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At least 307 records · Page 17Linked to original sources
PubMed2006

The IMAGE project: methodological issues for the molecular genetic analysis of ADHD.

The genetic mechanisms involved in attention deficit hyperactivity disorder (ADHD) are being studied with considerable success by several centres worldwide. These studies confirm prior hypotheses about the role of genetic variation within genes involved in the regulation of dopamine, norepinephrine and serotonin neurotransmission in susceptibility to ADHD. Despite the importance of these findings, uncertainties remain due to the very small effects sizes that are observed. We discuss possible reasons for why the true strength of the associations may have been underestimated in research to date, considering the effects of linkage disequilibrium, allelic heterogeneity, population differences and gene by environment interactions. With the identification of genes associated with ADHD, the goal of ADHD genetics is now shifting from gene discovery towards gene functionality--the study of intermediate phenotypes ('endophenotypes'). We discuss methodological issues relating to quantitative genetic data from twin and family studies on candidate endophenotypes and how such data can inform attempts to link molecular genetic data to cognitive, affective and motivational processes in ADHD. The International Multi-centre ADHD Gene (IMAGE) project exemplifies current collaborative research efforts on the genetics of ADHD. This European multi-site project is well placed to take advantage of the resources that are emerging following the sequencing of the human genome and the development of international resources for whole genome association analysis. As a result of IMAGE and other molecular genetic investigations of ADHD, we envisage a rapid increase in the number of identified genetic variants and the promise of identifying novel gene systems that we are not currently investigating, opening further doors in the study of gene functionality.

Journal Article↗
PubMed1999

Major Histocompatibility Complex.

At the 2nd Congress of Russian Immunologists, which is holding at the boundary not only two centuries, but and millennia, we had to present views, how the knowledge about major histocompatibility system has been changed (better to say has been progressed) for the brief historical period (50-60 years). 1. Having started from two, and then three component genetic HLA structure, the further studies gave image about multicomponent genetic composition of HLA, which is still not clarified up till now. At present, HLA accounts more than 10 structural units (subloci), some of which have only recently received the names. 2. The role of MHC in "cascading" of immune reactions is indeed global. Now, the view that immune reaction is developing by "cascade" type is not argued, and all the "cascade" is mediated through MHC. 3. The studies in the field of "HLA and diseases" are looking now in new light: the leitmotif of HLA C began to sound. 4. The structure of this system is indeed unique. Now discovered subunits in DRB1 locus, where each gene appeared to be in several subvariants (forms), not seldom differing only by single amino acid, pose classical genetics in difficult situation: what can be called with gene, allele, subgene, subvariant, suballele. 5. At last, the prospective is opened for HLA using in practical purposes, which earlier was not seen, namely: the transfusion of HLA typed platelets, leukocytes, lymphocytes for increasing not only therapeutic, but economical efficiency of such procedures.

Journal Article↗
PubMed2004

Autoradiographic imaging of altered synaptic alphabetagamma2 and extrasynaptic alphabeta GABAA receptors in a genetic mouse model of anxiety.

To image the possible alterations in brain regional GABAA receptor subtype properties in a genetic animal model of human anxiety, mice heterozygous for the deletion of GABAA receptor gamma2 subunit (gamma2+/-) were studied using ligand autoradiographic assays on brain cryostat sections. The [35S]TBPS binding assay was designed to reveal impaired GABA and channel site coupling shown to be more prominent in recombinant alpha1/6beta3 than in alpha1/2beta3gamma2 or beta2 subunit-containing GABAA receptors expressed in HEK 293 cells. Increased GABA-insensitive [35 S]TBPS binding in the gamma2+/- mouse brains was evident in the cerebral cortex and in subcortical regions, the alterations being regionally similar to the loss of gamma2 subnunit-dependent benzodiazepine (BZ) sites as revealed by [3H]Ro 15-4513 autoradiography. As the gamma2 subunit protein is needed for synaptic clustering of GABAA receptors, these results indicate that the extrasynaptic alphabeta3 receptors can be visualized in vitro as atypical GABA-insensitive [35S]TBPS binding sites. The results suggest that GABAAergic synaptic inhibition is widely decreased in the brains of anxiety-prone gamma2+/- mice, while extrasynaptic GABAA receptors are increased. These autoradiographic imaging findings further demonstrate the need to develop GABAA receptor subtype-selective in vivo ligands to aid in assessing the contributions of various subcellular receptor populations in anxious and other patient groups.

