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Showing papers by "University of Geneva published in 1994"


Journal ArticleDOI
17 Jun 1994-Cell
TL;DR: In vitro synthesis of endoplasmic reticulum-derived transport vesicles has been reconstituted with washed membranes and three soluble proteins and it is proposed that the coat structures be called COPI and COPII.

1,277 citations


Journal ArticleDOI
Hans Schmid1
TL;DR: In this paper, the authors reviewed the domain aspects of multi-ferroics, i.e. of materials, in which two or all three properties of the properties "ferroelectricity" and "ferromagnetism" occur simultaneously in the same phase, and in which the magnetic point group has been reliably established by magnetoelectric, optical, dielectric and related studies on single crystals and single domains.
Abstract: Domain aspects of multi-ferroics are reviewed, i.e. of materials, in which two or all three of the properties ‘ferroelectricity.’ ‘ferromagnetism’ and ‘ferroelasticity’ occur simultaneously in the same phase, and in which the magnetic point group has been reliably established by magnetoelectric, optical, dielectric, magnetic and related studies on single crystals and single domains. Nearly only members of the boracite crystal family are concerned, whereas for the perovskite family and other classes of material there is great paucity of data on single crystals. Polarized light microscopy is shown to be an indispensable tool for the study of multi-ferroics, in particular when ferroelasticity is involved. Potential multi-ferroic magnetoelectrics, so far only known in ceramic form, are excluded from the survey.

1,154 citations


Journal ArticleDOI
TL;DR: This new method permits measurement of high bond strengths without cohesive failure of dentin and it also permits multiple measurements to be made within a single tooth.

822 citations


Journal ArticleDOI
01 Jul 1994-Science
TL;DR: It is shown that CIITA expression is controlled and induced by IFN-gamma and is a general regulator of both inducible and constitutive MHC class II expression.
Abstract: Major histocompatibility complex (MHC) class II genes are expressed constitutively in only a few cell types, but they can be induced in the majority of them, in particular by interferon-gamma (IFN-gamma). The MHC class II transactivator gene CIITA is defective in a form of primary MHC class II deficiency. Here it is shown that CIITA expression is controlled and induced by IFN-gamma. A functional CIITA gene is necessary for class II induction, and transfection of CIITA is sufficient to activate expression of MHC class II genes in class II-negative cells in the absence of IFN-gamma. CIITA is therefore a general regulator of both inducible and constitutive MHC class II expression.

820 citations


Journal ArticleDOI
TL;DR: In this paper, the authors show that the κ-deformed Poincare quantum algebra proposed for particle physics has the structure of a Hopf algebra bicrossproduct U(so (1, 3)) T.

788 citations


Journal ArticleDOI
TL;DR: It is argued that temporal colinearity only occurs in cells with high mitotic rates, which results in a strong linkage between patterning and growth control and makes the patterning process unidirectional, from anterior, proximal and early, to posterior, distal and late, a model referred to as the 'Einbahnstrasse'.
Abstract: Vertebrate Hox genes are essential for the proper organization of the body plan during development. Inactivation of these genes usually leads to important alterations, or transformations, in the identities of the affected developing structures. Hox genes are activated in a progressive temporal sequence which is colinear with the position of these genes on their respective complexes, so that 'anterior' genes are activated earlier than 'posterior' ones (temporal colinearity). Here, an hypothesis is considered in which the correct timing of activation of this gene family is necessary in order to properly establish the various expression domains. Slight modifications in the respective times of gene activation (heterochronies) may shift expression domains along the rostrocaudal axis and thus induce concurrent changes in morphologies. It is further argued that temporal colinearity only occurs in cells with high mitotic rates, which results in a strong linkage between patterning and growth control and makes the patterning process unidirectional, from anterior, proximal and early, to posterior, distal and late, a model referred to as the 'Einbahnstrasse'. While the nature of the mechanism(s) behind temporal and spatial colinearities is unknown, it is proposed that such a mechanism relies on meta-cis interactions, that is it may necessitate gene contiguity. Such a mechanism would be based on DNA-specific, rather than gene-specific, features such as chromatin configurations or DNA replication. The existence of such a meta-cis mechanism would explain the extraoridinary conservation of this genetic system during evolution as its basic properties would be linked to that of the genetic material itself.(ABSTRACT TRUNCATED AT 250 WORDS)

