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PubMed2003

Functional dissociation among components of remembering: control, perceived oldness, and content.

Remembering is the ability to bring back to mind episodes from one's past and is presumably accomplished by multiple, interdependent processes. In the present functional magnetic resonance imaging study, neural correlates of three hypothesized components of remembering were explored, including those associated with control, perceived oldness, and retrieved content. Levels of each component were separately manipulated by varying study procedures and sorting trials by subject response. Results suggest that specific regions in the left prefrontal cortex, including anterior-ventral Brodmann's Area (BA) 45/47 and more dorsal BA 44, increase activity when high levels of control are required but do not necessarily modulate on the basis of perceived oldness. Parietal and frontal regions, particularly the left parietal cortex near BA 40/39, associate with the perception that information is old and generalize across levels of control and retrieved content. Activity in the parietal cortex correlated with perceived oldness even when judgments were in error. The inferior temporal cortex near BA 19/37 associated differentially with retrieval of visual object content. Within the ventral visual processing stream, content-based modulation was specific to late object-responsive regions, suggesting an efficient retrieval process that spares areas that process more primitive retinotopically mapped visual features. Taken collectively, the results identify neural correlates of distinct components of remembering and provide evidence for a functional dissociation. Frontal regions may contribute to control processes that interact with different posterior regions that contribute a signal that information is old and support the contents of retrieval.

Acoustic Stimulation↗
PubMed2006

Astrocyte-neuron vulnerability to prenatal stress in the adult rat brain.

Chronic activation of the stress response during pregnancy has been shown to be injurious to the development of the offspring. We have previously demonstrated that restraint prenatal stress inflicted during the last week of pregnancy in rats increased dopamine and glutamate receptors in forebrain areas of the adult offsprings. In this study, the same prenatal insult was employed to assess morphological changes in astrocytes and in the dendritic arborization in frontal cortex, striatum, and hippocampus of the adult rat brain. On postnatal day 90, brains were processed for immunocytochemistry using primary antibodies to glial fibrillary acidic protein (GFAP; the main cytoskeletal astroglial protein), S100B protein (an astroglial-derived neurotrophic factor), MAP-2 (a microtubule-associated protein present almost exclusively in dendrites), and synaptophysin (Syn; one major integral protein of the synaptic vesicles membrane). The results show a significant increase in the cell area of GFAP-immunoreactive (-IR) astrocytes, with high levels of S100B protein and a significant decrease in the relative area of MAP-2-IR neuronal processes in prenatally stressed adult rats. The expression of synaptophysin decreased in all areas studied. These results demonstrate that prenatal stress induces a long-lasting astroglial reaction and a reduced dendritic arborization, with synaptic loss in the brain of adult offspring. In addition to the neurochemical alterations previously reported, these morphological changes might be underlying the behavioral and learning impairment previously observed in prenatally stressed rats.

Animals↗
PubMed1987

RNA 3' processing regulates histone mRNA levels in a mammalian cell cycle mutant. A processing factor becomes limiting in G1-arrested cells.

Post-transcriptional regulation of histone gene expression in a mouse mastocytoma cell cycle mutant (21-Tb) depends largely on conserved DNA sequences that are essential for RNA 3' processing. We have analyzed whether this regulation occurs at the level of RNA 3' processing. We show, by RNase mapping, that nuclear H4 mRNA precursors, which are hardly detectable in total RNA from exponentially dividing cells, accumulate in G1-arrested cells, i.e. when mature mRNAs are drastically reduced. Furthermore, we show that a heat-labile component of the processing apparatus, recently identified in HeLa cell nuclear extracts, is limiting in extracts from G1-arrested 21-Tb cells. In contrast, this activity is in excess in extracts from exponentially dividing cells, whereas both extracts contain similar amounts of snRNPs of the Sm serotype. These fluctuations in the heat-labile activity may generally contribute to proliferation or cell cycle dependent histone gene regulation.

