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At least 667 records · Page 37Linked to original sources
PubMed2006

3D mapping of ventricular and corpus callosum abnormalities in HIV/AIDS.

OBJECTIVE: 40 million people worldwide are now infected with HIV/AIDS, an illness that often leads to rapidly progressing dementia and death. Even so, little is known about how AIDS affects the brain. Using computational anatomy techniques, we mapped how AIDS impacts the corpus callosum (CC) and ventricular system, two systems that show prominent changes on MRI. We (1) identified regions with greatest differences between AIDS patients and healthy controls and (2) correlated specific 3D patterns of structural differences with measures of immune system deterioration and cognitive decline. METHODS: 51 3D brain MRI scans from 30 non-demented AIDS patients (age: 43.4 years +/- 7.6 SD) and 21 HIV-seronegative controls (age: 39.5 years +/- 12.2) were aligned to ICBM standard space. 3D surface mesh reconstructions of the lateral ventricles and CC were spatially averaged and compared across diagnostic groups. Structural alterations were correlated with viral load, T cell counts, and cognitive impairment. RESULTS: Statistical maps revealed the 3D profile of ventricular expansion and callosal thinning in AIDS. Specific 3D ventricular changes were linked with immune system decline (CD4+ T cell counts; P < 0.001) and cognitive impairment (P < 0.009), but not viral load. Frontal horn maps distinguished AIDS patients from controls better than occipital and temporal horn measures. T cell decline linked with callosal thinning in anterior regions connecting frontal areas with greatest cortical atrophy. CONCLUSION: These maps (1) reveal how brain changes in HIV/AIDS relate to immune decline and impaired cognition, and, after further validation and testing, (2) may offer possible neuroimaging markers for anti-viral drug trials, which gauge how well treatments oppose disease progression in the brain.

AIDS Dementia Complex↗
PubMed1996

Co-localization of the ketohexokinase and glucokinase regulator genes to a 500-kb region of chromosome 2p23.

The glucokinase regulator (GCKR) is a 65-kDa protein that inhibits glucokinase (hexokinase IV) in liver and pancreatic islet. The role of glucokinase (GCK) as pancreatic beta cell glucose sensor and the finding of GCK mutations in maturity onset diabetes of the young (MODY) suggest GCKR as a further candidate gene for type 2 diabetes. The inhibition of GCK by GCKR is relieved by the binding of fructose-1-phosphate (F-1-P) to GCKR. F-1-P is the end product of ketohexokinase (KHK, fructokinase), which, like GCK and GCKR, is present in both liver and pancreatic islet. KHK is the first enzyme of the specialized pathway that catabolizes dietary fructose. We have isolated genomic clones containing the human GCKR and KHK genes. By fluorescent in situ hybridization (FISH), KHK maps to Chromosome (Chr) 2p23.2-23.3, a new assignment corroborated by somatic cell hybrid analysis. The localization of GCKR, originally reported by others as 2p22.3, has been reassessed by high-resolution FISH, indicating that, like KHK, GCKR maps to 2p23.2-23.3. The proximity of GCKR and KHK was further demonstrated both by two-color interphase FISH, which suggests that the two genes lie within 500 kb of each other, and by analysis of overlapping YAC and P1 clones spanning the interval between GCKR and KHK. A new microsatellite polymorphism was used to place the GCKR-KHK locus between D2S305 and D2S165 on the genetic map. The colocalization of these two metabolically connected genes has implications for the interpretation of linkage or allele association studies in type 2 diabetes. It also raises the possibility of coordinate regulation of GCKR and KHK by common cis-acting regulatory elements.

Base Sequence↗
PubMed1998

The molecular mechanism of B cell activation by toll-like receptor protein RP-105.

The B cell-specific transmembrane protein RP-105 belongs to the family of Drosophila toll-like proteins which are likely to trigger innate immune responses in mice and man. Here we demonstrate that the Src-family protein tyrosine kinase Lyn, protein kinase C beta I/II (PKCbetaI/II), and Erk2-specific mitogen-activated protein (MAP) kinase kinase (MEK) are essential and probably functionally connected elements of the RP-105-mediated signaling cascade in B cells. We also find that negative regulation of RP-105-mediated activation of MAP kinases by membrane immunoglobulin may account for the phenomenon of antigen receptor-mediated arrest of RP-105-mediated B cell proliferation.

