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At least 1,135 records · Page 63Linked to original sources
PubMed2005

Neuroanatomical differences between mouse strains as shown by high-resolution 3D MRI.

The search for new mouse models of human disease requires a sensitive metric to make three-dimensional (3D) anatomical comparisons in a rapid and quantifiable manner. This is especially true in the brain, where changes in complex shapes such as the hippocampus and ventricles are difficult to assess with 2D histology. Here, we report that the 3D neuroanatomy of three strains of mice (129S1/SvImJ, C57/Bl6, and CD1) is significantly different from one another. Using image co-registration, we 'morphed' together nine brains of each strain scanned by magnetic resonance imaging at (60 microm)3 resolution to synthesize an average image. We applied three methods of comparison. First, we used visual inspection and graphically examined the standard deviation of the variability in each strain. Second, we annotated 42 neural structures and compared their volumes across the strains. Third, we assessed significant local deviations in volume and displacement between the two inbred strains, independent of prior anatomical knowledge.

Algorithms↗
PubMed2006

Reproducibility of odor maps by fMRI in rodents.

The interactions of volatile odorants with the approximately 1000 types of olfactory receptor neurons in the olfactory mucosa are represented in the olfactory bulb by glomerular spatial activity maps. If these spatial maps underlie the perceptual identification of odorants then, for a given organism, they must be both specific and reproducible. However, this intra-organism reproducibility need not be present between organisms because genetic and developmental studies of olfactory bulb wiring suggest that there is substantial variation between the glomerular arrangements of closely related organisms and even between the two bulbs in a given animal. The ability of functional MRI (fMRI) to record responses of the entire rodent olfactory bulb repeatedly within the same subject has made it possible to assess the reproducibility of odor-induced spatial activity maps both within and between subjects exposed to equivalent stimuli. For a range of odorants, representing multiple chemical classes, a level of fMRI reproducibility (at 7.0 T and 9.4 T) comparable or superior to other cortical regions was demonstrated. While the responses of different bulbs to the same odorant could be localized within the same broad regions of the glomerular sheet, the precise magnitude and topology of the response within those regions were both often highly variable. These results demonstrate the robustness of high-field fMRI as a tool for assaying olfactory bulb function and provide evidence that equivalent perceptual outcomes may arise from divergent neural substrates.

Animals↗
PubMed2007

Magnetic resonance imaging of the visual system in vivo: transsynaptic illumination of V1 and V2 visual cortex.

Brain nuclei directly receiving retinal projections are readily labeled in magnetic resonance images following intraocular injection of manganese (Mn). To assess whether Mn in retinal ganglion cell axons can be transsynaptically delivered to visual cortex, mice that had previously received intraocular Mn injection were anesthetized with isoflurane, and T1-weighted data sets were acquired of the eyes and brain using a 7-T magnetic resonance imaging machine. Image intensity within contralateral brain structures was evaluated by assessing 1) signal-to-noise ratios, 2) mean image intensity, and 3) mean image intensity normalized to facial muscle intensity. Image intensity was increased throughout the visual pathway including within contralateral visual cortex areas V1 and V2L. Mean normalized image intensity was greater by 53% in the ipsilateral optic nerve and by 31% and 28% in the contralateral lateral geniculate nucleus and superior colliculus, respectively (N=5, P<0.02, paired t test). In contralateral visual cortex areas V1 and V2L, image intensity was increased by 7.5% and 6.8%, respectively (P<0.02 for both, paired t test). Power analysis of the different evaluation methods yielded evidence of superior sensitivity using the normalization method. Reconstruction of the visual system based upon threshold analysis allowed simultaneous visualization of all portions of the major retinal projections to the brain. These results support use of high magnetic field MRI imaging and data normalization for in vivo quantitative analysis of the mouse brain visual system including visual cortex.

Animals↗
PubMed2005

Integration of touch and sound in auditory cortex.

