bluuebunny/crossref_metadata_2025_split huggingface dataset:
NF‐κB: A Multifaceted Transcription Factor Regulated at Several Levels
Authors: Schmitz M. Lienhard , Mattioli Ivan , Buss Holger , Kracht Michael 
Published: September 2004

AbstractNF‐κB is a generic name for an evolutionarily conserved transcription‐factor system that contributes to the mounting of an effective immune response but is also involved in the regulation of cell proliferation, development, and apoptosis. The implication of NF‐κB in central biological processes and its extraordinary connectivity to other signaling pathways raise a need for highly controlled regulation of NF‐κB activity at several levels. While all NF‐κB activation pathways share a central and critical proteasome‐mediated step that leads to the degradation of inhibitory proteins and the release of DNA‐binding subunits, there is evidence for a downstream level of NF‐κB regulation that employs several mechanisms. These include promoter‐specific exchange of dimers and modification of the transactivating p65 subunit by phosphorylation, acetylation, ubiquitination, or prolyl isomerization. The signaling pathways and enzymes controlling this second level of regulation and their potential use as therapeutic targets for the treatment of NF‐κB‐associated pathologies are discussed here.
Systems Biology and the Molecular Circuits of Cancer
Authors: Alberghina Lilia , Chiaradonna Ferdinando , Vanoni Marco 
Published: September 2004

AbstractProliferative disorders are a major challenge for human health. The understanding of the organization of cell‐cycle events is of the utmost importance to devise effective therapeutic strategies for cancer. The awareness that cells and organisms are complex, modular, hierarchical systems and the availability of genome‐wide gene expression and protein analyses, should make it feasible to elucidate human diseases in terms of dysfunctions of molecular systems. Here we review evidence in support of a systems model of the cell cycle, in which two sequential growth‐sensitive thresholds control entry into S‐phase. The putative molecular determinants that set the threshold for entry into S‐phase are consistently altered in cancer cells. Such a framework could be useful in guiding both experimental investigation and data analysis by allowing wiring to other relevant cell modules thereby highlighting the differential responses, or lack of response of cancer cells to intra‐ and extracellular factors. Pharmacological approaches that take advantage of transformation‐induced fragility to glucose shortage are discussed. Extension of this hierarchical, modular approach to tumors as a whole holds promise for the development of effective drug discovery approaches and more efficient therapeutic protocols.
Preliminary Studies on the In Silico Evolution of Biochemical Networks
Authors: Deckard Anastasia , Sauro Herbert M 
Published: September 2004

AbstractDue to the variety and importance of roles performed by signalling networks, understanding their function and evolution is of great interest. Signalling networks allow organisms to process and react to changes in their internal and external environment. Current estimates suggest that two to three percent of all genomes code for proteins involved in signalling networks. The study of signalling networks is hindered by the complexities of the networks and difficulties in ascribing function to form. For example, a very complex dense network might comprise eighty or more densely connected proteins. In the majority of cases there is very little understanding of how these networks process signals. Unlike in electronics, where there is a broad practical and theoretical understanding of how to construct devices that can process almost any kind of signal, in biological signalling networks there is no equivalent theory. Part of the problem stems from the fact that in most cases it is unknown what particular signal processing circuits would look like in a biological form. This paper describes the evolutionary methods used to generate networks with particular signal‐ and computational‐processing capabilities. The techniques involved are described, and the approach is illustrated by evolving computational circuits such as multiplication, radicals and logarithmic functions. The experiments also illustrate the evolution of modularity within biochemical reaction networks.
mRNA Openers and Closers: Modulating AU‐Rich Element‐Controlled mRNA Stability by a Molecular Switch in mRNA Secondary Structure
Authors: Meisner Nicole‐Claudia , Hackermüller Jörg , Uhl Volker , Aszódi András , Jaritz Markus , Auer Manfred 
Published: September 2004

