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At least 1,369 records · Page 76Linked to original sources
PubMed2004

Characterizing the dynamic connectivity between genes by variable parameter regression and Kalman filtering based on temporal gene expression data.

MOTIVATION: One popular method for analyzing functional connectivity between genes is to cluster genes with similar expression profiles. The most popular metrics measuring the similarity (or dissimilarity) among genes include Pearson's correlation, linear regression coefficient and Euclidean distance. As these metrics only give some constant values, they can only depict a stationary connectivity between genes. However, the functional connectivity between genes usually changes with time. Here, we introduce a novel insight for characterizing the relationship between genes and find out a proper mathematical model, variable parameter regression and Kalman filtering to model it. RESULTS: We applied our algorithm to some simulated data and two pairs of real gene expression data. The changes of connectivity in simulated data are closely identical with the truth and the results of two pairs of gene expression data show that our method has successfully demonstrated the dynamic connectivity between genes. CONTACT: jiangtz@nlpr.ia.ac.cn.

Computer Simulation↗
PubMed1998

A map of the binding site for catalytic domain 5 in the core of a group II intron ribozyme.

Group II introns are ribozymes with a complex tertiary architecture that is of great interest as a model for RNA folding. Domain 5 (D5) is a highly conserved region of the intron that is considered one of the most critical structures in the catalytic core. Despite its central importance, the means by which D5 interacts with other core elements is unclear. To obtain a map of potential interaction sites, dimethyl sulfate was used to footprint regions of the intron that are involved in D5 binding. These studies were complemented by measurements of D5 binding to a series of truncated intron derivatives. In this way, the minimal region of the intron required for strong D5 association was defined and the sites most likely to represent thermodynamically significant positions of tertiary contact were identified. These studies show that ground-state D5 binding is mediated by tertiary contacts to specific regions of D1, including a tetraloop receptor and an adjacent three-way junction. In contrast, D2 and D3 are not found to stabilize D5 association. These data highlight the significance of D1-D5 interactions and will facilitate the identification of specific tertiary contacts between them.

Base Sequence↗
PubMed1989

Cytogenetic analysis of segregation distortion in Drosophila melanogaster: the cytological organization of the Responder (Rsp) locus.

The segregation distortion phenomenon occurs in Drosophila melanogaster males carrying an SD second chromosome and an SD+ homolog. In such males the SD chromosome is transmitted to the progeny more frequently than the expected 50% because of an abnormal differentiation of the SD+-bearing sperms. Three major loci are involved in this phenomenon: SD and Rsp, associated with the SD and SD+ chromosome, respectively, and E(SD). In the present work we performed a cytogenetic analysis of the Rsp locus which was known to map to the centromeric heterochromatin of the second chromosome. Hoechst- and N-banding techniques were used to characterize chromosomes carrying Responder insensitive (Rspi), Responder sensitive (Rsps) and Responder supersensitive (Rspss) alleles. Our results locate the Rsp locus to the h39 region of 2R heterochromatin. This region is a Hoechst-bright, N-banding negative heterochromatic block adjacent to the centromere. Quantitative variations of the h39 region were observed. The degree of sensitivity to Sd was found to be directly correlated with the physical size of that region, demonstrating that the Rsp locus is composed of repeated DNA.

Alleles↗
PubMed1989

Genetic and molecular characterization of suppressors of SIR4 mutations in Saccharomyces cerevisiae.

In order to learn more about other proteins that may be involved in repression of HML and HMR in Saccharomyces cerevisiae, extragenic suppressor mutations were identified that could restore repression in cells defective in SIR4, a gene required for function of the silencer elements flanking HML and HMR. These suppressor mutations, which define at least three new genes, SAN1, SAN2 and SAN3, arose at the frequency expected for loss-of-function mutations following mutagenesis. All san mutations were recessive. Suppression by san1 was allele-nonspecific, since san1 could suppress two very different alleles of SIR4, and was locus-specific since san1 was unable to suppress a SIR3 mutation or a variety of mutations conferring auxotrophies. The SAN1 gene was cloned, sequenced, and used to construct a null allele. The null allele had the same phenotype as the EMS-induced mutations and exhibited no pleiotropies of its own. Thus, the SAN1 gene was not essential. SAN1-mediated suppression was neither due to compensatory mutations in interacting proteins, nor to translational missense suppression. SAN1 may act posttranslationally to control the stability or activity of the SIR4 protein.

