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At least 793 records · Page 44Linked to original sources
PubMed2005

Gene ontology mapping as an unbiased method for identifying molecular pathways and processes affected by toxicant exposure: application to acute effects caused by the rodent non-genotoxic carcinogen diethylhexylphthalate.

Toxicogenomics has the potential to reveal the molecular pathways and cellular processes that mediate the adverse responses to a toxicant. However, the initial output of a toxicogenomic experiment often consists of large lists of genes whose expression is altered after toxicant exposure. To interpret gene expression changes in the context of underlying biological pathways and processes, new bioinformatics methods must be developed. We have used global gene expression profiling combined with an evaluation of Gene Ontology (GO) and pathway mapping tools as unbiased methods for identifying the molecular pathways and processes affected upon toxicant exposure. We chose to use the acute effects caused by the non-genotoxic carcinogen and peroxisome proliferator (PP) diethylhexylphthalate (DEHP) in the mouse liver as a model system. Consistent with what is known about the mode of action of DEHP, our GO analysis of transcript profiling data revealed a striking overrepresentation of genes associated with the peroxisomal cellular component, together with genes involved in carboxylic acid and lipid metabolism. Furthermore we reveal gene expression changes associated with additional biological functions, including complement activation, hemostasis, the endoplasmic reticulum overload response, and circadian rhythm. Together, these data reveal potential new pathways of PP action and shed new light on the mechanisms by which non-genotoxic carcinogens control hepatocyte hypertrophy and proliferation. We demonstrate that GO mapping can identify, in an unbiased manner, both known and novel DEHP-induced molecular changes in the mouse liver and is therefore a powerful approach for elucidating modes of toxicity based on toxicogenomic data.

Animals↗
PubMed1986

Regulation of microtubule composition and stability during nerve growth factor-promoted neurite outgrowth.

We have used the nerve growth factor (NGF)-responsive line of PC12 pheochromocytoma cells as a model system to study microtubule specializations associated with neurite outgrowth. PC12 cells treated with NGF cease proliferating and extend neurites. Long-term NGF treatment results in a two- to threefold increase in the proportion of total cellular tubulin that is polymerized in PC12 cells. The increase in this parameter first becomes apparent at 2-4 d with NGF and increases steadily thereafter. Several changes in microtubule-associated proteins (MAPs) of PC12 cells also occur after exposure to NGF. In immunoprecipitation assays, we observed the levels of MAP-2 to increase by at least several-fold after treatment with NGF. We also found that the compositions of three MAP classes with apparent Mr of 64K, 67K, and 80K are altered by NGF treatment. These MAPs, recently designated "chartins," are biochemically and immunologically distinct from the similarly-sized tau MAPs (Peng et al., 1985 Brain Res. 361: 200; Magendantz and Solomon, 1985 Proc. Natl. Acad. Sci. 82: 6581). In two-dimensional isoelectric focusing x SDS polyacrylamide gels, each chartin MAP class resolves into a set of proteins of similar apparent Mr but distinct pI. Peptide mapping analyses confirm that the isoelectric variants comprising each chartin MAP class are closely related in primary structure. Several striking differences in the composition of the chartin MAPs of PC12 cells grown with or without NGF were consistently observed. In particular, following longterm NGF treatment, the abundances of the more acidic variants of each chartin MAP class were markedly enhanced relative to the more basic members. This occurs without substantial changes in the abundance of each MAP class as a whole relative to total cell protein. The combined results of in vivo phosphorylation and peptide mapping experiments indicate that the NGF-inducible chartin MAP species are not primary translation products, but are generated posttranslationally, apparently by differential phosphorylation of other chartin MAPs. These observations suggest that NGF treatment of PC12 cells leads to changes in the posttranslational processing of the chartin MAPs. The time course of these changes closely resembles that for the increase in the proportion of cellular tubulin that is polymerized and for neurite outgrowth. One of the important events in the growth and stabilization of neurites appears to be the formation of microtubule bundles that extend from the cell body to the tips of the neurites.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1999

Design of trellis coded vector quantizers using Kohonen maps.

