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PubMed1978

The correlation between relatives with assortative mating.

The equilibrium correlation between various close relatives is calculated for phenotypic assortative mating for a character determined by additive loci without dominance and an uncorrelated environment. It is supposed that the phenotypes of spouses have a bivariate normal distribution and environment and heredity are normally distributed. Heredity is Gaussian if either there are many alleles with approximately normally distributed effects at each of an arbitrary number of loci or the trait is controlled by many loci, each of which makes only a small contribution. It is also assumed that the regression of the phenotype or genotype of an individual on the phenotype or genotype of any one of his relatives is linear. The results show that with the above assumptions Fisher's formulae for the correlation between relatives hold with no restrictions on the linkage map.

Female↗
PubMed1990

Standard maps of chromosome 10.

To achieve consensus more exact definitions of genetical maps are required, of which standard, comprehensive and skeletal might be some. A standard genetic map gives distance from pter in centimorgans (cM), uses the international nomenclature for assigned loci, is sex-specific, and allows as well as possible for interference and typing errors. A standard physical map gives distance from pter in megabases (Mb). A standard map is called comprehensive if it aims to include all syntenic loci, and skeletal if it is limited to loci whose order is well supported. Loci with established order are called skeletal, and are used to define regional assignments of other loci. These principles are illustrated using the CEPH data for chromosome 10. Map lengths by multiple 2-point analysis under supported interference are in good agreement with other evidence, but multipoint mapping gives a substantial overestimate. There are currently 21 loci in the skeletal genetic map and 40 loci in the comprehensive genetic map. From these data, cytogenetic assignments, and partial genetic maps the physical location has been estimated for 85 loci. MEN2A is in a region close to the centromere in which male recombination per megabase is much reduced. Order of DNA markers in this densely mapped region has not been determined, and therefore the exact location of MEN2A is uncertain, although it is likely to lie between D10S34 and D10S30 and close to D10S11.

Chi-Square Distribution↗
PubMed2005

Recording techniques for clinical electrophysiology.

The precise techniques employed in the electrophysiology laboratory influence the nature of the electrograms that are recorded during mapping procedures. Unipolar recordings that are minimally filtered can be useful for mapping focal arrhythmia sources, but have substantial far-field signal that can obscure low-amplitude signals of interest in abnormal regions. Bipolar recordings are standard in most laboratories because rejection of far-field signal facilitates identification of local potentials in abnormal areas, but the signal of interest can be beneath either recording electrode and far-field signals do occur. Simultaneously obtained unipolar recordings are a useful adjunct to bipolar recordings in some situations. High pass filtering and digital sampling also influence electrogram characteristics. High pass filtering of unipolar recordings can be useful to reduce far-field components, but limits inferences from electrogram morphology.

Arrhythmias, Cardiac↗
PubMed2005

Comparative study of apoptosis-related gene loci in human, mouse and rat genomes.

Many genes are involved in mammalian cell apoptosis pathway. These apoptosis genes often contain characteristic functional domains, and can be classified into at least 15 functional groups, according to previous reports. Using an integrated bioinformatics platform for motif or domain search from three public mammalian proteomes (International Protein Index database for human, mouse, and rat), we systematically cataloged all of the proteins involved in mammalian apoptosis pathway. By localizing those proteins onto the genomes, we obtained a gene locus centric apoptosis gene catalog for human, mouse and rat. Further phylogenetic analysis showed that most of the apoptosis related gene loci are conserved among these three mammals. Interestingly, about one-third of apoptosis gene loci form gene clusters on mammal chromosomes, and exist in the three species, which indicated that mammalian apoptosis gene orders are also conserved. In addition, some tandem duplicated gene loci were revealed by comparing gene loci clusters in the three species. All data produced in this work were stored in a relational database and may be viewed at http://pcas.cbi.pku.edu.cn/database/apd.php.

Animals↗
PubMed1972

Chromosome mapping in the mouse, fluorescence banding techniques permit assignment of most genetic linkage groups.

Chromosome banding techniques have permitted the identification of every normal chromosome in the mouse, Mus musculus, and the demonstration of strain differences. By identifying the chromosomes involved in a series of translocations, it has been possible to assign 14 of the 19 known linkage groups to 14 different chromosomes. These powerful cytological methods promise to revolutionize cytogenetic studies in higher organisms.

Animals↗
PubMed1997

Infrequent types of pallidal discharges during pallidotomy.

Pallidal discharges of patients with Parkinson's disease have been characterized as slow irregular or bursting discharges for the external pallidal segment (GPe) and fast discharges for the internal pallidal segment (GPi). Tremor-synchronous cells have also been described. Using microrecording techniques on 70 patients who underwent pallidotomy, we have recorded other types of pallidal discharges. In GPe, we recorded cells which fired fast, cells which were silent, and cells which fired tonically. In GPi, we recorded cells which burst following short segments of fast tonic discharges. We will demonstrate these cells and discuss their clinical significance.

Action Potentials↗
PubMed1986

Statistical decision rules concerning synteny or independence between markers.

Data on the segregation of human markers in somatic hybrids between permanent rodent cell lines and primary human cells were gathered and statistically analyzed, using various criteria of association. The analysis provides evidence that human chromosomes do not segregate independently in somatic cell hybrids. A statistical decision rule concerning synteny or independence between markers is proposed, and its utility in developing the gene maps of other species by means of somatic cell hybridization is explored.

Animals↗
PubMed2004

Inhibitors of protein kinase signaling pathways: emerging therapies for cardiovascular disease.

