Showing papers by "University of Konstanz published in 1995"
TL;DR: It is shown that glutamate can induce either early necrosis or delayed apoptosis in cultures of cerebellar granule cells, suggesting that mitochondrial function is a critical factor that determines the mode of neuronal death in excitotoxicity.
1,893 citations
TL;DR: The results suggest that the representation of different parts of the body in the primary somatosensory cortex of humans depends on use and changes to conform to the current needs and experiences of the individual.
Abstract: Magnetic source imaging revealed that the cortical representation of the digits of the left hand of string players was larger than that in controls. The effect was smallest for the left thumb, and no such differences were observed for the representations of the right hand digits. The amount of cortical reorganization in the representation of the fingering digits was correlated with the age at which the person had begun to play. These results suggest that the representation of different parts of the body in the primary somatosensory cortex of humans depends on use and changes to conform to the current needs and experiences of the individual.
1,821 citations
TL;DR: A very strong direct relationship is reported between the amount of cortical reorganization and the magnitude of phantom limb pain (but not non-painful phantom phenomena) experienced after arm amputation, indicating that phantom-limb pain is related to, and may be a consequence of, plastic changes in primary somatosensory cortex.
Abstract: Although phantom-limb pain is a frequent consequence of the amputation of an extremity, little is known about its origin. On the basis of the demonstration of substantial plasticity of the somatosensory cortex after amputation or somatosensory deafferentation in adult monkeys, it has been suggested that cortical reorganization could account for some non-painful phantom-limb phenomena in amputees and that cortical reorganization has an adaptive (that is, pain-preventing) function. Theoretical and empirical work on chronic back pain has revealed a positive relationship between the amount of cortical alteration and the magnitude of pain, so we predicted that cortical reorganization and phantom-limb pain should be positively related. Using non-invasive neuromagnetic imaging techniques to determine cortical reorganization in humans, we report a very strong direct relationship (r = 0.93) between the amount of cortical reorganization and the magnitude of phantom limb pain (but not non-painful phantom phenomena) experienced after arm amputation. These data indicate that phantom-limb pain is related to, and may be a consequence of, plastic changes in primary somatosensory cortex.
1,692 citations
TL;DR: It is shown that the long-range dependence property allows us to clearly distinguish between measured data and traffic generated by VBR source models currently used in the literature, and gives rise to novel and challenging problems in traffic engineering for high-speed networks.
Abstract: We analyze 20 large sets of actual variable-bit-rate (VBR) video data, generated by a variety of different codecs and representing a wide range of different scenes. Performing extensive statistical and graphical tests, our main conclusion is that long-range dependence is an inherent feature of VBR video traffic, i.e., a feature that is independent of scene (e.g., video phone, video conference, motion picture video) and codec. In particular, we show that the long-range dependence property allows us to clearly distinguish between our measured data and traffic generated by VBR source models currently used in the literature. These findings give rise to novel and challenging problems in traffic engineering for high-speed networks and open up new areas of research in queueing and performance analysis involving long-range dependent traffic models. A small number of analytic queueing results already exist, and we discuss their implications for network design and network control strategies in the presence of long-range dependent traffic. >
1,216 citations
Journal Article•
TL;DR: It is concluded that TNF-induced hepatocyte apoptosis is an early, general, and possibly causal event during experimental liver failure triggered by inflammatory stimuli.
Abstract: We investigated the role of hepatocyte apoptosis in four different murine models of acute inflammatory liver failure. Liver damage induced in D-galactosamine-sensitized mice by endotoxin infection was initiated by processes typical of apoptosis, ie, chromatin condensation, DNA fragmentation, and formation of intracellular apoptotic bodies. DNA was cleaved into oligonucleosomal fragments in the liver before a significant rise of alanine aminotransferase in plasma occurred. Passive immunization against tumor necrosis factor (TNF) completely inhibited the injury caused by endotoxin. Direct injection of recombinant TNF-alpha also caused DNA fragmentation followed by alanine aminotransferase release into the plasma. Pretreatment of mice with interleukin-1 beta, which is known to suppress TNF-induced lethality, completely prevented apoptosis and liver failure in this model. These results demonstrate the causal role of TNF in endotoxin-induced hepatic apoptosis. TNF-inducible hepatocyte apoptosis in vivo was not only observed in D-galactosamine-sensitized mice, but also when the alternative transcriptional inhibitor actinomycin D was used. In mice injected with the TNF-inducing T cell mitogen concanavalin A, hepatic apoptosis was even noticed without requirement of additional sensitizers. We conclude that TNF-induced hepatocyte apoptosis is an early, general, and possibly causal event during experimental liver failure triggered by inflammatory stimuli.
