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At least 1,675 records · Page 93Linked to original sources
PubMed1983

Post-transcriptional control of human cytomegalovirus gene expression.

During the immediate-early, early, and late phases of human cytomegalovirus infection in human fibroblasts, transcripts accumulated, respectively, from approximately 20, 75, and 90% of the sequences on the genome. Not all of the sequences which accumulated during the immediate-early and early phases were represented on polysomes, however. Four transcripts synthesized in cycloheximide-treated cells were studied in detail. A 2.2-kb transcript (0.713-0.733 map units) represented 95% of the polysome-associated RNA in cycloheximide-treated cells and was the first to be detected on polysomes at 2 hr postinfection in untreated cells. A second, less abundant, transcript of 5.2 kb (0.670-0.733 map units) was also found on polysomes in cycloheximide-treated cells, and preliminary evidence suggested that this transcript may be spliced during processing. A 3.25-kb transcript (0.190-0.217 map units) was identified also as a minor polysome-associated species of RNA. One transcript of 4.8 kb (0.630-0.670) remained associated with the nucleus and was not processed into mRNA in cycloheximide-treated cells. Differential stability between the various transcripts was observed, the 2.2-kb transcript being the most stable. The results showed that in human cytomegalovirus-infected cells controls exist at the level of transcript accumulation, transport into the cytoplasm, preferential association with polysomes, and relative stability of RNAs.

Cell Line↗
PubMed2006

Structures of p38alpha active mutants reveal conformational changes in L16 loop that induce autophosphorylation and activation.

p38 mitogen-activated protein (MAP) kinases function in numerous signaling processes and are crucial for normal functions of cells and organisms. Abnormal p38 activity is associated with inflammatory diseases and cancers making the understanding of its activation mechanisms highly important. p38s are commonly activated by phosphorylation, catalyzed by MAP kinase kinases (MKKs). Moreover, it was recently revealed that the p38alpha is also activated via alternative pathways, which are MKK independent. The structural basis of p38 activation, especially in the alternative pathways, is mostly unknown. This lack of structural data hinders the study of p38's biology as well as the development of novel strategies for p38 inhibition. We have recently discovered and optimized a novel set of intrinsically active p38 mutants whose activities are independent of any upstream activation. The high-resolution crystal structures of the intrinsically active p38alpha mutants reveal that local alterations in the L16 loop region promote kinase activation. The L16 loop can be thus regarded as a molecular switch that upon conformational changes promotes activation. We suggest that similar conformational changes in L16 loop also occur in natural activation mechanisms of p38alpha in T-cells. Our biochemical studies reveal novel mechanistic insights into the activation process of p38. In this regard, the results indicate that the activation mechanism of the mutants involves dimerization and subsequent trans autophosphorylation on Thr180 (on the phosphorylation lip). Finally, we suggest a model of in vivo p38alpha activation induced by the L16 switch with auto regulatory characteristics.

Amino Acid Sequence↗
PubMed2000

Role of prostanoids and nitric oxide inhibition in rats with experimental hepatic fibrosis.

Nitric oxide (NO) and prostaglandins have been proposed as vasodilator substances involved in peripheral vasodilatation characteristic of the liver cirrhosis. A link between NO and prostanoids has been suggested. The present study investigated the effect of simultaneous blockade of both, NO synthase (NOS) and cyclooxigenase (COX) in sham-operated (SO), or rats with bile-duct ligation (BDL) in the development of liver fibrosis. Animals were distributed in two groups SO (n=15) or BDL (n=15). Treatments (5 days) started three weeks after surgical procedure. Both, SO and BDL animals were treated with indomethacin (INDO) (5 mg/kg/day) alone, with NG-nitro-L-arginine-methyl-ester (NAME) (4 mg/kg/day) alone or with INDO and NAME combination at the same doses. At the end of follow-up body weight, packed cell volume, mean arterial blood pressure (MAP) and heart rate were measured. Liver tissue was processed for histological studies. In this study, BDL animals showed a decreased MAP. Treatment with L-NAME in BDL rats increased MAP. The chronic COX inhibition alone did not play an important role in the haemodynamic changes. The BDL produced a loss of hepatic structure, with ductular metaplasia that occupied the greater part of the hepatic parenchyma. Also, an important degree of fibrosis was observed. Both NO and PG synthesis inhibitors, alone or in combination, induced enhancing collagen fiber deposition in the hepatic parenchyma. These findings support the notion that the interaction between the NOS and COX pathways should be relevant in hepatic cirrhosis in which both NOS and COX are induced.

