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Showing papers by "Heidelberg University published in 1991"


Journal ArticleDOI
04 Oct 1991-Cell
TL;DR: It is shown that the genomic DNA sequences encoding the particular channel segment of all subunits harbor a glutamine codon (CAG), even though an arginine codon is found in mRNAs of three subunits.

1,445 citations


Journal ArticleDOI
TL;DR: In this article, a detailed derivation of the quantum molecular dynamics equation, discussed the various approximations necessary to derive this equation and to make actual calculations feasible, is presented, and the calculations presented aim at the solution of two of the most interesting questions of contemporary heavy ion physics: What causes a nucleus to fragment into many heavy pieces, and can we determine the nuclear equation of state from heavy ion reactions?

930 citations


Journal ArticleDOI
TL;DR: The data of the study indicate that the newly developed troponin T test improves the efficiency of serodiagnostic tools for the detection of myocardial cell necrosis as compared with conventionally used cardiac enzymes.
Abstract: BACKGROUNDThe present study was designed to evaluate the efficiency of a newly developed troponin T enzyme immunoassay for the detection of acute myocardial infarction.METHODS AND RESULTSThe study comprised 388 patients admitted with chest pain and suspected myocardial infarction and 101 patients with skeletal muscle damage and additional suspected myocardial cell damage. Troponin T was elevated to more than twice the analytical sensitivity of the assay (0.5 microgram/l) in all patients with non-Q wave (range, 1.2-5 micrograms/l) and Q wave infarction (range, 3-220 micrograms/l). Troponin T appeared in serum as early as 3 hours after onset of pain in 50% of the patients and remained elevated in all patients for more than 130 hours, revealing release kinetics of both free cytosolic and structurally bound molecules. The diagnostic efficiency of troponin T was superior to that of creatine kinase-MB (98% versus 97%) and remained at 98% until 5.5 days after admission, if patients with unstable angina were excl...

847 citations


Journal ArticleDOI
04 Oct 1991-Cell
TL;DR: Strong genetic evidence is reported that a gene, Bp1, having a major effect on blood pressure maps to rat chromosome 10 with a LOD score of 5.10 and is closely linked to the rat gene encoding angiotensin-converting enzyme (ACE), an enzyme that plays a major role in blood pressure homeostasis and is an important target of anti-hypertensive drugs.

729 citations


Journal ArticleDOI
TL;DR: Using synthetic peptides corresponding to the natural beta A4 sequence as well as analog peptides, this model suggests that the formation of aggregates depends upon a hydrophobic effect that leads to intra- and intermolecular interactions between hydrophilic parts of the beta A 4 sequence.

652 citations


Journal ArticleDOI
10 Oct 1991-Nature
TL;DR: Comparison of the human and rat genetic maps indicates that BP/SP-1 could reside on human chromosome 17q in a region that also contains the angiotensin l-converting enzyme gene (ACE)8, and is therefore a candidate gene in primary hypertension.
Abstract: The spontaneously hypertensive rat and the stroke-prone spontaneously hypertensive rat are useful models for human hypertension. In these strains hypertension is a polygenic trait, in which both autosomal and sex-linked genes can influence blood pressure. Linkage studies in crosses between the stroke-prone spontaneously hypertensive rat and the normotensive control strain Wistar-Kyoto have led to the localization of two genes, BP/SP-1 and BP/SP-2, that contribute significantly to blood pressure variation in the F2 population. BP/SP-1 and BP/SP-2 were assigned to rat chromosomes 10 and X, respectively. Comparison of the human and rat genetic maps indicates that BP/SP-1 could reside on human chromosome 17q in a region that also contains the angiotensin I-converting enzyme gene (ACE). This encodes a key enzyme of the renin-angiotensin system, and is therefore a candidate gene in primary hypertension. A rat microsatellite marker of ACE was mapped to rat chromosome 10 within the region containing BP/SP-1.