Animals↗
PubMed1997

Chromosomal mapping of the human and murine orphan receptors ERRalpha (ESRRA) and ERRbeta (ESRRB) and identification of a novel human ERRalpha-related pseudogene.

The estrogen-related receptors ERRalpha and ERRbeta (formerly ERR1 and ERR2) form a subgroup of the steroid/thyroid/retinoid receptor family. ERRalpha and ERRbeta are homologous to the estrogen receptor and bind similar DNA targets; however, they are unable to activate gene transcription in response to estrogens. We have used interspecific backcross analysis to map the murine Estrra locus to chromosome 19 and Estrrb to mouse chromosome 12. Using fluorescence in situ hybridization, we have mapped the human ESRRA gene to chromosome 11q12-q13 and the human ESRRB gene to chromosome 14q24.3. In addition, we report the isolation of a processed human ERRalpha pseudogene mapping to chromosome 13q12.1. To our knowledge, this represents the first report of a pseudogene associated with a member of the nuclear receptor superfamily.

Amino Acid Sequence↗
PubMedDate not supplied

The fallacy of the overhead quick fix.

Facing pressure from a few large, low-cost competitors, Thornton, an old-guard specialty-equipment manufacturer, fought back by eliminating overhead. Over two-years, it outsourced components and consolidated operations. But instead of cutting overhead, it added more and became still more uncompetitive. Thornton is not alone in either its predicament or its failed reaction. Many large manufacturing companies are finding themselves at a cost disadvantage in markets they have dominated for years. One reason is excessive overhead structures, the result of an unchecked buildup of indirect employees needed to control rising organizational complexity. Another reason is the emergence of the "robust" competitor, comparable in size and product scope but able to produce at a lower unit overhead cost. Data collected from more than 100 manufacturing plants worldwide illustrate the differences between overhead cost structures of bureaucratic, niche, and robust companies. The gulf between these groups highlights the need for action by bureaucratic companies, and, in some cases, by niche companies. But high-overhead companies are doomed if they cut overhead out of the system either by outsourcing or downsizing. If they expect to retain their size and also become more cost competitive, they must rethink their manufacturing systems. Well-designed and well-controlled processes mean higher product quality, faster cycle time, improved flexibility, and lower overhead costs. Sustainable overhead reduction means a commitment to continuous improvement. This includes segmenting, mapping, and measuring existing processes and then working to improve them.(ABSTRACT TRUNCATED AT 250 WORDS)

Cost Control↗
PubMed1999

Mapping of the feline calicivirus proteinase responsible for autocatalytic processing of the nonstructural polyprotein and identification of a stable proteinase-polymerase precursor protein.

Expression of the region of the feline calicivirus (FCV) ORF1 encoded by nucleotides 3233 to 4054 in an in vitro rabbit reticulocyte system resulted in synthesis of an active proteinase that specifically processes the viral nonstructural polyprotein. Site-directed mutagenesis of the cysteine (Cys1193) residue in the putative active site of the proteinase abolished autocatalytic cleavage as well as cleavage of the viral capsid precursor, suggesting that this "3C-like" proteinase plays an important role in proteolytic processing during viral replication. Expression of the region encoding the C-terminal portion of the FCV ORF1 (amino acids 942 to 1761) in bacteria allowed direct N-terminal sequence analysis of the virus-specific polypeptides produced in this system. The results of these analyses indicate that the proteinase cleaves at amino acid residues E960-A961, E1071-S1072, E1345-T1346, and E1419-G1420; however, the cleavage efficiency is varied. The E1071-S1072 cleavage site defined the N terminus of a 692-amino-acid protein that contains sequences with similarity to the picornavirus 3C proteinase and 3D polymerase domains. Immunoprecipitation of radiolabeled proteins from FCV-infected feline kidney cells with serum raised against the FCV ORF1 C-terminal region showed that this "3CD-like" proteinase-polymerase precursor protein is apparently stable and accumulates in cells during infection.