Animals↗
PubMed2005

Mapping brains without coordinates.

Brain mapping has evolved considerably over the last century. While most emphasis has been placed on coordinate-based spatial atlases, coordinate-independent parcellation-based mapping is an important technique for accessing the multitude of structural and functional data that have been reported from invasive experiments, and provides for flexible and efficient representations of information. Here. we provide an introduction to motivations, concepts, techniques and implications of coordinate-independent mapping of microstructurally or functionally defined brain structures. In particular, we explain the problems of constructing mapping paths and finding adequate heuristics for their evaluation. We then introduce the three auxiliary concepts of acronym-based mapping (AM), of a generalized hierarchy (GM ontology), and of a topographically oriented regional map (RM) with adequate granularity for mapping between individual brains with different cortical folding and between humans and non-human primates. Examples from the CoCoMac database of primate brain connectivity demonstrate how these concepts enhance coordinate-independent mapping based on published relational statements. Finally, we discuss the strengths and weaknesses of spatial coordinate-based versus coordinate-independent microstructural brain mapping and show perspectives for a wider application of parcellation-based approaches in the integration of multi-model structural, functional, and clinical data.

Anatomy, Comparative↗
PubMed2002

Bi-atrial mapping of atrial arrhythmias.

Cardiac mapping of atrial activation was originally performed in animals during open chest preparations, using epicardial electrodes. The development of endocardial egg-shaped multiple electrodes provided detailed assessment of the minimum number of wavelengths required to sustain atrial fibrillation (AF), as well as the role of interatrial connections during AF. Subsequently, several studies on bi-atrial epicardial high-density mapping in animals and humans also reported on the importance of interatrial connections, as well as the specific characteristics of the left atrium as compared with the right atrium during chronic AF. Endocardial bi-atrial mapping studies using electrode catheters were reported using basket-shaped catheters carrying 64 electrodes. Animal studies suggested that septal activation was asynchronous and discordant, while a human study outlined the multiple origins of atrial ectopic beats following DC cardioversion in patients with chronic atrial fibrillation. The advent of non-fluoroscopic mapping systems significantly changed our approach to percutaneous endocardial mapping. Simultaneous bi-atrial studies using electroanatomic mapping were performed in sinus rhythm as well as in atrial flutter. These studies demonstrated the predominance of interatrial conduction over Bachmann's Bundle and the coronary sinus-left atrial connection during respectively, sinus rhythm and atrial flutter. Simultaneous bi-atrial non-contact mapping was initially performed during porcine studies and later in humans, demonstrating asynchronous and discordant septal activation both during sinus rhythm or left lateral atrial pacing. Preliminary studies from simultaneous bi-atrial non-contact mapping in humans in whom AF occurred spontaneously or was induced suggests three main types of atrial activation, consisting of left atrial drivers causing the right atrium to fibrillate following conduction over interatrial connections, the right atrium independently sustaining AF, even after pulmonary vein disconnection, and both atria fibrillating independently without activation over interatrial connections. Bi-atrial mapping has been essential for our understanding of normal and abnormal atrial activation, and ultimately may provide new approaches for ablation of atrial fibrillation.

Animals↗
PubMed1991

Marfan syndrome: no evidence for heterogeneity in different populations, and more precise mapping of the gene.

Marfan syndrome is a dominantly inherited connective tissue disorder with manifestations in the cardiovascular, ocular, and skeletal systems. The diagnosis is hampered by both high variability in the phenotypic expression and late manifestation of symptoms. The cause of Marfan syndrome remains unknown, but our group has recently reported the genetic linkage of Marfan syndrome to a polymorphic marker on chromosome 15. To analyze the possible heterogeneity behind Marfan syndrome, we have performed linkage analyses for four chromosome 15 markers in 17 families from five different populations: Scottish, English, Swiss, American, and Finnish. By combining the linkage data of all the studied families into a LINKMAP analysis we obtained a maximal LOD score of 11.2, which maps the Marfan syndrome locus between D15S25 and D15S45 on the long arm of chromosome 15. The data reveal no evidence for genetic heterogeneity behind Marfan syndrome and provide us with a more precise location of both the Marfan syndrome locus and flanking markers. This information will provide the basis for the DNA diagnostics of Marfan syndrome in the future.