611 citations


Journal ArticleDOI
TL;DR: The deduced sequence of the Pc protein exhibits a homology to the heterochromatin-associated protein HP1 encoded by the suppressor of position effect variegation gene Su(var) 205, suggesting that Pc could use analogous mechanisms at the level of the higher order chromatin structure for the stable transmission of a determined state.
Abstract: The Polycomb (Pc) gene of Drosophila melanogaster is a member of a large class of genes (Pc group) required for the segment-specific repression of homeotic selector genes Mutations in Pc-group genes show strong posterior transformations in homozygous embryos resulting from an ectopic expression of homeotic genes in segments where they are not supposed to be active Genetic evidence suggests that Pc is part of a cellular memory mechanism responsible for the transmission of the homeotic expression pattern through developmental time We have determined the nucleotide sequence for the genomic DNA of the Pc gene and for cDNAs corresponding to the 25-kilobase Pc mRNA The deduced sequence of the Pc protein exhibits a homology to the heterochromatin-associated protein HP1 encoded by the suppressor of position effect variegation gene Su(var) 205 The homology is confined to a 37-amino acid domain in the N-terminal part of the two proteins Our findings extend to the molecule level the genetically identified parallels between the Pc-group genes and the modifiers of position effect variegation This suggests that Pc could use analogous mechanisms at the level of the higher order chromatin structure for the stable transmission of a determined state, as has been proposed for the clonal propagation of heterochromatin domains

591 citations


Journal ArticleDOI
TL;DR: The aims of the present study were to investigate the intracellular compartmentation of troponin T and to analyze the effects of AMI reperfusion on the appearance kinetics of cardiac trop on the first day after AMI, finding a marked peak in trop onin T serum concentrations at 14 hours after the onset of pain.
Abstract: In a previous study on the diagnostic efficiency of troponin T measurements in patients with suspected acute myocardial infarction (AMI), the authors found a high variability of troponin T serum concentration changes on day 1 in patients with AMI who underwent thrombolytic treatment. Therefore, the aims of the present study were to investigate the intracellular compartmentation of troponin T and to analyze the effects of AMI reperfusion on the appearance kinetics of cardiac troponin T in serum. Cardiac troponin T was measured with a newly developed bideterminant sandwich assay using cardiospecific, affinity-purified polyclonal antibodies and peroxidase-labeled monoclonal antibody. An unbound cytosolic troponin T pool was found in ultracentrifuged homogenates of myocardial tissue of different species ranging from 0.013 to 0.036 mg/g wet weight. The soluble troponin T molecule had electrophoretic properties identical to troponin T compartmented in the myofibrils. The clinical study group comprised 57 patients with AMI undergoing thrombolytic treatment. Blood flow to the infarct zone and point of time of reperfusion were tested by immediate and late angiography. The appearance of troponin T in serum on day 1 after the onset of AMI depended strongly on reperfusion and on duration of ischemia before reperfusion. Thus, in patients with early reperfused AMI, a marked peak in troponin T serum concentrations was found at 14 hours after the onset of pain. This early troponin T peak was absent in patients with AMI reperfusion occurring greater than 5.5 hours after the onset of pain and in patients with nonreperfused AMI. By contrast, the kinetics of troponin T release after the first day after AMI were unaffected by reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

565 citations


Journal ArticleDOI
01 May 1991-Neuron
TL;DR: The expression of two alternative splice variants, Flip and Flop, in mRNAs encoding the four AMPA-selective glutamate receptors was studied in the developing brain by in situ hybridization, and receptors carrying the Flop module appear to participate in mature receptor forms.

558 citations


Journal ArticleDOI
TL;DR: In this article, the distribution of GlyR subunit transcripts in rat brain and spinal cord was investigated by in situ hybridization using sequence-specific oligonucleotide probes, which revealed unexpected differences in the regional and developmental expression of the inhibitory glycine receptor (GlyR) subunit mRNAs.
Abstract: The inhibitory glycine receptor (GlyR) is a ligand-gated ion channel which mediates post-synaptic inhibition in spinal cord and other regions of the vertebrate central nervous system. Previous biochemical and molecular cloning studies have indicated heterogeneity of GlyRs during development. Here, the distribution of GlyR subunit transcripts in rat brain and spinal cord was investigated by in situ hybridization using sequence-specific oligonucleotide probes. In adult animals, GlyR alpha 1 subunit mRNA was abundant in spinal cord, but was also seen in a few brain areas, e.g. superior and inferior colliculi, whereas alpha 2 transcripts were found in several brain regions including layer VI of the cerebral cortex and hippocampus. GlyR alpha 3 subunit mRNA was expressed at low levels in cerebellum, olfactory bulb and hippocampus, while high amounts of beta subunit transcripts were widely distributed throughout spinal cord and brain. During development, alpha 2 mRNA accumulated already prenatally and decreased after birth, whereas alpha 1 and alpha 3 subunit transcripts appeared only in postnatal brain structures. Hybridization signals of beta subunit mRNA were seen already at early embryonic stages and continuously increased to high levels in adult rats. These data reveal unexpected differences in the regional and developmental expression of GlyR subunit mRNAs and point to novel functions of GlyR proteins in the mammalian central nervous system.