Alleles↗
PubMed2001

Molecular characterization of Pax6(2Neu) through Pax6(10Neu): an extension of the Pax6 allelic series and the identification of two possible hypomorph alleles in the mouse Mus musculus.

Phenotype-based mutagenesis experiments will increase the mouse mutant resource, generating mutations at previously unmarked loci as well as extending the allelic series at known loci. Mapping, molecular characterization, and phenotypic analysis of nine independent Pax6 mutations of the mouse recovered in mutagenesis experiments is presented. Seven mutations result in premature termination of translation and all express phenotypes characteristic of null alleles, suggesting that Pax6 function requires all domains to be intact. Of major interest is the identification of two possible hypomorph mutations: Heterozygotes express less severe phenotypes and homozygotes develop rudimentary eyes and nasal processes and survive up to 36 hr after birth. Pax6(4Neu) results in an amino acid substitution within the third helix of the homeodomain. Three-dimensional modeling indicates that the amino acid substitution interrupts the homeodomain recognition alpha-helix, which is critical for DNA binding. Whereas cooperative dimer binding of the mutant homeodomain to a paired-class DNA target sequence was eliminated, weak monomer binding was observed. Thus, a residual function of the mutated homeodomain may explain the hypomorphic nature of the Pax6(4Neu) allele. Pax6(7Neu) is a base pair substitution in the Kozak sequence and results in a reduced level of Pax6 translation product. The Pax6(4Neu) and Pax6(7Neu) alleles may be very useful for gene-dosage studies.

Alleles↗
PubMed1995

Analysis of the CD3 gene region and type 1 diabetes: application of fluorescence-based technology to linkage disequilibrium mapping.

The CD3 gene region on chromosome 11q23 has been implicated in susceptibility to type 1 (insulin-dependent) diabetes mellitus. Using semi-automated fluorescence-based technology, we have undertaken association and linkage analysis of a dinucleotide microsatellite in the CD3 delta (CD3D) gene. We have also performed a large case-control analysis of a restriction fragment length polymorphism (RFLP) in the CD3 epsilon (CD3E) gene, 26 kb from CD3D. We found no evidence for the previously reported association between the 8 kb allele of the RFLP and disease in a UK dataset of 403 diabetic patients and 446 nondiabetic controls. Furthermore, the use of the transmission/disequilibrium test (TDT) showed no evidence of linkage or association to type 1 diabetes at either marker locus. We conclude that the CD3 gene region does not contribute significantly to IDDM susceptibility. We have successfully applied semi-automated, fluorescence-based technology to undertake association analysis on the CD3D microsatellite. Moreover, by analysing 94 other dinucleotide repeat markers, we conclude that fluorescence-based methodology can generally be applied to large-scale, semi-automated association studies with most microsatellite markers.

Adolescent↗
PubMed1993

High-resolution EEG using spline generated surface Laplacians on spherical and ellipsoidal surfaces.

Spline generated surface Laplacians are introduced as an effective method for estimating neocortical source activity at moderate scales. The method appears to be robust to the unavoidable perturbations of measured potentials and errors of head geometry and resistivity that are certain to occur in clinical or research settings. In particular, we have derived the surface Laplacian for general ellipsoidal surfaces in terms of the spline function. The spline-Laplacian accurately estimates isolated dipoles or distributed sources, is insensitive to subcortical sources and to sources which originate outside the boundaries of the electrode array, and acts as a bandpass spatial filter whose characteristics appear to provide a good match to the volume conduction of intracranial sources through human heads. As a result, spatial resolution is improved over that obtained with conventional EEG by at least a factor of three. This improvement, whether obtained with spline-Laplacian or model-dependent methods, is likely to have a significant impact on both medical and cognitive studies involving EEG.

Action Potentials↗
PubMed2006

Neuroethics.

Neuroimaging, psychosurgery, deep-brain stimulation, and psychopharmacology hold considerable promise for more accurate prediction and diagnosis and more effective treatment of neurological and psychiatric disorders. Some forms of psychopharmacology may even be able to enhance normal cognitive and affective capacities. But the brain remains the most complex and least understood of all the organs in the human body. Mapping the neural correlates of the mind through brain scans, and altering these correlates through surgery, stimulation, or pharmacological interventions can affect us in both positive and negative ways. We need to carefully weigh the potential benefit against the potential harm of such techniques. This paper examines some of these techniques and explores the emerging ethical issues in clinical neuroscience.

Behavior Control↗