Animals↗
PubMed2005

Precision range image registration using a robust surface interpenetration measure and enhanced genetic algorithms.

This paper addresses the range image registration problem for views having low overlap and which may include substantial noise. The current state of the art in range image registration is best represented by the well-known iterative closest point (ICP) algorithm and numerous variations on it. Although this method is effective in many domains, it nevertheless suffers from two key limitations: It requires prealignment of the range surfaces to a reasonable starting point and it is not robust to outliers arising either from noise or low surface overlap. This paper proposes a new approach that avoids these problems. To that end, there are two key, novel contributions in this work: a new, hybrid genetic algorithm (GA) technique, including hillclimbing and parallel-migration, combined with a new, robust evaluation metric based on surface interpenetration. Up to now, interpenetration has been evaluated only qualitatively; we define the first quantitative measure for it. Because they search in a space of transformations, GAs are capable of registering surfaces even when there is low overlap between them and without need for prealignment. The novel GA search algorithm we present offers much faster convergence than prior GA methods, while the new robust evaluation metric ensures more precise alignments, even in the presence of significant noise, than mean squared error or other well-known robust cost functions. The paper presents thorough experimental results to show the improvements realized by these two contributions.

Algorithms↗
PubMed1996

Friedreich's ataxia with retained tendon reflexes: molecular genetics, clinical neurophysiology, and magnetic resonance imaging.

Lower limb areflexia is generally regarded as an essential criterion for the diagnosis of Friedreich's ataxia (FRDA). We describe a family with a recessive form of early-onset ataxia in which one member had a phenotype typical of FRDA whereas another, with retained tendon reflexes in the lower limbs, did not have electrophysiologic evidence of the usual severe afferent axonal neuropathy of FRDA. In contrast, somatosensory evoked potentials, eye-movement recordings, and MRI of the head and cervical cord provided results highly suggestive of FRDA in both patients. We performed genetic linkage analysis in this family, using markers tightly linked to the FRDA locus on chromosome 9. Inheritance of identical paternal and maternal genotypes by the affected members, but not by their unaffected siblings, provided supporting evidence that this disorder may result from mutation within the FRDA gene or is tightly linked to the investigated loci on chromosome 9.

Adult↗
PubMed1992

Bilateral striopallidodentate calcinosis: cerebrospinal fluid, imaging, and electrophysiological studies.

We report the genetic, clinical, electrophysiological, and imaging studies in a family with bilateral striopallidodentate calcinosis (Fahr's disease). The intracerebral calcium deposits occurred before onset of the symptoms in the third decade of life. Progressive neurological deterioration occurred in the fifth decade of life in the proband. Cerebrospinal fluid homocarnosine, a central nervous system-specific peptide, was increased twofold in patients with autosomal dominant bilateral stripallidodentate calcinosis; in sporadic cases, there was no detectable homocarnosine and a decreased level of histidine. With advancing age, the amount of calcification increases, but it has not been determined if a critical amount must be reached before symptoms occur. Computerized tomography is superior to magnetic resonance imaging for radiological diagnosis. Despite diffuse striatal calcification, striatal 6-[18F]fluoro-L-dopa uptake did not reveal any difference between patients and control subjects, from which we infer persisting integrity of the nigrostriatal dopaminergic pathway.

Adult↗
PubMed2003

Normalizing the background and removing the trend in one-dimensional DNA fingerprint images.

Maximizing an individual's genetic information from its DNA fingerprint image depends on the number of bands distinguished from the background. To approach this goal, the background should be normalized while the information is preserved. Morphological operators have been used by some authors to normalize the background for two-dimensional gel images. Methods such as mean, median and "maxpolygon" are presented in this work to normalize the background in DNA fingerprint images. Mean and median methods will lead to some deformations. Visual evaluation of the results show that the original shape of the column signals are better preserved by the maxpolygon.

DNA Fingerprinting↗
PubMed2005

Genetically encoded stress indicator for noninvasively imaging endogenous corticosterone in living mice.