537 citations


Journal ArticleDOI
TL;DR: In this article, a review of the potential-model approach is presented, together with a brief survey of the motivations for various potential models and the application of the developed theoretical framework.

Journal ArticleDOI
27 Jun 1991-Nature
TL;DR: A new member of the rat excitatory amino-acid receptor gene family, KA-1, that has a 30% sequence similarity with the previously characterized α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor subunits GluR-A to -D3–5 is described.
Abstract: KAINIC acid is a potent neurotoxin for certain neurons1. Its neurotoxicity is thought to be mediated by an excitatory amino-acid-gated ion channel (ionotropic receptor) possessing nanomolar affinity for kainate2. Here we describe a new member of the rat excitatory amino-acid receptor gene family, KA-1, that has a 30% sequence similarity with the previously characterized α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor subunits GluR-A to -D3–5. The pharmacological profile of expressed recombinant KA-1 determined in binding experiments with [3H]kainate is different from that of the cloned AMPA receptors and similar to the mammalian high-affinity kainate receptor (kainate > quisqualate > glutamate » AMPA) with a dissociation constant of about 5 nM for kainate2,6. The selectively high expression of KA-1 messenger RNA in the CA3 region of the hippocampus closely corresponds to autoradiographically located high-affinity kainate binding sites7–9. This correlation, as well as the particular in vivo pattern of neurodegeneration observed on kainate-induced neurotoxicity1,2, suggests that KA-1 participates in receptors mediating the kainate sensitivity of neurons in the central nervous system.

Journal ArticleDOI
TL;DR: In this paper, a generalized Brownian motion is given by creation and annihilation operators on a "twisted" Fock space of L2(ℝ), and the distribution of these operators with respect to the vacuum expectation is a generalized Gaussian distribution, in the sense that all moments can be calculated from second moments with the help of a combinatorial formula.
Abstract: We present an example of a generalized Brownian motion. It is given by creation and annihilation operators on a “twisted” Fock space ofL2(ℝ). These operators fulfill (for a fixed −1≦μ≦1) the relationsc(f)c*(g)−μc*(g)c(f)=〈f,g〉1 (f, g ∈L2(ℝ)). We show that the distribution of these operators with respect to the vacuum expectation is a generalized Gaussian distribution, in the sense that all moments can be calculated from the second moments with the help of a combinatorial formula. We also indicate that our Brownian motion is one component of ann-dimensional Brownian motion which is invariant under the quantum groupS ν U(n) of Woronowicz (withμ =v2).