581 citations



Journal Article
TL;DR: Several morphological and immunohistochemical differences exist between hypertrophic scar and keloid that are useful for the biological and pathological characterization of the two lesions.
Abstract: There are two types of excessive scarring, keloid and hypertrophic scar. Contrary to hypertrophic scars, keloids do not regress with time, are difficult to revise surgically, and do not provoke scar contractures. These two lesions require different therapeutic approaches but are often confused because of an apparent lack of morphological differences. We have investigated the collagen organization and the possible presence of alpha-smooth muscle (SM) actin-expressing myofibroblasts in these conditions. Keloids contain large, thick collagen fibers composed of numerous fibrils closely packed together. In contrast hypertrophic scars exhibit modular structures in which fibroblastic cells, small vessels, and fine, randomly organized collagen fibers are present. We confirm that such nodular structures are always present in hypertrophic scar and rarely in keloid. Furthermore, only nodules of hypertrophic scars contain alpha-SM actin-expressing myofibroblasts. Electron microscopic examination supports the above-mentioned differences in collagen organization and in fibroblastic features and shows the presence of an amorphous extracellular material surrounding fibroblastic cells in keloid. The presence in hypertrophic scar myofibroblasts of alpha-SM actin, the actin isoform typical of vascular SM cells, may represent an important element in the pathogenesis of contraction. Interestingly, when placed in culture fibroblasts from hypertrophic scars and keloid express similar amounts of alpha-SM actin, suggesting that local microenvironmental factors influence in vivo the expression of this protein. Thus several morphological and immunohistochemical differences exist between hypertrophic scar and keloid that are useful for the biological and pathological characterization of the two lesions.

524 citations


Journal ArticleDOI
01 Jan 1994-Genetics
TL;DR: It is shown that equally parsimonious trees yield very different estimates of population genetic diversity and genetic structure, as shown by null distributions of the population statistics, obtained by evaluation of 10,000 random MSTs.
Abstract: We formalize the use of allele frequency and geographic information for the construction of gene trees at the intraspecific level and extend the concept of evolutionary parsimony to molecular variance parsimony. The central principle is to consider a particular gene tree as a variable to be optimized in the estimation of a given population statistic. We propose three population statistics that are related to variance components and that are explicit functions of phylogenetic information. The methodology is applied in the context of minimum spanning trees (MSTs) and human mitochondrial DNA restriction data, but could be extended to accommodate other tree-making procedures, as well as other data types. We pursue optimal trees by heuristic optimization over a search space of more than 1.29 billion MSTs. This very large number of equally parsimonious trees underlines the lack of resolution of conventional parsimony procedures. This lack of resolution is highlighted by the observation that equally parsimonious trees yield very different estimates of population genetic diversity and genetic structure, as shown by null distributions of the population statistics, obtained by evaluation of 10,000 random MSTs. We propose a non-parametric test for the similarity between any two trees, based on the distribution of a weighted coevolutionary correlation. The ability to test for tree relatedness leads to the definition of a class of solutions instead of a single solution. Members of the class share virtually all of the critical internal structure of the tree but differ in the placement of singleton branch tips.

473 citations


Journal ArticleDOI
TL;DR: Functional analyses have revealed that this specific genetic order also coincides with a functional hierarchy among members of these complexes, so that the products of more posterior genes in the cluster tend to be prevalent over those of more anterior genes.