3C Viral Proteases↗
PubMed1995

Genomic cloning of mouse MIF (macrophage inhibitory factor) and genetic mapping of the human and mouse expressed gene and nine mouse pseudogenes.

The single functional mouse gene for MIF (macrophage migration inhibitory factor) has been cloned from a P1 library, and its exon/intron structure determined and shown to resemble that of the human gene. The gene was mapped to chromosome 10 using two multilocus crosses between laboratory strains and either Mus musculus musculus or Mus spretus. Nine additional loci containing related sequences, apparently all processed pseudogenes, were also mapped to chromosomes 1, 2, 3, 7, 8, 9, 12, 17, and 19. While most of these pseudogenes were found in inbred mice and M. spretus, some are species specific. This suggests that there have been active phases of pseudogene formation in Mus both before and after the separation of musculus and spretus. The human genome contains no pseudogenes; we assigned the human gene to chromosome 19, consistent with the location of mouse and human functional genes for MIF in a region of conserved linkage.

Amino Acid Sequence↗
PubMedDate not supplied

Mapping nursing intervention data into the Nursing Interventions Classification (NIC): process and rules.

TOPIC: Uniform language in nursing is needed to clearly depict the contributions of nursing in the healthcare arena but little data related to nursing interventions and patient outcomes are standardized. PURPOSE: To investigate the feasibility of mapping nonstandardized nursing interventions into standardized language using the Nursing Interventions Classification (NIC). SOURCE: Data from a Midwest community hospital's computerized information system. CONCLUSIONS: Results demonstrate that nonstandardized nursing orders can be mapped into standardized language using the NIC.

Data Collection↗
PubMed2001

p38 Map kinase regulates vascular smooth muscle cell collagen synthesis by angiotensin II in SHR but not in WKY.

Vascular remodeling in hypertension is associated with cell growth and increased deposition of extracellular matrix components, particularly collagen. Mechanisms underlying these processes are unclear, but MAP kinases, particularly ERK1/2 and p38 MAP kinase, may be important. We studied the role of ERK1/2 and p38 MAP kinase in vascular smooth muscle cell (VSMC) collagen synthesis and growth mediated by angiotensin (Ang) II in spontaneously hypertensive rats (SHR). Cultured mesenteric VSMC from Wistar-Kyoto rats and SHR were used. Phosphorylation of ERK1/2 and p38 MAP kinase were assessed by Western blots with phosphospecific antibodies. Ang II-stimulated DNA and collagen synthesis were determined by measuring incorporation of (3)H-thymidine and (3)H-proline, respectively. mRNA expression of procollagen I and III was determined by reverse transcription-polymerase chain reaction. Ang II increased ERK1/2 and p38 MAP kinase phosphorylation. Responses were augmented in SHR. Effects were inhibited by irbesartan, a selective AT(1) antagonist, but not by PD123319, a selective AT(2) blocker. Ang II stimulated (3)H-thymidine and (3)H-proline incorporation. These actions were enhanced 2- to 3-fold in SHR. PD98059, selective inhibitor of the ERK1/2 pathway, attenuated Ang II-induced growth and collagen effects and normalized responses in SHR. SB212190, a selective p38 MAP kinase inhibitor, did not alter Ang II-elicited DNA synthesis but reduced collagen production and mRNA expression of procollagen I and III in SHR. These data demonstrate that (1) Ang II-mediated activation of p38 and ERK1/2 is increased in SHR, (2) augmented growth responses are generated by ERK1/2-dependent, p38 MAP kinase-independent pathways, and (3) p38 MAP kinase influences Ang II-induced collagen production in SHR but not in Wistar-Kyoto rats. These results indicate differential roles of ERK1/2 and p38 MAP kinase in AT(1)-stimulated VSMC growth and collagen production, which may contribute to vascular remodeling in hypertension.

Angiotensin II↗
PubMed2002

Effects of low dietary magnesium intake on development of hypertension in stroke-prone spontaneously hypertensive rats: role of reactive oxygen species.