Journal ArticleDOI
TL;DR: Schwarz et al. as discussed by the authors found that respondents use the numeric values to disambiguate the meaning of scale labels, resulting in different interpretations and, accordingly, different subjective scale anchors.
Abstract: Three experiments indicate that the numeric values provided as part of a rating scale may influence respondents' interpretation of the endpoint labels. In experiment 1, a representative sample of German adults rated their success in life along an 11-point rating scale, with the endpoints labeled "not at all successful" and "extremely successful." When the numeric values ranged from 0 ("not at all successful") to 10 ("extremely successful"), 34 percent of the respondents endorsed values between 0 and 5. However, only 13 percent endorsed formally equivalent values between 5 and 0, when the scale ranged from -5 ("not at all successful") to +5 ("extremely successful"). Experiment 2 provided an extended conceptual replication of this finding, and experiment 3 demonstrates that recipients of a respondent's report draw different inferences from formally equivalent but numerically different values. In combination, the findings indicate that respondents use the numeric values to disambiguate the meaning of scale labels, resulting in different interpretations and, accordingly, different subjective scale anchors. NORBERT SCHWARZ iS program director at ZUMA and Privatdozent of psychology at the University of Heidelberg. BARBEL KNAUPER is research associate at ZUMA. HANS-J. HIPPLER iS project director at ZUMA. ELISABETH NOELLE-NEUMANN is founder and director of the Institute fur Demoskopie Allensbach, and professor emeritus of mass communication at the University of Mainz. LESLIE CLARK iS assistant professor of psychology at Purdue University. The reported research was supported by grant SWFOO44-6 from the Bundesminister fur Forschung und Technologie of the Federal Republic of Germany to Norbert Schwarz. We thank George Bishop, Tory Higgins, and Tracy Wellens for stimulating discussions. Correspondence should be addressed to Norbert Schwarz, ZUMA, P.O. Box 12 21 55, D-6800 Mannheim, Germany. Public Opinion Quarterly Volume 55 570-582 ? 1991 by the American Association for Public Opinion Research All rights reserved 0033-362X/91/5504-0008$02.50 This content downloaded from 40.77.167.53 on Fri, 09 Sep 2016 04:16:31 UTC All use subject to http://about.jstor.org/terms Changes in the Meaning of Scale Labels 571 Rating scales with labeled endpoints are probably the most widely used measurement instrument in social and psychological research. Leaving some concerns about their psychometric properties aside (see Nunnally 1978), the use of these scales does not seem to be very controversial (see Dawes and Smith [1985] for a careful discussion of their general properties and for empirical and psychological justifications for their use). In general, 7-point scales seem to be best in terms of reliability, percentage of undecided respondents, and respondents' ability to discriminate between the scale values (e.g., Cox 1980). Thus, seven plus or minus two is the usual recommendation. Moreover, respondents are able to use rating scales consistently, even in telephone interviews without visual aids (e.g., Hormuth and Bruckner 1985). In addition, verbal rating scales, which provide a label for each scale point, have been found to be more reliable than scales that provide labels for the endpoints only (Krosnick and Berent 1990). Finally, researchers have observed that the terms used to label the endpoints, or to designate the separate values of verbal rating scales, may affect the obtained distribution (e.g., Rohrmann 1978; Wegner, Faulbaum, and Maag 1982; Wildt and Mazis 1978). This suggests that respondents pay close attention to the meaning of the labels provided to them, much as one would hope. Whereas the number of scale points, the inclusion or omission of a neutral point, and the choice of scale labels have received considerable attention in the literature (see Dawes and Smith 1985), the specific numeric values provided have, to our knowledge, not been the topic of theoretical analysis and empirical investigation. Apparently, researchers assume that, for example, a 7-point scale that ranges from " 1 " to "7" is equivalent to a 7-point scale that ranges from " 3" to " + 3," as long as the same endpoint labels are provided. In the present article, we will question this assumption. Drawing on survey data from the Allensbach archive, we will first demonstrate that the specific numeric values provided in a rating scale can have a dramatic impact on the obtained results. We will then discuss different underlying processes and will test their viability in laboratory experiments. Experiments 1 and 2: The Impact of Numeric Values

Journal ArticleDOI
17 Jan 1991-Nature
TL;DR: The identification of β-COP as the 110K protein explains the blocking of secretion by the drug brefeldin A, indicating that they may be structurally related.
Abstract: Four high-molecular-weight proteins form the main subunits of the coat of Golgi-derived (non-clathrin) coated vesicles. One of these coat proteins, beta-COP, is identical to a Golgi-associated protein of relative mass 110,000 (110K) that shares homology with the adaptin proteins of clathrin-coated vesicles. This connection, and the comparable molecular weights of the coat proteins of Golgi-derived and clathrin-coated vesicles, indicates that they may be structurally related. The identification of beta-COP as the 110K protein explains the blocking of secretion by the drug brefeldin A.