Although the performance of trellis coded vector quantizers (TCVQs) is much better than that of conventional memoryless vector quantizers, designing the trellis in TCVQs has a certain amount of computational overhead. In this paper, we apply Kohonen maps to simplify the design process of the TCVQs by exploiting the ordering property of Kohonen maps. This new implementation of the TCVQs is named as trellis coded Kohonen maps (TCKMs). Simulation results show that, with such a simple design process, the performance of the TCKMs is still comparable to that of the conventional TCVQs.

Journal Article↗
PubMed2002

Mapping of sp2/sp3 in DLC thin film by signal processed ESI series energy-loss image.

A set of signal processing methods comprising fast Fourier transform interpolation, maximum entropy deconvolution and wavelet transformation has been successfully integrated to improve the equality of the extracted C K-edge spectra from electron spectroscopic imaging (ESI) series. Fast Fourier transform interpolation is used to improve the dispersion arising from discrete sampling of ESI series in the energy space. The maximum entropy method is used to dispel the convolution effect resulting from that ESI series acquired with a finite energy window. Wavelet transformation is applied to de-noise the extracted ESI spectrum. The post-processed ESI spectrum has quality as good as that of a probe-acquired spectrum and makes semi-quantitative analysis of the two-dimensional sp2/sp3 ratio map in diamond-like carbon thin film possible. In general, this method is applicable for reconstructing good quality core-loss electron energy-loss spectra from a nanometre-sized area, so that it may be possible to quantitatively analyse two-dimensional information about electronic structure in materials with near nanometre resolution.

Journal Article↗
PubMed1977

Replication process of the parvovirus H-1. IX. Physical mapping studies of the H-1 genome.

The cleavage map of H-1 replicative-form DNA to the bacterial restriction endonuclease EcoRI, HaeII, HaeIII, HindII, HindIII, and HpaII has been determined. The 5'-phosphoryl end of the viral strand is on the right end of the molecule at or near the replication origin. Evidence is presented for the presence of inverted self-complementary sequences at the right end that differ from those at the left end. These sequences allow a foldback of the DNA after denaturation, and a minority of the native replicative-form DNA has the foldback configuration. The possible role of these structures in H-1 DNA synthesis is discussed.

Base Sequence↗
PubMed2004

Temporally asymmetric learning supports sequence processing in multi-winner self-organizing maps.

We examine the extent to which modified Kohonen self-organizing maps (SOMs) can learn unique representations of temporal sequences while still supporting map formation. Two biologically inspired extensions are made to traditional SOMs: selection of multiple simultaneous rather than single "winners" and the use of local intramap connections that are trained according to a temporally asymmetric Hebbian learning rule. The extended SOM is then trained with variable-length temporal sequences that are composed of phoneme feature vectors, with each sequence corresponding to the phonetic transcription of a noun. The model transforms each input sequence into a spatial representation (final activation pattern on the map). Training improves this transformation by, for example, increasing the uniqueness of the spatial representations of distinct sequences, while still retaining map formation based on input patterns. The closeness of the spatial representations of two sequences is found to correlate significantly with the sequences' similarity. The extended model presented here raises the possibility that SOMs may ultimately prove useful as visualization tools for temporal sequences and as preprocessors for sequence pattern recognition systems.

Computer Simulation↗
PubMed1987

Patterns of dysgraphia and the nonlexical spelling process.

This article evaluates the hypothesis that phoneme-grapheme conversion is accomplished by a passive activation device in which the selection of mapping options in the process of assembling orthography is determined by the frequency of usage of that option in the language. The spelling performance of two brain-damaged, acquired dysgraphic patients is interpreted as support for the stated hypothesis.

Agraphia↗
PubMed2003

A hydrodynamic topographic map in the midbrain of goldfish Carassius auratus.

Sensory systems often consist of several parallel pathways. Within each pathway, sensory information may be processed in topographically arranged maps or in maps derived by neuronal computation. Parallel pathways have so far not been described in the central lateral line system of teleost fish at levels higher than the medulla, and evidence for midbrain lateral line maps in fish is still weak. We found two classes of units with different response patterns in the central lateral line nucleus in the torus semicircularis of the goldfish Carassius auratus. Units of one class responded to a passing sphere and to the wake caused by that sphere with excitation. Units of the second class also responded to the moving sphere. However, these units did not respond to the wake behind the sphere. Hydrodynamic information received by class two units was topographically organized in the torus semicircularis of goldfish in that anterior body areas projected to rostral midbrain and posterior body areas to caudal midbrain. Units that responded only to the passing sphere were on average located more ventrally in the lateral TS than the units that responded exclusively to a vibrating sphere.