Chromosome Mapping↗
PubMed2005

Exploration of the function and organization of the yeast early secretory pathway through an epistatic miniarray profile.

We present a strategy for generating and analyzing comprehensive genetic-interaction maps, termed E-MAPs (epistatic miniarray profiles), comprising quantitative measures of aggravating or alleviating interactions between gene pairs. Crucial to the interpretation of E-MAPs is their high-density nature made possible by focusing on logically connected gene subsets and including essential genes. Described here is the analysis of an E-MAP of genes acting in the yeast early secretory pathway. Hierarchical clustering, together with novel analytical strategies and experimental verification, revealed or clarified the role of many proteins involved in extensively studied processes such as sphingolipid metabolism and retention of HDEL proteins. At a broader level, analysis of the E-MAP delineated pathway organization and components of physical complexes and illustrated the interconnection between the various secretory processes. Extension of this strategy to other logically connected gene subsets in yeast and higher eukaryotes should provide critical insights into the functional/organizational principles of biological systems.

Cluster Analysis↗
PubMed1983

Order in the initial retinotectal map in Xenopus: a new technique for labelling growing nerve fibres.

Retinal nerve fibres form an orderly map of visual space in several centres in the vertebrate brain. Such topographic maps are a common feature of central nervous system organization, yet the way in which they develop is poorly understood. Early nerve projections in the fetal and neonatal mammalian brain have been found in several cases to be less restricted than those in the adult, suggesting that nerve fibres may initially form a diffuse set of connections in their target structure from which the adult map is sculpted by the elimination of terminals. Indeed, previous electrophysiological data indicate that the retinotectal map in Xenopus laevis might be initially disorganized. We report here, however, that the retinotectal projection is ordered from the beginning of tectal innervation (stage 39/40). We demonstrate this first autoradiographically by tracing groups of growing ganglion cell axons which we labelled by incubating sectors of eye rudiments, before axonal outgrowth, in 3H-proline and replacing them orthotopically. Separate labelling of dorsal and ventral parts of the initial projection showed that retinal fibres are organized topographically, as in the adult, in the tectal rudiment and throughout much of the pathway. Second, we show that visual responses are ordered in the tectum from the first stage that they can be mapped (stage 40). We conclude that the topographic ordering of retinotectal connections develops as a result of directed axonal outgrowth.

Animals↗
PubMed1994

CRAC, a cytosolic protein containing a pleckstrin homology domain, is required for receptor and G protein-mediated activation of adenylyl cyclase in Dictyostelium.

Adenylyl cyclase in Dictyostelium, as in higher eukaryotes, is activated through G protein-coupled receptors. Insertional mutagenesis into a gene designated dagA resulted in cells that cannot activate adenylyl cyclase, but have otherwise normal responses to exogenous cAMP. Neither cAMP treatment of intact cells nor GTP gamma S treatment of lysates stimulates adenylyl cyclase activity in dagA mutants. A cytosolic protein that activates adenylyl cyclase, CRAC, has been previously identified. We trace the signaling defect in dagA- cells to the absence of CRAC, and we demonstrate that dagA is the structural gene for CRAC. The 3.2-kb dagA mRNA encodes a predicted 78.5-kD product containing a pleckstrin homology domain, in agreement with the postulated interaction of CRAC with activated G proteins. Although dagA expression is tightly developmentally regulated, the cDNA restores normal development when constitutively expressed in transformed mutant cells. In addition, the megabase region surrounding the dagA locus was mapped. We hypothesize that CRAC acts to connect free G protein beta gamma subunits to adenylyl cyclase activation. If so, it may be the first member of an important class of coupling proteins.

Adenylyl Cyclases↗
PubMed2001

A graphical anatomical database of neural connectivity.