505 citations
TL;DR: It is confirmed that YBa{sub 2}Cu{sub 3}O{sub 7{minus}{delta}} satisfies the same universal relations in these quantities as the other high-{ital T}{sub {ital c}} superconducting cuprates.
Abstract: A direct determination of the relationship between ${\mathit{T}}_{\mathit{c}}$ and hole concentration p for ${\mathrm{Y}}_{1\mathrm{\ensuremath{-}}\mathit{x}}$${\mathrm{Ca}}_{\mathit{x}}$${\mathrm{Ba}}_{2}$${\mathrm{Cu}}_{3}$${\mathrm{O}}_{7\mathrm{\ensuremath{-}}\mathrm{\ensuremath{\delta}}}$ is obtained by investigating the properties of the fully oxygen-deficient (\ensuremath{\delta}\ensuremath{\approxeq}1.0) compound for which p=x/2. Measurements of ${\mathit{T}}_{\mathit{c}}$, the thermoelectric power S, and bond-valence sums calculated from neutron-diffraction refinements for various values of x and \ensuremath{\delta} allow the full determination of the relations p=p(\ensuremath{\delta}), ${\mathit{T}}_{\mathit{c}}$=${\mathit{T}}_{\mathit{c}}$(p), and S=S(T,p) confirming that ${\mathrm{YBa}}_{2}$${\mathrm{Cu}}_{3}$${\mathrm{O}}_{7\mathrm{\ensuremath{-}}\mathrm{\ensuremath{\delta}}}$ satisfies the same universal relations in these quantities as the other high-${\mathit{T}}_{\mathit{c}}$ superconducting cuprates.
502 citations
TL;DR: T-cell-dependent concanavalin A-induced apoptotic liver injury in mice is related to immunological and cytokinemediated disorders and possibly to autoreactive hepatic processes.
458 citations
Journal Article•
TL;DR: The TNF-R1 is not only necessary, but also sufficient for TNF signaling in murine hepatocytes, and the hepatotoxicity of TNF in D-galactosamine-sensitized mice is examined.
Abstract: The systemic inflammatory response is characterized by release of circulating TNF which may cause multiorgan failure including septic liver failure. We studied TNF signaling in an appropriate in vitro system with primary murine hepatocyte cultures from normal and genetically altered animals. Either one of the three different TNF species, huTNF-alpha, huTNF-beta, or muTNF-alpha (at concentrations > 1 ng/ml) induced direct hepatocytotoxicity preceded by DNA fragmentation in cells prepared from wild-type C57BL mice. TNF-induced cytotoxicity was preceded by oligonucleosomal DNA fragmentation. Further cellular responses to TNF exposure were induction of nitric oxide synthase and secretion of serum amyloid A. None of the above events occurred in hepatocytes lacking the gene for the 55-kDa TNF receptor (TNF-R1), even after stimulation with > 1 micrograms/ml TNF. However, selective stimulation of the TNF-R1 in wild-type hepatocytes with huTNF-alpha elicited a pattern of responses essentially similar to that seen with muTNF-alpha. We obtained analogous results when we examined the hepatotoxicity of TNF in D-galactosamine-sensitized mice, i.e., DNA fragmentation and liver failure was noted in wild-type mice, whereas TNF-R1-deficient mice were completely resistant. We conclude that the TNF-R1 is not only necessary, but also sufficient for TNF signaling in murine hepatocytes.
332 citations
TL;DR: The findings demonstrate that the major effect of G-CSF treatment is a change in the responsiveness of blood towards a variety of stimuli, which is interpreted as a shift toward an antiinflammatory cytokine response.
