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At least 1,459 records · Page 81Linked to original sources
PubMed2005

Nitric oxide synthase inhibition exaggerates the hypotensive response to ghrelin: role of calcium-activated potassium channels.

OBJECTIVE: To investigate the mechanism underlying the observation that infusion of the growth hormone secretagogue peptide, ghrelin, produces a decrease in mean arterial pressure (MAP) with no change in heart rate. METHOD: The effect of a single bolus infusion of ghrelin (12 nmol/kg intravenously) on the changes in MAP and heart rate was determined in 12-week-old male anaesthetized Sprague-Dawley rats subjected to pretreatment with either the nitric oxide synthase (NOS) inhibitor, N-nitro-L-arginine methyl ester (L-NAME; 0.7 mg/ml by mouth for 5 days), or vehicle (control). RESULTS: Ghrelin produced a significant decrease in MAP at 20 min (P < 0.05) after infusion in the control group, without any change in heart rate. The MAP recovered partially over 1 h. The ghrelin-evoked decrease in MAP was much greater (P < 0.01) and was sustained for 1 h in rats subjected to NOS inhibition. Pretreatment with the cyclo-oxygenase inhibitor, indomethacin, failed to affect the responses in either group. Intravenous infusion of 50 mug/kg each of apamin and charybdotoxin (ChTX), a combination that is known to block Ca-activated K channels or the endothelium-derived hyperpolarization process, attenuated the decrease in MAP evoked by ghrelin in both control and NOS-inhibited rats. A sodium nitroprusside-induced decrease in MAP was unaffected in the presence of apamin-ChTX, but acetylcholine-evoked hypotension was significantly reduced in both groups. CONCLUSION: These data suggest that the Ca-activated, K-channel-mediated, ghrelin-evoked decrease in MAP may be significant in states of endothelial dysfunction associated with reduced nitric oxide availability.

Anesthesia↗
PubMed1995

Matrix/integrin interaction activates the mitogen-activated protein kinase, p44erk-1 and p42erk-2.

Cell adhesion to extracellular matrix proteins is a dynamic process leading to dramatic changes in the cell phenotype. Integrins are one of the major receptor families that mediate cell-matrix contact. Evidence that integrins can act as signal transducing molecules has accumulated over the past few years. We report here that p44erk-1 and p42erk-2 mitogen-activated protein (MAP) kinases are rapidly phosphorylated on tyrosine residues upon adhesion of human skin fibroblasts to fibronectin or upon cross-linking of beta 1 integrins with antibody. The tyrosine phosphorylation of both kinases is associated with increased enzymatic activity. Pretreatment of the cells with cytochalasin D, which selectively disrupts the network of the actin filaments, completely inhibits this adhesion-mediated MAP kinase activation. Thus, our findings indicate that ligation of beta 1 integrins induces an increase in both tyrosine phosphorylation and enzymatic activity of p44erk-1 and p42erk-2 MAP kinases, and that the integrity of the actin cytoskeleton is essential in this process. Since MAP kinase behaves as a convergence point for diverse receptor-initiated signaling events at the plasma membrane, this serine/threonine kinase plays a key role and helps to account for the diversity of integrin-dependent cell functions.

Calcium-Calmodulin-Dependent Protein Kinases↗
PubMed2002

Asymmetric exclusion process and extremal statistics of random sequences.

A mapping is established between sequence alignment, one of the most commonly used tools of computational biology, at a certain choice of scoring parameters and the asymmetric exclusion process, one of the few exactly solvable models of nonequilibrium physics. The statistical significance of sequence alignments is characterized through studying the total hopping current of the discrete time and space version of the asymmetric exclusion process.

Algorithms↗
PubMed2002

Cell adhesion differentially regulates the nucleocytoplasmic distribution of active MAP kinases.

