bluuebunny/crossref_metadata_2025_split huggingface dataset:
Can the calculation of ligand binding free energies be improved with continuum solvent electrostatics and an ideal‐gas entropy correction?
Authors: Schwarzl Sonja M. , Tschopp Thomas B. , Smith Jeremy C. , Fischer Stefan 
Published: August 2002

AbstractThe prediction of a ligand binding constant requires generating three‐dimensional structures of the complex concerned and reliably scoring these structures. Here, the scoring problem is investigated by examining benzamidine‐like inhibitors of trypsin, a system for which errors in the structures are small. Precise and consistent binding free energies for the inhibitors are determined experimentally for this test system. To examine possible improvement of scoring methods, we test the suitability of continuum electrostatics to account for solvation effects and use an ideal‐gas entropy correction to account for the changes in the degrees of freedom of the ligand. The small observed root‐mean‐square deviation of 0.55 kcal/mol of the calculated relative to the experimental values indicates that the essentials of the binding process have been captured. Even though all six ligands make the same salt bridge and H‐bonds to the protein, the electrostatic contribution varies among the ligands by as much as 2 kcal/mol. Moreover, although the ligands are rigid and similar in size, the entropic terms also significantly affect the relative binding affinities (by up to 2.7 kcal/mol). The present approach to solvation and entropy may allow the ranking of the ligands to be considerably improved at a cost that makes the method applicable to the optimization of lead compounds or to the screening of small collections of ligands. © 2002 Wiley Periodicals, Inc. J Comput Chem 23: 1143–1149, 2002
The development of a scoring system for the Gerontological Apperception Test
Authors: Hayslip Bert , Francis Jacqueline , Radika Lisa M. , Lambert Paul , Panek Paul E. , Bosmajian Linda 
Published: August 2002

AbstractTo explore the viability of a revised and more differentiated scoring system for use with the Gerontological Apperception Test (GAT; Wolk & Wolk, 1971), 102 older adults (mean age = 68.3 years) were administered the GAT. Scoring criteria were developed to reflect a variety of constructs speaking to the interpersonal, health‐related, and intrapsychic dimensions of the experience of later life. For each of these 20 GAT variables, indices of interscorer agreement exceeded 80%. Bivariate correlations suggested that 12 of 20 GAT dimension scores were related to chronological age as well as to scores derived from measures of crystallized and fluid ability. This also was true for 2 of 5 GAT factor scores. Not only do these data suggest that newly developed GAT variables can be reliably scored, but they also indicate that these more carefully differentiated variables relate to measures of intellectual functioning in theoretically meaningful ways. These findings therefore speak to the utility of the GAT using more carefully defined scoring criteria. © 2002 Wiley Periodicals, Inc. J Clin Psychol 58: 471–478, 2002.
p38 MAP kinase mediates platelet‐derived growth factor‐stimulated migration of hepatic myofibroblasts
Authors: Tangkijvanich Pisit , Santiskulvong Chintda , Melton Andrew C. , Rozengurt Enrique , Yee, Hal F. 
Published: August 2002

AbstractAlthough the migration of hepatic myofibroblasts (HMFs) contributes to the development of fibrosis, the signals regulating migration of these cells are poorly understood. In this study, we tested the hypothesis that HMF migration is stimulated by platelet‐derived growth factor‐BB (PDGF‐BB) through p38 mitogen‐activated protein (MAP) kinase and extracellular signal‐regulated kinase (ERK) signaling pathways. This hypothesis was addressed by directly visualizing the migration of cultured human HMFs into a wound. PDGF‐BB stimulated membrane ruffling, migration, and proliferation. PDGF‐BB also induced activation of p38 MAP kinase, its downstream effector, heat shock protein (HSP) 27, ERK 1 and ERK 2, and p125 focal adhesion kinase (FAK). Selective antagonism of p38 MAP kinase blocked PDGF‐BB‐stimulated HSP 27 phosphorylation, membrane ruffling, and migration, but did not alter PDGF‐BB‐induced proliferation. Selective antagonism of ERK kinase inhibited PDGF‐BB‐induced ERK phosphorylation and proliferation, but did not affect PDGF‐BB‐stimulated migration. Concentrations of PDGF‐BB that stimulated migration and proliferation did not influence myosin‐dependent contractility. Neither selective inhibition of p38 MAP kinase nor ERKs altered PDGF‐BB‐induced activation of FAK. In conclusion, these results provide novel evidence indicating that (1) HMF migration is stimulated by PDGF‐BB through the regulation of membrane ruffling by a p38 MAP kinase signaling pathway, (2) whereas p38 MAP kinase mediates PDGF‐BB‐stimulated migration, but not proliferation, ERKs mediate PDGF‐induced proliferation, but not migration, and (3) increases in myosin‐dependent contractility are not required for PDGF‐BB‐stimulated migration. © 2002 Wiley‐Liss, Inc.
Role of protein kinase Cδ in transmitting hypoxia signal to HSF and HIF‐1
Authors: Baek Sun‐Hee , Lee U‐Youn , Park Eun‐Mi , Han Mi‐Young , Lee Yun‐Sil , Park Young‐Mee 
Published: August 2002