455 citations


Journal ArticleDOI
11 Mar 1994-Cell
TL;DR: The discovery of a specific association between RNAase E and PNPase raises the intriguing possibility that these enzymes act cooperatively in the processing and degradation of RNA.

Journal ArticleDOI
TL;DR: The balance of LDH, plasma membrane lactate transport, and mitochondrial glycerol phosphate dehydrogenase activities appear to be important in beta- and INS-1 cell glucose recognition to ensure that mitochondrial oxidation is the principle fate of pyruvate and NADH produced by glycolysis.

Journal ArticleDOI
TL;DR: Investigation of point mutations of the ras gene in the DNA of plasma, blood cells and bone marrow of 10 patients suffering from AML or MDS indicates that a bone marrow biopsy or aspiration does not necessarily contain all the malignant clones involved in the disease.
Abstract: Oncogene mutations are frequently found in several tumour types and, among these, point mutations of the ras gene are particularly significant. A predominance of N-ras mutations has been found in the bone marrow DNA of patients with myelodysplastic syndrome (MDS) or acute myelogenous leukaemia (AML). On the other hand, increased levels of plasma DNA have previously been observed in patients suffering from various malignant diseases. In the present work we have investigated, by polymerase chain reaction (PCR), point mutations of the N-ras gene in the DNA of plasma, blood cells and bone marrow of 10 patients suffering from AML or MDS. The different ras mutations detected in five cases were always present in the plasma DNA while sometimes absent in the DNA of peripheral blood cells or bone marrow. This indicates that a bone marrow biopsy or aspiration does not necessarily contain all the malignant clones involved in the disease. Plasma could thus prove to be an easily accessible and useful material for detection and monitoring of myeloid disorders.


Journal ArticleDOI
TL;DR: The results indicate that collagen contributes about 30% of the UTS of mineralized dentin, which is higher than was expected, and the ultimate tensile strength and modulus of elasticity of mineralization and demineralized Dentin are compared.
Abstract: The relative contribution of the matrix of dentin to the physical properties of dentin is unknown but thought to be small. The objective of this study was to test the hypothesis that the demineralized matrix of dentin contributes little to the strength of dentin by measuring and comparing the ultimate tensile strength and modulus of elasticity of mineralized and demineralized dentin. Small slabs (4 x 0.5 x 0.5 mm) of bovine and human dentin were tested in a microtensile testing device in vitro. Human coronal mineralized dentin gave a mean ultimate tensile strength (UTS) of 104 MPa. Bovine incisor coronal dentin exhibited a UTS of 91 MPa, and bovine root dentin failed at 129 MPa. The modulus of elasticity of mineralized bovine and human dentin varied from 13 to 15 MPa. When dentin specimens were demineralized in EDTA, the UTS and modulus of elasticity fell to 26-32 MPa and 0.25 GPa, respectively, depending on dentin species. The results indicate that collagen contributes about 30% of the UTS of mineralized...

Journal ArticleDOI
27 Oct 1994-Nature
TL;DR: The genetic analysis suggests that the chromatin modelling function of the GAGA factor is not restricted to promoter regions, and the Trithorax-like gene described here is required for the normal expression of the homeotic genes and is a modifier of position-effect variegation.
Abstract: LITTLE is known about the way higher-order chromatin structure influences gene expression and chromosome topology in general. Genetic analysis in Drosophila has led to the discovery of two classes of genes, the regulators of homeotic genes and the modifiers of position-effect variegation, which seem to be good candidates for encoding some of the factors regulating chromatin functions1,2. The Trithorax-like gene we describe here is required for the normal expression of the homeotic genes and is a modifier of position-effect variegation. We found that Trithorax-like encodes the GAGA factor which is involved in the formation of an accessible chromatin structure at promoter sequences3. Our genetic analysis suggests that the chromatin modelling function of the GAGA factor is not restricted to promoter regions.

