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At least 1,369 records · Page 76Linked to original sources
PubMed1997

p38-2, a novel mitogen-activated protein kinase with distinct properties.

Mitogen-activated protein (MAP) kinases are involved in many cellular processes. Here we describe the cloning and characterization of a new MAP kinase, p38-2. p38-2 belongs to the p38 subfamily of MAP kinases and shares with it the TGY phosphorylation motif. The complete p38-2 cDNA was isolated by polymerase chain reaction. It encodes a 364-amino acid protein with 73% identity to p38. Two shorter isoforms missing the phosphorylation motif were identified. Analysis of various tissues demonstrated that p38-2 is differently expressed from p38. Highest expression levels were found in heart and skeletal muscle. Like p38, p38-2 is activated by stress-inducing signals and proinflammatory cytokines. The preferred upstream kinase is MEK6. Although p38-2 and p38 phosphorylate the same substrates, the site specificity of phosphorylation can differ as shown by two-dimensional phosphopeptide analysis of Sap-1a. Additionally, kinetic studies showed that p38-2 appears to be about 180 times more active than p38 on certain substrates such as ATF2. Both kinases are inhibited by a class of pyridinyl imidazoles. p38-2 phosphorylation of ATF2 and Sap-1a but not Elk1 results in increased transcriptional activity of these factors. A sequential kinetic mechanism of p38-2 is suggested by steady state kinetic analysis. In conclusion, p38-2 may be an important component of the stress response required for the homeostasis of a cell.

Activating Transcription Factor 2↗
PubMed2004

Combining different 'omics' technologies to map and validate protein-protein interactions in humans.

The mapping of protein-protein interactions is key to understanding biological processes. Many technologies have been reported to map interactions and these have been systematically applied in yeast. To date, the number of reported yeast protein interactions that have been truly validated by at least one other approach is low. The mapping of human protein interaction networks is even more complicated. Thus, it is unreasonable to try to map the human interactome; instead, interaction mapping in human cell lines should be focused along the lines of diseases or changes that can be associated with specific cells. In this paper, an approach for combining different 'omics' technologies to achieve efficient mapping and validation of protein interactions in human cell lines is presented.

Cell Line↗
PubMed1993

Integrating order and distance relationships from heterogeneous maps.

There is no automatic mechanism to integrate information between heterogeneous genome maps. Currently, integration is a difficult, manual process. We have developed a process for knowledge base design, and we use this to integrate order and distance relationships between genetic linkage, radiation hybrid, and physical maps. Until now, the only way to develop a persistent, knowledge-intensive application was to either develop a new knowledge base from scratch or coerce the application to fit an existing knowledge base. This was not from lack of interest by the knowledge base or database community, but merely from a lack of theoretical tools powerful enough to tackle the problem. We import formalisms from knowledge representation, natural language semantics, programming language research, and databases. These form a strong, theoretical foundation for knowledge base design upon which we have implemented the knowledge base design tool called WEAVE.

Artificial Intelligence↗
PubMed2000

Practice-related functional activation changes in a working memory task.

The effects of practice on the functional anatomy of a visuospatial working memory (VSWM) task were studied using functional Magnetic Resonance Imaging (fMRI). Functional imaging was conducted as subjects completed a moderate (Experiment 1) or extensive (Experiment 2) amount of practice on a delayed-match-to-sample task. While improvement in task performance was seen with practice, the task's dependence upon VSWM did not change. Activations in frontal (inferior, middle, and precentral gyri and superior frontal sulcus), parietal (intra-parietal sulcus, inferior parietal lobule, and precuneus) and cingulate (anterior and posterior) regions were observed as were bilateral insular and occipital activations. With the exception of the posterior cingulate, practice produced activation decreases in these regions, thus providing little evidence for a re-organization of the functional neuroanatomy. Fewer regions passing statistical criteria were observed at the end of practice relative to early in practice. Regions that were lost were mostly posterior (occipital and precuneus) but also included the left middle frontal gyrus, left precentral gyrus, and right insula suggesting that a more precise VSWM functional map can be observed once processes specific to encountering a novel task are removed. Little further activation changes were observed after extensive practice. These results suggest, minimally, that practice effects should be considered so as to avoid incorrectly attributing functional activation to a cognitive process of interest. Further, these data show that the dynamics of functional change can be tracked while a task is being learned and as an important cognitive process becomes more skilled.

Adult↗
PubMed1993

Refined mapping of the GM2 activator protein (GM2A) locus to 5q31.3-q33.1, distal to the spinal muscular atrophy locus.