Animals↗
PubMed1988

Implications of ERP data for psychological theories of attention.

The contribution of the event-related potential (ERP) research to understanding human selective attention will be evaluated. A closely related issue, the starting point of the present treatment, involves the nature and extent of automaticity in information processing. The mismatch-negativity component of the ERP suggests that the basic, obligatory, processing of the physical features of auditory stimuli is unaffected by the direction of attention. These data also reveal a possible mechanism for attention switching to stimulus change occurring in the unattended input, observed by cognitive psychologists. The N1 wave of the ERP might in turn provide a data base for explaining similar attention switches to stimulus onsets after breaks in stimulation and to offsets of long-duration stimuli. With regard to selective attention, the processing negativity might make it possible to delineate the central principle of stimulus selection in attention, a goal probably inaccessible to non-physiological attention research. In the visual modality, cognitive psychologists have found that spatial attention is more fundamental and powerful in stimulus selection than any other form of visual selective attention. Consistently, ERP data show that the exogenous components in vision are enhanced by spatial selective attention but not when attended and unattended stimuli are not spatially separated. Also, ERP data (the P3 wave) give support to certain forms of resource-allocation theories of attention. In addition, with regard to the currently popular distinction between automatic versus controlled processing, these data strongly suggest that extended consistent-mapping training does not lead to a "genuine" automatization of a search process in the sense of independence of a limited-capacity system.

Attention↗
PubMed1996

What was where? Memory for object locations.

Three experiments are reported on short-term memory for object location. Stimulus displays containing different numbers and types of objects were presented for 30 seconds, after which subjects were required to relocate the various objects within the display, merely to reconstruct positions, or to assign objects correctly to an equal number of premarked positions. In all experiments half the trials were performed with concurrent articulatory suppression. The results support the hypothesis that two processes can be distinguished: one that underlies the construction of a positional map and one that assigns objects to positions. These processes are differentially affected by object numbers and articulatory suppression. This hypothesis is discussed in terms of Baddeley's (1986) working memory model and Kosslyn's (1987) distinction between "categorical" and "coordinate" spatial relations.

Adult↗
PubMed2004

Semi-automated, single-band peak-fitting analysis of hydroxyl radical nucleic acid footprint autoradiograms for the quantitative analysis of transitions.

Hydroxyl radical footprinting can probe the solvent accessibility of the ribose moiety of the individual nucleotides of DNA and RNA. Semi-automated analytical tools are presented for the quantitative analyses of nucleic acid footprint transitions in which processes such as folding or ligand binding are followed as a function of time or ligand concentration. Efficient quantitation of the intensities of the electrophoretic bands comprising the footprinting reaction products is achieved by fitting a series of Lorentzian curves to line profiles obtained from gels utilizing sequentially relaxed constraints consistent with electrophoretic mobility. An automated process of data 'standardization' has been developed that corrects for differences in the loading amounts in the electrophoresis. This process enhances the accuracy of the derived transitions and makes generating them easier. Together with visualization of the processed footprinting in false-color two-dimensional maps, DNA and RNA footprinting data can be accurately, precisely and efficiently processed allowing transitions to be objectively and comprehensively analyzed. The utility of this new analysis approach is illustrated by its application to the ion-meditated folding of a large RNA molecule.

Autoradiography↗
PubMed1998

A self-organizing neural network architecture for navigation using optic flow.

This article describes a self-organizing neural network architecture that transforms optic flow and eye position information into representations of heading, scene depth, and moving object locations. These representations are used to navigate reactively in simulations involving obstacle avoidance and pursuit of a moving target. The network's weights are trained during an action-perception cycle in which self-generated eye and body movements produce optic flow information, thus allowing the network to tune itself without requiring explicit knowledge of sensor geometry. The confounding effect of eye movement during translation is suppressed by learning the relationship between eye movement outflow commands and the optic flow signals that they induce. The remaining optic flow field is due to only observer translation and independent motion of objects in the scene. A self-organizing feature map categorizes normalized translational flow patterns, thereby creating a map of cells that code heading directions. Heading information is then recombined with translational flow patterns in two different ways to form maps of scene depth and moving object locations. Most of the learning processes take place concurrently and evolve through unsupervised learning. Mapping the learned heading representations onto heading labels or motor commands requires additional structure. Simulations of the network verify its performance using both noise-free and noisy optic flow information.