To form a coherent percept of the environment, our brain combines information from different senses. Such multisensory integration occurs in higher association cortices; but supposedly, it also occurs in early sensory areas. Confirming the latter hypothesis, we unequivocally demonstrate supra-additive integration of touch and sound stimulation at the second stage of the auditory cortex. Using high-resolution fMRI of the macaque monkey, we quantified the integration of auditory broad-band noise and tactile stimulation of hand and foot in anaesthetized animals. Integration was found posterior to and along the lateral side of the primary auditory cortex in the caudal auditory belt. Integration was stronger for temporally coincident stimuli and obeyed the principle of inverse effectiveness: greater enhancement for less effective stimuli. These findings demonstrates that multisensory integration occurs early and close to primary sensory areas and--because it occurs in anaesthetized animals--suggests that this integration is mediated by preattentive bottom-up mechanisms.

Animals↗
PubMed2004

Alignment of glial cells stimulates directional neurite growth of CNS neurons in vitro.

Olfactory ensheathing cells (OECs) together with olfactory nerve fibroblasts (ONFs) and neonatal astrocytes are potent stimulators of neurite growth in adulthood and during development, respectively. Since it is known that alignment of glial cells is important for the correct outgrowth of axon tracts, it was hypothesized that the alignment of glial cells stimulates directional and enhanced neurite outgrowth. Adult OEC/ONF and neonatal astrocytes were cultured either on biodegradable poly(d,l)-lactide matrices or in Petri dishes for 4 days. Thereafter neonatal cerebral cortical neurons were added. After a 2-days coculture period the cultures were fixed and processed for a combined MAP-2 and phosphorylated neurofilament (RT97) staining. The neurite growth (neurite elongation and neurite formation) and the neurite direction were assessed. We show that (1). OEC/ONF cultures are more potent in stimulating the length of the longest neurite of cocultured neurons, (2). alignment of glial is achieved in vitro on our biomatrices, (3). aligned glial/biomatrix complexes do not enhance neurite growth, and (4). aligned glial/biomatrix complexes direct neurite outgrowth. These data have significant implications for in vivo experiments focusing on glial transplantation. Transplanting glial/biomatrix complexes may stimulate the directional regrowth of severed axons across a lesion site.

Animals↗
PubMed2005

Expression of the glucocorticoid-induced receptor mRNA in rat brain.

The glucocorticoid-induced receptor (GIR) is an orphan G-protein-coupled receptor awaiting pharmacological characterization. GIR was originally identified in murine thymoma cells, and shows a widespread, yet not completely complementary distribution in mouse and human brain. Expression of the mouse GIR gene is modulated by dexamethasone in the brain and periphery, suggesting that GIR function is directly responsive to glucocorticoid signals. The rat GIR was cloned from rat prefrontal cortex by our group and was shown to be up-regulated following chronic amphetamine. The physiological role of GIR in the rat is not known at present. In order to gain a clearer understanding of the potential functions of GIR in the rat, we performed a detailed mapping of GIR mRNA expression in the rat brain. GIR mRNA showed widespread distribution in forebrain limbic and thalamic structures, and a more restricted distribution in hindbrain areas such as the spinal trigeminal nucleus and the median raphe nucleus. Areas with moderate to high levels of GIR include olfactory regions such as the nucleus of olfactory tract, hippocampus, various thalamic nuclei, cortical layers, and some hypothalamic nuclei. In comparison with previous studies, significant regional differences exist in GIR distribution in mouse and rat brain, particularly in the thalamus, striatum and in hippocampus at a cellular level. Overall, the expression of GIR in rat brain more closely approaches that seen previously in human than mouse, suggesting that rat models may be more informative for understanding the role of GIR in glucocorticoid physiology and glucocorticoid-related disease states. GIR mRNA distribution in the rat indicates a potential role of this receptor in the control of feeding and ingestive behavior, regulation of stress and emotional behavior, learning and memory, and, drug reinforcement and reward.