280 citations
TL;DR: Democracies are Janus-faced as discussed by the authors, and they are frequently involved in militarized disputes and wars with authoritarian regimes, while they do not fight each other, they are often involved in military conflicts.
Abstract: Democracies are Janus-faced. While they do not fight each other, they are frequently involved in militarized disputes and wars with authoritarian regimes. The article argues that these two empirica...
232 citations
TL;DR: The experimental observation of the rate which approaches this linear nonclassical behavior of a three level atom driven with squeezed vacuum via a two-photon excitation process is presented.
Abstract: The recent development of frequency tunable nonclassical light sources have opened up possibilities for performing spectroscopy with nonclassical light. Various different avenues in this new field can be naturally organized in two groups: atomic measurements with the sensitivity beyond the standard quantum limit and fundamental alterations of atomic radiative processes due to nonclassical nature of the e.-m. field. While the number of theoretical predictions has been rapidly growing for the last decade[1] the experimental progress has been achieved only recently and so far only in the first group: sub-shot-noise spectroscopy[2,3]. We report here the first experiment that belongs to the second group: driving multilevel atoms with nonclassical light. More precisely we report the observation of the fundamental nonclassical behavior of a three level atom driven with squeezed vacuum via a two-photon excitation process. It is well known that the rate of the two-photon excitation Г2 for thermal or coherent light is proportional to the square of the intensity of the excitation field (only weak excitation is considered here, i.e., no saturation effects are involved). By contrast, the manifestly quantum correlations of squeezed vacuum can enhance this rate such that it becomes a linear function of intensity [4]. We present here the experimental observation of the rate which approaches this linear nonclassical behavior.
TL;DR: It is demonstrated that the histone-like protein H-NS is also a component of a complex regulatory network that controls stationary-phase induction and osmotic regulation of many genes in Escherichia coli, in which it functions as a global inhibitor of gene expression during the exponential phase of growth.
Abstract: The sigma S subunit of RNA polymerase (encoded by the rpoS gene) is the master regulator in a complex regulatory network that controls stationary-phase induction and osmotic regulation of many genes in Escherichia coli. Here we demonstrate that the histone-like protein H-NS is also a component of this network, in which it functions as a global inhibitor of gene expression during the exponential phase of growth. On two-dimensional gels, at least 22 sigma S-controlled proteins show increased expression in an hns mutant. H-NS also inhibits the expression of sigma S itself by a mechanism that acts at the posttranscriptional level. Our results indicate that relief of repression by H-NS plays a role in stationary-phase induction as well as in hyperosmotic induction of rpoS translation. Whereas certain sigma S-dependent genes (e.g., osmY) are only indirectly regulated by H-NS via its role in the control of sigma S expression, others are also H-NS-regulated in a sigma S-independent manner. (For this latter class of genes, rpoS hns double mutants show higher levels of expression than mutants deficient in rpoS alone.) In addition, we demonstrate that the slow-growth phenotype of hns mutants is suppressed in hns rpoS double mutants and that many second-site suppressor mutants that spontaneously arise from hns strains carry lesions that affect the expression of sigma S.
TL;DR: In this article, the cosmological consequences of an induced gravity theory coupled to the minimal standard model of particle physics are considered, and the contrast of density perturbations required to explain the seed of astronomic structures are obtained for very large values of the Higgs mass ( MH ⪢ G F − 1 2 ).
TL;DR: For example, the authors focused on social transfers as the depen dent variable in welfare states and as demographic changes make social services increasingly important ingredi ents of welfare states, while most of the comparative research on welfare states has focused on the social transfers.
Abstract: Comparative research on welfare states has most focused on social transfers as the depen dent variable As demographic changes make social services increasingly important ingredi ents of welfare st
TL;DR: The effect of boundary surfaces on phase separation and micro-phase separation in binary polymer blends and block copolymers has gained increasing attention over the last 5 years as mentioned in this paper, and the possibility to actively control the domain morphologies via surface interactions in view of possible technological applications.
