Dosage-sensitive X-linked locus influences the development of amygdala and orbitofrontal cortex, and fear recognition in humans.

The amygdala, which plays a critical role in emotional learning and social cognition, is structurally and functionally sexually dimorphic in humans. We used magnetic neuroimaging and molecular genetic analyses with healthy subjects and patients possessing X-chromosome anomalies to find dosage-sensitive genes that might influence amygdala development. If such X-linked genes lacked a homologue on the Y-chromosome they would be expressed in one copy in normal 46,XY males and two copies in normal 46,XX females.

Assessment of genome-wide protein function classification for Drosophila melanogaster.

The functional classification of genes on a genome-wide scale is now in its infancy, and we make a first attempt to assess existing methods and identify sources of error. To this end, we compared two independent efforts for associating proteins with functions, one implemented by FlyBase and the other by PANTHER at Celera Genomics. Both methods make inferences based on sequence similarity and the available experimental evidence.

Health care resource use and stroke outcome. Multinational comparisons within the GAIN International trial.

Background And Purpose: Outcome in patients hospitalized for acute stroke varies considerably between populations. Within the framework of the GAIN International trial, a large multicenter trial of a neuroprotective agent (gavestinel, glycine antagonist), stroke outcome in relation to health care resource use has been compared in a large number of countries, allowing for differences in case mix.

Methods: This substudy includes 1,422 patients in 19 countries grouped into 10 regions.

Computer-assisted imaging to assess brain structure in healthy and diseased brains.

Neuroanatomical structures may be profoundly or subtly affected by the interplay of genetic and environmental factors, age, and disease. Such effects are particularly true in healthy ageing individuals and in those who have neurodegenerative diseases. The ability to use imaging to identify structural brain changes associated with different neurodegenerative disease states would be useful for diagnosis and treatment.

Functional magnetic resonance imaging technology and traumatic brain injury rehabilitation: guidelines for methodological and conceptual pitfalls.

Objectives: To illuminate the current methodological and conceptual pitfalls inherent in conducting functional magnetic resonance imaging (fMRI) research with individuals who have sustained traumatic brain injury (TBI) and to discuss appropriate remedies. The aim is describe fMRI research, its limitations, and how to best use this technology to examine TBI.

Discussion: The topics discussed in this article include issues regarding signal detection, brain activation measurement, head movement, and sources of signal artifact.

Modeling regional and psychophysiologic interactions in fMRI: the importance of hemodynamic deconvolution.

The analysis of functional magnetic resonance imaging (fMRI) time-series data can provide information not only about task-related activity, but also about the connectivity (functional or effective) among regions and the influences of behavioral or physiologic states on that connectivity. Similar analyses have been performed in other imaging modalities, such as positron emission tomography. However, fMRI is unique because the information about the underlying neuronal activity is filtered or convolved with a hemodynamic response function.

Changes in cerebral morphology consequent to peripheral autonomic denervation.

Pure autonomic failure (PAF) is characterized by an acquired, selective, peripheral denervation of the autonomic nervous system. Patients with PAF fail to generate bodily states of arousal via the autonomic nervous system in response to physical or cognitive effort. We used voxel-based morphometry to test the hypothesis that changes in the morphology of brain regions involved in autonomic control would arise as a consequence to the longstanding absence of peripheral autonomic responses in PAF patients.

A methodology to migrate the gene ontology to a description logic environment using DAML+OIL.

The Gene Ontology Next Generation Project (GONG) is developing a staged methodology to evolve the current representation of the Gene Ontology into DAML+OIL in order to take advantage of the richer formal expressiveness and the reasoning capabilities of the underlying description logic. Each stage provides a step level increase in formal explicit semantic content with a view to supporting validation, extension and multiple classification of the Gene Ontology. The paper introduces DAML+OIL and demonstrates the activity within each stage of the methodology and the functionality gained.

A novel system of fertility rescue in Drosophila hybrids reveals a link between hybrid lethality and female sterility.

Hybrid daughters of crosses between Drosophila melanogaster females and males from the D. simulans species clade are fully viable at low temperature but have agametic ovaries and are thus sterile. We report here that mutations in the D.

On ontologies for biologists: the Gene Ontology--untangling the web.

The mantra of the 'post-genomic' era is 'gene function'. Yet surprisingly little attention has been given to how functional and other information concerning genes is to be captured, made accessible to biologists or structured in a computable form. The aim of the Gene Ontology (GO) Consortium is to provide a framework for both the description and the organisation of such information.

Systematic determination of patterns of gene expression during Drosophila embryogenesis.

Background: Cell-fate specification and tissue differentiation during development are largely achieved by the regulation of gene transcription.

Results: As a first step to creating a comprehensive atlas of gene-expression patterns during Drosophila embryogenesis, we examined 2,179 genes by in situ hybridization to fixed Drosophila embryos. Of the genes assayed, 63.

The transposable elements of the Drosophila melanogaster euchromatin: a genomics perspective.

Background: Transposable elements are found in the genomes of nearly all eukaryotes. The recent completion of the Release 3 euchromatic genomic sequence of Drosophila melanogaster by the Berkeley Drosophila Genome Project has provided precise sequence for the repetitive elements in the Drosophila euchromatin. We have used this genomic sequence to describe the euchromatic transposable elements in the sequenced strain of this species.

Annotation of the Drosophila melanogaster euchromatic genome: a systematic review.