We describe a graphical anatomical database program, called XANAT (so named because it was developed under the X window system in UNIX), that allows the results of numerous studies on neuroanatomical connections to be stored, compared and analysed in a standardized format. Data are entered into the database by drawing injection and label sites from a particular tracer study directly onto canonical representations of the neuroanatomical structures of interest, along with providing descriptive text information. Searches may then be performed on the data by querying the database graphically, for example by specifying a region of interest within the brain for which connectivity information is desired, or via text information, such as keywords describing a particular brain region, or an author name or reference. Analyses may also be performed by accumulating data across multiple studies and displaying a colour-coded map that graphically represents the total evidence for connectivity between regions. Thus, data may be studied and compared free of areal boundaries (which often vary from one laboratory to the next), and instead with respect to standard landmarks, such as the position relative to well-known neuro-anatomical substrates or stereotaxic coordinates. If desired, areal boundaries may also be defined by the user to facilitate the interpretation of results. We demonstrate the application of the database to the analysis of pulvinar-cortical connections in the macaque monkey, for which the results of over 120 neuro-anatomical experiments were entered into the database. We show how these techniques can be used to elucidate connectivity trends and patterns that may otherwise go unnoticed.

Animals↗
PubMed1994

Tn10-mediated inversions fuse uridine phosphorylase (udp) and rRNA genes of Escherichia coli.

Two strains carrying metE::Tn10 insertions (upstream of the udp gene) were used to isolate mutants of Escherichia coli overexpressing udp. These strains differ in their gene order; one contains an inversion between the rrnD and rrnE rRNA operons. Selection was based on the ability of overexpressed Udp to complement thymine auxotrophy. Chromosomal rearrangements that connect the udp gene and promoters of different rrn operons were obtained by this selection. Seven of 14 independent mutants selected in one of the initial strains contained similar inversions of the metE-rrnD segment of the chromosome (about 12% of its length). Another mutant contained traces of a more complicated event, inversion between rrnB and rrnG operons, which was followed by reinversion of the segment between metE and the hybrid rrnG/B operon. Similar inversions (udp-rrn) in a strain already carrying an rrnE-rrnD inversion flip the chromosomal segment between metE and rrnD/E in the opposite direction. In this case, inversions are also accompanied by duplications of the chromosomal region between the rrnA and hybrid udp-rrnD/E operons. PCR amplification with a set of oligonucleotides from the rrn, Tn5, and met genes was used for more detailed mapping. Amplified fragments of the rearranged chromosomes connecting rrnD sequences and insertion elements were sequenced, and inversion endpoints were established.

Base Sequence↗
PubMed1998

Design and implementation of a CORBA-based genome mapping system prototype.

MOTIVATION: CORBA (Common Object Request Broker Architecture), as an open standard, is considered to be a good solution for the development and deployment of applications in distributed heterogeneous environments. This technology can be applied in the bioinformatics area to enhance utilization, management and interoperation between biological resources. RESULTS: This paper investigates issues in developing CORBA applications for genome mapping information systems in the Internet environment with emphasis on database connectivity and graphical user interfaces. The design and implementation of a CORBA prototype for an animal genome mapping database are described. AVAILABILITY: The prototype demonstration is available via: http://www.ri.bbsrc.ac.uk/ark_corba/. CONTACT: jian.hu@bbsrc.ac.uk

Chromosome Mapping↗
PubMed1997

Complexities in the thalamocortical and corticothalamic pathways.

It is now a century since Kölliker (Handbuch der Gewebelehre des Menschen. Nervensystemen des Menschen und der Thiere, Vol. 2, 6th edn. Engelmann, Leipzig, 1896) described the thalamic reticular nucleus as the 'Gitterkern' or lattice nucleus on the basis of the fibrous latticework that is the characteristic feature of this part of the ventral thalamus and adjacent parts of the internal capsule. We suggest that the fibre reorganization produced in this lattice is a fundamental requirement for linking orderly maps in the thalamus to corresponding cortical maps by two-way thalamocortical and corticothalamic connections; these connections involve divergence, convergence and mirror reversals, which all have to occur between the thalamus and the cortex. Apart from the thalamic reticular nucleus, two transient groups of cells, the perireticular nucleus (located in the internal capsule lateral to the reticular nucleus) and the cells of the cortical subplate, are prominent along the course of axons linking the cortex and thalamus early in development. The functions of these two cell groups are not known. However, since early in development complex patterns of reorganization, defasciculation and crossings occur in the regions of these cells, it is likely that they play a role in creating the latticework of the adult. The latticework that characterizes the thalamic reticular nucleus of mammals can also be identified in the ventral thalamus of non-mammalian brains, formed along the course of the fibres that join the dorsal thalamus to the telencephalon. We suggest that the ubiquitous presence of such a zone of fibre reorganization is integral to the functioning of the thalamocortical pathways, and that the complexity of thalamic connections produced in the lattice has been central to the evolutionary success of the thalamotelencephalic system.