AbstractApproximately 3 000 genes are regulated in a time‐, tissue‐, and stimulus‐dependent manner by degradation or stabilization of their mRNAs. The process is mediated by interaction of AU‐rich elements (AREs) in the mRNA's 3′‐untranslated regions with trans‐acting factors. AU‐rich element‐controlled genes of fundamentally different functional relevance depend for their activation on one positive regulator, HuR. Here we present a methodology to exploit this central regulatory process for specific manipulation of AU‐rich element‐controlled gene expression at the mRNA level. With a combination of single‐molecule spectroscopy, computational biology, and molecular and cellular biochemistry, we show that mRNA recognition by HuR is dependent on the presentation of the sequence motif NNUUNNUUU in single‐stranded conformation. The presentation of the HuR binding site in the mRNA secondary structure appears to act analogously to a regulatory on/off switch that specifically controls HuR access to mRNAs in cis. Based on this finding we present a methodology for manipulating ARE mRNA levels by actuating this conformational switch specifically in a target mRNA. Computationally designed oligonucleotides (openers) enhance the NNUUNNUUU accessibility by rearranging the mRNA conformation. Thereby they increase in vitro and endogenous HuR–mRNA complex formation which leads to specific mRNA stabilization (as demonstrated for TNFα and IL‐2, respectively). Induced HuR binding both inside and outside the AU‐rich element promotes functional IL‐2 mRNA stabilization. This opener‐induced mRNA stabilization mimics the endogenous IL‐2 response to CD28 stimulation in human primary T‐cells. We therefore propose that controlled modulation of the AU‐rich element conformation by mRNA openers or closers allows message stabilization or destabilization in cis to be specifically triggered. The described methodology might provide a means for studying distinct pathways in a complex cellular network at the node of mRNA stability control. It allows ARE gene expression to be potentially silenced or boosted. This will be of particular value for drug‐target validation, allowing the diseased phenotype to ameliorate or deteriorate. Finally, the mRNA openers provide a rational starting point for target‐specific mRNA stability assays to screen for low‐molecular‐weight compounds acting as inhibitors or activators of an mRNA structure rearrangement.
Laminar organization of the developing lateral olfactory tract revealed by differential expression of cell recognition molecules
Authors: Inaki Koichiro , Nishimura Sachiko , Nakashiba Toshiaki , Itohara Shigeyoshi , Yoshihara Yoshihiro 
Published: September 2004

AbstractThe projection neurons in the olfactory bulb (mitral and tufted cells) send axons through the lateral olfactory tract (LOT) onto several structures of the olfactory cortex. However, little is known of the molecular and cellular mechanisms underlying establishment of functional connectivity from the bulb to the cortex. Here, we investigated the developmental process of LOT formation by observing expression patterns of cell recognition molecules in embryonic mice. We immunohistochemically identified a dozen molecules expressed in the developing LOT and some of them were localized to subsets of mitral cell axons. Combinatorial immunostaining for these molecules revealed that the developing LOT consists of three laminas: superficial, middle, and deep. Detailed immunohistochemical, in situ hybridization, and 5‐bromodeoxyuridine labeling analyses suggested that the laminar organization reflects: 1) the segregated pathways from the accessory and main olfactory bulbs, and 2) the different maturity of mitral cell axons. Mitral cell axons of the accessory olfactory bulb were localized to the deep lamina, segregated from those of the main olfactory bulb. In the main olfactory pathway, axons of mature mitral cells, whose somata is located in the apical sublayer of the mitral cell layer, were localized to the middle lamina within LOT, while those of immature mitral cells that located in the basal sublayer were complementarily localized to the superficial lamina. These results suggest that newly generated immature axons are added to the most superficial lamina of LOT successively, leading to the formation of piled laminas with different maturational stages of the mitral cell axons. J. Comp. Neurol. 479:243–256, 2004. © 2004 Wiley‐Liss, Inc.
Colocalization of urocortin and neuronal nitric oxide synthase in the hypothalamus and Edinger‐Westphal nucleus of the rat
Authors: Spina Mariarosa G. , Langnaese Kristina , Orlando Gabriella F. , Horn Thomas F.W. , Rivier Jean , Vale Wylie W. , Wolf Gerald , Engelmann Mario 
Published: September 2004

