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PubMedDate not supplied

Immediate-early gene expression in the barrel cortex.

Since their detection in the early 1980s immediate-early genes (most of them being inducible transcription factors) have been regarded as molecular keys to the orchestration of late-effector genes that ultimately would enable functional and structural adaptation of the brain to changing external and internal demands. This is called neuronal plasticity and it has been intensively studied in the somatosensory (barrel) cortex of rodents. This brain region is intimately involved in the processing and probably also the storage of tactile information, stemming from the large facial whiskers, necessary for object detection or spatial navigation in the environment. On the other hand, several of the inducible transcription factors have been found to function as neuronal activity markers providing a cellular resolution, thus, enabling the cell-type specific mapping of activated neuronal circuits. Some recent data on both topics in the rodent barrel cortex will be presented in this topical review.

Animals↗
PubMed2004

Chicken genomics charts a path to the genome sequence.

In this paper, the current status of chicken genomics is reviewed. This is timely given the current intense activity centred on sequencing the complete genome of this model species. The genome project is based on a decade of map building by genetic linkage and cytogenetic methods, which are now being replaced by high-resolution radiation hybrid and bacterial artificial chromosome (BAC) contig maps. Markers for map building have generally depended on labour-intensive screening procedures, but in recent years this has changed with the availability of almost 500,000 chicken expressed sequence tags (ESTs). These resources and tools will be critical in the coming months when the chicken genome sequence is being assembled (eg cross-checked with other maps) and annotated (eg gene structures based on ESTs). The future for chicken genome and biological research is an exciting one, through the integration of these resources. For example, through the proposed chicken Ensembl database, it will be possible to solve challenging scientific questions by exploiting the power of a chicken model. One area of interest is the study of developmental mechanisms and the discovery of regulatory networks throughout the genome. Another is the study of the molecular nature of quantitative genetic variation. No other animal species have been phenotyped and selected so intensively as agricultural animals and thus there is much to be learned in basic and medical biology from this research.

Animals↗
PubMed1995

An algorithm for analysing probed partial digestion experiments.

A partial digestion of DNA (e.g. cosmid. Lambda, YAC, chromosome) is performed and the lengths of thoses fragments which hybridize to a labeled probe are measured using gel electrophoresis. We give an efficient algorithm that takes as input this experimental data and proposes one or more candidate solutions. Each solution designates the location of each restriction site and specifies the endpoints of each fragment. (Further experiments can then be designed to select the correct solution from this small set of candidates.) The algorithm works well even when the experiment gives inexact values for the lengths.

Algorithms↗
PubMed2004

Reconstructing biological networks using conditional correlation analysis.

MOTIVATION: One of the present challenges in biological research is the organization of the data originating from high-throughput technologies. One way in which this information can be organized is in the form of networks of influences, physical or statistical, between cellular components. We propose an experimental method for probing biological networks, analyzing the resulting data and reconstructing the network architecture. METHODS: We use networks of known topology consisting of nodes (genes), directed edges (gene-gene interactions) and a dynamics for the genes' mRNA concentrations in terms of the gene-gene interactions. We proposed a network reconstruction algorithm based on the conditional correlation of the mRNA equilibrium concentration between two genes given that one of them was knocked down. Using simulated gene expression data on networks of known connectivity, we investigated how the reconstruction error is affected by noise, network topology, size, sparseness and dynamic parameters. RESULTS: Errors arise from correlation between nodes connected through intermediate nodes (false positives) and when the correlation between two directly connected nodes is obscured by noise, non-linearity or multiple inputs to the target node (false negatives). Two critical components of the method are as follows: (1) the choice of an optimal correlation threshold for predicting connections and (2) the reduction of errors arising from indirect connections (for which a novel algorithm is proposed). With these improvements, we can reconstruct networks with the topology of the transcriptional regulatory network in Escherichia coli with a reasonably low error rate.

Algorithms↗
PubMed1997

The preliminary transcript map of a human skeletal muscle.

By sequencing 11,405 individual expressed sequence tags (ESTs) from a cDNA library of a human skeletal muscle, we identified 1945 individual transcripts, 725 of which showed no correspondence with known human genes. We report here the chromosomal localization of 267 of these, obtained by radiation hybrid (RH) mapping. The map position of additional 242 ESTs from the same library, corresponding to known human genes, is also reported. The resulting information provides a preliminary genomic transcriptional profile of a human muscle. Several genes occur in clusters on different chromosomes. Moreover, chromosomes 17, 19, 21 and X appear to be significantly rich in muscle ESTs. By analysing several collections of ESTs from different tissues, we observed significant deviations in the distribution of ESTs by chromosome in fetal heart, adult brain and adult retina, supporting the hypothesis that a non-random localization of genes expressed in specific tissues might not be uncommon. The selective concentration of expressed genes in some chromosomes and in specific chromosomal subregions in a given tissue might reflect the existence of batteries of genes under the same control mechanisms, regulating tissue-specific gene expression.

Chromosome Mapping↗
PubMed2003

Detection and analysis of spliced chimeric mRNAs in sequence databanks.

