bluuebunny/crossref_metadata_2025 huggingface dataset:
Intracellular localization of the Epstein‐Barr virus BFRF1 gene product in lymphoid cell lines and oral hairy leukoplakia lesions
Authors: Farina Antonella , Cardinali Giorgia , Santarelli Roberta , Gonnella Roberta , Webster‐Cyriaque Jennifer , Bei Roberto , Muraro Raffaella , Frati Luigi , Angeloni Antonio , Torrisi Maria Rosaria , Faggioni Alberto
Published: November 2003

A novel protein encoded by the BFRF1 gene of the Epstein‐Barr virus was identified recently [Farina et al. (2000) J Virol 74:3235–3244], which is antigenic “in vivo” and expressed early in the viral replicative cycle. In the present study, its subcellular localization was examined in greater detail comparing Epstein‐Barr virus (EBV) induced producing and nonproducing cell lines by immunofluorescence: in 12‐0‐tetradecanoyl phorbol‐13‐acetate (TPA)‐induced Raji and B95‐8 cells, as well as in anti‐IgG‐stimulated Akata cells, the protein appeared to be localized over the cell nuclear membrane. A similar nuclear membrane localization was observed in epithelial cells of oral hairy leukoplakia, a pathological manifestation of permissive EBV infection. In contrast, upon transfection of BFRF1 in the EBV‐negative Burkitt's lymphoma cell line DG75, the protein was localized predominantly over the plasma membrane. The membrane localization was abolished when DG75 cells were transfected with a C‐terminal deletion mutant of BFRF1 lacking the transmembrane domain. Because induced Raji cells do not produce virus, the above observations indicate that the nuclear membrane localization is not associated with viral production, but requires the expression of EBV genes, and suggest that additional proteins, expressed early during viral lytic infection, might be necessary to target the protein to the nuclear membrane. Immunogold electron microscopy on ultrathin cryosections of induced B95‐8 cells showed that BFRF1 on the nuclear membranes was concentrated over multilayered domains representing areas of active viral replication or at the sites of viral budding, suggesting that BFRF1 is involved in the process of viral assembly. J. Med. Virol. 72:102–111, 2004. © 2004 Wiley‐Liss, Inc.
Role of phosphatidylinositol 3‐kinase in neuronal survival and axonal outgrowth of adult mouse dorsal root ganglia explants
Authors: Edström Anders , Ekström Per A.R.
Published: November 2003

Adult ganglionic peripheral neurons have lost dependence on target‐derived neurotrophin signaling for survival and regeneration after injury. To understand the mechanisms required to sustain such processes at maturity, we are studying neuronal survival and axonal outgrowth of adult mouse dorsal root ganglia (DRG) explants. We have here examined the role of phosphatidylinositol 3‐kinase (PI3‐K) activity. Both neuronal survival and axonal outgrowth of spontaneously growing preparations were decreased significantly by the PI3‐K inhibitor LY294002 as was the increased outgrowth caused by nerve growth factor or glial cell line‐derived factor. Inhibition of PI3‐K activity promoted neuronal cell death to the same extent in the presence as in the absence of a growth factor, whereas inhibition of mitogen‐activated protein kinase, MAPK, lacked effect. Using a compartmentalized system, it could be shown that only axonal outgrowth was decreased when the outgrowth region only was exposed to LY294002. Already‐formed growth cones showed morphological changes within 5–10 min after exposure to LY294002. Akt (PKB) is one downstream effector of PI3‐K. Immunofluorescence revealed the presence of activated Akt in DRG cell bodies and in axonal growth cones. Immunoreactivity was decreased by PI3‐K inhibition. The results suggest that Akt is constitutively active in adult DRG neurons, and that PI3‐K mediated processes are involved in neuronal survival of one or more DRG neuronal subpopulations and also in axonal elongation. The possible significance of Akt signaling for these effects is discussed. © 2003 Wiley‐Liss, Inc.
Protective effects of extracellular glutathione against Zn2+‐induced cell death in vitro and in vivo
Authors: Cho Ik Hyun , Im Joo‐Young , Kim Doyeun , Kim Kyoung‐Shim , Lee Ja‐Kyeong , Han Pyung‐Lim
Published: November 2003