AbstractDifferent lines of studies suggest that both the corticotropin‐releasing hormone‐related peptide Urocortin I (Ucn) and the neuromodulator nitric oxide (NO) are involved in the regulation of the complex mechanisms controlling feeding and anxiety‐related behaviors. The aim of the present study was to investigate the possible interaction between Ucn and NO in the hypothalamic paraventricular nucleus (PVN), an area known to be involved in the modulation of these particular behaviors. Therefore, we mapped local mRNA and peptide/protein presence of both Ucn and the NO producing neuronal NO synthase (nNOS). This investigation was extended to include the hypothalamic supraoptic nucleus (SON) and the Edinger‐Westphal nucleus area (EW), the latter being one of the major cellular Ucn‐expressing sites. Furthermore, we compared the two predominantly used laboratory rat strains, Wistar and Sprague‐Dawley. Ucn mRNA and immunoreactivity were detected in the SON and in the EW. A significant difference between Wistar and Sprague‐Dawley rats was found in mRNA levels in the EW. nNOS was detected in all brain areas analyzed, showing a significantly lower immunoreactivity in the PVN and EW of Sprague‐Dawley versus Wistar rats. Contrary to some previous reports, no Ucn mRNA and only a very low immunoreactivity were detectable in the PVN of either rat strain. Interestingly, double‐labeling immunofluorescence revealed that in the SON ∼75% of all cells immunoreactive for Ucn were colocalized with nNOS, whereas in the EW only ∼2% of the Ucn neurons were found to contain nNOS. These findings suggest an interaction between Ucn and NO signaling within the SON, rather than the PVN, that may modulate the regulation of feeding, reproduction, and anxiety‐related behaviors. J. Comp. Neurol. 479:271–286, 2004. © 2004 Wiley‐Liss, Inc.
Time course of embryonic midbrain and thalamic auditory connection development in mice as revealed by carbocyanine dye tracing
Authors: Gurung Bina , Fritzsch Bernd 
Published: September 2004

AbstractCentral auditory connections develop in mice before the onset of hearing, around postnatal day 7. Two previous studies have investigated the development of auditory nuclei projections and lateral lemniscal nuclear projections in embryonic rats, respectively. Here, we provide detail for the first time of the initiation and progression of projections from the inferior colliculus (IC) to the medial geniculate body (MGB) and from the MGB to the auditory cortex (AC). Overall, the developmental progression of projections follows that of terminal mitoses in various nuclei, suggesting the consistent use of a developmental timetable at a given nucleus, independent of that of other nuclei. Our data further suggest that neurons project specifically and reciprocally from the MGB to the AC as early as embryonic day 14.5. These projections develop approximately a day before the reciprocal connections between the MGB and IC and before development of projections from the auditory nuclei to the IC. The development of IC projections is prolonged and progresses from rostral to caudal areas. Brainstem nuclear projections to the IC arrive first from the lateral lemniscus nuclei then the superior olive and finally the cochlear nuclei. Overall, the auditory connection development strongly suggests that most of the overall specificity of nuclear connections is set up at least 2 weeks before the onset of sound‐mediated cochlea responses in mice and, thus, is likely governed predominantly by molecular genetic clues. J. Comp. Neurol. 479:309–327, 2004. © 2004 Wiley‐Liss, Inc.
GABAergic and glycinergic presympathetic neurons of rat medulla oblongata identified by retrograde transport of pseudorabies virus and in situ hybridization
Authors: Stornetta Ruth L. , McQuiston Travis J. , Guyenet Patrice G. 
Published: September 2004

AbstractElectron microscopy suggests that up to half the synaptic input to sympathetic preganglionic neurons (SPGNs) is GABAergic or glycinergic. A proportion of this input is suspected to originate from neurons located within the medulla oblongata. The present study provides definitive evidence for the existence of these supraspinal presympathetic (PS) neurons with inhibitory phenotypes. PS neurons were identified by retrograde trans‐synaptic migration of pseudorabies virus (PRV) injected into the adrenal gland. GABAergic or glycinergic cell bodies were identified by the presence of glutamate decarboxylase (GAD)‐67 mRNA or glycine transporter (GlyT)‐2 mRNA detected with in situ hybridization (ISH). Neither GABAergic nor glycinergic PS neurons were tyrosine hydroxylase (TH)‐immunoreactive (ir). GABAergic PS neurons were located within the ventral gigantocellular nucleus, gigantocellular nucleus alpha, and medial reticular formation, mostly medial to the TH‐ir PS neurons. About 30% of GABAergic PS neurons were serotonergic cells located in the raphe pallidus (RPa) and parapyramidal region (PPyr). Glycinergic PS neurons had the same general distribution as the GABAergic cells, except that no glycinergic neurons were located in the RPa or PPyr and none were serotonergic. PRV immunohistochemistry combined with ISH for both GlyT2 and GAD‐67 mRNAs showed that at least 63% of midline medulla GABAergic PS neurons were also glycinergic and 76% of glycinergic PS neurons were GABAergic. In conclusion, the rostral ventromedial medulla contains large numbers of GABAergic and glycinergic neurons that innervate adrenal gland SPGNs. Over half of these PS neurons may release both transmitters. The physiological role of this medullary inhibitory input remains to be explored. J. Comp. Neurol. 479:257–270, 2004. © 2004 Wiley‐Liss, Inc.
Seismic tests on reinforced concrete and steel frames retrofitted with dissipative braces
Authors: Molina F. J. , Sorace S. , Terenzi G. , Magonette G. , Viaccoz B. 
Published: September 2004