AbstractAn hypoxic microenvironment is an important modulator of gene expression in many pathophysiological conditions. In this study, we show a coordinate activation of heat shock transcription factor (HSF) and hypoxia‐inducible factor‐1 (HIF‐1) in RIF tumor cells by hypoxia. Since heat shock protein (hsp) and angiogenic factor genes that are regulated by HSF and HIF‐1 are thought to contribute to the malignant progression of hypoxic tumor cells, it was of our major interest to identify the components that are responsible for the activation of both HSF and HIF‐1. Our finding that a bioflavonoid quercetin (QCT), a well known inhibitor of hsp gene expression, significantly inhibited the transcriptional activation of HSF and HIF‐1 strongly suggests that QCT‐sensitive molecule(s) is involved in the transcriptional activation of HSF and HIF‐1 by hypoxia. Our results revealed that PCKα, δ and ϵ isoforms are expressed in RIF cells, but only PKCδ was specifically translocated to the membrane by hypoxia. Our results also revealed that the translocation of PKCδ was completely abrogated by QCT. Moreover, inhibiting the PKCδ activation, either pharmacologically with phorbol 12‐myristate 13‐acetate or with bisindolymaleimide II or genetically by transient transfection of a dominant negative PKCδ, significantly inhibited the transcriptional activation of HSF and HIF‐1 by hypoxia. These results strongly substantiate a view that the PKCδ isozyme is the QCT‐sensitive molecule that plays an important role in transmitting hypoxia signals to both HSF and HIF‐1. Here we show that the membrane translocation of PKCδ is dependent on the activation of phosphoinositol 3‐kinase (PI3K). Treatment with PI3K inhibitor, wortmannin or LY294002, abrogated not only PKCδ translocation but the subsequent transcriptional activation of HSF and HIF‐1 by hypoxia. Together, our study shows that the PKCδ isozyme acts as a shared component in transmitting hypoxia‐induced signals to both HSF and HIF‐1, and that the upstream regulator of PKCδ is PI3K. © 2001 Wiley‐Liss, Inc.
Microglia in HIV‐associated neurological diseases
Authors: Glass Jonathan D. , Wesselingh Steve L. 
Published: August 2002

AbstractHuman immunodeficiency virus type‐1 (HIV‐1) is a neurotropic virus linked to a variety of progressive neurologic disorders. This review describes our current understanding of how HIV‐1 enters the nervous system and interacts with neuronal and non‐neuronal cells to initiate and sustain neurologic dysfunction. The overwhelming majority of cells infected with HIV‐1 in the nervous system are microglia/macrophages. Microglial/macrophage infection leads to immune dysregulation as well as production and release of cytotoxic molecules. Interaction of these infected cells with astrocytes may accelerate neurotoxic mechanisms. A hypothetical scenario for how HIV‐1 infection leads to neurologic disease is presented. Microsc. Res. Tech. 54:95–105, 2001. © 2001 Wiley‐Liss, Inc.
Freeze tolerance in the gray treefrog: Cryoprotectant mobilization and organ dehydration
Authors: Layne Jack R. , Jones Adrienne L. 
Published: August 2002