Cells decide whether to undergo processes, such as proliferation, differentiation and apoptosis, based upon the cues they receive from both circulating factors and integrin-mediated adhesion to the extracellular matrix. Integrins control the activation of the early signaling pathways. For example, growth factor activation of the ERK cascade is enhanced when cells are adherent. In addition, adhesion receptors oversee the cellular localization of critical signaling components. We have recently shown that ERK signaling to the nucleus is regulated by cell adhesion at the level of nucleocytoplasmic trafficking. Since the ERKs are only one class of MAP kinase, we extended these studies to include both JNK and p38 MAP kinases. We have rendered JNK and p38 activation in NIH 3T3 fibroblasts anchorage-independent either by treatment with anisomycin or by expression of upstream activators. Under conditions whereby JNK activation is anchorage-independent, we show that localization of JNK to the nucleus and JNK-mediated phosphorylation of c-Jun and Elk-1 is not altered by loss of adhesion. Likewise, the ability of activated p38 to accumulate in the nucleus was similar in suspended and adherent cells. Finally, we show that expression of a form of ERK, which is activated and resistant to nuclear export, reverses the adhesion-dependency of ERK phosphorylation of Elk-1. Thus, adhesion differentially regulates the nucleocytoplasmic distribution of MAP kinase members; ERK accumulation in the nucleus occurs more efficiently in adherent cells, whereas nuclear accumulation of active p38 and active JNK are unaffected by changes in adhesion.

3T3 Cells↗
PubMed1995

Male and female cooperate in the prohormone-like processing of a Drosophila melanogaster seminal fluid protein.

Acp26Aa is a Drosophila seminal fluid protein that plays a role in the elevation of egg-laying by the mated female and has structural features of a prohormone. The protein, which has a region of sequence similarity to the egg-laying hormone of Aplysia, is transferred to the Drosophila female during mating. Acp26Aa is processed in the mated female's genital tract. We show here that the processing involves sequential proteolytic cleavages, and we map the position of these cleavages. Although Acp26Aa is not cleaved in the male, its processing in the mated female requires activities donated by the male. Acp26Aa ectopically expressed in unmated females is not processed. Processing of Acp26Aa in wild-type females mated to males with altered seminal fluid is dependent on the presence and amount of male accessory gland secretions. The need for molecular cooperation between the sexes for processing of Acp26Aa could restrict its activity to the mated female.

Amino Acid Sequence↗
PubMed1992

Changes in microtubules, microtubule-associated proteins, and intermediate filaments during the differentiation of HL-60 leukemia cells.

The cytoskeleton is composed mainly of microtubules (MT), microfilaments, and intermediate filaments (IF) that form a structural network which connects cellular membranes, cytoplasmic organelles, and the nucleus. Since the cytoskeleton may be involved in modulating signal transduction and in the morphological and structural changes that occur during cellular proliferation and differentiation, cytoskeletal changes were measured by immunofluorescence microscopy and fluorescence-activated cell sorter analysis during the differentiation of HL-60 leukemia cells induced by retinoic acid (RA). Differentiated HL-60 cells exhibited increased staining intensity and altered organization of MT and IF, as visualized by immunofluorescence microscopy with anti-tubulin monoclonal antibody and anti-vimentin antibody, respectively. A new procedure was developed and used to measure the content of the cytoskeletal components of HL-60 cells during the process of maturation. HL-60 cells were fixed with formaldehyde in an MT-stabilizing buffer, permeabilized using L-lysophosphatidylcholine, stained for immunofluorescent measurement with antibodies specific for particular cytoskeletal components, and analyzed by flow cytometry. Terminally differentiated cells produced by exposure to RA contained larger amounts of MT and the IF vimentin. During the course of the maturation process, a transient increase in the amounts of the microtubule-associated proteins, (MAPs) MAP2 and tau, occurred. An RA-supersensitive clone, designated HL-60/S4, and an RA-resistant clone, designated HL-60/R3, were developed by mutagenization and selection. Use of these clones supported the concept that the observed changes in MT, MAPs, and vimentin were associated with the differentiation process rather than being due to other effects produced by the retinoid. Thus, the findings suggest that changes in MT, MAPs, and IF are important to the terminal maturation of leukemia cells.

Cell Differentiation↗
PubMed1992

Xenopus MAP kinase activator is a serine/threonine/tyrosine kinase activated by threonine phosphorylation.