Journal ArticleDOI
TL;DR: Results show that a low concentration of plasma DD measured by the ELISA technique might be used to rule out VTE in clinically suspected patients, and the clinical usefulness of the DD ELISA test should now be assessed in management trials under routine conditions, in the frame of clinical decision-making diagnostic processes.
Abstract: This paper reviews the published experience with plasma measurement of D-dimer (DD), a specific degradation product of crosslinked fibrin, in the diagnostic approach of venous thromboembolism (VTE). Pooling 11 studies (with weighting of the figures according to sample size) with a total of 1337 patients clinically suspected of deep venous thrombosis (DVT) (prevalence of DVT 35%) disclosed an average weighted sensitivity of 96.8% (95% CI: 95.2-98.4) and specificity of 35.2% (95% CI: 32.0-38.4) for the presence of DVT when the ELISA technique was used. In 908 patients suspected of pulmonary embolism (PE) from 9 trials (prevalence of PE 38%), the ELISA technique was associated with a weighted sensitivity of 96.8% (95% CI: 95.0-98.6) and specificity of 45.1% (95% CI: 40.8-49.4) for the disease. Figures obtained with latex assays were definitely lower, precluding their use in the diagnostic approach of VTE. These results show that a low concentration of plasma DD measured by the ELISA technique (usually less than 500 micrograms/l) might be used to rule out VTE in clinically suspected patients. Increased plasma concentrations are of no utility because of the low specificity of this test result. The clinical usefulness of the DD ELISA test should now be assessed in management trials under routine conditions, in the frame of clinical decision-making diagnostic processes. Lastly, the promising data obtained in a small number of asymptomatic, postoperative patients at risk of VTE deserve confirmation before the test can be recommended for initial screening in thrombo-prophylactic trials.

Journal ArticleDOI
TL;DR: In this paper, the Schrodinger invariance criterion for strongly anisotropic or dynamical scaling to local scale invariance is investigated, and a simple scaling form of the two-point function close to a free surface which can be either spacelike or timelike.
Abstract: The extension of strongly anisotropic or dynamical scaling to local scale invariance is investigated. For the special case of an anisotropy or dynamical exponent θ=z=2, the group of local scale transformation considered is the Schrodinger group, which can be obtained as the nonrelativistic limit of the conformal group. The requirement of Schrodinger invariance determines the two-point function in the bulk and reduces the three-point function to a scaling form of a single variable. Scaling forms are also derived for the two-point function close to a free surface which can be either spacelike or timelike. These results are reproduced in several exactly solvable statistical systems, namely the kinetic Ising model with Glauber dynamics, lattice diffusion, Lifshitz points in the spherical model, and critical dynamics of the spherical model with a nonconserved order parameter. For generic values of θ, evidence from higher-order Lifshitz points in the spherical model and from directed percolation suggests a simple scaling form of the two-point function.

Journal ArticleDOI
TL;DR: A regulatory element in the Ubx gene that responds to Pc‐G and trx‐G genes is identified and establishes a repressive complex that keeps enhancers repressed in cells in which they were originally repressed and maintains this state through many cell divisions.
Abstract: Segmentation genes provide the signals for the activation and regulation of homeotic genes in Drosophila but cannot maintain the resulting pattern of expression because their activity ceases halfway through embryogenesis. Maintenance of the pattern is due to the Polycomb group of genes (Pc-G) and the trithorax group of genes (trx-G), responsible for the persistence of the active or repressed state of homeotic genes. We have identified a regulatory element in the Ubx gene that responds to Pc-G and trx-G genes. Transposons carrying this element create new binding sites for Pc-G products in the polytene chromosomes. This Pc-G maintenance element (PRE), establishes a repressive complex that keeps enhancers repressed in cells in which they were originally repressed and maintains this state through many cell divisions. The trx-G products stimulate the expression of enhancers in cells in which they were originally active. This mechanism is responsible for the correct regulation of imaginal disc enhancers, which lack themselves antero-posterior positional information. The PRE also causes severe variegation of the mini-white gene present in the transposon, a phenomenon very similar to heterochromatic position-effect variegation. The significance of this mechanism for homeotic gene regulation is discussed.