Computer Simulation↗
PubMed2002

Myths and truths in functional MRI: a basic guide for practitioners.

Since the first successful demonstration of primary visual cortex "activation" by Sokoloff in 1961, activation studies based on regional blood flow alteration became one of the gold standards for neuroscientific investigation. The rapid advancement of non-invasive imaging techniques provided an appropriate stage for the human application of this original method. Following the tremendous success of positron emission tomography (PET) utilizing O(15) labeled H(2)O (H(2)O(15)-PET), the magnetic resonance imaging (MRI) version, which is now referred to as functional MRI (fMRI), was introduced. fMRI is the method created based on the empirical observation that MRI exhibits spontaneous signal alteration associated with blood flow changes. It is now believed that the principle of fMRI is identical to H(2)O(15)-PET, namely, that it is blood flow based in accordance with the well-known Munro-Kellie doctrine which predicts a decline in cerebral venous blood volume secondary to an increase in cerebral arterial blood volume. The method is inherently qualitative and does not provide quantitative information regarding flow alteration. With the growing use of fMRI, however, exponentially increasing well founded criticism questioning the validity of fMRI data has been raised. The majority of validation issues arise during the process of obtaining raw images, which eventually provides raw numerical data for post-processing statistical analysis. This article provides a distillation of the essential knowledge necessary for the non-MR physicist fMRI investigator.

Brain Mapping↗
PubMedDate not supplied

Event-related potential maps depend on prestimulus brain electric microstate map.

The brain functional microstate immediately before each of about 3000 identical tone stimuli was classified using extracted reference-free descriptors (locations of maximal and minimal potential) of the landscape of the brain's momentary electric field, in 8 volunteers. Six prestimulus microstate map classes occurred more than 30 times in each subject, and were clustered into two map class types (totals of 242 and 283 cases, respectively, on the average per subject). Event-related potential (ERP) map series were averaged for each subject and prestimulus map class. Map descriptors were extracted from the ERP maps at times of maximal Global Field Power during the component time windows N100, P200 and P330. Discriminant functions were estimated; for the maps of N100 and P330, the discriminant scores differed significantly between the maps associated with the two prestimulus map class types (paired t-tests, df = 7, p = .014 and p = .005, respectively). The dominant axis of the poststimulus class type II ERP maps deviated clockwise from that of the type I ERP maps in all components. We conclude that subtle changes in the brain's spontaneous momentary functional microstate (as classified by spatial descriptors of a single map) influence event-related information processing by the brain, following common rules over subjects.

Adult↗
PubMed2002

Tracking meaning over time in the UMLS Metathesaurus.

The Unified Medical Language System(R) (UMLS) Metathesaurus contains records arranged by concept or meaning. Each concept contains a unique identifier (CUI) that can be used to track the concept over time. Since the January 2001 release, the Metathesaurus has included the file MRCUI that contains mappings for CUIs that disappear. This paper describes the processes that facilitated this effort and the ongoing effort to find suitable mappings for concepts whose meanings no longer exist in the Metathesaurus. This study highlights the need to identify missed synonymy prior to a release. It also shows a need to work more closely with source providers to identify the closest match in the Metathesaurus when they eliminate terms from their vocabularies.

National Library of Medicine (U.S.)↗
PubMed1979

Fate maps and cell differentiation in the amphibian embryo--an experimental study.