Animals↗
PubMed2000

Condition number as a measure of noise performance of diffusion tensor data acquisition schemes with MRI.

Diffusion tensor mapping with MRI can noninvasively track neural connectivity and has great potential for neural scientific research and clinical applications. For each diffusion tensor imaging (DTI) data acquisition scheme, the diffusion tensor is related to the measured apparent diffusion coefficients (ADC) by a transformation matrix. With theoretical analysis we demonstrate that the noise performance of a DTI scheme is dependent on the condition number of the transformation matrix. To test the theoretical framework, we compared the noise performances of different DTI schemes using Monte-Carlo computer simulations and experimental DTI measurements. Both the simulation and the experimental results confirmed that the noise performances of different DTI schemes are significantly correlated with the condition number of the associated transformation matrices. We therefore applied numerical algorithms to optimize a DTI scheme by minimizing the condition number, hence improving the robustness to experimental noise. In the determination of anisotropic diffusion tensors with different orientations, MRI data acquisitions using a single optimum b value based on the mean diffusivity can produce ADC maps with regional differences in noise level. This will give rise to rotational variances of eigenvalues and anisotropy when diffusion tensor mapping is performed using a DTI scheme with a limited number of diffusion-weighting gradient directions. To reduce this type of artifact, a DTI scheme with not only a small condition number but also a large number of evenly distributed diffusion-weighting gradients in 3D is preferable.

Algorithms↗
PubMed1992

Mapping of the motor pathways in rats: c-fos induction by intracortical microstimulation of the motor cortex correlated with efferent connectivity of the site of cortical stimulation.

The general goal of the present study was to investigate structural components of a neural system anatomically as well as functionally. The rat motor system, which is reasonably well understood, was selected and a new procedure was developed to combine a functional marker with axonal tracing methods (in the same animal). This was achieved by mapping c-fos induction immunocytochemically as a result of intracortical microstimulation in the distal forelimb area of the motor cortex. The anterograde tracers Phaseolus vulgaris-leucoagglutinin or biocytin were deposited at the site of intracortical microstimulation, the former three weeks and the latter two to three days before stimulation. Neuronal nuclei, labeled for the expressed c-fos protein, were present and mapped in the following structures: motor cortex; basal ganglia (caudate-putamen, globus pallidus); thalamus (reticular, ventromedial and posterior nuclei); subthalamic nucleus; substantia nigra; tectum; red nucleus; pontine nuclei; inferior olive; external cuneate nucleus; cerebellar cortex; deep cerebellar nuclei. Labeling was often bilateral but generally more substantial ipsilaterally, except in the cerebellum where it was mainly contralateral. Axonal labeling, including terminal branches and boutons, was also found in most of the above structures with the exception of the globus pallidus, deep cerebellar nuclei, cerebellar cortex and external cuneate nucleus. These expected exceptions demonstrate that activity changes in these latter structures, as revealed by c-fos labeled neurons, were induced over more than one synapse. This combined procedure might, therefore, be useful in deciding whether two structures in a given system are linked directly (monosynaptically) or indirectly (polysynaptically) to each other. In contrast to the 2-deoxyglucose technique, functional mapping by means of c-fos induction provides cellular resolution, making it possible to establish fine details of axonal contacts with target neurons: boutons in close apposition to c-fos labeled neurons were clearly observed here, for instance in the cerebral cortex, caudate-putamen, thalamus, subthalamic nucleus and pontine nuclei. Surprisingly, the ventrolateral and ventrobasalis nuclei of the thalamus contained numerous and dense axon terminals labeled with Phaseolus vulgaris-leucoagglutinin or biocytin, but the contacted neurons in the ventrolateral and ventrobasalis nuclei were not marked with c-fos. However, with respect to directly connected structures, there was, in general, a good correlation between structures with axonal labeling and those with c-fos labeled neurons.