The GM2 activator locus (GM2A) had previously been considered as a candidate gene for some forms of spinal muscular atrophy (SMA; mapped to 5q11.2-q13.3). It was eliminated as a possible candidate because PCR-based mapping failed to localize the gene to chromosome 5, as was previously reported using an ELISA-based methodology. However, we demonstrated that the PCR primers used preferentially amplified a processed pseudogene (GM2AP) that we mapped to chromosome 3 and that GM2A was located on chromosome 5. In this report, we reconsider the candidacy of GM2A by refining its localization on chromosome 5 using fluorescence in situ hybridization. We localize GM2A to 5q31.3-q33.1; thus, it is not a candidate gene for SMA.

Cells, Cultured↗
PubMed1988

An allele of the Prot locus in maize is a variant for the site of protein processing.

An allele of the Prot locus, which encodes a major globulin of the maize scutellum, is a variant for a site of protein processing. Segregation analysis and recombination mapping indicate that the variant is an allele of the Prot locus. Designated Prot-V, this allele specifies three polypeptides, V1, V2, and V3. The V1 polypeptide is incompletely processed during the proteolytic processing step catalyzed by the product of the Mep locus. Cyanogen bromide cleavage studies support the precursor-product relationship between V1 and V2. The V1 product is shortened with respect to other PROT' proteins and it is postulated that the normal site of MEP processing has been removed by this foreshortening.

Alleles↗
PubMed1999

MAP kinase pathways.

MAP kinases help to mediate diverse processes ranging from transcription of protooncogenes to programmed cell death. More than a dozen mammalian MAP kinase family members have been discovered and include, among others, the well studied ERKs and several stress-sensitive enzymes. MAP kinases lie within protein kinase cascades. Each cascade consists of no fewer than three enzymes that are activated in series. Cascades convey information to effectors, coordinates incoming information from other signaling pathways, amplify signals, and allow for a variety of response patterns. Subcellular localization of enzymes in the cascades is an important aspect of their mechanisms of action and contributes to cell-type and ligand-specific responses. Recent findings on these properties of MAP kinase cascades are the major focus of this review.

Animals↗
PubMed2006

Linkage maps of the dwarf and Normal lake whitefish (Coregonus clupeaformis) species complex and their hybrids reveal the genetic architecture of population divergence.

Elucidating the genetic architecture of population divergence may reveal the evolution of reproductive barriers and the genomic regions implicated in the process. We assembled genetic linkage maps for the dwarf and Normal lake whitefish species complex and their hybrids. A total of 877 AFLP loci and 30 microsatellites were positioned. The homology of mapped loci between families supported the existence of 34 linkage groups (of 40n expected) exhibiting 83% colinearity among linked loci between these two families. Classes of AFLP markers were not randomly distributed among linkage groups. Both AFLP and microsatellites exhibited deviations from Mendelian expectations, with 30.4% exhibiting significant segregation distortion across 28 linkage groups of the four linkage maps in both families (P < 0.00001). Eight loci distributed over seven homologous linkage groups were significantly distorted in both families and the level of distortion, when comparing homologous loci of the same phase between families, was correlated (Spearman R = 0.378, P = 0.0021). These results suggest that substantial divergence incurred during allopatric glacial separation and subsequent sympatric ecological specialization has resulted in several genomic regions that are no longer complementary between dwarf and Normal populations issued from different evolutionary glacial lineages.

Animals↗
PubMed1984

Multiple factors and processes involved in host cell killing by bacteriophage Mu: characterization and mapping.

The regions of bacteriophage Mu involved in host cell killing were determined by infection of a lambda-immune host with 12 lambda pMu-transducing phages carrying different amounts of Mu DNA beginning at the left end. Infecting lambda pMu phages containing 5.0 (+/- 0.2) kb or less of the left end of Mu DNA did not kill the lambda-immune host, whereas lambda pMu containing 5.1 kb did kill, thus locating the right end of the kil gene between approximately 5.0 and 5.1 kb. For the Kil+ phages the extent of killing increased as the multiplicity of infection (m.o.i.) increased. In addition, killing was also affected by the presence of at least two other regions of Mu DNA: one, located between 5.1 and 5.8 kb, decreased the extent of killing; the other, located between 6.3 and 7.9 kb, greatly increased host cell killing. Killing was also assayed after lambda pMu infection of a lambda-immune host carrying a mini-Mu deleted for most of the B gene and the middle region of Mu DNA. Complementation of mini-Mu replication by infecting B+ lambda pMu phages resulted in killing of the lambda-immune, mini-Mu-containing host, regardless of the presence or absence of the Mu kil gene. The extent of host cell killing increased as the m.o.i. of the infecting lambda pMu increased, and was further enhanced by both the presence of the kil gene and the region located between 6.3 and 7.9 kb. These distinct processes of kil-mediated killing in the absence of replication and non-kil-mediated killing in the presence of replication were also observed after induction of replication-deficient and kil mutant prophages, respectively.