Journal ArticleDOI
TL;DR: In this paper, a theoretical model of assimilation and contrast effects in part-whole question sequences is pre-sented, which is supported by experimental data and provides a coherent account of apparently contradictory findings previously reported in the survey liter-
Abstract: A theoretical model of the emergence of assimilation and contrast effects in part-whole question sequences is pre- sented. When one specific question precedes a general question and the two are not assigned to the same conversational context, respondents use the information primed by the specific question to form the general judgment. This results in part-whole assimila- tion effects. If both questions are perceived as belonging to- gether, however, conversational norms of nonredundancy pro- hibit the repeated use of information that has already been provided in response to the specific question when making the general judgment. Accordingly, respondents interpret the general question to refer to aspects other than the ones covered by the specific question. Contrast effects may emerge in that case under specified conditions. If several specific questions precede the general question, however, the general one is always interpreted as a request for a summary judgment. This results in assimilation effects, even under conditions that would foster contrast effects if only one specific question is asked. The model is supported by experimental data and provides a coherent account of apparently contradictory findings previously reported in the survey liter-

Journal ArticleDOI
TL;DR: It is demonstrated that electrical stimulation of the sciatic nerve at Aδ/C‐fiber (not Aα/β-fiber) intensity strongly induces the expression of these immediate‐early gene‐encoded proteins.
Abstract: We present the first comparative investigation of the basal and transsynaptically induced expression of c-JUN, JUN B, JUN D, c-FOS, FOS B, and KROX-24 proteins in the spinal cord, using immunocytochemistry with specific antibodies. We demonstrate that electrical stimulation of the sciatic nerve at A delta/C-fiber (not A alpha/beta-fiber) intensity strongly induces the expression of these immediate-early gene-encoded proteins. Basal immunoreactivity was found for c-JUN in motoneurons, for JUN D in almost every cell of the gray matter, and for KROX-24 in the superficial dorsal horn. One hour after electrical stimulation of the sciatic nerve at A delta/C-fiber intensity, expression of all proteins except JUN D reached its maximum. Initially immunoreactivity was restricted to the ipsilateral dorsal horn, but after 4 hours appeared contralaterally. Expression of JUN D was increased only after 4 hours. Within the dorsal horn, the expression of c-JUN, JUN B, FOS B, and KROX-24 was mainly restricted to the superficial layers. Immunoreactivity decreased to basal levels between 8 and 16 hours. c-FOS and JUN D were expressed in both the superficial and deep dorsal horn; in the latter, c-FOS and JUN D persisted longer. Induced JUN D was present the longest and was still visible after 32 hours. In motoneurons of the ipsilateral ventral horn, c-JUN, JUN D, and c-FOS appeared after 8 hours. Surgical exposure of the sciatic nerve evoked a strikingly prolonged expression of all proteins compared to that following electrical stimulation of the sciatic nerve. Our results demonstrate that stimulation of nociceptive A delta- and C-fibers induces early and late expression of proteins encoded by immediate-early genes with a specific temporal and spatial distribution of the expression of each protein. Furthermore, the extent of protein expression reflects the intensity of noxious stimulation.

Journal ArticleDOI
TL;DR: The findings indicate that affective disorders play an important role in the post-acute phase after AMI although the extent of myocardial infarction and behaviour responses are not significantly related to one another.
Abstract: Psychological data from 560 male survivors of acute myocardial infarction (AMI) were documented in the third week after onset of AMI. The psychodiagnostic assessment was designed to detect different forms of depression as well as hyperactive behaviour. A complete follow-up of these patients, which covers a period of 6 months, is available. Our findings indicate that affective disorders play an important role in the post-acute phase after AMI although the extent of myocardial infarction (as defined by an ECG score) and behaviour responses are not significantly related to one another. Different subforms of depression are not influenced by a history of angina pectoris, the degree and location of myocardial infarction, the occurrence of late potentials and age, whereas dyspnoea ( P < 0·001) and the recurrence of myocardial infarction ( P < 0·001) favour depressive mood states. Twelve cardiac deaths and 17 arrhythmic events occurred during the study period; they were significantly predicted by severe forms of post-AMI depression as revealed by univariate analysis. The evidence was stronger for predicting cardiac death ( P < 0·001) than for arrhythmic events ( P = < 0·035). The effect remains of borderline significance for cardiac death if all risk factors with a significant univariate influence are included in a multiple logistic regression model. The effect of depression is illustrated by Kaplan—Meier survival curves separated for patient groups with high as compared to low degrees of depression. Hyperactivity showed no impact on patient survival.

