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At least 109 records · Page 6Linked to original sources
PubMed1982

Simian virus 40 large T antigen is phosphorylated at multiple sites clustered in two separate regions.

The phosphorylation sites of simian virus 40 large T antigen were determined within the primary structure of the molecule. Exhaustive digestion of (32)P-labeled large T antigen with trypsin generated six major phosphopeptides which could be separated in a newly developed isobutyric acid-containing chromatography system. By partial tryptic digestion, large T antigen was cleaved into an amino-terminal fragment of 17,000 daltons and overlapping fragments from the carboxy-terminal region ranging in size between 71,000 and 13,000 daltons. The location of the phosphopeptides was then determined by fingerprint analyses of individual fragments. Their physical properties were analyzed by sizing on polyacrylamide gels and by sequential digestion and peptide mapping; their amino acid composition was determined by differential labeling with various amino acids. The amino-terminal 17,000-dalton fragment gave rise to only one phosphopeptide (phosphopeptide 3) that contained half of the phosphate label incorporated into large T antigen. It contained phosphoserine and phosphothreonine sites, all of which were clustered within a small segment between Cys(105) and Lys(127). This segment contained five serines and two threonines. Among these, Ser(106), Ser(123), and Thr(124) were identified as phosphorylated residues; in addition, either one or both of Ser(111) and Ser(112) were phosphorylated. The neighboring residues, Ser(123) and Thr(124), were found in three different phosphorylation states in that either Ser(123) or Thr(124) or both were phosphorylated. Phosphopeptides 1, 2, 4, 5, and 6 were all derived from a single fragment extending 26,000 daltons upstream from the carboxy terminus of large T antigen. Phosphopeptide 6 was identical with the previously determined phosphothreonine peptide phosphorylated at Thr(701). Phosphopeptides 1, 2, 4, and 5 contained only serine-bound phosphate. Phosphopeptides 1, 2, and 4 represented overlapping peptides, all of which were phosphorylated at Ser(639) located next to a cluster of six acidic residues. In phosphopeptide 5, a large peptide ranging from Asn(653) to Arg(691), at least two of seven serines were phosphorylated. Thus, large T antigen contains at least eight phosphorylation sites. Their clustering within two separate regions might correlate with structural and functional domains of this protein.

Adenosine Diphosphate Ribose↗
PubMed1991

Fos is phosphorylated by p34cdc2, cAMP-dependent protein kinase and protein kinase C at multiple sites clustered within regulatory regions.

The proto-oncogene c-fos encodes a nuclear protein (Fos) that functions in transcriptional regulation in response to extracellular signals. Fos is extensively modified in the nucleus by serine and threonine phosphorylation. It has been suggested that phosphorylation may play an important role in regulating Fos function in normal and transformed cells. As a first step in addressing this issue, we have used purified Fos as a substrate for several serine-threonine protein kinases, including cAMP-dependent protein kinase (PKA), protein kinase C (PKC) and p34cdc2. Each of these kinases phosphorylated Fos at several unique sites. These sites were located within two regions that were previously shown to reduce the transcriptional activity of Fos in vitro. Several of the sites modified in vitro were also shown to be phosphorylated in serum-stimulated fibroblasts. These findings demonstrate that Fos is a target for several protein kinases involved in signal transduction and suggest that phosphorylation could regulate the transcriptional properties of Fos.

Amino Acid Sequence↗
PubMed1994

Gene loss and gain in the evolution of the vertebrates.

Homeobox cluster genes (Hox genes) are highly conserved and can be usefully employed to study phyletic relationships and the process of evolution itself. A phylogenetic survey of Hox genes shows an increase in gene number in some more recently evolved forms, particularly in vertebrates. The gene increase has occurred through a two-step process involving first, gene expansion to form a cluster, and second, cluster duplication to form multiple clusters. We also describe data that suggests that non-Hox genes may be preferrentially associated with the Hox clusters and raise the possibility that this association may have an adaptive biological function. Hox gene loss may also play a role in evolution. Hox gene loss is well substantiated in the vertebrates, and we identify additional possible instances of gene loss in the echinoderms and urochordates based on PCR surveys. We point out the possible adaptive role of gene loss in evolution, and urge the extension of gene mapping studies to relevant species as a means of its substantiation.

Amino Acid Sequence↗
PubMed2004

Tracking evolving communities in large linked networks.

We are interested in tracking changes in large-scale data by periodically creating an agglomerative clustering and examining the evolution of clusters (communities) over time. We examine a large real-world data set: the NEC CiteSeer database, a linked network of >250,000 papers. Tracking changes over time requires a clustering algorithm that produces clusters stable under small perturbations of the input data. However, small perturbations of the CiteSeer data lead to significant changes to most of the clusters. One reason for this is that the order in which papers within communities are combined is somewhat arbitrary. However, certain subsets of papers, called natural communities, correspond to real structure in the CiteSeer database and thus appear in any clustering. By identifying the subset of clusters that remain stable under multiple clustering runs, we get the set of natural communities that we can track over time. We demonstrate that such natural communities allow us to identify emerging communities and track temporal changes in the underlying structure of our network data.