Background: The recent completion of the Drosophila melanogaster genomic sequence to high quality and the availability of a greatly expanded set of Drosophila cDNA sequences, aligning to 78% of the predicted euchromatic genes, afforded FlyBase the opportunity to significantly improve genomic annotations. We made the annotation process more rigorous by inspecting each gene visually, utilizing a comprehensive set of curation rules, requiring traceable evidence for each gene model, and comparing each predicted peptide to SWISS-PROT and TrEMBL sequences.

Results: Although the number of predicted protein-coding genes in Drosophila remains essentially unchanged, the revised annotation significantly improves gene models, resulting in structural changes to 85% of the transcripts and 45% of the predicted proteins.

A hat trick--Plasmodium, Anopheles and Homo.

The genomes of the malaria parasite, its vector and its host are now sequenced. This has been a tremendous scientific achievement. But will it offer hope to the millions who die from malaria each year? Yes, but only if combined with political will and social change.

The precision of anatomical normalization in the medial temporal lobe using spatial basis functions.

We investigated the accuracy of spatial basis function normalization using anatomical landmarks to determine how precisely homologous regions are colocalized. We examined precision in terms of: (1) the number of nonlinear basis functions used by the normalization procedure; (2) the degree of (Bayesian) regularization; and (3) the effect of substituting different templates and how this interacted with the number of basis functions. The face validity of spatial normalization was assessed as a function of these parameters, using the colocalization of homologous landmarks in a test sample of 20 normally developing children and 5 children with bilateral hippocampal pathology.

Automatic differentiation of anatomical patterns in the human brain: validation with studies of degenerative dementias.

We compared voxel-based morphometry (VBM) with independent accurate region-of-interest (ROI) measurements of temporal lobe structures in order to validate the usefulness of this fully automated and unbiased technique in Alzheimer's disease (AD) and semantic dementia (SD). In AD, ROI analyses appear more sensitive to volume loss in the amygdalae, whereas VBM analyses appear more sensitive to right middle temporal gyrus and regional hippocampal volume loss. In SD, ROI analyses appear more sensitive to left middle and inferior temporal gyrus volume loss, whereas VBM appears more sensitive to regional hippocampal volume loss.

Distributional assumptions in voxel-based morphometry.

In this paper we address the assumptions about the distribution of errors made by voxel-based morphometry. Voxel-based morphometry (VBM) uses the general linear model to construct parametric statistical tests. In order for these statistics to be valid, a small number of assumptions must hold.

Taking stock of our models: the function and future of stock centres.

Stock centres for our animal models are as important as other scientific resources, such as the primary literature or genome databases. But they need forward planning, international cooperation and secure funding to keep pace with the explosion in functional genomics that relies so heavily on them.

Classical and Bayesian inference in neuroimaging: applications.

In Friston et al. ((2002) Neuroimage 16: 465-483) we introduced empirical Bayes as a potentially useful way to estimate and make inferences about effects in hierarchical models. In this paper we present a series of models that exemplify the diversity of problems that can be addressed within this framework.

Classical and Bayesian inference in neuroimaging: theory.

This paper reviews hierarchical observation models, used in functional neuroimaging, in a Bayesian light. It emphasizes the common ground shared by classical and Bayesian methods to show that conventional analyses of neuroimaging data can be usefully extended within an empirical Bayesian framework. In particular we formulate the procedures used in conventional data analysis in terms of hierarchical linear models and establish a connection between classical inference and parametric empirical Bayes (PEB) through covariance component estimation.

Image distortion correction in fMRI: A quantitative evaluation.

A well-recognized problem with the echo-planar imaging (EPI) technique most commonly used for functional magnetic resonance imaging (fMRI) studies is geometric distortion caused by magnetic field inhomogeneity. This makes it difficult to achieve an accurate registration between a functional activation map calculated from an EPI time series and an undistorted, high resolution anatomical image. A correction method based on mapping the spatial distribution of field inhomogeneities can be used to reduce these distortions.

MRI analysis of an inherited speech and language disorder: structural brain abnormalities.

Analyses of brain structure in genetic speech and language disorders provide an opportunity to identify neurobiological phenotypes and further elucidate the neural bases of language and its development. Here we report such investigations in a large family, known as the KE family, half the members of which are affected by a severe disorder of speech and language, which is transmitted as an autosomal-dominant monogenic trait. The structural brain abnormalities associated with this disorder were investigated using two morphometric methods of MRI analysis.

An assessment of the ability of diplomates, practitioners, and students to describe and interpret recordings of heart murmurs and arrhythmia.

The ability of clinicians, ie, 10 veterinary students, 10 general practitioners, and 10 board certified internists, to describe and interpret common normal and abnormal heart sounds was assessed. Recordings of heart sounds from 7 horses with a variety of normal and abnormal rhythms, heart sounds, and murmurs were analyzed by digital sonography. The perception of the presence or absence of the heart sounds S1, S2, and S4 was similar for clinicians irrespective of their level of training and was in agreement with the sonographic interpretation on 89, 82, and 78% of occasions, respectively.

Mapping and identification of essential gene functions on the X chromosome of Drosophila.

The Drosophila melanogaster genome consists of four chromosomes that contain 165 Mb of DNA, 120 Mb of which are euchromatic. The two Drosophila Genome Projects, in collaboration with Celera Genomics Systems, have sequenced the genome, complementing the previously established physical and genetic maps. In addition, the Berkeley Drosophila Genome Project has undertaken large-scale functional analysis based on mutagenesis by transposable P element insertions into autosomes.