Journal ArticleDOI
TL;DR: The results demonstrate that specificity of gonadotropin receptors is determined by a high affinity hormone binding site formed by the amino‐terminal leucine‐rich receptor repeats.
Abstract: Recombinant expression of truncated receptors for luteinizing hormone/chorionic gonadotropin (LH/CG) revealed that the amino-terminal leucine-rich repeats 1-8 of the extracellular receptor domain bind human chorionic gonadotropin (hCG) with an affinity (Kd = 0.72 +/- 0.2 nM) similar to that of the native LH/CG receptor (Kd = 0.48 +/- 0.05 nM). LH/CG receptor leucine-rich repeats 1-8 were used to replace homologous sequences in the closely related receptor for follicle stimulating hormone (FSH). Cells expressing such chimeric LH/CG-FSH receptors bind hCG and show elevated cylic AMP levels when stimulated by hCG but not by recombinant human FSH (rhFSH). Similarly, a chimeric LH/CG receptor in which leucine-rich repeats 1-11 originated from the FSH receptor is activated by rhFSH but not by hCG. For this chimera, no residual [125I] hCG binding was observed in a range of 2 pM to 10 nM. Our results demonstrate that specificity of gonadotropin receptors is determined by a high affinity hormone binding site formed by the amino-terminal leucine-rich receptor repeats.

Journal ArticleDOI
TL;DR: In this article, a data set illuminating 10- to 104-yr variability refines our understanding of oceanic versus geomagnetic or solar forcing of atmospheric 14C12C ratios.

Journal ArticleDOI
TL;DR: The 'motor coordination' soft signs were found to correlate with morphological alterations in the basal ganglia and were significantly correlated with some BPRS subscales, in particular 'thought disorder'.

Journal ArticleDOI
TL;DR: The clinical course and outcome of 55 fetuses with complete atrioventricular (AV) block detected prenatally were studied to identify factors that affect the natural history of this lesion.


Journal ArticleDOI
TL;DR: In this paper, the experimental sensitivity of the electron EDM in various models of {ital CP} violation is discussed. But the authors focus on the prediction of the expected experimental sensitivity to electron EDMs in different models of violation.
Abstract: Recent experimental progress in the search for atomic electric dipole moments (EDMs) {ital d}{sub {ital A}} of cesium and thallium leads in particular to a substantially increased sensitivity to a possible electron EDM {ital d}{sub {ital e}} compared with existing upper bounds. Further considerable improvement in the measurement of {ital d}{sub Tl} is likely. After a brief synopsis of the theory of atomic EDMs, the authors discuss---in view of the expected experimental sensitivity to {ital d}{sub {ital e}}---the predictions for the electron EDM in various models of {ital CP} violation.

Journal ArticleDOI
TL;DR: In this article, the authors propose a plug-in estimator to estimate the asymptotically optimal bandwidth from the data, which is then used to select the smoothing parameter.
Abstract: The choice of smoothing parameter or bandwidth is crucial when applying nonparametric regression estimators such as kernel estimators. The optimal choice depends on the data at hand. A data-driven bandwidth selection, close to the optimal one, would make these curve estimators objective, more reliable, and easier to use. Minimizing residual mean squared error criteria, such as cross-validation, have been frequently proposed to estimate the optimal smoothing parameter. Empirical and theoretical evidence indicates that cross-validation rules and related methods lead to rather variable estimated optimal bandwidths. The method presented here builds on estimating the asymptotically optimal bandwidth from the data. Since estimators for the residual variance and for an asymptotic expression for the bias are plugged into the asymptotic formula, such selection rules are called “plug-in” estimators. The functional that quantifies bias is approximated by the integrated squared second derivative of the regre...