Cluster Analysis↗
PubMed2003

Hox cluster duplications and the opportunity for evolutionary novelties.

Hox genes play a key role in animal body plan development. These genes tend to occur in tightly linked clusters in the genome. Vertebrates and invertebrates differ in their Hox cluster number, with vertebrates having multiple clusters and invertebrates usually having only one. Recent evidence shows that vertebrate Hox clusters are structurally more constrained than invertebrate Hox clusters; they exclude transposable elements, do not undergo tandem duplications, and conserve their intergenic distances and gene order. These constraints are only relaxed after a cluster duplication. In contrast, invertebrate Hox clusters are structurally more plastic; tandem duplications are common, the linkage of Hox genes can change quickly, or they can lose their structural integrity completely. We propose that the constraints on vertebrate Hox cluster structure lead to an association between the retention of duplicated Hox clusters and adaptive radiations. After a duplication the constraints on Hox cluster structure are temporarily lifted, which opens a window of evolvability for the Hox clusters. If this window of evolvability coincides with an adaptive radiation, chances are that a modified Hox cluster becomes recruited in an evolutionary novelty and then both copies of duplicated Hox clusters are retained.

Animals↗
PubMed1996

Spatiotemporal analysis of prepyriform, visual, auditory, and somesthetic surface EEGs in trained rabbits.

1. Spatial ensemble averages were computed for 64 traces of electroencephalograms (EEGs) simultaneously recorded from 8 x 8 arrays over the epidural surfaces of the prepyriform cortex (PPC) and visual, somatic, and auditory cortices. They revealed a common waveform across each array. Examination of the spatial amplitude modulation (AM) of the waveform revealed classifiable spatial pattern in short time segments. The AM patterns varied within trials after presentation of identical conditioned stimuli, and also between trials with differing stimuli. 2. PPC EEGs revealed strong correlates with the respiratory rhythm; neocortical EEGs did not. 3. Time ensemble averaging of the PPC EEG attenuated the oscillatory bursts, indicating that olfactory gamma oscillations (20-80 Hz) were not phase-locked to the times of stimulus delivery but instead to inhalations. Time ensemble averages of neocortical recordings across trials revealed average evoked potentials starting 30-50 ms after the arrival of the stimulus. 4. Average temporal fast Fourier transform (FFT) power spectral densities (PSDs) from pre- and poststimulus PPC EEG segments revealed a peak of gamma activity in olfactory bursts. 5. The logarithm of the average temporal FFT PSDs from pre- and poststimulus neocortical EEG segments, when plotted against log frequency, revealed 1/f-type spectra in both pre- and poststimulus segments for negative/aversive conditioned stimuli (CS-) and positive/rewarding conditioned stimuli (CS+). The alpha'- and beta'-coefficients from the regression of Eq. 2 onto the average PSDs were significantly different between pre- and poststimulus segments, owing to the evoked potentials, but not between CS- and CS+ stimulus segments. 6. Spatiotemporal patterns were invariant over all frequency bins in the 1/f domain (20-100 Hz). Spatiotemporal patterns in the 2- to 20-Hz domain progressively differed from the invariant patterns with decreasing frequency. 7. In the spatial frequency domain, the logarithm of the average spatial FFT power spectra from pre- and poststimulus neocortical EEG segments, when plotted against the log spatial frequency, fell monotonically from the maximum at the lowest spatial frequency, downwardly curving to a linear 1/f spectral domain. This curve in the 1/f spectral domain extended from 0.133 to 0.880 cycles/mm in the PPC and from 0.095 to 0.624 cycles/mm in the neocortices. 8. Methods of FFT and principal component analysis (PCA) EEG decomposition were used to extract the broad-spectrum waveform common to all 64 EEGs from an array. AM patterns for the FFT and PCA components were derived by regression. They were shown by cross-correlation to yield spatial patterns that were equivalent to each other and to AM patterns from calculation of the 64 root-mean-square amplitudes of the segments. 9. Each spatial AM pattern was expressed by a 1 x 64 column vector and a point in 64-space. Similar patterns formed clusters, and dissimilar patterns gave multiple clusters. A statistical test was devised to evaluate dissimilarity by a Euclidean distance metric in 64-space. 10. Significant spatial pattern classification of CS- versus CS+ trials (below the 1% confidence limit for 20 of each) was found in discrete temporal segments of poststimulus data after digital temporal and spatial filter optimization. 11. Varying the analysis window duration from 10 to 500 ms yielded a window length of 120 ms as optimal for pattern classification. A 120-ms window was subsequently stepped across each record in overlapping intervals of 20 ms. Windows in which episodic, significant CS+/CS- differences occurred lasted 50-200 ms and were separated by 100-200 ms in the poststimulus period. 12. Neocortical spatial patterns changed under reinforcement contingency reversal, showing a lack of invariance in respect to stimuli and a dependence on context and learning, as previously found for the olfactory bulb and PPC.