AbstractSeismic tests have been conducted on two 3‐storey structures protected with pressurized fluid‐viscous spring damper devices. One of the structures was a reinforced concrete frame with clay elements in the slabs, while the other one was a steel frame with steel/concrete composite slabs. The spring dampers were installed through K bracing in between the floors. The tests were performed by means of the pseudodynamic method, which allowed the use of large and full‐size specimens, and by implementing a specific compensation strategy for the strain‐rate effect at the devices. The test results allowed the verification of the adequacy of the attachment system as well as the comparison of the behaviour of the unprotected buildings with several protected configurations, showing the benefits of the application of the devices and the characteristics of their performance. The response of the protected structures was always safer than that of the unprotected ones mainly due to a significant increase of equivalent damping. The increase in the damping ratio depends on the level of deformation. Copyright © 2004 John Wiley & Sons, Ltd.
Response of SDOF system to non‐stationary earthquake excitation
Authors: Jangid R. S. 
Published: September 2004

AbstractEarthquake excitation is often modelled by non‐stationary random process (i.e. uniformly modulated broad‐band excitation) for analysis of structural safety subjected to seismic hazards. In this paper, the non‐stationary response of a single‐degree‐of‐freedom (SDOF) system to non‐stationary earthquake motion is investigated for different shapes of modulating functions. The evolutionary power‐spectral density function (PSDF) of the displacement of the SDOF system is obtained using the time‐varying frequency response function and the PSDF of the earthquake excitation. The close form expressions for time‐varying frequency response function are derived for different shapes of the modulating functions. In order to study the effects of the shape of the modulating function, a comparison of the non‐stationary earthquake response of the SDOF system is also made for different modulating functions having the same energy content. Copyright © 2004 John Wiley & Sons, Ltd.
Inelastic spectra for infilled reinforced concrete frames
Authors: Dolšek Matjaž , Fajfar Peter 
Published: September 2004

AbstractIn two companion papers a simplified non‐linear analysis procedure for infilled reinforced concrete frames is introduced. In this paper a simple relation between strength reduction factor, ductility and period (R–µ–T relation) is presented. It is intended to be used for the determination of inelastic displacement ratios and of inelastic spectra in conjunction with idealized elastic spectra. The R–µ–T relation was developed from results of an extensive parametric study employing a SDOF mathematical model composed of structural elements representing the frame and infill. The structural parameters, used in the proposed R–µ–T relation, in addition to the parameters used in a usual (e.g. elasto‐plastic) system, are ductility at the beginning of strength degradation, and the reduction of strength after the failure of the infills. Formulae depend also on the corner periods of the elastic spectrum. The proposed equations were validated by comparing results in terms of the reduction factors, inelastic displacement ratios, and inelastic spectra in the acceleration–displacement format, with those obtained by non‐linear dynamic analyses for three sets of recorded and semi‐artificial ground motions. A new approach was used for generating semi‐artificial ground motions compatible with the target spectrum. This approach preserves the basic characteristics of individual ground motions, whereas the mean spectrum of the whole ground motion set fits the target spectrum excellently. In the parametric study, the R–µ–T relation was determined by assuming a constant reduction factor, while the corresponding ductility was calculated for different ground motions. The mean values proved to be noticeably different from the mean values determined based on a constant ductility approach, while the median values determined by the different procedures were between the two means. The approach employed in the study yields a R–µ–T relation which is conservative both for design and performance assessment (compared with a relation based on median values). Copyright © 2004 John Wiley & Sons, Ltd.
X‐ray crystallographic analysis and differential scanning calorimetry of two polymorphic forms of 2,6‐diphenyl‐1,4‐dithiin
Authors: Piao Xuehua , Sugihara Yoshiaki , Nakayama Juzo 
Published: September 2004