Journal ArticleDOI
TL;DR: The observations support the notion that J1/tenascin is a multifunctional extracellular matrix molecule that contains a neurite outgrowth promoting domain that is distinguishable from the cell-binding site and presumably not involved in the inhibition of neurites outgrowth or cell spreading.
Abstract: The influence of J1/tenascin adsorbed to polyornithine-conditioned plastic (substrate-bound J1/tenascin) and J1/tenascin present in the culture medium (soluble J1/tenascin) on neurite outgrowth was studied with cultured single cells from hippocampus and mesencephalon of embryonic rats. Neurons at low density grew well on J1/tenascin substrates and extended neurites that were approximately 40% longer than on the polyornithine control substrate after 24 h in vitro. The neurite outgrowth promoting effect of substrate bound J1/tenascin was largely abolished in the presence of mAb J1/tn2, but not by mAb J1/tn1. In contrast to the neurite growth-promoting effects of substrate bound J1/tenascin, neurite outgrowth on polyornithine, laminin, fibronectin, or J1/tenascin as substrates was inhibited by addition of soluble J1/tenascin to the cultures. Neither of the two mAbs neutralized the neurite outgrowth-inhibitory properties of soluble J1/tenascin. In contrast to their opposite effects on neurite outgrowth, both substrate-bound and soluble J1/tenascin reduced spreading of the neuronal cell bodies, suggesting that the neurite outgrowth-promoting and antispreading effects are mediated by two different sites on the molecule. This was further supported by the inability of the mAb J1/tn2 to neutralize the antispreading effect. The J1/tn2 epitope localizes to a fibronectin type III homology domain that is presumably distinct from the putative Tn68 cell-binding domain of chicken tenascin for fibroblasts, as shown by electronmicroscopic localization of antibody binding sites. We infer from these experiments that J1/tenascin contains a neurite outgrowth promoting domain that is distinguishable from the cell-binding site and presumably not involved in the inhibition of neurite outgrowth or cell spreading. Our observations support the notion that J1/tenascin is a multifunctional extracellular matrix molecule.

Journal ArticleDOI
TL;DR: A preferential localization of APP is reported at synaptic sites of human and rat brain and at neuromuscular junctions, implying a role of APP in physiological synaptic activity and a potential and early impairment of central synapses when synaptic APP is converted to beta A4 amyloid during the pathological evolution of Alzheimer's disease and Down's syndrome.

Journal ArticleDOI
17 Oct 1991-Nature
TL;DR: It is shown that at least one of these subunits is encoded by the mouse MHC in the region between the K locus and the MHC class II region, and inducible by interferon-γ, raising the intriguing possibility thatThe MHC encodes not only the M HC class I molecules themselves but also proteases involved in the formation of MHC-binding peptides.
Abstract: CYTOTOXIC T lymphocytes recognize fragments (peptides) of protein antigens presented by major histocompatibility complex (MHC) class I molecules. In general, the peptides are derived from cytosolic proteins and are then transported to the endoplasmic reticulum where they assemble with the MHC class I heavy chains and β2-microglobulin to form stable and functional class I molecules1–4. The proteases involved in the generation of these peptides are unknown. One candidate is the proteasome, a non-lysosomal proteinase complex abundantly present in the cytosol. Proteasomes have several proteolytically active sites and are complexes of high relative molecular mass (Mr about 600K), consisting of about 20–30 subunits with Mrs between 15 and 30K (refs 5–10). Here we show that at least one of these subunits is encoded by the mouse MHC in the region between the K locus and the MHC class II region, and inducible by interferon-γ. This raises the intriguing possibility that the MHC encodes not only the MHC class I molecules themselves but also proteases involved in the formation of MHC-binding peptides.

Journal ArticleDOI
TL;DR: In this article, a method for analyzing the modality of a distribution is proposed based on the excess mass functional, which measures excessive empirical mass in comparison with multiples of uniform distribution.
Abstract: We propose and study a method for analyzing the modality of a distribution. The method is based on the excess mass functional. This functional measures excessive empirical mass in comparison with multiples of uniform distribution. By the excess mass approach we separate the investigation about the number of modes from questions concerning their location. For distributions on the line, the excess mass functional can be estimated at a square-root rate. The asymptotic behavior of estimators is studied, and tests for multimodality based on the excess mass are derived.

Journal ArticleDOI
TL;DR: In differentiated neurons in vivo these IEG proteins can be expressed either independently or concomitantly depending on the type of stimulus.