Physical and emotional stress is one of the major controllers of physiological reactions and homeostasis in living animals. A stress hormone, corticosterone, is secreted from the adrenal cortex into the blood vessels when animals sense the stress. The quantitative evaluation of corticosterone in living animals has been limited because of the unavailability of suitable methods in vivo. For a noninvasive molecular imaging of the stress, we developed a method for detecting physiological increases in the endogenous corticosterone caused by exo- and endogenous stress in living animals. We constructed a pair of genetically encoded indicators composed of cDNAs of glucocorticoid receptor (GR), split Renilla luciferase (RLuc), and a Synechocystis sp. DnaE intein. The GR fused with C-terminal halves of RLuc and DnaE is localized in the cytosol, whereas a fusion protein of N-terminal halves of RLuc and DnaE is localized in the nucleus. If corticosterone induces GR translocation into the nucleus, the C-terminal RLuc meets the N-terminal one in the nucleus, and full-length RLuc is reconstituted by protein splicing with DnaE. Cell-based methods provided a quantitative bioluminescence assay of the extent of GR translocation into the nucleus. We further demonstrated that the indicator enabled noninvasive imaging against two different types of imposed stress: a forced swimming and metabolic perturbation caused by 2-deoxy-D-glucose. This stress indicator should be valuable for screening pharmacological compounds and for tools to study the mechanism of physiological stress.

Animals↗
PubMed1999

[Genetic analysis of anatomical and morphologic traits of the brain, determined by magnetic resonance imaging in families of schizophrenic patients].

Genetic analysis of clinical data and data obtained by magnetic resonance imaging (MRI) on 26 families of schizophrenic patients (26 probands who were patients with schizophrenia, 47 parents, and 15 siblings) revealed an enlargement of the ventricular brain system both in probands and their affected and healthy relatives. Most MRI parameters had high coefficients of inheritance and tended to be linked with positive and negative psychopathological symptoms. Our results confirm the hypothesis of genetic predisposition to the structural changes in the brains of schizophrenic patients and suggest that such MRI characteristics as the width of the anterior horn of the left lateral ventricle in the region of the caudate nucleus, the width of the central region of the left lateral ventricle, the width of the anterior horn of the right lateral ventricle in the region of the caudate nucleus, and the width of the central region of the right lateral ventricle may serve as a marker of predisposition to schizophrenia.

Adult↗
PubMed1995

[Population sturcture of the Gorno-Mariĭskiĭ region of the Mariĭ El Republic].

The genetic structure of the population of the Gorno-Mariiskii raion, Marii El Republic, was studied. The population consists of two major groups, highland Mari and Russians. The former constitute the majority of the rural population, and the latter, the majority of the urban one. A marked ethnicity-related marriage assortation was found. The value of random inbreeding was estimated using frequencies of surnames. It varied from 0.00015 to 0.00069 (the weighted average was 0.00026). The local inbreeding (a) for Gorno-Mariiskii raion estimated according to Malecot was 0.00029. The local inbreeding for marriages between Mari (0.0022) was five times higher than for marriages between Russians. The indices of endogamy were 0.84 in the rural population and 0.14 in the urban population. The matrix of genetic distances and its image in the form of genetic landscape suggest a regularly distorted isolation by distance and realized panmixia.

Consanguinity↗
PubMed2002

Secondary prevention: screening and surveillance of persons at average and high risk for colorectal cancer.

Secondary prevention of colorectal cancer with FOBT and endoscopy with polypectomy decreases cancer deaths. Other available modalities include genetic tests and imaging studies, but outcomes data are not yet available. Issues remain concerning the most appropriate test, the optimal intervals, and cost-efficacy. Patients may be stratified by personal and family risk, and specific strategies may be used. Newer developments in genetic tests and imaging, including virtual colonoscopy, hold promise for the future. The most important issue at present is to have people screened or surveilled by any of the recommended modalities.

Adenoma↗
PubMed2004

Novel genetic-neuro-fuzzy filter for speckle reduction from sonography images.

Edge-preserving speckle noise reduction is essential to computer-aided ultrasound image processing and understanding. A new class of genetic-neuro-fuzzy filter is proposed to optimize the trade-off between speckle noise removal and edge preservation. The proposed approach combines the advantages of the fuzzy, neural, and genetic paradigms. Neuro-fuzzy approaches are very promising for nonlinear filtering of noisy images. Fuzzy reasoning embedded into the network structure aims at reducing errors while fine details are being processed. The learning method based on the real-time genetic algorithms (GAs) performs an effective training of the network from a collection of training data and yields satisfactory results after a few generations. The performance of the proposed filter has been compared with that of the commonly used median and Wiener filters in reducing speckle noises on ultrasound images. We evaluate this filter by passing the filter's output to the edge detection algorithm and observing its ability to detect edge pixels.Experimental results show that the proposed genetic-neuro-fuzzy technique is very effective in speckle noise reduction as well as detail preserving even in the presence of highly noise corrupted data, and it works significantly better than other well-known conventional methods in the literature.