The aim of this paper is to test two different fate maps for the amphibian blastula with respect to their predictions concerning the process of cell differentiation. The first of these fate maps is the one proposed by Vogt, according to which all three germ layers can be projected on to the surface of the embryo. The second is a revision which claims that only endoderm and ectoderm are located in the surface, while the mesoderm is represented by free cells in the interior of the embryo. The testing has been performed by observing the differentiation of small explants of cells taken from various regions of the embryo. It was found that the spontaneous cell differentiation comprises three patterns: undifferentiated cells (free interior cells and circumpolar endodermal cells), fibroblast-like cells (the remaining endodermal cells) and epidermis (ectodermal cells). Further differentiation occurs only through induction, exerted either by the fibroblast-like endodermal cells or by heparan sulphate. When induced, the equatorial ectodermal cells give rise to swollen, hyaline cells (chordocytes), while the remaining ectodermal cells form a sequence of cell differentiation patterns, mesenchyme cells, nerve cells, melanophores and xanthophores. The free interior cells differentiate into striated muscle cells and elongated collagen-producing fibroblasts. Our results thus confirm the revised fate map, and they also give an insight into the mechanisms of the initial cell differentiations in the amphibian embryo.

Ambystoma↗
PubMed1997

An interpretation of the internal desynchronizations based on dynamics of the two-process model.

Daan's two-process model is known to be one of the most powerful models, covering various situations from free-running to sleep deprivation. In this study, bifurcation properties of the model dynamics are clarified using a circle map. In addition, the two-process model is applied to simulate the two distinct patterns (the period-prolonged: I and the period-shortened: II) of sleep-wake cycles during internal desynchronizations. We propose the novel interpretation that types I and II could be regarded as mutual entrainments between the body temperature rhythm and the sleep-wake cycle with the period ratios 3:4 and 3:2, respectively. From the bifurcation properties of the two-process model obtained above, the model is shown to be able to generate the respective type of mutual entrainment with an appropriate range of a parameter value, i.e, a gap between thresholds. The variable behavior of human circadian rhythm is suggested to be systematically understood based on the bifurcation properties of the two-process model.

Activity Cycles↗
PubMed2006

A real-time EMG pattern recognition system based on linear-nonlinear feature projection for a multifunction myoelectric hand.

This paper proposes a novel real-time electromyogram (EMG) pattern recognition for the control of a multifunction myoelectric hand from four channel EMG signals. To extract a feature vector from the EMG signal, we use a wavelet packet transform that is a generalized version of wavelet transform. For dimensionality reduction and nonlinear mapping of the features, we also propose a linear-nonlinear feature projection composed of principal components analysis (PCA) and a self-organizing feature map (SOFM). The dimensionality reduction by PCA simplifies the structure of the classifier and reduces processing time for the pattern recognition. The nonlinear mapping by SOFM transforms the PCA-reduced features into a new feature space with high class separability. Finally, a multilayer perceptron (MLP) is used as the classifier. Using an analysis of class separability by feature projections, we show that the recognition accuracy depends more on the class separability of the projected features than on the MLP's class separation ability. Consequently, the proposed linear-nonlinear projection method improves class separability and recognition accuracy. We implement a real-time control system for a multifunction virtual hand. Our experimental results show that all processes, including virtual hand control, are completed within 125 ms, and the proposed method is applicable to real-time myoelectric hand control without an operational time delay.

Action Potentials↗
PubMed2000

Analysing complex genetic traits with chromosome substitution strains.

Many valuable animal models of human disease are known and new models are continually being generated in existing inbred strains,. Some disease models are simple mendelian traits, but most have a polygenic basis. The current approach to identifying quantitative trait loci (QTLs) that underlie such traits is to localize them in crosses, construct congenic strains carrying individual QTLs, and finally map and clone the genes. This process is time-consuming and expensive, requiring the genotyping of large crosses and many generations of breeding. Here we describe a different approach in which a panel of chromosome substitution strains (CSSs) is used for QTL mapping. Each of these strains has a single chromosome from the donor strain substituting for the corresponding chromosome in the host strain. We discuss the construction, applications and advantages of CSSs compared with conventional crosses for detecting and analysing QTLs, including those that have weak phenotypic effects.

Animals↗
PubMed1994

Three dimensional representation of brain electrical activity.

Brain topography mapping is a useful technique for the representation of electrical activity recorded on the scalp. It clarifies spatial and temporal relationships between different cortical areas. In this work we propose a system which includes several enhancements over those previously proposed, such as an optimised interpolation method and a three dimensional reconstruction of maps. This system is available in a personal computer environment. Results clearly show a superiority of the 3D representation over 2D maps obtained with different projections. The performance of this system in terms of speed and precision is comparable to that of dedicated image processing and image synthesis workstations proposed for brain mapping.