OBJECTIVES: To investigate whether low dietary Mg2+ intake influences the development of hypertension in stroke-prone spontaneously hypertensive rats (spSHRs) and whether these effects are associated with vascular functional and structural changes, and to assess the role of reactive oxygen species and the activation of vascular mitogen-activated protein (MAP) kinases in these processes. METHODS: Six-week-old male spSHRs (n = 18) were divided into three groups: control (normal chow, 0.21% Mg2+ ), low Mg2+ group (Mg2+ -free diet), and high Mg2+ group (Mg2+ -rich diet, 0.75%). Systolic blood pressure (SBP) was assessed weekly for 16 weeks. In a second series of experiments, 6-week-old spSHRs (n = 18) were divided into three groups and studied weekly for 7 weeks: control group, low Mg2+ group, and low Mg2+ group receiving the superoxide dismutase mimetic, tempol (1 mmol/l). RESULTS: The low Mg2+ diet caused an initial decrease in SBP followed, 5 weeks later, by an exacerbated development of hypertension. This was associated with a transient reduction in the plasma concentrations of substances associated with the thiobarbituric acid reaction (markers of oxidative stress), which increased rapidly 2 weeks later. In the low Mg2+ group, acetylcholine-induced vasodilatation was decreased compared with that in controls ( P<0.05). The media : lumen ratio was greater in rats receiving a low Mg2+ diet than in those fed a high Mg2+ diet ( P<0.05). Mg2+ depletion was associated with increased vascular superoxide anion compared with that in Mg2+ -supplemented rats (1.2 0.24 compared with 0.65 0.1 nmol/min per mg). Phosphorylation of MAP kinases was increased two- to threefold in Mg2+ -deficient rats. Tempol prevented the progression of hypertension and normalized the vascular changes in rats fed a low Mg2+ diet. CONCLUSIONS: Chronic Mg2+ deficiency leads to development of severe hypertension, endothelial dysfunction and vascular remodelling. These processes are associated with oxidative stress and upregulation of redox-dependent MAP kinases. Tempol normalized vascular changes and attenuated the development of hypertension. Our findings suggest that reactive oxygen species play an important part in vascular processes that are associated with progression of hypertension in Mg2+ -deficient spSHRs.

Animals↗
PubMed1987

A sharp retinal image increases the topographic precision of the goldfish retinotectal projection during optic nerve regeneration in stroboscopic light.

Locally-correlated neural activity appears to play a key role in refining topographically mapped projections. The retinotectal projection of the goldfish normally regains a high degree of spatial precision after regeneration of a cut optic nerve, but it fails to do so if retinal ganglion cell activity is blocked by tetrodotoxin, or if local correlations in activity are masked by the synchronizing effect of stroboscopic light. A sharp retinal image is not normally needed for a sharp map because local correlation occurs even in darkness or diffuse light, but the possibility that a sharp image might restore local correlation and sharpen the map in stroboscopic light, though taken into account in earlier experiments, has not previously been tested. The precision of the retinotectal map was therefore studied, by retrograde transport of WGA-HRP from a standard tectal injection site and quantitative analysis of the labelled ganglion cell distribution, after regeneration of a cut optic nerve for 83-84 days in either continuous stroboscopic light or normal diurnal light. The lens of the eye was either ablated to blur the retinal image or sham-operated. Two different strobe flash patterns used in previous experiments were also compared. With the lens ablated, stroboscopic light impaired map refinement significantly, confirming previous results. A rapid, irregular flash pattern averaging about 5 Hz was rather more effective than a regular 1 Hz pattern. With the lens intact, however, neither pattern had any detectable effect. The significant gain in precision resulting from a sharp retinal image in these circumstances suggests that common mechanisms could underlie both the internal refinement of the retinotectal map and such directly experience-sensitive processes as the experimental realignment of binocular maps in the frog Xenopus, and of auditory and visual maps in the barn owl.