The central nervous system reserves high concentrations of free Zn2+ in certain excitatory synaptic vesicles. In pathological conditions such as transient cerebral ischemia, traumatic brain injury, and kainic acid (KA)‐induced seizure, free Zn2+ is released in excess at synapses, which causes neuronal and glial death. We report here that glutathione (GSH) can be used as an effective means for protection of neural cells from Zn2+‐induced cell death in vitro and in vivo. Chronic treatment with 35 μM Zn2+ led to death of primary cortical neurons and primary astrocytes. The Zn2+ toxicity of cortical neurons was partially protected by 1 mM of GSH, whereas the Zn2+ toxicity of primary astrocyte cultures was blocked completely by 100 μM of GSH. To evaluate the beneficial effects of GSH in vivo, an excitotoxin‐induced neural cell death model was established by intracerebroventricular (i.c.v.) injection of 0.94 nmol (0.2 μg) KA, which produced selective neuronal death, especially in CA1 and CA3 hippocampal regions. The i.c.v. co‐injection of 200 pmol of GSH significantly attenuated KA‐induced neuronal cell death and reactive gliosis in hippocampus. The results of this study suggest the contribution of Zn2+ in the excitotoxin‐induced neural cell death model and a potential value of GSH as a therapeutic means against Zn2+‐induced pathogenesis in brain. © 2003 Wiley‐Liss, Inc.
Inhibition of NMDA receptors induces delayed neuronal maturation and sustained proliferation of progenitor cells during neocortical development
Authors: Hirasawa Takae , Wada Hidenori , Kohsaka Shinichi , Uchino Shigeo
Published: November 2003

To elucidate the role of N‐methyl‐D‐aspartate (NMDA) receptors during the early stage of cerebral neocortical development, we investigated the effect of an NMDA receptor antagonist, D(−)‐2‐amino‐5‐phosphonopentanoic acid (D‐APV), on cell migration and proliferation in slice cultures and dissociated primary cultures prepared from rat cerebral neocortex at embryonic Day 17. Pulse‐labeling experiments with 5‐bromo‐2′‐deoxyuridine (BrdU) showed that chronic exposure to D‐APV in slices delayed neuronal migration. Calcium imaging experiments revealed that functional NMDA receptors were expressed in neurons and the treatment with D‐APV delayed neuronal maturation judging from the subunit composition of NMDA receptor subtypes. The results using pulse‐labeling with BrdU indicated that exposure to D‐APV for 3 days induced a clear increase in the number of proliferating progenitor cells in the ventricular zone in neocortical slices. Exposure to D‐APV in primary cultures also increased the proliferation of progenitor cells. The effect of D‐APV on progenitor cell proliferation was possibly mediated through neuronal cells. To elucidate the mechanism of enhanced progenitor cell proliferation induced by D‐APV, we investigated expression of Hes1 and Hes5 mRNA in the ventricular zone of neocortical slices by reverse transcription‐polymerase chain reaction. Tissue exposed to D‐APV for 3 days showed higher expression of Hes1 and Hes5 mRNA than did unexposed control tissue. These results suggest that NMDA receptors expressed in neurons function in neuronal migration and maturation and in the proliferation of progenitor cells. © 2003 Wiley‐Liss, Inc.
Learning more by crossing levels: evidence from airplanes, hospitals, and orchestras
Authors: Hackman J. Richard
Published: November 2003

Scholars generally conduct research at a single level of analysis (such as the individual, the group, or the organization level), although they often turn to the next‐lower level for explanatory mechanisms. I suggest that robust understanding of social and organizational dynamics requires attention to higher as well as lower levels of analysis. The benefits of research and theory that ‘brackets’ one's focal phenomenon by attending to constructs at both higher and lower levels of analyses are illustrated with findings from research on aircraft cockpit crews, hospital patient care teams, and professional musical ensembles. Copyright © 2003 John Wiley & Sons, Ltd.
The effects of job complexity and autonomy on cohesiveness in collectivistic and individualistic work groups: a cross‐cultural analysis
Authors: Man Derek C. , Lam Simon S. K.
Published: November 2003

Increased job complexity and autonomy have often been associated with improved performance in work groups. This study examines the mediating effect of group cohesiveness. The moderating effects of individualism/collectivism on the relationship between job characteristics (both complexity and autonomy) and cohesiveness are also tested. The sample consists of 381 teams drawn from the Hong Kong and U.S. branches of an international bank. The findings indicate that an increase in job complexity and/or task autonomy will increase group cohesiveness, which subsequently translates to better performance. The positive effects of job complexity and autonomy on group cohesiveness are also found to be more prominent for individualistic rather than collectivistic work groups. The theoretical implications of the results and the limitations of the study are also discussed. Copyright © 2003 John Wiley & Sons, Ltd.
Understanding the emotional labor process: a control theory perspective
Authors: Diefendorff James M. , Gosserand Robin H.
Published: November 2003