Afferent Pathways↗
PubMed1987

Plasticity in the organization of adult cerebral cortical maps: a computer simulation based on neuronal group selection.

Recent experimental evidence from the somatosensory, auditory, and visual systems documents the existence of functional plasticity in topographic map organization in adult animals. This evidence suggests that an ongoing competitive organizing process controls the locations of map borders and the receptive field properties of neurons. A computer model based on the process of neuronal group selection has been constructed that accounts for reported results on map plasticity in somatosensory cortex. The simulations construct a network of locally connected excitatory and inhibitory cells that receives topographic projections from 2 receptor sheets corresponding to the glabrous and dorsal surfaces of the hand (a typical simulation involves approximately 1500 cells, 70,000 intrinsic and 100,000 extrinsic connections). Both intrinsic and extrinsic connections undergo activity-dependent modifications according to a synaptic rule based on heterosynaptic interactions. Repeated stimulation of the receptor sheet resulted in the formation of neuronal groups-local sets of strongly interconnected neurons in the network. Cells in most groups were found to have similar receptive fields: they were exclusively glabrous or dorsal despite equal numbers of anatomical connections from both surfaces. The sharpness of map borders was due to the sharpness of the underlying group structure; shifts in the locations of these borders resulted from competition between groups. Following perturbations of the input, the network underwent changes similar to those observed experimentally in monkey somatosensory cortex. Repeated local tapping on the receptor sheet resulted in a large increase in the magnification factor of the stimulated region. Transection of the connections from a glabrous region resulted in the organization of a new representation of corresponding dorsal region. The detailed simulations provide several insights into the mechanisms of such changes, as well as a series of predictions about cortical behavior for further experimental test.

Brain Mapping↗
PubMed2005

Neuroanatomical correlates of phonological processing of Chinese characters and alphabetic words: a meta-analysis.

We used the activation likelihood estimation (ALE) method to quantitatively synthesize data from 19 published brain mapping studies of phonological processing in reading, six with Chinese and 13 with alphabetic languages. It demonstrated high concordance of cortical activity across multiple studies in each written language system as well as significant differences of activation likelihood between languages. Four neural systems for the phonological processing of Chinese characters included: (1) a left dorsal lateral frontal system at Brodmann area (BA) 9; (2) the dorsal aspect of left inferior parietal system; (3) a bilateral ventral-occipitotemporal system including portions of fusiform gyrus and middle occipital gyrus; and (4) a left ventral prefrontal system covering the superior aspect of inferior frontal gyrus. For phonological processing of written alphabetic words, cortical areas identified here are consistent with the three neural systems proposed previously in the literature: (1) a ventral prefrontal system involving superior portions of left inferior frontal gyrus; (2) a left dorsal temporoparietal system including mid-superior temporal gyri and the ventral aspect of inferior parietal cortex (supramarginal region); and (3) a left ventral occipitotemporal system. Contributions of each of these systems to phonological processing in reading were discussed, and a covariant learning hypothesis is offered to account for the findings that left middle frontal gyrus is responsible for addressed phonology in Chinese whereas left temporoparietal regions mediate assembled phonology in alphabetic languages. Language form, cognitive process, and learning strategy drive the development of functional neuroanatomy.

Brain↗
PubMed2003

Localization of jointless-2 gene in the centromeric region of tomato chromosome 12 based on high resolution genetic and physical mapping.

Abscission is a universal process whereby plants shed their organs, such as flowers, fruit and leaves. In tomato, the non-allelic mutations jointless and jointless-2 have been discovered as recessive mutations that completely suppress the formation of pedicel abscission zones. A high resolution genetic map of jointless-2 was constructed using 1,122 jointless F2 plants. Restriction fragment length polymorphism (RFLP) marker RPD140 completely co-segregated with the jointless-2 locus and mapped in a 2.4 cM interval between RFLP markers CD22 and TG618. To chromosome walk to jointless-2, all three markers were used to screen a bacterial artificial chromosome (BAC) library and contigs were developed. Intensive efforts to expand and merge the BAC contigs were unsuccessful because of the highly repetitive sequence content on the distal ends of each contig. To determine the physical distance between and the orientation of the three contigs, we used high resolution pachytene fluorescence in situ hybridization (FISH) mapping. The RPD140 contig was positioned in the centromeric region of chromosome 12 between two large pericentric heterochromatin blocks, about 50 Mb from the TG618 contig on the short arm and 10 Mb from the CD22 contig on the long arm, respectively. Based on high resolution genetic and physical mapping, we conclude that the jointless-2 gene is located within or near the chromosome 12 centromere where 1 cM is approximately 25 Mb in length.