Animals↗
PubMed2004

A posttranscriptional regulator of Kaposi's sarcoma-associated herpesvirus interacts with RNA-binding protein PCBP1 and controls gene expression through the IRES.

Kaposi's sarcoma-associated herpesvirus (KSHV; also known as human herpesvirus 8, HHV-8) belongs to the gamma-herpesvirus subfamily. The KSHV ORF57 gene is thought to be a homolog of posttranscriptional regulators that are conserved in the herpesvirus family and are essential for replication. We generated specific monoclonal antibodies (mAbs) against the ORF57 protein that detected the 51-kDa protein expressed in the nucleus of KSHV-infected cells. We also found that the ORF57 protein interacted with poly(rC)-binding protein 1 (PCBP1), a cellular RNA-binding, posttranscriptional regulator. ORF57's interaction with PCBP1 enhanced the activity of not only poliovirus internal ribosome-entry site (IRES)-dependent translation but also X-linked inhibitor of apoptosis (XIAP) and KSHV vFLIP IRES. Actually, when ORF57 expression was induced by the expression of replication and transcription activator (RTA) in KSHV-infected cells, the expression of XIAP was enhanced. These results suggest that ORF57 binds to PCBP1 as a functional partner for posttranscriptional regulation and is involved in the regulation of the expression of both cellular and viral genes through IRESs.

Base Sequence↗
PubMed1997

Cellobiohydrolase I from Trichoderma reesei: identification of an active-site nucleophile and additional information on sequence including the glycosylation pattern of the core protein.

(R,S)-3,4-Epoxybutyl beta-cellobioside, but not the corresponding propyl and pentyl derivatives, inactivates specifically and irreversibly cellobiohydrolase I from Trichoderma reesei by covalent modification of Glu212, the putative active-site nucleophile. The position and identity of the modified amino acid residue were determined using a combination of comparative liquid chromatography coupled on-line to electrospray ionization mass spectrometry, tandem mass spectrometry and microsequencing. It was found that the core protein corresponds to the N-terminal sequence pyrGlu1-Gly434 (Gly435) of intact cellobiohydrolase I. In the particular enzyme samples investigated, the asparagine residues in positions 45, 270 and 384 are each linked to a single 2-acetamido-2-deoxy-D-glucopyranose residue.

Amino Acid Sequence↗
PubMed2000

Glucagon-induced expression of the MAP kinase phosphatase MKP-1 in rat hepatocytes.

BACKGROUND & AIMS: Glucagon exerts pleiotropic effects on liver function, but the underlying signal transduction is incompletely understood. We investigated the effect of glucagon on the mitogen-activated protein (MAP) kinase phosphatase MKP-1 expression. METHODS: The effect of glucagon on MKP-1 expression was studied in cultured rat hepatocytes. RESULTS: Glucagon (10-100 nmol/L) and 8-CPT-cAMP (10 or 50 micromol/L) stimulated in rat hepatocytes the expression of MKP-1 messenger RNA and protein, which became maximal within 30 minutes and declined to nearly basal levels after 60 minutes. MKP-1 induction by glucagon was sensitive to inhibition of adenylate cyclase and protein kinase A. The protein kinases G and C, Ca(2+), MAP kinases, reactive oxygen intermediates, and cellular dehydration were not involved in the glucagon-induced signaling to MKP-1. MKP-1 expression correlated with glucagon-induced antagonization of MAP kinase phosphorylation by epidermal growth factor in hepatocytes. CONCLUSIONS: The MKP-1 response to glucagon produces an additional level of interaction with MAP kinase-dependent processes, which may contribute to the regulation of liver function by glucagon or other cAMP-elevating agents.

Animals↗
PubMed1985

Characterization of recombinant human interleukin-2 with micromethods.