Animals↗
PubMed2003

Mammographic-pathologic correlation of apocrine metaplasia diagnosed using vacuum-assisted stereotactic core-needle biopsy: our 4-year experience.

OBJECTIVE: To determine whether focal apocrine metaplasia of the breast has distinctive mammographic characteristics, we evaluated apocrine metaplasia diagnosed by vacuum-assisted stereotactic core-needle biopsy and correlated mammographic imaging and histopathologic findings. MATERIALS AND METHODS: We retrospectively reviewed our institutional database for records of all vacuum-assisted stereotactic core-needle biopsies performed during a 4-year period. Five hundred thirty-eight lesions were biopsied, of which 302 (56%) were benign. Apocrine metaplasia was diagnosed in 37 lesions. In 11 of these 37 lesions, apocrine metaplasia made up more than 50% of the lesion sampled. RESULTS: On mammography, eight cases (73%) appeared as new or increasing calcifications, and three cases (27%) appeared as new or enlarging equal-density masses (0.6-1.2 cm). Calcifications were heterogeneous in five lesions (63%), amorphous in two (25%), and punctate in one (12%); one heterogeneous cluster of calcifications (12%) also contained milk of calcium. The pattern of calcification distribution was clustered in five lesions (63%), multiple clusters in two (25%), and linear in one (12%). Two masses (67%) were lobular, and one (33%) was round. Two borders (67%) were microlobulated, and one (33%) was circumscribed. CONCLUSION: Apocrine metaplasia is a benign condition commonly associated with other fibrocystic changes. Lesions composed of more than 50% focal apocrine metaplasia are relatively uncommon. A new or enlarging lobular, microlobulated mass or heterogeneous calcification cluster may represent apocrine metaplasia. Because no distinguishing mammographic features are present to require follow-up by imaging, needle biopsy is required for definitive diagnosis.

Adult↗
PubMed2002

Towards a better understanding of the metabolic system for amylopectin biosynthesis in plants: rice endosperm as a model tissue.

Starch is made up of amylose (linear alpha-1,4-polyglucans) and amylopectin (alpha-1,6-branched polyglucans). Amylopectin has a distinct fine structure called multiple cluster structure and is synthesized by multiple subunits or isoforms of four classes of enzymes: ADPglucose pyrophosphorylase, soluble starch synthase (SS), starch branching enzyme (BE), and starch debranching enzyme (DBE). In the present paper, based on analyses of mutants and transgenic lines of rice in which each enzyme activity is affected, the contribution of the individual isoform to the fine structure of amylopectin in rice endosperm is evaluated, and a new model referred to as the "two-step branching and improper branch clearing model" is proposed to explain how amylopectin is synthesized. The model emphasizes that two sets of reactions, alpha-1,6-branch formation and the subsequent alpha-1,4-chain elongation, are catalyzed by distinct BE and SS isoforms, respectively, are fundamental to the construction of the cluster structure. The model also assesses the role of DBE, namely isoamylase or in addition pullulanase, to remove unnecessary alpha-1,6-glucosidic linkages that are occasionally formed at improper positions apart from two densely branched regions of the cluster.

1,4-alpha-Glucan Branching Enzyme↗
PubMed2001

Susceptibility and modifier genes in cutaneous basal cell carcinomas and their associations with clinical phenotype.

While ultraviolet radiation (UV) is critical in the pathogenesis of basal cell carcinomas (BCC), its role in determining the phenotypic variation shown by patients is unknown. Thus, patients manifest variation in BCC numbers, patterns of presentation and tumour site. We have used this diversity to classify patients into subgroups that are associated with different risks of developing tumours. Two phenotypes are particularly interesting. Firstly, presentation with clusters of BCC. These patients, termed multiple presentation phenotype (MPP), had two to five BCC at one presentation, suggesting rapid accrual over short periods of time. They comprised 15% of our 1200 BCC patients. A minority of patients demonstrated multiple clustering events, a phenomenon that is associated with a genetic pre-disposition. The second risk phenotype, characterised by tumours on the trunk, is also associated with a pre-disposition. Both phenotypes were characterised by a susceptibility to develop numerous BCC. Thus, all our patients with more than five BCC had one or both of these phenotypes. We are using a candidate gene approach to identify loci associated with risk of these phenotypes (susceptibility genes) and tumour numbers in them (modifier genes). Interestingly, we did not identify differences in UV exposure between patients with high- and low-risk phenotypes.