We have developed a databank screening procedure, the In Silico Trans-splicing Retrieval System (ISTReS), to identify heterologous, spliced mRNAs with potential origin from chromosomal translocations, mRNA trans-splicing and multi-locus transcription. A parsing algorithm to screen cDNA versus genome Blast outputs was implemented. Key filtering criteria were Blast scores of > or =300, match lengths of > or =95% of the query sequences, junction of the two partners at exon-exon borders and concordant 'sense/sense' reading orientation. ISTReS was validated by the successful identification of bona fide chromosomal translocation-derived fusion transcripts in the HGI and RefSeq databanks. The performance of ISTReS was verified against recently identified chimeric antisense transcripts, where it revealed essentially no independent proof of antisense transcription and absence of exon-exon borders at the chimeric join, consistent with an artefactual origin. Analysis of the UNIGENE database revealed 21 742 chimeric sequences overall that correspond to approximately 1% of the database transcripts. Novel FOP-Rho GAP and methionyl tRNA synthetase-advillin chimeric mRNAs with the canonical features of heterologous-genes spliced-transcripts were identified among 246 chimeras from the RefSeq databank. This suggests a frequency of canonically-spliced chimeras of approximately 1% of all the hybrid sequences in current databanks. These findings demonstrate the efficiency of ISTReS and the overall feasibility of sequence/structure-based strategies to search for chimeric mRNAs candidate to derive from the splicing of heterologous transcripts.

Algorithms↗
PubMedDate not supplied

Alphabetical list of the genes of domestic fowl.

An alphabetical list of over 250 loci of the domestic chicken is presented. Also included is a set of nomenclature rules and a proposal that the prefix Ea (erythrocyte antigen) be used with blood group symbolism in order to distinguish them from other loci with the same letter designation. These proposals grew out of the 1977 symposium on "Mutant Nomenclature and Gene Symbolism".

Animals↗
PubMed1999

Spatial assessment of the dynamics of lactate formation in focal ischemic rat brain.

Early identification of the potentially salvageable penumbra is critical for the determination of therapeutic intervention strategies in acute focal cerebral ischemia. This study differentiates the ischemic penumbra from the core on the basis of the dynamics of lactate formation. This was tested in a rat model of focal cerebral ischemia by infusion of [1-13C]-glucose, using lactate-edited magnetic resonance spectroscopic imaging techniques. The authors detected essentially no enrichment of lactate with 13C-label from the infused 13C-glucose in the ischemic core. However, in borderzone areas, 13C was incorporated into lactate, which could point toward compromised but potentially viable tissue. The authors' findings suggest that this combination of 13C-glucose infusion with the proposed magnetic resonance methods may aid in differentiating the penumbra from the core in cerebral ischemia.

Animals↗
PubMed2005

Comparisons between Alzheimer disease, frontotemporal lobar degeneration, and normal aging with brain mapping.

Alzheimer disease (AD) and frontotemporal lobar degeneration (FTLD) are both common degenerative dementias in the under 65 age group. Although clinical criteria have been defined for both diseases, there is considerable overlap in clinical features, and hence, diagnosis still can be very difficult particularly in the early stages of the disease. As a result, there has been increasing interest in using magnetic resonance imaging to better characterize these diseases and to aid in diagnosis. Voxel-based morphometry (VBM) is an automated technique that assesses patterns of regional gray matter atrophy on magnetic resonance imaging between 2 groups of subjects. It is unbiased in that it looks throughout the whole brain and does not require any a priori assumptions concerning which structures to assess, giving it a significant advantage over traditional region of interest-based methods. Voxel-based morphometry has been widely used to assess patterns of regional atrophy in subjects with AD and FTLD. These studies have demonstrated specific patterns of regional loss in both diseases, compared the 2 diseases to look for differences that could be diagnostically useful, and have correlated regions of gray matter loss to cognitive and behavioral deficits in these subjects. This article will review the findings of these studies and discuss the role of VBM in these neurodegenerative diseases.

Aging↗
PubMed2005

Discrepancy between feedback negativity and subjective evaluation in gambling.

Feedback negativity is a negative event-related potential elicited by feedback indicating incorrect performance or monetary loss. It is unclear whether this negativity is elicited by neutral feedback (e.g. a draw in gambling) or is affected by the subjective rating of punishment. To investigate these issues, we performed a modified and computerized game of 'rock-paper-scissors' as a gambling task and measured feedback negativity in response to feedback indicating the outcome, which was accompanied by a monetary reward. The data demonstrated that feedback negativity was elicited not only by a monetary loss but also by an even outcome and was independent of the magnitude of monetary loss. Our results suggest feedback negativity is not always specific to both monetary loss and subjective rating of punishment.

Adult↗
PubMed2001

Chloroplast and mitochondrial proteases in Arabidopsis. A proposed nomenclature.

