in children and adolescents increasing? Results from ISAAC phase I and phase III surveys in Münster, Germany.

Objective: To assess time trends in symptoms of asthma, allergic rhinitis, and atopic eczema among children in Münster, Germany.

Methods: Two cross-sectional surveys 5-years apart (1994/1995, 1999/2000) using ISAAC core written and video questionnaires and applying the ISAAC protocol. Two main age groups (6-7 and 13-14 year olds) were designated with information collected by parental and self-report for both age groups, respectively.

Non-invasive mapping of connections between human thalamus and cortex using diffusion imaging.

Evidence concerning anatomical connectivities in the human brain is sparse and based largely on limited post-mortem observations. Diffusion tensor imaging has previously been used to define large white-matter tracts in the living human brain, but this technique has had limited success in tracing pathways into gray matter. Here we identified specific connections between human thalamus and cortex using a novel probabilistic tractography algorithm with diffusion imaging data.

The role of nitrogen-efficient cultivars in sustainable agriculture.

To improve nitrogen (N) efficiency in agriculture, integrated N management strategies that take into consideration improved fertilizer, soil, and crop management practices are necessary. This paper reports results of field experiments in which maize (Zea mays L.) and oilseed rape (Brassica napus L.

Visualization of the genesis and fate of isotype-switched B cells during a primary immune response.

The life history of isotype-switched B cells is unclear, in part, because of an inability to detect rare antigen-specific B cells at early times during the immune response. To address this issue, a small population of B cells carrying targeted antibody transgenes capable of class switching was monitored in immunized mice. After contacting helper T cells, the first switched B cells appeared in follicles rather than in the red pulp, as was expected.

Interferon-inducible gene expression signature in peripheral blood cells of patients with severe lupus.

Systemic lupus erythematosus (SLE) is a complex, inflammatory autoimmune disease that affects multiple organ systems. We used global gene expression profiling of peripheral blood mononuclear cells to identify distinct patterns of gene expression that distinguish most SLE patients from healthy controls. Strikingly, about half of the patients studied showed dysregulated expression of genes in the IFN pathway.