Bacteriophage lambda↗
PubMed2004

Functional brain mapping of extraversion and neuroticism: learning from individual differences in emotion processing.

This review outlines how functional brain imaging, using an individual-differences approach in the processing of emotional stimuli, has begun to reveal the neural basis of extraversion (E) and neuroticism (N), two traits that are linked to both emotion and health. Studies using functional magnetic resonance imaging have shown that individual differences in participants' E and N scores are correlated with individual differences in brain activation in specific brain regions that are engaged during cognitive-affective tasks. Imaging studies using genotyped participants have begun to address the molecular mechanisms that may underlie these individual differences. The multidisciplinary integration of brain imaging and molecular genetic methods offers an exciting and novel approach for investigators who seek to uncover the biological mechanisms by which personality and health are interrelated.

Amygdala↗
PubMed2003

Conformational changes in the multidrug transporter EmrE associated with substrate binding.

EmrE is a bacterial multidrug transporter of the small multidrug resistance family, which extrudes large hydrophobic cations such as tetraphenylphosphonium (TPP(+)) out of the cell by a proton antiport mechanism. Binding measurements were performed on purified EmrE solubilized in dodecylmaltoside to determine the stoichiometry of TPP(+) binding; the data showed that one TPP(+) molecule bound per EmrE dimer. Reconstitution of purified EmrE at low lipid:protein ratios in either the presence or the absence of TPP(+) produced well ordered two-dimensional crystals. Electron cryo-microscopy was used to collect images of frozen hydrated EmrE crystals and projection maps were determined by image processing to 7A resolution. An average native EmrE projection structure was calculated from the c222 and p222(1) crystals, which was subsequently subtracted from the average of two independent p2 projection maps of EmrE with TPP(+) bound. The interpretation of the difference density image most consistent with biochemical data suggested that TPP(+) bound at the monomer-monomer interface in the centre of the EmrE dimer, and resulted in the movement of at least one transmembrane alpha-helix.

Antiporters↗
PubMed1984

KLONER; a computer program to simulate recombinant DNA strategies by restriction map manipulation.

A computer program is described which allows for the manipulation of restriction maps of various DNA fragments to demonstrate techniques used in DNA cloning and to predict and/or confirm experimental results. This program is capable of reading in restriction enzyme cleavage sites for several different DNA molecules of interest. This information is then compiled in order to form restriction maps which can then be processed by digestion with restriction endonucleases and treatment with other common DNA modifying enzymes. Ligation can then be simulated by joining fragments with complementary ends in all possible orientations, producing restriction maps of the products. The resulting recombinants can then be further analyzed by physical mapping with appropriate restriction endonucleases. This program was written in Pascal on an Apple II computer.

Base Sequence↗
PubMed2006

Topology-induced coarsening in language games.

We investigate how very large populations are able to reach a global consensus, out of local "microscopic" interaction rules, in the framework of a recently introduced class of models of semiotic dynamics, the so-called naming game. We compare in particular the convergence mechanism for interacting agents embedded in a low-dimensional lattice with respect to the mean-field case. We highlight that in low dimensions consensus is reached through a coarsening process that requires less cognitive effort of the agents, with respect to the mean-field case, but takes longer to complete. In one dimension, the dynamics of the boundaries is mapped onto a truncated Markov process from which we analytically computed the diffusion coefficient. More generally we show that the convergence process requires a memory per agent scaling as N and lasts a time N1+2/d in dimension d < or = 4 (the upper critical dimension), while in mean field both memory and time scale as N3/2 , for a population of agents. We present analytical and numerical evidence supporting this picture.

Journal Article↗
PubMedDate not supplied

Physiological role of salsolinol: its hypophysiotrophic function in the regulation of pituitary prolactin secretion.

We have recently observed that 1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (salsolinol) produced by hypothalamic neurons can selectively release prolactin from the anterior lobe (AL) of the pituitary gland. Moreover, high affinity binding sites for SAL have been detected in areas, like median eminence (ME) and the neuro-intermediate lobe (NIL) that are known terminal fields of the tuberoinfundibular DAergic (TIDA) and tuberohypophysial (THDA)/periventricular (PHDA) DAergic systems of the hypothalamus, respectively. However, the in situ biosynthesis and the mechanism of action of SAL are still enigmatic, these observations clearly suggest that sites other than the AL might be targets of SAL action. Based on our recent observations it may be relevant to postulate that an "autosynaptocrine" regulatory mechanism functioning at the level of the DAergic terminals localized in both the ME and NIL, may play a role in the hypophyseotrophic regulation of PRL secretion. Furthermore, SAL may be a key player in these processes. The complete and precise mapping of these intra-terminal mechanisms should help us to understand the tonic DAerg regulation of PRL secretion. Moreover, it may also give insight into the role of pre-synaptic processes that most likely have distinct and significant functional as well as pathological roles in other brain areas using DAergic neurotransmission, like striatonigral and mesolimbic systems.