Animals↗
PubMed2000

The human homolog of Saccharomyces cerevisiae Apg7p is a Protein-activating enzyme for multiple substrates including human Apg12p, GATE-16, GABARAP, and MAP-LC3.

Autophagy is a process that involves the bulk degradation of cytoplasmic components by the lysosomal/vacuolar system. In the yeast, Saccharomyces cerevisiae, an autophagosome is formed in the cytosol. The outer membrane of the autophagosome is fused with the vacuole, releasing the inner membrane structure, an autophagic body, into the vacuole. The autophagic body is subsequently degraded by vacuolar hydrolases. Taking advantage of yeast genetics, apg (autophagy-defective) mutants were isolated that are defective in terms of formation of autophagic bodies under nutrient starvation conditions. One of the APG gene products, Apg12p, is covalently attached to Apg5p via the C-terminal Gly of Apg12p as in the case of ubiquitylation, and this conjugation is essential for autophagy. Apg7p is a novel E1 enzyme essential for the Apg12p-conjugation system. In mammalian cells, the human Apg12p homolog (hApg12p) also conjugates with the human Apg5p homolog. In this study, the unique characteristics of hApg7p are shown. A two-hybrid experiment indicated that hApg12p interacts with hApg7p. Site-directed mutagenesis revealed that Cys(572) of hApg7p is an authentic active site cysteine residue essential for the formation of the hApg7p.hApg12p intermediate. Overexpression of hApg7p enhances the formation of the hApg5p.hApg12p conjugate, indicating that hApg7p is an E1-like enzyme essential for the hApg12p conjugation system. Cross-linking experiments and glycerol-gradient centrifugation analysis showed that the mammalian Apg7p homolog forms a homodimer as in yeast Apg7p. Each of three human Apg8p counterparts, i.e. the Golgi-associated ATPase enhancer of 16 kDa, GABA(A) receptor-associated protein, and microtubule-associated protein light chain 3, coimmunoprecipitates with hApg7p and conjugates with mutant hApg7p(C572S) to form a stable intermediate via an ester bond. These results indicate that hApg7p is an authentic protein-activating enzyme for hApg12p and the three Apg8p homologs.

Adaptor Proteins, Signal Transducing↗
PubMedDate not supplied

Evaluation of Meta-1 for a concept-based approach to the automated indexing and retrieval of bibliographic and full-text databases.

SAPHIRE is a concept-based approach to information retrieval in the biomedical domain. Indexing and retrieval are based on a concept-matching algorithm that processes free text to identify concepts and map them to their canonical form. This process requires a large vocabulary containing a breadth of medical concepts and a diversity of synonym forms, which is provided by the Meta-1 vocabulary from the Unified Medical Language System Project of the National Library of Medicine. This paper describes the use of Meta-1 in SAPHIRE and an evaluation of both entities in the context of an information retrieval study.

Abbreviations as Topic↗
PubMed2006

V2 thin stripes contain spatially organized representations of achromatic luminance change.

A considerable amount of research over the last decades has focused on the apparent specialization of V2 thin stripes for the processing of color in diurnal primates. However, because V2 thin stripes are functionally heterogeneous in that they consist of largely separate color- and luminance-preferring domains and because the color-preferring domains contain a systematic representation of hue, we hypothesized that they contained functional maps that subserve luminance processing. Here we show, using optical imaging of intrinsic cortical signals and microelectrode recording, that the V2 thin stripe luminance-preferring domains contain spatially segregated modules that encode the direction of relative luminance change. Quantitative analysis of the cortical responses to luminance increments or decrements indicates that these luminance-sensitive modules also encode the magnitude of the luminance change by the magnitude of the evoked cortical response. These results demonstrate an important role of V2 thin stripes in the processing of luminance and thus suggest that thin stripes are involved in the overall processing of the surface properties of objects rather than simply the processing of color.