Centromere↗
PubMed2006

Is this a dax which I see before me? Use of the logical argument disjunctive syllogism supports word-learning in children and adults.

Many authors have argued that word-learning constraints help guide a word-learner's hypotheses as to the meaning of a newly heard word. One such class of constraints derives from the observation that word-learners of all ages prefer to map novel labels to novel objects in situations of referential ambiguity. In this paper I use eye-tracking to document the mental computations that support this word-learning strategy. Adults and preschoolers saw images of known and novel objects, and were asked to find the referent of known and novel labels. Experiment 1 shows that adults systematically reject a known distractor (e.g. brush) before mapping a novel label (e.g. "dax") to a novel object. This is consistent with the proposal that participants worked through a Disjunctive Syllogism (i.e. Process-of-Elimination) to motivate the mapping of the novel label to the novel object. Experiment 2 shows that processing is similar for adults performing an implicit Disjunctive Syllogism (e.g. "the winner is the dax") and an explicit Disjunctive Syllogism (e.g. "the winner is not the iron"). Experiment 3 reveals that similar processes govern preschoolers' mapping of novel labels. Taken together, these results suggest that word-learners use Disjunctive Syllogism to motivate the mapping of novel labels to novel objects.

Adolescent↗
PubMed2005

Oscillatory beta activity predicts response speed during a multisensory audiovisual reaction time task: a high-density electrical mapping study.

Bisensory redundant targets are processed faster than the respective unisensory target stimuli alone as evidenced by substantially faster reaction times (RTs). This multisensory RT facilitation has been interpreted as an expression of integrative processing between the different sensory modalities. However, the neuronal mechanisms underlying the RT facilitation effect are not well understood. Oscillatory responses in the beta frequency range (13-30 Hz) have been related to sensory-motor processing. Here, we investigated whether modulation of beta responses might also underlie the faster RTs seen for multisensory stimuli. Using high-density electrical mapping, we explored the association between early (50-170 ms) multisensory processing in the evoked beta response and RTs recorded during a simple RT task. Subjects were instructed to indicate the appearance of any stimulus in a stream of auditory-alone (A), visual-alone (V), and multisensory (AV) stimuli by a button press. Beta responses were analyzed using Morlet wavelet transformations. Multisensory interactions were found over frontal, occipital, central, and sensory-motor regions. Critically, beta activity correlated with mean RTs over all stimulus types. Significant negative correlations were found for frontal, occipital, and sensory-motor scalp regions. We conclude that the association between oscillatory beta activity and integrative multisensory processing is directly linked to multisensory RT facilitation effects.

Acoustic Stimulation↗
PubMed2006

Natural variation for carbohydrate content in Arabidopsis. Interaction with complex traits dissected by quantitative genetics.

Besides being a metabolic fuel, carbohydrates play important roles in plant growth and development, in stress responses, and as signal molecules. We exploited natural variation in Arabidopsis (Arabidopsis thaliana) to decipher the genetic architecture determining carbohydrate content. A quantitative trait locus (QTL) approach in the Bay-0 x Shahdara progeny grown in two contrasting nitrogen environments led to the identification of 39 QTLs for starch, glucose, fructose, and sucrose contents representing at least 14 distinct polymorphic loci. A major QTL for fructose content (FR3.4) and a QTL for starch content (ST3.4) were confirmed in heterogeneous inbred families. Several genes associated with carbon (C) metabolism colocalize with the identified QTL. QTLs for senescence-related traits, and for flowering time, water status, and nitrogen-related traits, previously detected with the same genetic material, colocalize with C-related QTLs. These colocalizations reflect the complex interactions of C metabolism with other physiological processes. QTL fine-mapping and cloning could thus lead soon to the identification of genes potentially involved in the control of different connected physiological processes.

Arabidopsis↗