Xenopus MAP kinase activator, a 45 kDa protein, has been shown to function as a direct upstream factor sufficient for full activation and both tyrosine and serine/threonine phosphorylation of inactive MAP kinase. We have now shown by using an anti-MAP kinase activator antiserum that MAP kinase activator is ubiquitous in tissues and is regulated post-translationally. Activation of MAP kinase activator is correlated precisely with its threonine phosphorylation during the oocyte maturation process. It is a key question whether MAP kinase activator is a kinase or not. We have shown that Xenopus MAP kinase activator purified from mature oocytes is capable of undergoing autophosphorylation on serine, threonine and tyrosine residues. Dephosphorylation of purified activator by protein phosphatase 2A treatment inactivates its autophosphorylation activity as well as its activator activity. Thus, Xenopus MAP kinase activator is a protein kinase with specificity for both serine/threonine and tyrosine. Partial protein sequencing of purified activator indicates that it contains a sequence homologous to kinase subdomains VI and VII of two yeast protein kinases, STE7 and byrl.

Amino Acid Sequence↗
PubMed1991

Mapping of evoked magnetic field with visual stimulation: a secondary projection and processing area.

Visual evoked fields (VEFs) were measured in four subjects, using magnetoencephalography (MEG) and a flashed checkerboard pattern stimulation with a duration of 20 ms. The left hemisphere was searched for the primary and the secondary projection areas with a full-field stimulus. Typical VEFs were found in the occipital area, which is considered to be the primary projection; and a secondary projection area was found in the dorsal temporal area in all subjects. The negative VEF in the secondary projection area was robust and stable, with a range of latencies from 200 to 230 ms. The amplitude was more than -400 femtotesla (fT), as high as the VEF in the occipital area. However, we were unable to localize the position of a dipole, since only one amplitude maxima was found.

Adult↗
PubMed1998

On the temporal relations between memory scanning and response preparation.

Three experiments were conducted to investigate whether response processes can start before memory scanning has finished when both are required in the same task. In Experiment 1 the color of a stimulus letter determined which hand might respond, and the letter's memory set membership determined whether that response should be made or withheld. Electrophysiological data suggested that lateralized response preparation was not initiated until memory scanning finished. Experiment 2 replicated these results with a consistent stimulus-response mapping to make the scanning process easier. Experiment 3 tested for earlier response priming with a probe reaction time paradigm, and the results suggested that color information can be used to activate a response before memory scanning is finished. The results of Experiments 1-3 suggest that interference between memory scanning and response preparation precludes the concurrent operation of these processes.

Adult↗
PubMed2001

The process of falling asleep.

The process of falling asleep can best be measured by considering a convergence of behavioural, EEG, physiological and subjective information. Doing so allows one to see sleep processes as they unfold, but relying on any single sleep index can bias the description of this complex process. The studies reviewed do not support the idea that sleep begins "in a moment", but rather that entry into sleep is a continuous, interwoven series of changes which begin in relaxed drowsiness and continue through stage 1, often into the first minutes of stage 2. The transition from waking brain to sleeping brain is traced accurately by Hori's nine-stage EEG system. Event-related potential (ERP) studies map complex changes in information processing as sleep begins, while quantitative EEG investigations have identified important spatiotemporal re-organisations of primary EEG frequencies which take place as one moves from waking to sleeping mode. To consider evidence from multiple levels of analysis, a three step electrophysiological model of central nervous system (CNS) regulation during sleep onset is proposed: initial processes appear to be alpha-related; intermediate processes, poorly studied to date, parallel the development of theta and vertex sharp wave activity, while the processes which terminate wakefulness are sigma sleep spindle-related. Clinical investigations of the sleep onset period in people with narcolepsy, insomnia, depression or sleep apnoea appear to indicate the presence of relatively unique electrophysiological signatures which may be of clinical significance. 2001 Harcourt Publishers Ltd

Journal Article↗
PubMed1996

Culex annulirostris breeding sites in urban areas: using remote sensing and digital image analysis to develop a rapid predictor of potential breeding areas.

A rapid technique is being developed and assessed to identify urban breeding sites of Culex annulirostris, which is a vector of an arbovirus (Ross River virus). Field survey and laboratory identification were used to identify breeding sites for the species. Ephemeral sites became the focus of the research and other mosquito species were recorded. The sites were located on digitized images of 1: 30,000 color aerial photographs. Training sites were used to create "themes" for the main ephemeral breeding sites and the MicroBRIAN image processing package was used to map the themes to each image. The accuracy and completeness of identification were evaluated with reference to the original field site identification and by further field checks. The accuracy was 87% and the completeness was 75%.