AbstractFreeze tolerance in the frog Rana sylvatica is supported by nonanticipatory mobilization of cryoprotectant (glucose) and redistribution of organ water. Other freeze‐tolerant frogs may manifest these responses but differences exist. For example, the gray treefrog (Hyla versicolor) accumulates mostly glycerol as opposed to glucose. The current study reports additional novel features about cryoprotection in H. versicolor. Frogs were acclimated to low temperature for 12 weeks and frozen for 3 days at –2.4°C. Some frogs were then thawed at 3°C for 4 hr. Calorimetry revealed that frozen frogs had 53.9% ± 11.1% of their body water in ice, and all frogs recovered following this procedure. Plasma glucose was low prior to the onset of freezing (1.1 ± 0.9 μmol/ml) and it was 20× higher in postfreeze frogs. Constituting nearly 30% of plasma solute, glycerol was 117.2 ± 13.6 μmol/ml prior to freezing and it remained equally high in postfreeze frogs. Liver water content was moderately lower in frozen frogs when compared to controls (62.9% ± 3.7% vs. 68.6% ± 1.7%), whereas postfreeze frogs excessively hydrated their livers (75.7% ± 2.1%). Less‐pronounced changes were seen in muscle water content. H. versicolor can mobilize its major cryoprotectant, glycerol, in response to extended cold acclimation, which is unique in comparison to other freeze‐tolerant frogs, and it experiences only moderate organ dehydration during freezing. This species conforms with other freeze‐tolerant frogs, however, by mobilizing glucose as a direct response to tissue freezing. J. Exp. Zool. 290:1–5, 2001. © 2001 Wiley‐Liss, Inc.
Oncoretroviral gene transfer to NOD/SCID repopulating cells using three different viral envelopes
Authors: Relander Thomas , Karlsson Stefan , Richter Johan 
Published: August 2002

AbstractBackgroundThe aim of this study was to investigate gene transfer to human umbilical cord blood (CB) CD34+/CD38low and NOD/SCID repopulating cells using oncoretroviral vectors and to compare the transduction efficiency using three different viral envelopes.MethodsCB cells were transduced on Retronectin using an MSCV‐based vector with the gene for GFP (MGIN), which was packaged into three different cell lines giving different envelopes: PG13‐MGIN (GALV), 293GPG‐MGIN (VSV‐G) or AM12‐MGIN (amphotropic).ResultsSorted CD34+/CD38low cells were efficiently transduced after 3 days of cytokine stimulation and the percentage of GFP‐positive cells was 61.8±6.6% (PG13‐MGIN), 26.9±3.5% (293GPG‐MGIN), and 39.3±4.8% (AM12‐MGIN). For transplantation experiments, CD34+ cells were pre‐stimulated for 2 days before transduction on Retronectin preloaded with vector and with the addition of 1/10th volume of viral supernatant on day 3. On day 4, the expanded equivalent of 2.5×105 cells was injected into irradiated NOD/SCID mice. All three pseudotypes transduced NOD/SCID repopulating cells (SRCs) equally well in the presence of serum, but engraftment was reduced when compared with freshly thawed cells. Simultaneous transduction with all three vector pseudotypes increased the gene transfer efficiency to SRCs but engraftment was significantly impaired. There were difficulties in producing amphotropic vectors at high titers in serum‐free medium and transduction of CD34+ cells using VSV‐G‐pseudotyped vectors under serum‐free conditions was very inefficient. In contrast, transduction with PG13‐MGIN under serum‐free conditions resulted in the maintenance of SRCs during transduction, high levels of engraftment (29.3±6.6%), and efficient gene transfer to SRCs (46.2±4.8%).ConclusionsThe best conditions for transduction and engraftment of CB SRCs were obtained with GALV‐pseudotyped vectors using serum‐free conditions. Copyright © 2002 John Wiley & Sons, Ltd.
Enzymatic synthesis and biodistribution in mice of β‐O‐D‐galactopyranosyl‐(1,4′)‐2′‐[18F]fluoro‐2′‐deoxy‐D‐glucopyranose (2′‐[18F]fluorodeoxylactose]
Authors: Bormans G. , Verbruggen A. 
Published: August 2002

AbstractWe have synthesized β‐O‐D‐galactopyranosyl‐(1,4′)‐2′‐[18F]fluoro‐2′‐deoxy‐D‐glucopyranose (2′‐[18F]fluorodeoxylactose, 18FDL) using an enzymatic method starting from 18FDG in order to evaluate this compound with regard to its usefulness for in vivo visualization of the expression of the LacZ gene. Incubation of 18FDL with β‐galactosidase results in the formation of 18FDG. Biodistribution studies in normal mice showed that 18FDL is cleared by urinary excretion and is not retained in any tissue. Biodistribution in Rosa‐26 mice is identical to the biodistribution in normal mice, suggesting that 18FDL is not able to cross the cell membrane. Copyright © 2001 John Wiley & Sons, Ltd.
The dorsal fin engine of the seahorse (Hippocampus sp.)
Authors: Consi T.R. , Seifert P.A. , Triantafyllou M.S. , Edelman E.R. 
Published: August 2002