Brain↗
PubMed1996

Analysis of stimulus-response chains using nonlinear dynamics.

Stimulus chains represent those series of coupled biochemical events through which receptor occupation is transformed into physiological or pharmacological responses. These events are commonly modeled as sets of sequential hyperbolic responses that may be treated mathematically as an iterative process. Methods used in the analysis of iterated map functions such as bifurcation analysis and graphical iteration are applied to the stimulus sequence to understand the dynamics of the process. Examples are given to illustrate determination of fixed points of the map as well as techniques for determining their stability. When present, a central repelling fixed point reveals the existence and location of a stimulus threshold, while the upper attracting fixed point determines the size of the terminal stimulus (S omega) in the signaling pathway. Estimates of S omega are used to develop equations for predicting changes in agonist EC50S at each point in the stimulus chain. Similarly, Lyapunov exponents are found to provide a link between changes in cell or tissue parameters and changes in the rate of stimulus amplification and agonist maximal response. These findings demonstrate that techniques of nonlinear dynamics when combined with biochemical studies of cellular signaling, provide useful new approaches for quantitative and qualitative analysis of drug action.

Dose-Response Relationship, Drug↗
PubMed1989

Recognition and cleavage signals for mRNA processing lie within local domains of the phage f1 RNA precursors.

In Escherichia coli infected with the filamentous phage f1, a number of the abundant phage mRNAs, species C-G, are products of post-transcriptional processing. The approach of cloning the phage sequences likely to include the processing signals in a plasmid under transcriptional control of the lambda PL promoter (Blumer, K. J., and Steege, D. A. (1984) Nucleic Acids Res. 12, 1847-1861) was extended to additional sites to show that processing at all five major sites is mediated by nuclease activity encoded by the bacterial genome. Primer extension methods were used to map more accurately in the f1 DNA sequence the 5' end points of the processed RNAs. The DNA segments that encode the mRNA processing signals were delimited from parallel series of 5'-3' and 3'-5' deletions made into the regions in which the RNA 5' ends map. For each deletion variant, in vivo f1 mRNA processing activity was assessed by primer extension and S1 nuclease mapping methods. The data indicate that the processing signals are comprised of relatively local regions near the point of RNA cleavage. Whereas cleavage occurs at the 5' border of the sequences that comprise the D, E, and F processing sites and thereby places most of the recognition information in the mature or product portion of the precursor, it occurs more centrally within the region comprising the C site. The C and D sites function independently as substrates for cleavage, with the necessary information contained in regions of 70 and 90 nucleotides, respectively. Cleavage at the E site appears to require a region of 130 nucleotides which completely contains the F site. From the effects on processing activity of deleting sequences in this region, the overlapping E and F processing sites appear to consist functionally of two subdomains. Each has a cleavage site at its immediate 5' end which can be substituted by foreign sequences, but both utilize a common recognition domain downstream from the point of strand scission.

Base Sequence↗
PubMed2002

Primer on medical genomics part II: Background principles and methods in molecular genetics.

The nucleus of every human cell contains the full complement of the human genome, which consists of approximately 30,000 to 70,000 named and unnamed genes and many intergenic DNA sequences. The double-helical DNA molecule in a human cell, associated with special proteins, is highly compacted into 22 pairs of autosomal chromosomes and an additional pair of sex chromosomes. The entire cellular DNA consists of approximately 3 billion base pairs, of which only 1% is thought to encode a functional protein or a polypeptide. Genetic information is expressed and regulated through a complex system of DNA transcription, RNA processing, RNA translation, and posttranslational and cotranslational modification of proteins. Advances in molecular biology techniques have allowed accurate and rapid characterization of DNA sequences as well as identification and quantification of cellular RNA and protein. Global analytic methods and human genetic mapping are expected to accelerate the process of identification and localization of disease genes. In this second part of an educational series in medical genomics, selected principles and methods in molecular biology are recapped, with the intent to prepare the reader for forthcoming articles with a more direct focus on aspects of the subject matter.

Animals↗