Journal ArticleDOI
25 Feb 1994-Cell
TL;DR: Using the highly AT-specific fluorochrome daunomycin, a longitudinal optical signal called AT queue, thought to arise from a line-up of thehighly AT-rich scaffold-associated regions (SARs) by the scaffolding, was identified in native chromosomes.

Journal ArticleDOI
TL;DR: Low water sorption, a high filler-resin ratio, reduced particle size and hardness, and an optimal filler-matrix coupling system were related to improved composite resistance to discoloration.

Journal ArticleDOI
TL;DR: PROSITE is a compilation of sites and patterns found in protein sequences that can be used as a method of determining the function of uncharacterized proteins translated from genomic or cDNA sequences.
Abstract: PROSITE is a compilation of sites and patterns found in protein sequences; it can be used as a method of determining the function of uncharacterized proteins translated from genomic or cDNA sequences

Journal ArticleDOI
TL;DR: The data support previous observations that microvascular pathology is found in aging and in Alzheimer's disease and found that heparan sulfate proteoglycan is present in senile plaques and neurons not only as previously reported in Alzheimer’s disease, but also in Down syndrome and Guam cases.
Abstract: Alterations of the cerebral microvasculature have been reported in aging and in neurodegenerative disorders such as Alzheimer's disease. However, the exact role of microvascular alterations in the pathogenesis of neurodegeneration remains unknown. In the present report, the cerebral cortex microvasculature was studied by immunohistochemistry using a monoclonal antibody against vascular heparan sulfate proteoglycan protein core in normal aging controls. Alzheimer's disease, Down syndrome, Guam amyotrophic lateral sclerosis/parkinsonian dementia complex, Pick's disease and dementia pugilistica. In all dementing illnesses, increased microvascular pathology was evident compared to normal controls. Decreased microvascular density and numerous atrophic vessels were the primary abnormalities observed in all dementing disorders. These microvascular abnormalities demonstrated regional and laminar selectivity, and were primarily found in layers III and V of frontal and temporal cortex. Quantitative analysis employing computer-assisted microscopy demonstrated that the decrease in microvascular density in Alzheimer's disease was statistically significant compared to age-matched controls. In addition, extracellular heparan sulfate proteoglycan deposits were observed which colocalized with thioflavine S-positive senile plaques in Alzheimer's disease, Down syndrome and selected Guam dementia cases. In some cases, heparan sulfate proteoglycan was seen in senile plaques that appeared to be diffuse or primitive plaques that stained weakly with thioflavine. Heparan sulfate proteoglycan-containing neurons were also observed in Alzheimer's disease, as well as in Down syndrome and Guam cases. Glial staining for heparan sulfate proteoglycan was never observed. Our data support previous observations that microvascular pathology is found in aging and in Alzheimer's disease. The changes in Alzheimer's disease exceed those found in normal aging controls. We also found microvascular pathology in all other dementing disorders studied. Our studies further demonstrated that the microvascular pathology displays regional and laminar patterns which parallel patterns of neuronal loss. Finally, we also found that heparan sulfate proteoglycan is present in senile plaques and neurons not only as previously reported in Alzheimer's disease, but also in Down syndrome and Guam cases. Heparan sulfate proteoglycan in senile plaques may be derived from either the degenerating microvasculature or from degenerating neurons.(ABSTRACT TRUNCATED AT 400 WORDS)