AbstractThe muscles, fin ray joints, and supporting structures underlying the dorsal fin are described for two seahorse species: Hippocampus zosterae and Hippocampus erectus. A fan‐shaped array of cartilaginous bones, the pterigiophores, form the internal supporting structure of the dorsal fin. Each pterigiophore is composed of a proximal radial that extends from a vertebra to the dorsal side of the animal, where it fuses to a middle radial. The middle radials fuse with each other to form a dorsal ridge upon which sit the spheroidal distal radials. Each distal radial articulates with a fin ray on its dorsal side and is attached to the dorsal ridge on its ventral side by a material that has been histologically identified as elastic cartilage. Together these connections form a two‐axis joint that permits elevation, depression, and inclination of the ray. Each fin ray is actuated by two bilateral pairs of muscles, an anterior pair of inclinators, and a posterior pair of depressors. The anteriormost fin ray is actuated by three bilateral pair of muscles, the inclinators, the depressors, and a pair of elevator muscles that are positioned anterior to the inclinators. Preliminary examinations of the ray joints of the pectoral and anal fins of adult H. zostera and the pectoral fins of newborn H. erectus revealed structures similar to that seen in the dorsal fins. To further explore the structure and function of the dorsal fin gross dissections and simple functional tests were performed on H. erectus and H. barbouri and behavioral observations were made of all three species plus Hippocampus kuda. J. Morphol. 248:80–97, 2001. © 2001 Wiley‐Liss, Inc.
Accelerated coronary MRA by simultaneous acquisition of multiple 3D stacks
Authors: Manke Dirk , Böornert Peter , Nehrke Kay , Nagel Eike , Döossel Olaf 
Published: August 2002

AbstractThe implementation and first in vivo results of a novel coronary magnetic resonance angiography (MRA) protocol allowing simultaneous acquisition of multiple geometrically independent 3D imaging stacks are presented. Each imaging stack is acquired in a separate cardiac phase using an individual magnetization preparation and navigator‐based gating and prospective motion correction. Each stack covers one of the main coronary vessels. Thus, an improvement of scan efficiency was achieved, which was used in this study to reduce total scan time at standard image quality. Experiments performed in healthy volunteers and in patients using a two‐stack approach yielded a total scan time reduction of 50% with an image quality equivalent to standard single‐stack coronary MRA. J. Magn. Reson. Imaging 2001;14:478–483. © 2001 Wiley‐Liss, Inc.
Detection of enteroviruses ribonucleic acid sequences in endomyocardial tissue from adult patients with chronic dilated cardiomyopathy by a rapid RT‐PCR and hybridization assay
Authors: Rey Laurent , Lambert Valérie , Wattré Pierre , Andréoletti Laurent 
Published: August 2002

AbstractA rapid reverse transcription polymerase chain reaction (RT‐PCR) and microwell capture hybridisation assay with general specificity for enteroviruses was developed and compared with an improved nested RT‐PCR for the detection of enteroviral RNA sequences in endomyocardial tissue from patients with chronic dilated cardiomyopathy. This method could detect as few as 20 genomic RNA copies per 100 mg of heart tissue homogenate and results could be obtained within 8 hours. Of the 55 biopsy specimens aseptically collected from the explanted hearts of 55 patients, 21 (38.2%) were positive by RT‐PCR microplate assay, whereas only 19 (34.5%) were positive by nested RT‐PCR assay and none were positive by classical cell culture assays. No enterovirus was detectable by RT‐PCR or classical cell culture assays in any of the 55 heart biopsy specimens taken from organ donors without any known heart disease. Moreover, the nucleotide sequences of EV nested RT‐PCR products showed greatest similarity to group B Coxsackieviruses [CVB3 (n = 12) or CVB5 (n = 3)], but also to group A Coxsackieviruses (CVA21 (n = 1) or CVA9 ( n= 3)]. The described RT‐PCR and microwell capture hybridisation assay can be applied to the virological diagnosis of human enteroviral cardiac infections. Moreover our findings suggest that group B and group A Coxsackieviruses can persist in heart tissue from patients with end‐stage chronic cardiomyopathy, supporting the hypothesis that these viruses could be implicated in the etiology of idiopathic dilated cardiomyopathy. J. Med. Virol. 64:133–140, 2001. © 2001 Wiley‐Liss, Inc.
Epidemiology of human sapporo‐like caliciviruses in the South West of England: Molecular characterisation of a genetically distinct isolate*
Authors: Robinson Samantha , Clarke Ian N. , Vipond I. Barry , Caul E. Owen , Lambden Paul R. 
Published: August 2002