Abstract: The effect of boundary surfaces on phase separation and microphase separation in binary polymer blends and block copolymers respectively, has gained increasing attention over the last 5 years. It has been realized that the complex interplay between wetting and phase separation may severely influence the phase separation process thereby leading to near-surface domain structures, which differ distinctly from the respective bulk morphologies. In the present article, we try to summarize the basic features of surface directed (micro-) phase separation in immiscible polymer systems. For both polymer blends and block copolymers a brief review of the historical development is given, followed by a list of selected examples representing the large number of current research activities in these fields. Particular attention is given to the possibility to actively control the domain morphologies via surface interactions in view of possible technological applications.
TL;DR: It is demonstrated for the first time that inducible transcription factors such as c‐Fos and JunB are an essential part of fundamental biological processes in the adult mammalian nervous system, e.g. of light‐induced phase shifts of the circadian pacemaker.
Abstract: Light-induced phase shifts of circadian rhythmic locomotor activity are associated with the expression of c-Jun, JunB, c-Fos and FosB transcription factors in the rat suprachiasmatic nucleus, as shown in the present study. In order to explore the importance of c-Fos and JunB, the predominantly expressed AP-1 proteins for the phase-shifting effects of light, we blocked the expression of c-Fos and JunB in the suprachiasmatic nucleus of male rats, housed under constant darkness, by intracerebroventricular application of 2 microliters of 1 mM antisense phosphorothioate oligodeoxynucleotides (ASO) specifically directed against c-fos and junB mRNA. A light pulse (300 lux for 1 h) at circadian time 15 induced a significant phase shift (by 125 +/- 15 min) of the circadian locomotor activity rhythm, whereas application of ASO 6 h before the light pulse completely prevented this phase shift. Application of control nonsense oligodeoxynucleotides had no effect. ASO strongly reduced the light-induced expression of c-Fos and JunB proteins. In contrast, light pulses with or without the control nonsense oligodeoxynucleotides evoked strong nuclear c-Fos and JunB immunoreactivity in the rat suprachiasmatic nucleus. These results demonstrate for the first time that inducible transcription factors such as c-Fos and JunB are an essential part of fundamental biological processes in the adult mammalian nervous system, e.g. of light-induced phase shifts of the circadian pacemaker.
Journal Article•
TL;DR: The study suggests the existence of specific down-modulatory mechanisms related to NO-induced apoptotic DNA fragmentation, and investigates interfering biochemical signaling pathways.
Abstract: Endogenously generated or exogenously applied nitric oxide (NO) redox species induce apoptotic cell death in murine RAW 264.7 macrophages. Activation of the inducible NO synthase by incubation of cells with a combination of lipopolysaccharide and interferon-gamma produced internucleosomal DNA fragmentation and morphological alterations, i.e., chromatin condensation, indicative of apoptotic cell death. These alterations, reflecting the production of NO, were prevented by an inhibitor of NO synthase, NG-monomethyl-L-arginine. Moreover, NO derived from endogenous or exogenous sources caused accumulation of the tumor suppressor gene p53. Proposing a link between NO generation and DNA fragmentation, we investigated interfering biochemical signaling pathways. Therefore, we tested the ability of four NO-releasing compounds [sodium nitroprusside (SNP), 3-morpholinosydnonimine (SIN-1), S-nitroso-N-acetylpenicillamine (SNAP), and S-nitrosoglutathione (GSNO)] to cause specific DNA fragmentation. All NO donors induced DNA fragmentation in a time- and concentration-dependent manner. However, substance-specific differences became obvious. After an 8-hr incubation period, GSNO proved to be the strongest apoptotic inducer, whereas SIN-1 was much less active. Apoptosis was rapid with GSNO and SNP, yielding specific DNA fragments after 4 hr and 5 hr, respectively. In contrast, SNAP and SIN-1 produced DNA fragmentation after considerable lag times of 9 hr and 14 hr, respectively. Furthermore, an inhibitory effect of protein kinase C (PKC) and cAMP-dependent protein kinase became apparent. 12-O-Tetradecanoylphorbol-13-acetate, an activator of PKC, inhibited DNA fragmentation by all four NO donors, whereas PKC inhibitors such as staurosporine and calphostin C sensitized macrophages to apoptosis induced by SNP and GSNO. Lipophilic cAMP analogues suppressed SNP-, SIN-1, and SNAP-induced DNA fragmentation. Thus, our study suggests the existence of specific down-modulatory mechanisms related to NO-induced apoptotic DNA fragmentation.