Animals↗
PubMed1996

The gene for human U2 snRNP auxiliary factor small 35-kDa subunit (U2AF1) maps to the progressive myoclonus epilepsy (EPM1) critical region on chromosome 21q22.3.

We used targeted exon trapping to clone portions of genes from human chromosome 21q22.3. One trapped sequence showed complete homology with the cDNA of human U2AF35 (M96982; HGM-approved nomenclature U2AF1), which encodes for the small 35-kDa subunit of the U2 snRNP auxiliary factor. Using the U2AF1 cDNA as a probe, we mapped this gene to cosmid Q15D2, a P1, and YAC 350F7 of the Chumakov et al. (Nature 359: 380, 1992) contig, close to the cystathionine-beta-synthase gene (CBS) on 21q22.3. This localization was confirmed by PCR using oligonucleotides from the 3' UTR and by FISH. As U2AF1 associates with a number of different factors during mRNA splicing, overexpression in trisomy 21 individuals could contribute to some Down syndrome phenotypes by interfering with the splicing process. Furthermore, because this gene maps in the critical region for the progressive myoclonus epilepsy I locus (EPM1), mutation analysis will be carried out in patients to evaluate the potential role of U2AF1 as a candidate for EPM1.

Base Sequence↗
PubMed2026

Genetic overlap between depression and C-reactive protein levels: Evidence from a cross-trait analysis.

Inflammation and depression have been consistently associated, with elevated C-reactive protein (CRP) levels observed in a significant subset of affected individuals. However, the genetic mechanisms underlying this association remain poorly understood. We integrated results from large-scale genome-wide association studies (GWAS) of depression and CRP levels in a cross-trait analysis specifically focusing on identifying horizontally pleiotropic loci. Identified variants were stratified as concordant versus discordant based on their direction of effects on the two traits and followed up using functional annotation, gene set enrichment, and colocalization analyses. We also explored causal relationships using Mendelian Randomization (MR) analysis with extensive sensitivity analyses, including adjustment for body mass index (BMI). We identified 9 novel loci. Functional analyses revealed that concordant loci were enriched in genes linked to immune and inflammatory processes, while discordant loci mostly mapped to metabolic pathways, including lipid regulation. MR provided strong evidence for body mass index driving a causal relationship between the genetic liability of depression on CRP levels. Our findings suggest that the association between depression and CRP levels is partly driven by shared genetic influences, pointing to different biological pathways depending on whether genetic effects are concordant or discordant. These results underscore the importance of considering effect direction when assessing the genetic overlap between depression and inflammatory processes. In addition, they highlight BMI as a key factor in the causal relationship between depression and systemic inflammation.

C-Reactive Protein↗
PubMed1987

Ferric-coprogen receptor FhuE of Escherichia coli: processing and sequence common to all TonB-dependent outer membrane receptor proteins.

Iron transport via siderophores requires outer membrane receptor proteins and the TonB protein. The FhuE protein of Escherichia coli functions as the receptor for ferric coprogen and ferric-rhodotorulic acid. A chromosomal DNA fragment bearing the fhuE gene was cloned into pACYC184. The gene was localized by insertion mutagenesis by using the transposon Tn1000. Expression in minicells revealed a FhuE precursor with an apparent molecular weight of 82,000 and a FhuE protein with a molecular weight of 76,000. The transcription polarity of the fhuE gene was deduced from the size of truncated polypeptides derived from Tn1000 insertions, which were mapped by restriction analysis. The processing of truncated precursors that were synthesized by insertion mutants was strongly reduced even when the insertion site was close to the carboxy terminus of the FhuE protein. It is concluded that either the efficient insertion of proFhuE into the cytoplasmic membrane or the rate of cleavage of the signal peptide requires a particular conformation of the proFhuE protein, which is only formed by the complete primary structure. The amino-terminal amino acid sequence deduced from the nucleotide sequence was confirmed by gas-phase sequencing of the precursor and the mature form, which were separated by electrophoresis on polyacrylamide gels. The precursor contained an unusually long signal peptide of 36 amino acids. The amino-terminal end of the mature form contained the sequence Glu-Thr-Val Ile-Val. A pentapeptide starting with either Glu or Asp, followed by Thr, and two uncharged residues ending with Val were found in all outer membrane receptor proteins that were constituents of TonB-dependent transport systems.