A dynamic, process‐oriented approach to understanding emotional labor is presented, utilizing concepts from control theory models of behavioral self‐regulation. Emotional labor is characterized as involving a discrepancy monitoring and reduction process, whereby perceptions of emotional displays and emotional display rules are continuously compared. If a discrepancy between emotional displays and display rules is detected, individuals are proposed to use emotion regulation strategies to reduce the discrepancy. The goal hierarchy aspect of control theory is used to describe emotional labor in the broader context of job performance and explain how positive and negative outcomes can result from the emotional labor process. Propositions are developed throughout the paper. Copyright © 2003 John Wiley & Sons, Ltd.
Situational and dispositional predictors of displays of positive emotions
Authors: Tan Hwee H. , Foo Maw D. , Chong Chee L. , Ng Renee
Published: November 2003

The study examined the effects of situational (store busyness and customer demand) and dispositional (extraversion, neuroticism, and psychoticism) factors on the display of positive emotions. We found that for situational factors, customer demand was positively related to displayed positive emotions. For personality factors, extraversion was positively related to displayed positive emotions and neuroticism was negatively related to displayed positive emotions. Usefulness analysis showed that both situational and personality factors contributed significantly to explain the level of positive displayed emotion. Copyright © 2003 John Wiley & Sons, Ltd.
Practice makes perfect: Putting learning to use in today's organizations
Authors: Holland Deryn , Firsht Linda , Wickes Stuart
Published: November 2003

Despite the enormous investments of time and money that organizations put into learning initiatives, little
attention is paid to putting what is learned into practice. This results in waste, lost opportunities, and
frustration. A study done at the BBC, which suspected that learning wasn't being leveraged as much as it
could be, examined the reasons why learning is often not put to use.
Class acts: When leaders are teachers, good things happen
Authors: Betof Edward
Published: November 2003

More and more companies seeking a systematic approach to leadership development are creating corporate
universities. At least one company has instituted as an integral element of its corporate university the practice
of having most of the programs taught by the organization's own leaders. So far the benefits–for the
leaders, the program participants, and the organization–have been impressive.
The limits to the growth of multinational firms in a foreign market
Authors: Tan Danchi
Published: November 2003

Theories of growth for firms have suggested that slow managerial growth is a major constraint why firms cannot grow faster. This paper is built on such a view and explores the factors that may influence the growth rate of Japanese firms in a given US industry. It is found that Japanese firms that allocated more internal and international managerial resources (proxied by expatriates) to their US operations tended to achieve higher growth rates. Japanese firms that were geographically diversified and those that spread their international investment projects evenly over time also achieved higher growth rates. Copyright © 2003 John Wiley & Sons, Ltd.
Branch decompositions and minor containment
Authors: Hicks Illya V.
Published: November 2003

Given a simple graph G, a simple connected graph H, and a branch decomposition of G of width k, we present a practical algorithm to test if H is a minor of G. The notion of branch decompositions and its related connectivity invariant for graphs, branchwidth, were introduced by Robertson and Seymour. The algorithm that we present follows the general framework for such an algorithm sketched by Robertson and Seymour with the addition of pruning techniques for runtime speedup. © 2003 Wiley Periodicals, Inc.
Simplicial edge representation of protein structures and alpha contact potential with confidence measure
Authors: Li Xiang , Hu Changyu , Liang Jie
Published: November 2003

Protein representation and potential function are two important ingredients for studying protein folding, equilibrium thermodynamics, and sequence design. We introduce a novel geometric representation of protein contact interactions using the edge simplices from the alpha shape of the protein structure. This representation can eliminate implausible neighbors that are not in physical contact, and can avoid spurious contact between two residues when a third residue is between them. We developed statistical alpha contact potential using an odds‐ratio model. A studentized bootstrap method was then introduced to assess the 95% confidence intervals for each of the 210 propensity parameters. We found, with confidence, that there is significant long‐range propensity (>30 residues apart) for hydrophobic interactions. We tested alpha contact potential for native structure discrimination using several sets of decoy structures, and found that it often performs comparably with atom‐based potentials requiring many more parameters. We also show that accurate geometric representation is important, and that alpha contact potential has better performance than potential defined by cutoff distance between geometric centers of side chains. Hierarchical clustering of alpha contact potentials reveals natural grouping of residues. To explore the relationship between shape and physicochemical representations, we tested the minimum alphabet size necessary for native structure discrimination. We found that there is no significant difference in performance of discrimination when alphabet size varies from 7 to 20, if geometry is represented accurately by alpha simplicial edges. This result suggests that the geometry of packing plays an important role, but the specific residue types are often interchangeable. Proteins 2003;53:000–000. © 2003 Wiley‐Liss, Inc.
Combination of scoring functions improves discrimination in protein–protein docking
Authors: Murphy John , Gatchell David W. , Prasad Jahnavi C. , Vajda Sandor
Published: November 2003