TL;DR: Water-soluble UV-A/B-absorbing pigments secreted by cells of the cosmopolitan terrestrial cyanobacterium Nostoc commune are the first mycosporines to be described covalently linked to oligosaccharides.
TL;DR: Application of adiabatic passage in a strongly coupled atom-cavity system to "map" atomic ground-state Zeeman coherence onto the cavity-mode field is discussed, with particular consideration given to a possible scheme for quantum measurements of the intracavity photon number.
Abstract: A scheme for the preparation of Fock states and general superposition states of the electromagnetic field in a cavity is studied in detail. The scheme uses adiabatic passage in a strongly coupled atom-cavity system to "map" atomic ground-state Zeeman coherence onto the cavity-mode field. We model photon-counting and homodyne measurements of the field exiting the cavity and demonstrate the possibility of generating and detecting highly nonclassical states of the field parameter values close to currently realizable experimental values. The adiabatic passage process is also reversible, enabling cavity-mode fields to be mapped onto atomic ground-state Zeeman coherence. Application of this property to the measurement of cavity fields is discussed, with particular consideration given to a possible scheme for quantum measurements of the intracavity photon number.
TL;DR: This paper summarizes the user modeling services that BGP-MS provides to application programs at runtime, discusses the representational and inferential foundations that determine the scope and the limits of these services, and gives a detailed example illustrating the interaction between the various system components.
Abstract: BGP-MS is a user modeling shell system that can assist interactive software systems in adapting to their current users by taking the users' presumed knowledge, beliefs, and goals into account. It offers applications several methods for communicating observations concerning the user to BGP-MS, and for obtaining information on currently held assumptions about the user from BGP-MS. It provides a choice of two integrated formalisms for representing beliefs and goals, and includes several types of inferences for drawing additional assumptions based on an initial interview, observed user actions, and stereotypical knowledge about pre-defined user subgroups. BGP-MS is a customizable software system that is independent from applications, operates concurrently with them, and interacts with them through inter-process communication. For tailoring BGP-MS to a specific application domain, the developer must select those components of BGP-MS that are needed in this domain and fill them with relevant domain-dependent user modeling knowledge. This paper first summarizes the user modeling services that BGP-MS provides to application programs at runtime. It discusses the representational and inferential foundations that determine the scope and the limits of these services, and also gives a detailed example illustrating the interaction between the various system components. It describes interfaces that are available to application developers for tailoring BGP-MS to the specific user modeling needs of their application domains. Finally, it compares the system with all other major user modeling shell systems, and describes a first application that employs BGP-MS for adapting hypertext to users' terminological knowledge.
TL;DR: The data imply that the active form of an Mcm protein is not a monomer, but a protein complex that includes an McM3/Cdc46 dimer, and that DNA polymerase alpha is notA component of this complex.
Abstract: Human nuclear proteins P1Mcm3 and P1Cdc46 have high sequence similarities with the corresponding yeast proteins known to be required for the initiation of genome replication. Nuclei of proliferating HeLa cells contain relatively high amounts of P1Mcm3 (about 10(6) molecules/nucleus) of which only a small fraction is bound to a nuclear structure, most probably chromatin. At 0.5 M NaCl, the structure-bound nuclear protein can be partially solubilized as a dimer composed of P1Mcm3 and the related protein P1Cdc46. However, most protein P1Mcm3 is not bound to a nuclear structure and appears in the nucleoplasm. About 10% of protein P1Mcm3 in the soluble fraction is free and uncomplexed, and the remaining P1Mcm3 forms stable complexes with protein P1Cdc46. These P1Mcm3/Cdc46 complexes occur as dimers and in high-molecular-mass complexes (approximately 500 kDa). The high-molecular-mass complexes dissociate in 0.5 M NaCl and release P1Mcm3/Cdc46 dimers. It has frequently been proposed that the Mcm proteins may function as licensing factors for genome replication. Our data imply that the active form of an Mcm protein is not a monomer, but a protein complex that includes an Mcm3/Cdc46 dimer. DNA polymerase alpha is not a component of this complex.