Animals↗
PubMed1995

Dissociating automatic and controlled processes in a memory-search task: beyond implicit memory.

Our goal in this paper was to examine the processes that give rise to action slips. Procedures used to examine implicit memory and automatic processes were found to be unsatisfactory. However, the process-dissociation procedure proved useful for examining the contribution of the automatic and controlled processes underlying performance. The procedure was used in conjunction with a Sternberg memory-search task to examine the effects of set size, response speed, and stimulus-response mapping on controlled and automatic processes. The formulation allowed us to predict accurately how subjects would perform in a varied mapping condition. Moreover, set size and response speed were found to influence the controlled search process, but to leave the automatic influences unaffected. Stimulus-response mapping, on the other hand, was found to lead to probability matching in the automatic processes; this pattern was found to remain constant across changes in set size and response speed.

Adult↗
PubMed1990

Self-organizing maps for internal representations.

One of the biological mechanisms that has so far been poorly understood is the ability of the brain to form representations of primary sensory experiences at increasingly higher levels of abstraction. At many lower perceptual levels, sensory information first becomes represented in topographically ordered sensory maps. In these maps neurons become tuned in a regular manner to simple stimulus features, such as amplitude, frequency, or direction of sound. In this paper it is shown that a model, originally devised by Kohonen for the understanding of the self-organized formation of such "lower-level maps," can also explain the formation of more abstract maps, such as adaptive maps for use in motor control, or maps in which, during a learning stage, the neurons become tuned in an orderly fashion to aspects of the semantic meaning of words. The actual presence of such maps in the brain is speculative at present, but many maps of simpler type have been found. It is argued that the process of the adaptive formation of maps may offer a way to a more unified understanding of many aspects of information processing in the brain.

Animals↗
PubMed2004

An information-processing analysis of the functional architecture of the primate neocortex.

Working at the systems level of analysis, we will use the term functional architecture to concern what processing components exist, how they are interconnected, and what information-processing functions each is involved in. In this paper, experimental evidence for the primate neocortex is analysed for conclusions concerning the existence of neural areas, for corticocortical connectivity among neural areas, and for the involvement of each cortical neural area in the functioning of the brain. We characterize the information-processing function for each neural area in terms of the types of information it is associated with, and conceive of its activity as processing, storage and transmission of data of the corresponding types for that area. We also adapt concepts of goal, plan, sequence, event and context for the description of information processing in the neocortex. This analysis shows that the primate neocortex consists in the main of a perception hierarchy, an action hierarchy and connections between them. In other words, from an information-processing point of view, the primate neocortex has a hierarchical perception-action architecture.

Animals↗
PubMed2004

Epitope mapping of the melanosomal matrix protein gp100 (PMEL17): rapid processing in the endoplasmic reticulum and glycosylation in the early Golgi compartment.

Melanosomes, specific organelles produced only by melanocytes, undergo a unique maturation process that involves their transition form amorphous rounded vesicles to fibrillar ellipsoid organelles, during which they move from the perinuclear to the distal areas of the cells. This depends upon the trafficking and processing of gp100 (also known as Pmel17 and the silver protein), a protein of great interest, because it elicits immune responses in melanoma patients but in which specific function(s) remains elusive. In this study, we have used biochemical and immunochemical approaches to more critically assess the synthesis, processing, glycosylation, and trafficking of gp100. We now report that gp100 is processed and sorted in a manner distinct from other melanosomal proteins (such as tyrosinase, Tyrp1 and Dct) and is predominantly delivered directly to immature melanosomes following its rapid processing in the endoplasmic reticulum and cis-Golgi. Following its arrival, gp100 is cleaved at the amino and at the carboxyl termini in a series of specific steps that result in the reorganization of immature melanosomes to the fibrillar mature melanosomes. Once this structural reorganization occurs, melanogenic enzymes begin to be targeted to the melanosomes, which are then competent to synthesize melanin pigment.

Antibodies, Monoclonal↗