Highly purified recombinant human interleukin-2, expressed in Escherichia coli, was analyzed by micromethods. N-Terminal sequence analysis showed that methionine at position 0 was found in 90% of the molecules and not completely removed in post-ribosomal processing. A complete peptide map of the reduced and S-carboxymethylated protein was obtained by high-performance liquid chromatography after tryptic digestion, and the fragments were identified by amino acid analysis and automated Edman sequence analysis. Using a double-label S-carboxymethylation procedure, it was determined that there is a disulfide linkage between the cysteine residues at positions 58 and 105. The third cysteine residue at position 125 was found to be present as the free sulfhydryl.

Amino Acid Sequence↗
PubMed1985

Does A-H interval accurately represent intranodal conduction time during ectopic rhythms?

In order to determine whether the A-H interval of the His bundle electrogram accurately represents the AV nodal conduction time under various conditions, His bundle and coronary sinus electrograms were recorded in isolated perfused rabbit hearts, with atrial stimulation from eight different sites. The S-A (stimulus to the A wave) interval was significantly longer, whereas the A-H interval was shorter on stimulations from the coronary sinus and the left atrium than on sinus nodal stimulation. Stimulations from the fossa ovalis and right atrial appendage did not significantly alter the A-H interval. The effective and functional refractory periods of the AV node were almost identical with stimulations from the sinus node, low right atrial appendage, low left atrial appendage or the ostium of coronary sinus. Mapping of the excitation process with microelectrodes revealed that the activation times in low interatrial septal fibers bordering the His bundle [abbreviated as AP(III)] was closest to the A wave as compared with the activation in the ostium of the coronary sinus [AP(I)] or near the AN region [AP(II)] on stimulation from both sinus nodal and coronary sinus regions. On sinus nodal stimulation, AP(III) preceded AP(I) and AP(II) but lagged behind the A wave by 6 msec, whereas AP(III) preceded the A wave by 5 msec on coronary sinus stimulation. Thus, the A-H interval may not always accurately represent the intranodal conduction time, as relative timing of atrial activation responsible for the A wave and that of invasion of the AV node by the atrial wavefront can be grossly altered by different atrial excitation patterns.

Action Potentials↗
PubMed2003

Phonology and syntax in specific language impairment: evidence from a connectionist model.

Difficulties in resolving pronominal anaphora have been taken as evidence that Specific Language Impairment (SLI) involves a grammar-specific impairment. The present study explores an alternative view, that grammatical deficits in SLI are sequelae of impaired speech perception. This perceptual deficit specifically affects the use of phonological information in working memory, which in turn leads to poorer than expected syntactic comprehension. This hypothesis was explored using a connectionist model of sentence processing that learned to map sequences of words to their meanings. Anaphoric resolution was represented in this model by recognizing the semantics of the correct antecedent when a bound pronoun was input. When the model was trained on distorted phonological inputs-simulating a perceptual deficit-it exhibited marked difficulty resolving bound anaphors. However, many other aspects of sentence comprehension were intact; most importantly, the model could still resolve pronouns using gender information. In addition, the model's deficit was graded rather than categorical, as it was able to resolve pronouns in some sentences, but not in others. These results are consistent with behavioral data concerning syntactic deficits in SLI. The model provides a causal demonstration of how a perceptual deficit could give rise to grammatical deficits in SLI.

Child↗
PubMed1996

Computer assisted three-dimensional reconstruction of brain regions from serial section digitized images. Application to the organization of striato-nigral relationships in the rat.