TL;DR: It is demonstrated that the binding-protein-dependent ProU transport system of E. coli mediates the efficient uptake of the osmoprotectants glycine betaine and proline betaine.
Abstract: The ProP and ProU transport systems of Escherichia coli mediate the uptake of several osmoprotectants including glycine betaine. Here we report that both ProP and ProU are involved in the transport of the potent osmoprotectant proline betaine. A set of isogenic E. coli strains carrying deletions in either the proP or proU loci was constructed. The growth properties of these mutants in high osmolarity minimal media containing 1 mM proline betaine demonstrated that the osmoprotective effect of this compound was dependent on either an intact ProP or ProU uptake system. Proline betaine competes with glycine betaine for binding to the proU-encoded periplasmic substrate binding protein (ProX) and we estimate a KD of 5.2 μM for proline betaine binding. This value is similar to the binding constant of the ProX protein determined previously for the binding of glycine betaine (KD of 1.4 μM). Our results thus demonstrate that the binding-protein-dependent ProU transport system of E. coli mediates the efficient uptake of the osmoprotectants glycine betaine and proline betaine.
TL;DR: A model which groups response regulators into two classes, common to both classes is the interaction between receiver and output domain in the unphosphorylated protein, and phosphorylation relieves inhibition, thereby activating the output domain.
Abstract: During signal transduction, response regulators of two-component systems are phosphorylated in a conserved receiver module. Phosphorylation induces activation of the non-conserved output domain. We fused various domains of the response regulators NtrC, PhoB or CheB to the DNA binding domain of lambda repressor. Analysis of these hybrid proteins shows that the receiver modules of NtrC and PhoB are potential dimerization domains. In the unphosphorylated proteins, the ability of the receiver modules to dimerize is masked due to inhibition by their output domains. Inhibition can be relieved in two ways: phosphorylation of the receiver module or deletion of the output domain. In contrast, the receiver module of CheB lacks this ability for dimerization. We propose a model which groups response regulators into two classes. Common to both classes is the interaction between receiver and output domain in the unphosphorylated protein. In class I (e.g. NtrC and PhoB), this interaction leads to the inhibition of the receiver module. Phosphorylation relieves inhibition, thereby inducing activation via dimerization of the receiver modules. In class II (e.g. CheB), the interaction between receiver and output domain results in inhibition of the output domain. Phosphorylation relieves inhibition, thereby activating the output domain.
TL;DR: Three studies psychophysically measured people's discrimination among different sizes of monetary net gains or net losses and found that discrimination was enhanced when the motivational features of the imagined event were either both the same as or both different from a person's self-discrepancy.
Abstract: Three studies psychophysically measured people's discrimination among different sizes of monetary net gains or net losses. Participants imagined either gains or nonlosses (i.e., net gains) or losses or nongains (i.e., net losses). Participants discriminated more when the identical event was framed as the presence (gains and losses) versus the absence (nonlosses and nongains) of an outcome, presumably because the latter is harder to represent. Discrimination was enhanced when the motivational features of the imagined event were either both the same as or both different from a person's selfdiscrepancy. Discrimination was reduced when only one of the motivational features was different. A model of excitations, inhibitions, and disinhibitions between mental representation is suggested to account for these findings. When people perceive an increase in the loudness of a tone as a result of an increase in its sound pressure, their sensory apparatus discriminates between these two physical sound pressures. They experience this increase in stimulus intensity as an increase in loudness. A highly discriminating sensory system tracks the slightest variation of stimulus intensity. It is sensitive to differences in stimulus intensity, such as sound pressure differences. In contrast, a nondiscriminat ing system does not detect variations in stimulus intensity, even when they are fairly large. Such a system is insensitive to differences in stimulus intensity. Different sensory systems can have different discriminations or one system can have different discriminations as a function of specific variables. Positive and negative events can also have different stimulus intensities. For example, when people perceive a difference in the "intensities" of two monetary losses, such as the difference between a $50 loss and a $60 loss, their "affective apparatus" discriminates between two stimulus intensities (here money
TL;DR: Current evidence for the involvement of apoptosis in the cytotoxicity of nitric oxide is summarized and possible mechanisms that may lead to cell death are discussed.