Protein kinases are enzymes that covalently modify proteins by attaching phosphate groups (from ATP) to serine, threonine, and/or tyrosine residues. In so doing, the functional properties of the protein kinase's substrates are modified. Protein kinases transduce signals from the cell membrane into the interior of the cell. Such signals include not only those arising from ligand-receptor interactions but also environmental perturbations such as when the membrane undergoes mechanical deformation (ie, cell stretch or shear stress). Ultimately, the activation of signaling pathways that use protein kinases often culminates in the reprogramming of gene expression through the direct regulation of transcription factors or through the regulation of mRNA stability or protein translation. Protein kinases regulate most aspects of normal cellular function. The pathophysiological dysfunction of protein kinase signaling pathways underlies the molecular basis of many cancers and of several manifestations of cardiovascular disease, such as hypertrophy and other types of left ventricular remodeling, ischemia/reperfusion injury, angiogenesis, and atherogenesis. Given their roles in such a wide variety of disease states, protein kinases are rapidly becoming extremely attractive targets for drug discovery, probably second only to heterotrimeric G protein-coupled receptors (eg, angiotensin II). Here, we will review the reasons for this explosion in interest in inhibitors of protein kinases and will describe the process of identifying novel drugs directed against kinases. We will specifically focus on disease states for which drug development has proceeded to the point of clinical or advanced preclinical studies.

Animals↗
PubMedDate not supplied

Automatic resolution of ambiguous terms based on machine learning and conceptual relations in the UMLS.

UNLABELLED: Motivation. The UMLS has been used in natural language processing applications such as information retrieval and information extraction systems. The mapping of free-text to UMLS concepts is important for these applications. To improve the mapping, we need a method to disambiguate terms that possess multiple UMLS concepts. In the general English domain, machine-learning techniques have been applied to sense-tagged corpora, in which senses (or concepts) of ambiguous terms have been annotated (mostly manually). Sense disambiguation classifiers are then derived to determine senses (or concepts) of those ambiguous terms automatically. However, manual annotation of a corpus is an expensive task. We propose an automatic method that constructs sense-tagged corpora for ambiguous terms in the UMLS using MEDLINE abstracts. METHODS: For a term W that represents multiple UMLS concepts, a collection of MEDLINE abstracts that contain W is extracted. For each abstract in the collection, occurrences of concepts that have relations with W as defined in the UMLS are automatically identified. A sense-tagged corpus, in which senses of W are annotated, is then derived based on those identified concepts. The method was evaluated on a set of 35 frequently occurring ambiguous biomedical abbreviations using a gold standard set that was automatically derived. The quality of the derived sense-tagged corpus was measured using precision and recall. RESULTS: The derived sense-tagged corpus had an overall precision of 92.9% and an overall recall of 47.4%. After removing rare senses and ignoring abbreviations with closely related senses, the overall precision was 96.8% and the overall recall was 50.6%. CONCLUSIONS: UMLS conceptual relations and MEDLINE abstracts can be used to automatically acquire knowledge needed for resolving ambiguity when mapping free-text to UMLS concepts.

Abbreviations as Topic↗
PubMed2003

Tools and approaches for the construction of knowledge models from the neuroscientific literature.

Within this paper, we describe a neuroinformatics project (called "NeuroScholar," http://www.neuroscholar.org/) that enables researchers to examine, manage, manipulate, and use the information contained within the published neuroscientific literature. The project is built within a multi-level, multi-component framework constructed with the use of software engineering methods that themselves provide code-building functionality for neuroinformaticians. We describe the different software layers of the system. First, we present a hypothetical usage scenario illustrating how NeuroScholar permits users to address large-scale questions in a way that would otherwise be impossible. We do this by applying NeuroScholar to a "real-world" neuroscience question: How is stress-related information processed in the brain? We then explain how the overall design of NeuroScholar enables the system to work and illustrate different components of the user interface. We then describe the knowledge management strategy we use to store interpretations. Finally, we describe the software engineering framework we have devised (called the "View-Primitive-Data Model framework," [VPDMf]) to provide an open-source, accelerated software development environment for the project. We believe that NeuroScholar will be useful to experimental neuroscientists by helping them interact with the primary neuroscientific literature in a meaningful way, and to neuroinformaticians by providing them with useful, affordable software engineering tools.

Artificial Intelligence↗
PubMed2006

[Genetics in eating disorders: extending the boundaries of research].

OBJECTIVE: To review the recent literature relevant to genetic research in eating disorders and to discuss unique issues which are crucial for the development of a genetic research project in eating disorders in Brazil. METHOD: A computer literature review was conducted in the Medline database between 1984 and may 2005 with the search terms "eating disorders", "anorexia nervosa", "bulimia nervosa", "binge eating disorder", "family", "twin" and "molecular genetic" studies. RESULTS: Current research findings suggest a substantial influence of genetic factors on the liability to anorexia nervosa and bulimia nervosa. Genetic research with admixed populations should take into consideration sample size, density of genotyping and population stratification. Through admixture mapping it is possible to study the genetic structure of admixed human populations to localize genes that underlie ethnic variation in diseases or traits of interest. CONCLUSIONS: The development of a major collaborative genetics initiative of eating disorders in Brazil and South America would represent a realistic possibility of studying the genetics of eating disorders in the context of inter ethnic groups, and also integrate a new perspective on the biological etiology of eating disorders.

Anorexia Nervosa↗