We have developed a software which allows the three-dimensional reconstruction of brain regions from serial section digitized images. This software, which generates wire-frame three dimensional models, requires at least a 486 PC microcomputer running Microsoft Windows (3.x or 95). Mosaics of high resolution images, covering large brain areas, digitized by means of a camera fitted on a microscope equipped with a motorized stage, are handled by our software as single high resolution images. Serial sets of such images may be segmented and manually aligned. We have utilized this software to study the organization of striatal efferences within the substantia nigra pars reticulata, as well as the distribution of neuronal cell bodies within the substantia nigra pars compacta after micro-ionophoretic application of wheat germ agglutinin conjugated to horseradish peroxidase into the orofacial sensorimotor region of the striatum. The three dimensional representation of anterogradely labeled striatal efferences confirmed and determined the lamellar organization previously postulated from serial plane section micrographs. The distribution in the rat brain of retrogradely labeled nigro-striatal cell bodies, which had not yet been studied after injection of tracer into functionally identified regions of the striatum, revealed two subpopulations: a first one rather dense, located in the anterior half of the substantia nigra pars compacta, which was in close register with the striatal efferences, and a second one, much more scattered and less numerous, located in the posterior part of the structure which extended far from the substantia nigra along the medio-lateral axis. Our three dimensional reconstruction software will now be used to study the neuronal connectivity within the basal ganglia and other brain regions.

Animals↗
PubMed2002

Proteomics in experimental gerontology.

The first gerontological studies using two-dimensional gel electrophoresis (2DGE) were frustrating since it was very difficult, when not impossible, to identify the proteins for which an age-related change in expression level was suspected. Reproducibility was also a main pitfall. Accumulated progress in 2DGE and especially the development of mass spectrometry of proteins and peptides gave accessibility to the routine identification of differentially expressed proteins. A new paradigm was born: proteomics. In addition to expression changes, post-translational modifications are included in proteomics, and will be more and more studied using mass spectrometry. After a review of the current developments of 2DGE and mass spectrometry, we shall discuss how the technologies currently available in proteomics could give fresh impetus to experimental gerontology, complementary to more recent approaches based on wide expression analysis tools such as DNA and protein arrays.

Aging↗
PubMed1998

Identifying proteins and post-translational modifications by mass spectrometry.

Major recent advances in hardware performance, sample-handling procedures and software algorithms now allow reliable and sensitive mass spectrometric identification of proteins. Mass spectrometry vastly outperforms traditional sequencing technologies and thereby greatly facilitates the elucidation of the functions of individual proteins as well as multiprotein complexes and larger protein assemblages.

Amino Acid Sequence↗
PubMed2003

The variance of icosahedral virus models is a key indicator in the structure determination: a model-free reconstruction of viruses, suitable for refractory particles.

A model-free method to determine the three-dimensional structure of icosahedral viruses is described. The novel strategy is based upon the approximate principle that correct virus structures have high variance as do all other well-detailed structures, even wrong ones. The original projections of individual particles are reduced to a radius of 25 pixels and are used to compute single particle reconstruction models by assigning them 1800 different Euler triads. The variance of the models obtained from all projections is stored in maps and a decimation process is carried out. In a first stage, thresholds are adopted for the variance values, and in a second stage, carried out by correspondence analysis and classification, 30 clusters of models are sorted out. The clusters are refined to yield models contained in boxes of 64(3) voxels. The refined models with highest variance and closest similarity represent the correct solution. Once enlarged, these models can be used to align all available projections in their original scale in a customary projection-matching process. The method has proved successful in determining the structures of poliovirus, of the empty and filled capsids of L-A virus, and of a modified capsid of hepatitis B virus.

Capsid↗
PubMed2002

A mechanism of cell survival: sequestration of Fas by the HGF receptor Met.

Death receptors such as Fas are present in a variety of organs including liver and play an important role in homeostasis. What prevents these harmful receptors from forming homooligomers, clustering, and initiating the apoptotic pathway is not known. Here, we report the discovery of a cell survival mechanism by which Met, a growth factor receptor tyrosine kinase, directly binds to and sequesters the death receptor Fas in hepatocytes. This interaction prevents Fas self-aggregation and Fas ligand binding, thus inhibiting Fas activation and apoptosis. Our results describe a direct link between growth factor tyrosine kinase receptors and death receptors to establish a novel paradigm in growth regulation.

Animals↗