Animals↗
PubMed2002

[The advances on the research of the body surface mapping].

Body surface mapping is introduced in this paper. The research of body surface mapping involves two main aspects: data acquiring system and data processing methods. The recommended design utilizes the virtual instruments concept and high-speed open bus standard. The data processing methods involve qualitative and quantitative methods. Dynamic and static mapping techniques are introduced here as the qualitative methods while statistical methods, inverse calculation and principle component analysis are introduced as the quantitative methods.

Algorithms↗
PubMed1998

Management and prevention of personal problems in older adolescents via schematic maps and peer feedback.

The purpose of the present study was to provide a basis for enhancing personal development in older adolescents by examining the usefulness of two information-processing tools in solving personal problems: schematic maps and peer feedback. Ninety-five college students were assigned to either a schematic map group or an essay group, and further subdivided into groups that worked alone or with a vicarious partner. Assessment consisted of analyzing and generating alternatives to a scenario involving a college student with a drinking problem. Results indicated that alternative generation, an important step in the problem-solving process, is susceptible to experimental manipulation. Schematic maps facilitate the generation of wider-ranging, viable, synergistic alternatives to an uncomfortable situation. Maps help illustrate the complex systems within which problems occur and how patterns of behavior are maintained through reinforcement. Peer feedback may provide information about strategies for the development of additional options.

Adolescent↗
PubMed1992

Real-time quantitative elemental analysis and mapping: microchemical imaging in cell physiology.

Recent advances in widely available microcomputers have made the acquisition and processing of digital quantitative X-ray maps of one to several cells readily feasible. Here we describe a system which uses a graphics-based microcomputer to acquire spectrally filtered X-ray elemental image maps that are fitted to standards, to display the image in real time, and to correct the post-acquisition image map with regard to specimen drift. Both high-resolution quantitative energy-dispersive X-ray images of freeze-dried cyrosections and low-dose quantitative bright-field images of frozen-hydrated sections can be acquired to obtain element and water content from the same intracellular regions. The software programs developed, together with the associated hardware, also allow static probe acquisition of data from selected cell regions with spectral processing and quantification performed on-line in real time. In addition, the unified design of the software program provides for off-line processing and analysing by several investigators at microcomputers remote from the microscope. The overall experimental strategy employs computer-aided imaging, combined with static probes, as an essential interactive tool of investigation for biological analysis. This type of microchemical microscopy facilitates studies in cell physiology and pathophysiology which focus on mechanisms of ionic (elemental) compartmentation, i.e. structure-function correlation at cellular and subcellular levels; it allows investigation of intracellular concentration gradients, of the heterogeneity of cell responses to stimuli, of certain fast physiological events in vivo at ultrastructural resolution, and of events occurring with low incidence or involving cell-to-cell interactions.

Animals↗
PubMed2006

Hippocampal place cells, context, and episodic memory.

Although most observers agree that the hippocampus has a critical role in learning and memory, there remains considerable debate about the precise functional contribution of the hippocampus to these processes. Two of the most influential accounts hold that the primary function of the hippocampus is to generate cognitive maps and to mediate episodic memory processes. The well-documented spatial firing patterns (place fields) of hippocampal neurons in rodents, along with the spatial learning impairments observed with hippocampal damage support the cognitive mapping hypothesis. The amnesia for personally experienced events seen in humans with hippocampal damage and the data of animal models, which show severe memory deficits associated with hippocampal lesions, support the episodic memory account. Although an extensive literature supports each of these hypotheses, a specific contribution of place cells to episodic memory has not been clearly demonstrated. Recent data from our laboratory, together with previous findings, indicate that hippocampal place fields and neuronal responses to task-relevant stimuli are highly sensitive to the context, even when the contexts are defined by abstract task demands rather than the spatial geometry of the environment. On the basis of these findings, it is proposed that place fields reflect a more general context processing function of the hippocampus. Hippocampal context representations could serve to differentiate contexts and prime the relevant memories and behaviors. Since episodic memories, by definition, include information about the time and place where the episode occurred, contextual information is a necessary prerequisite for any episodic memory. Thus, place fields contribute importantly to episodic memory as part of the needed context representations. Additionally, recent findings indicate that hippocampal neurons differentiate contexts at progressively finer levels of detail, suggesting a hierarchical coding scheme which, if combined with temporal information, could provide a means of differentiating memory episodes.

Action Potentials↗