The identity and scope of chloroplast and mitochondrial proteases in higher plants has only started to become apparent in recent years. Biochemical and molecular studies suggested the existence of Clp, FtsH, and DegP proteases in chloroplasts, and a Lon protease in mitochondria, although currently the full extent of their role in organellar biogenesis and function remains poorly understood. Rapidly accumulating DNA sequence data, especially from Arabidopsis, has revealed that these proteolytic enzymes are found in plant cells in multiple isomeric forms. As a consequence, a systematic approach was taken to catalog all these isomers, to predict their intracellular location and putative processing sites, and to propose a standard nomenclature to avoid confusion and facilitate scientific communication. For the Clp protease most of the ClpP isomers are found in chloroplasts, whereas one is mitochondrial. Of the ATPase subunits, the one ClpD and two ClpC isomers are located in chloroplasts, whereas both ClpX isomers are present in mitochondria. Isomers of the Lon protease are predicted in both compartments, as are the different forms of FtsH protease. DegP, the least characterized protease in plant cells, has the most number of isomers and they are predicted to localize in several cell compartments. These predictions, along with the proposed nomenclature, will serve as a framework for future studies of all four families of proteases and their individual isomers.

Arabidopsis↗
PubMed2005

Intramolecular disulphide bond arrangements in nonhomologous proteins.

The presence and location of intramolecular disulphide bonds are a key determinant of the structure and function of proteins. Intramolecular disulphide bonds in proteins have previously been analyzed under the assumption that there is no clear relationship between disulphide arrangement and disulphide concentration. To investigate this, a set of sequence nonhomologous protein chains containing one or more intramolecular disulphide bonds was extracted from the Protein Data Bank, and the arrangements of the bonds, Protein Data Bank header, and Structural Characterization of Proteins fold were analyzed as a function of intramolecular disulphide bond concentration. Two populations of intramolecular disulphide bond-containing proteins were identified, with a naturally occurring partition at 25 residues per bond. These populations were named intramolecular disulphide bond-rich and -poor. Benefits of partitioning were illustrated by three results: (1) rich chains most frequently contained three disulphides, explaining the plateaux in extant disulphide frequency distributions; (2) a positive relationship between median chain length and the number of disulphides, only seen when the data were partitioned; and (3) the most common bonding pattern for chains with three disulphide bonds was based on the most common for two, only when the data were partitioned. The two populations had different headers, folds, bond arrangements, and chain lengths. Associations between IDSB concentration, IDSB bonding pattern, loop sizes, SCOP fold, and PDB header were also found. From this, we found that intramolecular disulphide bond-rich and -poor proteins follow different bonding rules, and must be considered separately to generate meaningful models of bond formation.

Algorithms↗
PubMed1993

Diagnosis by electroencephalographic topography.

In 5 patients, electroencephalographic (EEG) topography (Fourier analysis and topographic display of EEG data) demonstrated clinically significant acute brain lesions not seen by magnetic resonance imaging or computed tomography. EEG topography contributed to patient management more than standard EEG. Additional, carefully designed, prospective studies may indicate how frequently and in which settings EEG topography is a valuable diagnostic test.

Adult↗
PubMed2006

Endothelial nitric oxide synthase is a molecular vascular target for the Chinese herb Danshen in hypertension.

Danshen, a Chinese herb, reduces hypertension in Oriental medicine. We hypothesized that Danshen acts partially through endothelial nitric oxide synthase (eNOS) signaling mechanisms. We tested the hypothesis using tanshinone II(A), an active ingredient of Danshen, and the two-kidney, one-clip renovascular hypertension model in hamsters. Oral tanshinone (50 microg/100 g body wt) reduced mean arterial pressure (MAP) from 161.2 +/- 6.9 to 130.0 +/- 7.8 mmHg (mean +/- SE; P < 0.05) in hypertensive hamsters. MAP in sham-operated hamsters was 114.3 +/- 9.2 mmHg. Topical tanshinone at 1 microg/ml and 5 microg/ml increased normalized arteriolar diameter from 1.00 to 1.25 +/- 0.08 and 1.57 +/- 0.11, respectively, and increased periarteriolar nitric oxide concentration from 87.1 +/- 11.3 to 146.9 +/- 23.1 nM (P < 0.05) at 5 microg/ml in hamster cheek pouch. N(G)-monomethyl-L-arginine inhibited tanshinone-induced vasodilation. Hypertension reduced eNOS protein relative to sham-operated control. Tanshinone prevented the hypertension-induced reduction of eNOS and increased eNOS expression to levels higher than sham-operated control in hamster cheek pouch. Topical tanshinone increased normalized arteriolar diameter from 1.0 to 1.47 +/- 0.08 in the cremaster muscle of control mice and to 1.12 +/- 0.13 in cremasters of eNOS knockout mice. In ECV-304 cells transfected with eNOS-green fluorescent protein, tanshinone increased eNOS protein expression 1.35 +/- 0.05- and 1.85 +/- 0.07-fold above control after 5-min and 1-h application, respectively. Tanshinone also increased eNOS phosphorylation 1.19 +/- 0.07- and 1.72 +/- 0.20-fold relative to control after 5-min and 1-h application. Our data provide a basis to understand the action of a Chinese herb used in alternative medicine. We conclude that eNOS stimulation is one mechanism by which tanshinone induces vasodilation and reduces blood pressure.

Animals↗