Journal ArticleDOI
15 Sep 1994-Nature
TL;DR: This work uses a yeast two-hybrid screen to show that a new human cyclin (cyclin H) is a MO15-associated protein and enhances the kinase activity of MO15 towards Cdk2/cyclin A, demonstrating that a cyclin/kinase complex can function as a regulator of other cyclin-dependent kinases complexes, and suggesting that cyclin /kinase cascades may exist.
Abstract: The eukaryotic cell cycle is regulated by the sequential activation of cyclin-dependent kinases (CDKs). CDK activation is dependent on cyclin binding and phosphorylation of a conserved threonine (T161 in Cdc2) mediated by the CDK-activating kinase CAK. A CDK-related kinase, MO15 (ref. 10), has been identified as the catalytic subunit of CAK (refs 11-13). Here we use a yeast two-hybrid screen to show that a new human cyclin (cyclin H) is a MO15-associated protein. Cyclin H is a major MO15 partner in vivo and enhances the kinase activity of MO15 towards Cdk2/cyclin A. These findings demonstrate that a cyclin/kinase complex can function as a regulator of other cyclin/kinase complexes, and suggest that cyclin/kinase cascades may exist.

Journal ArticleDOI
TL;DR: In this paper, a laser diffraction grain size analyser, the Coulter LS-100 (range claimed by the manufacturer: 0.4-900 mum in a single measurement), is evaluated on sediments of fluvial and lacustrine origin.
Abstract: The qualities of a laser diffraction grain size analyser, the Coulter LS-100 (range claimed by the manufacturer: 0.4-900 mum in a single measurement), are evaluated on sediments of fluvial and lacustrine origin. Accuracy and resolution of measurement on standard latex spheres are excellent. Reproducibility of the results on natural sediments appears to be satisfactory, but the method underestimates the fraction of clay particles with an efficiency of detection (36-70%) proportional to the clay content determined from pipette analysis. This efficiency is somewhat higher than those reported from other instruments of the same generation. Comparison of the Coulter LS-100 with other sizing techniques shows good agreement with the sieving method but some differences appear with the electroresistance particle technique: median and mean size values measured by the Coulter Counter TA1 are systematically lower than those obtained by the Coulter LS-100. Analyses show good correlation with those of a Malvern Laser particle analyser but a discrepancy appears with very fine silt and clay sized sediments. The Coulter LS-100 detects a higher clay content than that measured with the Malvern Laser Sizer 2600. Except when precise measurements of clay content are needed, the Coulter LS-100 produces precise and accurate results in size ranges required for geological and environmental studies.

Journal ArticleDOI
TL;DR: In this paper, the authors performed a quantitative neuropathologic evaluation of a large series of elderly patients representing the entire autopsy population for the year 1989 from a geriatric hospital in order to investigate the distribution of lesions associated with aging and with the earliest symptoms of senile dementia.
Abstract: Detailed analyses of the neuropathologic changes in the cerebral cortex of elderly individuals and Alzheimer's disease patients have demonstrated that certain components of the neocortical and hippocampal circuits are likely to be selectively vulnerable Based on the distribution of neurofibrillary tangles (NFTs) and senile plaques, it has been proposed that a global corticocortical disconnection leads to the loss of integrated functions observed in Alzheimer's disease In order to investigate the distribution of lesions associated with aging as well as with the earliest symptoms of senile dementia, we performed a quantitative neuropathologic evaluation of a large series of elderly patients representing the entire autopsy population for the year 1989 from a geriatric hospital Among the 145 cases quantitatively assessed, there were 102 nondemented patients, 33 patients presenting clinically with globally intact intellectual function but early signs of impairment of specific cognitive functions, and 10 cases with senile dementia of the Alzheimer type All of the cases had NFTs in layer II of the entorhinal cortex, regardless of their clinical diagnosis, and most cases had some NFTs in the CA1 field of the hippocampus Severe pathologic changes within the inferior temporal neocortex were observed only in the demented cases The extent of amyloid deposition was not correlated with the clinical diagnosis and seemed to be present in the neocortical areas earlier than in the hippocampal formation Also, several cases contained NFTs without amyloid deposition, but amyloid never occurred without NFTs These results suggest that involvement of certain structures within the hippocampal formation is a consistent feature of aging Thus, involvement of the hippocampal formation may be a necessary, but not sufficient, condition for the clinical expression of dementia, which is likely to be more closely related to the progressive degeneration of select neuronal populations in the neocortex

Journal ArticleDOI
TL;DR: In this article, a 2 × 1 structure is observed on pure calcite imaged by atomic force microscopy in air and under water and supports observations made previously using low energy electron diffraction (LEED) in vacuum.