Basal Cell Carcinoma↗
PubMed2005

Anomalous nucleation far from equilibrium.

We present precision Monte Carlo data and analytic arguments for an asymmetric exclusion process, involving two species of particles driven in opposite directions on a 2xL lattice. To resolve a stark discrepancy between earlier simulation data and an analytic conjecture, we argue that the presence of a single macroscopic cluster is an intermediate stage of a complex nucleation process: in smaller systems, this cluster is destabilized while larger systems form multiple clusters. Both limits lead to exponential cluster size distributions, controlled by very different length scales.

Journal Article↗
PubMed2000

[Symptomatic cluster headache. Expression of multiple sclerosis relapse with magnetic resonance tomography detection of pontomedullary lesion in the ipsilateral trigeminal nucleus area].

We describe a 25-year-old male who developed, in the course of an acute exacerbation of his multiple sclerosis, cluster headache-like attacks which responded to oxygen therapy. Magnetic resonance imaging revealed a lesion in the area of the ipsilateral pontomedullary trigeminal nuclei. This symptomatic case and other published cases are most probably explained by an activation of the trigeminovascular system as it is assumed for primary headache syndromes.

Adult↗
PubMed2006

GOurmet: a tool for quantitative comparison and visualization of gene expression profiles based on gene ontology (GO) distributions.

BACKGROUND: The ever-expanding population of gene expression profiles (EPs) from specified cells and tissues under a variety of experimental conditions is an important but difficult resource for investigators to utilize effectively. Software tools have been recently developed to use the distribution of gene ontology (GO) terms associated with the genes in an EP to identify specific biological functions or processes that are over- or under-represented in that EP relative to other EPs. Additionally, it is possible to use the distribution of GO terms inherent to each EP to relate that EP as a whole to other EPs. Because GO term annotation is organized in a tree-like cascade of variable granularity, this approach allows the user to relate (e.g., by hierarchical clustering) EPs of varying length and from different platforms (e.g., GeneChip, SAGE, EST library). RESULTS: Here we present GOurmet, a software package that calculates the distribution of GO terms represented by the genes in an individual expression profile (EP), clusters multiple EPs based on these integrated GO term distributions, and provides users several tools to visualize and compare EPs. GOurmet is particularly useful in meta-analysis to examine EPs of specified cell types (e.g., tissue-specific stem cells) that are obtained through different experimental procedures. GOurmet also introduces a new tool, the Targetoid plot, which allows users to dynamically render the multi-dimensional relationships among individual elements in any clustering analysis. The Targetoid plotting tool allows users to select any element as the center of the plot, and the program will then represent all other elements in the cluster as a function of similarity to the selected central element. CONCLUSION: GOurmet is a user-friendly, GUI-based software package that greatly facilitates analysis of results generated by multiple EPs. The clustering analysis features a dynamic targetoid plot that is generalizable for use with any clustering application.

Artificial Intelligence↗
PubMed1990

Do nurses or doctors have an increased risk of developing multiple sclerosis?

A cluster of multiple sclerosis (MS) patients has been reported in seven of 307 nurses in Key West, Florida. The MS death rates in British nurses and qualified medical practitioners were looked at and no increased mortality from multiple sclerosis was found. Neither was there an increase in mortality from motor neuron disease (amyotrophic lateral sclerosis), the control disease. Death rates from MS vary with social class, being highest in social class IIIN (skilled non-manual) and lowest in social class II (intermediate). These different rates may be due to MS causing health related occupational mobility. Allowance for the inter-class variability in MS death rates did not materially affect the conclusion that death from MS appears to be no more common than expected among nurses and doctors than in the general population. Possible explanations for the cluster of multiple sclerosis among nurses in Key West are discussed.

Adult↗
PubMed1993

HOM/Hox type homeoboxes in the chelicerate Limulus polyphemus.

The polymerase chain reaction was used to survey HOM/Hox type homeobox genes in the North American horseshoe crab, Limulus polyphemus. The survey reveals 28 different homeobox fragments possessing 44-80% nucleotide sequence similarity with HOM-C sequences in Drosophila and Hox B sequences in mouse. Limulus has one to four representatives of HOM/Hox cognates when fragments are assigned according to amino acid identity. A parsimony analysis including the Limulus sequences and homologous mouse Hox B and Drosophila HOM-C sequences reveals several instances of monophyletic groupings of Limulus homeoboxes with a Drosophila or mouse gene as the sister branch. Under the current model of HOM/Hox cluster evolution, these results suggest that Limulus has as many as four HOM/Hox type clusters. This is the first evidence suggesting the presence of multiple clusters in a nonvertebrate taxon. Putative homologs of mouse Hoxb-3 in Limulus suggest that the gene was present in the common ancestor of arthropods and vertebrates and has been lost in Drosophila.

Amino Acid Sequence↗