Abstract2,6‐Diphenyl‐1,4‐dithiin 2 exists in the two polymorphic forms. The dithiin 2L, mp 62–63°C, was assigned as the metastable form, while the dithiin 2H, mp 79–80°C, was assigned as the stable form, mainly on the basis of differential scanning calorimetry (DSC) analysis. X‐Ray crystallographic analysis showed that the largest difference in the molecular structure between 2L and 2H is found in the coplanarity between the benzene ring and the double bond part of the dithiin ring; the benzene ring and the double bond are nearly coplanar for 2L, whereas these are far from being coplanar for 2H. © 2004 Wiley Periodicals, Inc. Heteroatom Chem 15:424–427, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20035
Zeolite‐catalyzed simple synthesis of different heterocyclic rings, part 2
Authors: Hegedüs Adrienn , Vígh Ilona , Hell Zoltán 
Published: September 2004

AbstractA simple and environmentally friendly synthesis was developed for the preparation of 2‐arylimidazoline derivatives and 2‐arylbenzoxazole derivatives using a small pore size zeolite. The similar reaction was not applicable to the preparation of the sulfur‐containing analogs cysteamine or 2‐aminothiophenol, probably because of a disadvantageous reaction between the zeolite and the thio compound. © 2004 Wiley Periodicals, Inc. Heteroatom Chem 15:428–431, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20036
Indolizines, triazolo[4,3‐a]pyridines, benzimidazo[1,2‐d]oxadiazoles, and pyrazolo[1,5‐c]triazoles via nitrogen and sulfur ylides
Authors: Dawood Kamal M. 
Published: September 2004

AbstractThe pyridinium salts 2a,b reacted with dimethyl acetylenedicarboxylate (DMAD) to give the indolizine derivatives 6a,b. Pyridinium salts 2a,b also reacted with pyrazole‐5‐diazonium salt to afford the hydrazonoyl bromides 8a,b, which on treatment with aqueous ethanolic sodium carbonate furnished the 8aH‐1,2,4‐triazolo[4,3‐a]pyridine 10. When sulfonium bromide 11 was treated with nitrous acid and with pyrazole‐5‐diazonium salt, it afforded the new hydroximoyl and hydrazonoyl halides 12 and 17, respectively. Compound 12 reacted with 2‐methylthiobenzimidazole to furnish benzimidazo[1,2‐d]‐1,2,4‐oxadiazole derivative 14. Treatment of either 12 with 3‐phenyl‐5‐aminopyrazole or 17 with triethylamine resulted in the formation of the same product: pyrazolo[1,5‐c]‐1,2,4‐triazole derivative 16. © 2004 Wiley Periodicals, Inc. Heteroatom Chem 15:432–436, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20037
Reaction of chlorides of phosphoric, sulfonic, and carboxylic acids on solid potassium carbonate surface under PTC circumstances
Authors: Jászay Zsuzsa M. , Petneházy Imre , Tőke László 
Published: September 2004

AbstractSimple syntheses of phosphoric (4) and carboxylic (6) acid anhydrides have been elaborated by means of solid potassium carbonate in phase‐transfer catalytic acylation. Behavior of various acid chlorides, phosphoric (1), sulfonic (2), and carboxylic (8), have also been studied toward potassium carbonate in the presence of lipophilic quaternary ammonium salt. © 2004 Wiley Periodicals, Inc. Heteroatom Chem 15:447–450, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20039
Synthesis and characterization of two novel tin(IV) compounds containing 12‐membered metallarings
Authors: Vargas‐Pineda Gabriela , López‐Cardoso Marcela , García Patricia García y , Cea‐Olivares Raymundo 
Published: September 2004

Abstract12‐Chloro‐12‐n‐butyl‐1,11‐dioxa‐4,8‐ dithia‐12‐stannacyclododecane (3a) and 12‐chloro‐ 12‐n‐butyl‐1,4,8,11‐tetrathia‐12‐stannacyclododecane (3b) have been prepared by reacting n‐butyltin trichloride with 1,11‐dioxa‐4,8‐dithiaundecane and 1,4,8,11‐tetrathiaundecane, respectively. Complexes 3a,b were characterized by elemental analyses, IR, electron impact mass spectrometry, and multinuclear NMR (1H, 13C, and 119Sn). The spectroscopic data are consistent with bonding of the ligands through both sulfur and oxygen atoms in 3a and through all sulfur atoms in 3b to the Sn(IV) center. We suggest hexacoordination around the Sn atoms. © 2004 Wiley Periodicals, Inc. Heteroatom Chem 15:451–453, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20040