Journal ArticleDOI
TL;DR: To show the subjective and cardiovascular effects of khat leaves having a standardized content of cathinone, a large number of patients with a history of heart disease and stroke have had treatment with khat leaf extract.
Abstract: Objectives To show the subjective and cardiovascular effects of khat leaves having a standardized content of cathinone. Background The main effect of khat is an increase of energy and alertness. This effect is thought to be attributable to the phenylalkylamine cathinone, but no controlled clinical trials have been published. Design The design was balanced and double blind. Six drug-naive volunteers received a single dose of khat corresponding to 0.8 mg/kg body weight, as well as alkaloid-free khat as a placebo. Psychologic effects were evaluated by the Addiction Research Center Inventory (ARCI) and visual analog scales. Physiologic measures were systolic blood pressure, diastolic blood pressure, and heart rate. Plasma concentrations of cathinone and its metabolites norephedrine and R,R-(—) norpseudoephedrine were determined by HPLC. Results Maximal plasma concentrations of cathinone (127 ± 53 [SD] ng/ml) were attained after 127 ± 30 minutes. The area under the plasma concentration—time curve from 0 to 9 hours was 415 ± 207 ng/ml · hr, and the terminal elimination half-life was 260 ± 102 minutes. An effect of khat was observed in the ARCI scales Abuse Potential (p < 0.01), Motor Stimulation (p < 0.02), Amphetamine-Like Effect (p < 0.005), and Stimulation-Euphoria (p < 0.005), as well as in the visual analog scales Excited-Calm (p < 0.001) and Energetic-Lethargic (p < 0.001). Conclusions Our results provide objective evidence for the amphetamine-like stimulatory effects of khat leaves. These effects were closely similar to those observed after cathinone, 0.5 mg/kg body weight, although peak plasma concentrations of cathinone after khat were delayed. Clinical Pharmacology and Therapeutics (1994) 55, 556–562; doi:10.1038/clpt.1994.69

Journal ArticleDOI
TL;DR: The results indicate that polyadenylation is not required for the splicing of the last DBP intron, and the physical isolation of nascent transcripts also yields reliable measurements of relative transcription rates.
Abstract: In order to examine whether splicing can occur cotranscriptionally in mammalian nuclei, we mapped exon-intron boundaries on nascent RNA chains transcribed by RNA polymerase II. A procedure that allows fractionation of nuclei into a chromatin pellet containing DNA, histones, and ternary transcription complexes and a supernatant containing the bulk of the nonhistone proteins and RNAs that are released from their DNA templates was developed. The transcripts of the genes encoding DBP, a transcriptional activator protein, and HMG coenzyme A reductase recovered from the chromatin pellet and the supernatant were analyzed by S1 nuclease mapping. The large majority of the RNA molecules from the pellet appeared to be nascent transcripts, since, in contrast to the transcripts present in the supernatant, they were not cleaved at the polyadenylation site but rather contained heterogeneous 3' termini encompassing this site. Splicing intermediates could be detected among nascent and released transcripts, suggesting that splicing occurs both cotranscriptionally and posttranscriptionally. Our results also indicate that polyadenylation is not required for the splicing of the last DBP intron. In addition to allowing detailed structural analysis of nascent RNA chains, the physical isolation of nascent transcripts also yields reliable measurements of relative transcription rates.

Journal ArticleDOI
TL;DR: In this paper, the κ-deformation of the D-dimensional Poincare algebra with any signature is given, and the quadratic Poisson brackets, determined by the classical r-matrix, are calculated.