Amino Acid Sequence↗
PubMed1987

The immunoglobulin heavy chain switch: structural features of gamma 1 recombinant switch regions.

The immunoglobulin heavy chain isotype switch is mediated by a DNA rearrangement involving specific genomic segments referred to as switch regions. Switch regions are composed of tandemly repeated simple sequences. The role of the tandemly repeated structure of switch regions in the switch recombination process is not understood. We mapped eight recombination sites--six in the gamma 1 and two in the gamma 3 tandem arrays. In addition, we obtained molecular clones representing three of the six gamma 1 rearrangements, and determined the nucleotide sequences of the recombination sites in each. In general, the rearrangements are confined to the tandem repeat units, and are not clustered in a particular portion of either the gamma 3 or gamma 1 switch region. Nucleotide sequence analysis of one of the recombinant clones, gamma M35, reveals evidence for a successive switch event wherein a recombination between S mu and S gamma 3 was followed by recombination 57 bp downstream with S gamma 1. gamma 1 sequence data from the molecular clones we obtained, together with similar data from other investigators regarding the gamma 1, gamma 2b, and gamma 2a switch regions, reveals that recombinations tend to occur at homologous positions of the respective gamma-unit repeats, adjacent to the elements AGCT and GGGG found in each. This finding suggests that the cutting and religation step of the recombination process is mediated by a recombinase common to the four gamma-isotypes.

Animals↗
PubMed1997

Body surface Laplacian mapping of bioelectrical activity.

A method is described to process and interpret multi-channel bioelectrical signals. The bioelectrical signals were recorded noninvasively over the body surface of human subjects at 120 sites. The body surface Laplacian maps were then constructed from the multi-channel bioelectrical potential measurement. The method was evaluated by means of computer simulations, and applied to imaging cardiac electrical activity. The present investigation suggests body surface Laplacian mapping provides an important means in interpreting bioelectrical signals.

Body Surface Potential Mapping↗
PubMed2006

Unified approach for multiple sclerosis lesion segmentation on brain MRI.

The presence of large number of false lesion classification on segmented brain MR images is a major problem in the accurate determination of lesion volumes in multiple sclerosis (MS) brains. In order to minimize the false lesion classifications, a strategy that combines parametric and nonparametric techniques is developed and implemented. This approach uses the information from the proton density (PD)- and T2-weighted and fluid attenuation inversion recovery (FLAIR) images. This strategy involves CSF and lesion classification using the Parzen window classifier. Image processing, morphological operations, and ratio maps of PD- and T2-weighted images are used for minimizing false positives. Contextual information is exploited for minimizing the false negative lesion classifications using hidden Markov random field-expectation maximization (HMRF-EM) algorithm. Lesions are delineated using fuzzy connectivity. The performance of this algorithm is quantitatively evaluated on 23 MS patients. Similarity index, percentages of over, under, and correct estimations of lesions are computed by spatially comparing the results of present procedure with expert manual segmentation. The automated processing scheme detected 80% of the manually segmented lesions in the case of low lesion load and 93% of the lesions in those cases with high lesion load.

Adult↗
PubMed2003

Dynamic 3He imaging for quantification of regional lung ventilation parameters.

Dynamic ventilation imaging using laser-polarized (3)He has a promising potential for elucidating the physiology and physiopathology of the lungs. In this study, a methodological approach is proposed for the assessment and quantification of local ventilation parameters. High-temporal-resolution coronal ventilation image series were obtained with a projection-reconstruction (PR) sequence combined with the sliding-window technique. After image series were processed, parametric pixel-by-pixel maps of the gas arrival time, filling time constant, inflation rate, and gas volume were generated. The acquisition technique and the signal processing procedure, which are referred to collectively as sliding pulmonary imaging for respiratory overview (SPIRO), were tested in vivo in healthy rat lungs using a contrast media injector for controlled (3)He flow and volume injection in the animal lungs. The same protocol was applied to broncho-constriction animal models using intravenous injection of methacholine solution. Inflation rate values measured in the lungs were found to decrease with increasing doses of injected methacholine solution. This study demonstrates that it is possible to obtain quantitative regional gas dynamic information using the SPIRO technique in a single polarized gas inspiration.

Animals↗