TL;DR: The findings suggest that endogenous TNF‐α down‐regulate the early and up‐regulates the late LPS‐induced IL‐10 synthesis in vivo and that the liver is the major source of circulating IL-10 after stimulation with LPS.
Abstract: Interleukin (IL)-10 is known to protect mice against the lethal effects of lipopolysaccharides (LPS) and is considered to be an anti-inflammatory cytokine which suppresses the production of pro-inflammatory cytokines. We have examined the interactions of the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) with IL-10. Neutralization of TNF-alpha in murine bone marrow-derived macrophages resulted in a significant reduction of LPS-inducible IL-10 production. In mice, injection of 5 mg/kg LPS induced circulating IL-10 with a biphasic time course exhibiting an early peak 1.5 h after challenge (synchronous with TNF-alpha) and, after a nadir at 6 h, a second increase between 8 and 12 h. Treatment of mice with neutralizing anti-mouse TNF-alpha antiserum significantly increased LPS-induced IL-10 plasma levels between 1.5 and 6 h but diminished those at 12 h, while circulating IL-6, interferon-gamma (IFN-gamma) and granulocyte colony-stimulating factor (G-CSF) concentrations were attenuated overall, without a biphasic response. Analysis of LPS-induced IL-10 mRNA expression in different tissues 1 h and 8 h after LPS or LPS plus anti-TNF-alpha revealed that the amount of transcripts in the liver correlated with circulating early and late IL-10 levels. Our findings suggest that endogenous TNF-alpha down-regulates the early and up-regulates the late LPS-induced IL-10 synthesis in vivo and that the liver is the major source of circulating IL-10 after stimulation with LPS.
TL;DR: The nuclear envelope allows entry of XMCM3 into the nucleus, but regulates its binding to chromatin; binding requires a loading factor which cannot cross the nuclear envelope, so replication licensing is resolved into two stages.
TL;DR: Two studies show that repeated expression accounts for at least part of the attitude polarization observed in the typical studies on group polarization and that this effect is augmented by social interaction, i.e., it occurs particularly in an environment where group members repeat and validate each other's ideas.
Abstract: Classic explanations of the "group polarization phenomenon" emphasize interpersonal processes such as informational influence and social comparison (Myers & Lamm, 1976). Based on earlier research, we hypothesized that at least part of the polarization observed during group discussion might be due to repeated attitude expression. Two studies provide support for this hypothesis. In Study 1, we manipulated how often each group member talked about an issue and how often he or she heard other group members talk about the issue. We found that repeated expression produced a reliable shift in extremity. A detailed coding of the groups' discussions showed that the effect of repeated expression on attitude polarization was enhanced in groups where the group members repeated each other's arguments and used them in their own line of reasoning. Study 2 tested for this effect experimentally. The results showed that the effect of repeated expression was augmented in groups where subjects were instructed to use each others' arguments compared to groups where instructions were given to avoid such repetitions. Taken together, these studies show that repeated expression accounts for at least part of the attitude polarization observed in the typical studies on group polarization and that this effect is augmented by social interaction, i.e., it occurs particularly in an environment where group members repeat and validate each other's ideas.
TL;DR: The present article attempts to combine existing information on the distribution of fast and slow myosin isoforms in histochemically distinct muscle fibres to create a spectrum of fibre types.
Abstract: The present article attempts to combine existing information on the distribution of fast and slow myosin isoforms in histochemically distinct muscle fibres. Four myosin heavy chain (MHC) isoforms, MHCI, MHCIIa, MHCIIb, and MHCIId(x), have been identified in small mammals and have been assigned to the histochemically defined fibre types I, IIA, IIB, and IID(X), respectively. These fibres express only one MHC isoform and are called pure fibre types. Hybrid fibres expressing two MHC isoforms are regarded as transitory between respective pure fibre types. The existence of pure and hybrid fibres even in normal muscles under steady state conditions creates a spectrum of fibre types. The multiplicity of fibre types is even greater when myosin light chains are taken into account. A large number of isomyosins results from the combinatorial patterns of various myosin light and heavy chains isoforms, further increasing the diversity of muscle fibres. As shown by comparative studies, the distribution of different fibre types varies in a muscle-specific, as well as a species-specific manner.