Animals↗
PubMed1996

Regional distribution of the anticonvulsant and behavioural effects of muscimol injected into the substantia nigra of rats.

Previous anatomical investigations have reported a direct projection from substantia nigra pars lateralis to the dorsal midbrain anticonvulsant zone. The present study tested the hypothesis that the anticonvulsant properties of nigral inhibition previously attributed to substantia nigra pars reticulata were, in fact, due to the suppression of neural activity in the adjacent pars lateralis. Using the electroshock model of epilepsy, a systematic map of the anticonvulsant effects of bilateral injections of muscimol (60 ng/0.5 mu l per side) into different parts of substantia nigra was constructed. Electroshock (1 s of 40 mA 50 Hz AC) was administered via ear-clip electrodes 5 or 60 min following injections of muscimol, or 60 min after control injections of saline. To provide insight into the functional mechanisms whereby nigral inhibition might suppress tonic seizures the behavioural effects elicited by muscimol were also noted. No evidence supporting the experimental prediction was found. The most sensitive region of substantia nigra for suppressing tonic hindlimb extension was caudal pars reticulata. These data indicate a serious mismatch between the results of microinjection mapping studies and underlying patterns of anatomical connectivity. The behavioural reaction most closely associated with tonic seizure suppression was stereotyped locomotion; both were obtained maximally from caudal pars reticulata. Rostral substantia nigra was associated more with oral stereotypy, while a raised head position was observed at lateral injection sites and a lowered positioning of the head at medial locations. These data suggest that the rat substantia nigra may contain a functional organization based on a form of somatomotor topography. This organization may influence which part of the substantia nigra is most effective in suppressing seizures expressed by different muscle groups of the body.

Animals↗
PubMed1988

[Combined effect of intracerebroventricular injections of angiotensin II, met-enkephalin and acetylcholine on mean arterial pressure in albino rats].

Single and combined effects of intracerebroventricular bolus injection of Ang. II (200 ng), ACh (6 micrograms) and met-enkephalin (50 micrograms) on mean arterial pressure (MAP), was tested in Sprague-Dawley albino rats. A metallic cannula was implanted in the third ventricle according to standard stereotaxic procedures under pentobarbital anesthesia (35 mg/kg). On the third day, the animal was anesthetized again, a carotid artery was cannulated and connected to a pressure transducer for recording of MAP. Ang. II increased MAP; ACh produced a significant increase in the initial 5 minutes after injection and met-enkephalin did not induce any significant changes in MAP. The combined effect showed interesting results. Instead of a potentiation of the rise in MAP, Ang. II and ACh, when given together, did not show any significant changes. Also, met-enkephalin blocked the hypertensive response due to Ang. II, if given combined. This is compatible with an inhibitory action of met-enkephalin on an angiotensinergic neuronal system. A simplified hypothetical model that explains the findings described above is proposed as a working hypothesis.

Acetylcholine↗
PubMed1987

Interferon-inducible gene maps to a chromosomal band associated with a (4;11) translocation in acute leukemia cells.

An interferon-inducible cytokine, IP-10, containing homology to a family of proteins having chemotactic (platelet factor 4, beta-thromboglobulin) and mitogenic (connective tissue-activating peptide III) activities has been mapped to chromosome 4 at band q21, a locus associated with an acute monocytic/B-lymphocyte lineage leukemia that exhibits the nonrandom translocation t(4;11)(q21;q23). In situ hybridization of t(4;11)(q21;q23)-carrying leukemic cells revealed that the IP-10 gene is proximal to the breakpoint of this translocation. No DNA rearrangement was evident when the IP-10 gene was hybridized to genomic DNA isolated from two patients' leukemic cells that contain t(4;11)(q21;q23). However, restriction fragment length polymorphism in the 5' region of the IP-10 gene was detected. The ETS1 protooncogene is located at 11q23 and is known to translocate to chromosome 4 in t(4;11) (q21;q23) and into the interferon gene cluster in (9;11) (p22;q23). Both translocations are associated with acute monocytic leukemia. These results suggest a model in which juxtaposition of genetic loci regulated by antiproliferative signals, such as interferon, next to an oncogene, like ETS1, could effectively short circuit homeostatic control circuits and contribute to the neoplastic state.

Blood Proteins↗