AbstractHuman enteric caliciviruses have been assigned to two distinct genera: the Norwalk‐like viruses (NLVs) and the Sapporo‐like viruses (SLVs). During a 3‐year surveillance of gastroenteritis in the South West of England during November 1997–2000, a total of 27 clinical samples containing SLVs were collected. PCR amplicons covering a region of the RNA polymerase gene were obtained from 18 of the SLV samples. Sequence analysis of the PCR products indicated that the SLV isolates could be assigned to one of the two major genetic groups represented by Sapporo and London/92 caliciviruses. One of these isolates belonging to the London/92 group (Bristol/98) was subjected to a complete genome sequence analysis. The full genomic sequence of the Bristol/98 isolate was determined from RNA extracted from a single stool sample and consists of 7490 nucleotides, excluding the poly(A) tail. The genome is organised into two open reading frames (ORFs), similar to that of Manchester SLV although the small ORF overlapping the region encoding the capsid protein observed in Manchester SLV is absent in Bristol/98 SLV. The polyprotein (ORF1) of Bristol/98 SLV consists of 2,280 amino acids and, as observed in all SLVs, the structural protein is encoded in frame and contiguous with the 3′ terminus of the ORF1. Phylogenetic studies based on complete capsid sequences and genome arrangements within the SLVs indicate that the human enteric viruses within the “Sapporo‐like” virus clade should be divided into two distinct genetic groups analogous to the assignment of the Norwalk‐like viruses. J. Med. Virol. 67:282–288, 2002. © 2002 Wiley‐Liss, Inc.
TLM method and acoustics
Authors: Portí Jorge A. , Morente Juan A. 
Published: August 2002

AbstractIn this paper, the application of the transmission line modelling method (TLM) to acoustic problems is considered. The formal coupling of a parallel and three series circuits is used to present a new three‐dimensional symmetrical condensed node for acoustics. Some considerations about the analogy, field excitation, and different boundary conditions are also included. Finally, examples are given demonstrating the suitability of the proposed TLM node to describe acoustic phenomena. Copyright © 2001 John Wiley & Sons, Ltd.
Caspases on the brain
Authors: Troy Carol M. , Salvesen Guy S. 
Published: August 2002

AbstractThe basic mechanisms that underlie neurodegenerative diseases are unknown. Loss of function of specific regions of the brain is due to incapacitation of cells that constitute those regions. Cells can simply stop functioning normally (neurons may cease to transmit signals), or they may die. There is now evidence that the pathology of several neurodegenerative diseases is due to inappropriate apoptosis. This being the case, an understanding of the mediators of apoptosis, their identities, and their role in orchestrating death would be a vital step toward remedying the diseases. The central components of apoptotic pathways, proteases of the caspase family, are present in latent forms in all nucleated cells. Their activity is balanced by specific activation and inactivation events, and the molecular and biochemical controls have been well established in vitro and in model transformed cell lines. In this Mini‐Review, we consider the current status of the basic control mechanisms and how these may be subverted during neurodegeneration. © 2002 Wiley‐Liss, Inc.
H2O2 induces upregulation of Fas and Fas ligand expression in NGF‐differentiated PC12 cells: Modulation by cAMP
Authors: Facchinetti F. , Furegato S. , Terrazzino S. , Leon A. 
Published: August 2002

AbstractFas, (APO‐1/CD95), a transmembrane glycoprotein belonging to the tumor necrosis (TNF) receptor superfamily, transduces apoptotic death upon crosslinking by its cognate ligand (FasL). As upregulation of Fas/FasL expression occurs in neuropathological conditions (e.g., stroke, central nervous system [CNS] trauma and seizures) associated with oxidative damage, we questioned whether reactive oxygen species (ROS) can directly affect Fas and FasL expression in neuronal cells. Utilizing rat PC12 cells neuronally differentiated with nerve growth factor (NGF), we observed that concentrations of H2O2 inducing apoptotic cell death rapidly trigger the expression of Fas mRNA and protein as well as FasL mRNA. Although NGF‐addition to naive PC12 downregulated constitutive Fas and FasL transcription, the H2O2‐induced Fas and FasL mRNA upregulation invariably occurred either in the presence or in the absence of NGF. Similarly, phorbol 1,2‐myristate 1, 3‐acetate (PMA), a potent protein kinase C (PKC) activator, did not modify Fas and FasL mRNA upregulation subsequent to H2O2 exposure. On the contrary, forskolin and dibutyryl cAMP, which elevate intracellular cAMP by independent mechanisms, both counteracted H2O2‐induced Fas, but not FasL, mRNA upregulation and increased constitutive expression of FasL mRNA. Altogether, our data show that oxidative stress is a major stimulus in eliciting Fas and FasL expression in NGF‐differentiated PC12 cells. Moreover, we describe here for the first time the existence of cAMP‐dependent mechanism(s) modulating Fas and FasL expression. © 2002 Wiley‐Liss, Inc.