Algorithms↗
PubMed1996

[Comparative genomic hybridization in pathology. A new molecular cytogenetic method].

Comparative genomic hybridisation (CGH) is a new cytogenetic method, which is based on a combination of fluorescence microscopy and digital image analysis. The molecular genetic basis is the hybridization of a mixture of fluorescein labeled test-DNA and reference-DNA on normal metaphase chromosomes. Comparative analysis allows the identification of all unbalanced chromosomal aberrations of the test-DNA in a single experimental step. The resulting DNA gains or DNA losses on the chromosomal or subchromosomal level mirror possible amplifications of oncogenes or losses of suppress orgenes. As CGH can be performed with genomic DNA of formalin-fixed and fresh-frozen tissue or cells, this new method is a very effective tool for pathologists and cytologists in the extended genomic screening of tumors and genetically altered tissues. Despite CGH analysis at present is restricted to research applications; its widespread dissemination as a routine method in diagnostic pathology can be expected in the near future.

Animals↗
PubMed2006

Golgi twins in late mitosis revealed by genetically encoded tags for live cell imaging and correlated electron microscopy.

Combinations of molecular tags visible in light and electron microscopes become particularly advantageous in the analysis of dynamic cellular components like the Golgi apparatus. This organelle disassembles at the onset of mitosis and, after a sequence of poorly understood events, reassembles after cytokinesis. The precise location of Golgi membranes and resident proteins during mitosis remains unclear, partly due to limitations of molecular markers and the resolution of light microscopy. We generated a fusion consisting of the first 117 residues of alpha-mannosidase II tagged with a fluorescent protein and a tetracysteine motif. The mannosidase component guarantees docking into the Golgi membrane, with the tags exposed in the lumen. The fluorescent protein is optically visible without further treatment, whereas the tetracysteine tag can be reduced acutely with a membrane-permeant phosphine, labeled with ReAsH, monitored in the light microscope, and used to trigger the photoconversion of diaminobenzidine, allowing 4D optical recording on live cells and correlated ultrastructural analysis by electron microscopy. These methods reveal that Golgi reassembly is preceded by the formation of four colinear clusters at telophase, two per daughter cell. Within each daughter, the smaller cluster near the midbody gradually migrates to rejoin the major cluster on the far side of the nucleus and asymmetrically reconstitutes a single Golgi apparatus, first in one daughter cell and then in the other. Our studies provide previously undescribed insights into Golgi disassociation and reassembly during mitosis and offer a powerful approach to follow recombinant protein distribution in 4D imaging and correlated high-resolution analysis.

Cysteine↗
PubMed2006

Heterozygous mutations affecting the epimerase domain of the GNE gene causing distal myopathy with rimmed vacuoles in a Taiwanese family.

OBJECTIVES: Studies of distal myopathy with rimmed vacuoles (DMRV) revealed that most patients had mutations in the UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) gene. However, the correlation between GNE mutations and clinical features was not fully understood. PURPOSES: To report the correlation between the clinical features and genetic analysis of DMRV patients. PATIENTS AND METHODS: The clinical presentations, histopathological findings, image studies, and genetic analyses of two patients with DMRV from a Taiwanese family were studied. RESULTS: Two compound heterozygous mutations, Ile 241 Ser and Arg 246 Gln, located in the epimerase domain, were identified in both patients, who were of the same generation. In addition, the elder sister showed a progressive muscular dystrophy course with severe quadriceps and trunk muscle involvement. CONCLUSION: The compound heterozygous mutations in the epimerase domain of the GNE gene are important in the severe phenotype of DMRV. However, the mechanisms leading to this phenotypic heterogeneity still remain to be elucidated.

Adult↗
PubMed2003

Fluorescence imaging of physiological activity in complex systems using GFP-based probes.

Genetically encoded probes for the optical imaging of excitable cell activity have been constructed by fusing fluorescent proteins to functional proteins that are involved in physiological signaling systems, such as those that control membrane potential, free calcium and cyclic nucleotide concentrations and pH. Using specific promoters and targeting signals, the probes are introduced into an intact organism and directed to specific tissue regions, cell types, and subcellular compartments, thereby extracting specific signals more efficiently and in a more relevant physiological context than before. Optical imaging using genetically encoded probes has enabled us to decipher spatio-temporal information coded in complex tissues.

Animals↗