Two structure‐based potentials are used for both filtering (i.e., selecting a subset of conformations generated by rigid‐body docking), and rescoring and ranking the selected conformations. ACP (atomic contact potential) is an atom‐level extension of the Miyazawa–Jernigan potential parameterized on protein structures, whereas RPScore (residue pair potential score) is a residue‐level potential, based on interactions in protein–protein complexes. These potentials are combined with other energy terms and applied to 13 sets of protein decoys, as well as to the results of docking 10 pairs of unbound proteins. For both potentials, the ability to discriminate between near‐native and non‐native docked structures is substantially improved by refining the structures and by adding a van der Waals energy term. It is observed that ACP and RPScore complement each other in a number of ways (e.g., although RPScore yields more hits than ACP, mainly as a result of its better performance for charged complexes, ACP usually ranks the near‐native complexes better). As a general solution to the protein‐docking problem, we have found that the best discrimination strategies combine either an RPScore filter with an ACP‐based scoring function, or an ACP‐based filter with an RPScore‐based scoring function. Thus, ACP and RPScore capture complementary structural information, and combining them in a multistage postprocessing protocol provides substantially better discrimination than the use of the same potential for both filtering and ranking the docked conformations. Proteins 2003. © 2003 Wiley‐Liss, Inc.
Construction of molecular assemblies via docking: Modeling of tetramers with D2 symmetry
Authors: Berchanski Alexander , Eisenstein Miriam
Published: November 2003

Comparative modeling methods are commonly used to construct models of homologous proteins or oligomers. However, comparative modeling may be inapplicable when the number of subunits in a modeled oligomer is different than in the modeling template. Thus, a dimer cannot be a template for a tetramer because a new monomer‐monomer interface must be predicted. We present in this study a new prediction approach, which combines protein‐protein docking with either of two tetramer‐forming algorithms designed to predict the structures of tetramers with D2 symmetry. Both algorithms impose symmetry constraints. However, one of them requires identification of two of the C2 dimers within the tetramer in the docking step, whereas the other, less demanding algorithm, requires identification of only one such dimer. Starting from the structure of one subunit, the procedures successfully reconstructed 16 known D2 tetramers, which crystallize with either a monomer, a dimer or a tetramer in the asymmetric unit. In some cases we obtained clusters of native‐like tetramers that differ in the relative rotation of the two identical dimers within the tetramer. The predicted structural pliability for concanavalin‐A, phosphofructokinase, and fructose‐1,6‐bisphosphatase agrees semiquantitatively with the observed differences between the several experimental structures of these tetramers. Hence, our procedure identifies a structural soft‐mode that allows regulation via relative rigid‐body movements of the dimers within these tetramers. The algorithm also predicted three nearly correct tetramers from model structures of single subunits, which were constructed by comparative modeling from subunits of homologous tetrameric, dimeric, or hexameric systems. Proteins 2003. © 2003 Wiley‐Liss, Inc.
Analysis of protein structures reveals regions of rare backbone conformation at functional sites
Authors: Petock John M. , Torshin Ivan Y. , Weber Irene T. , Harrison Robert W.
Published: November 2003

Regions of rare conformation were located in 300 protein crystal structures representing seven major protein folds. A distance matrix algorithm was used to search rapidly for 9‐residue fragments of rare backbone conformation using a comparison to a relational database of encoded fragments derived from the database of nonredundant structures. Rare fragments were found in 61% of the analyzed protein structures. Detailed analysis was performed for 78 proteins of different folds. The rare fragments were located near functional sites in 72% of the protein structures. The rare fragments often formed parts of ligand‐binding sites (59%), protein‐protein interfaces (8%), and domain‐domain contacts (5%). Of the remaining structures, 5% had a high average B‐factor or high local B‐factors. Statistical analysis suggests that the association between ligands and rare regions does not occur by chance alone. The present study is likely to underestimate the number of functional sites, because not all analyzed protein structures contained a ligand. The results suggest that rapid searches for regions with rare local backbone conformations can assist in prediction of functional sites in novel proteins. Proteins 2003. © 2003 Wiley‐Liss, Inc.
Hydrophobic moments of tertiary protein structures
Authors: Silverman B. David
Published: November 2003

The helical hydrophobic moment is a measure of the amphiphilicity of a segment of protein secondary structure. Such measure yields information of potential relevance for issues relating to cell surface binding and secondary structure function. The present article describes a global analog of the helical hydrophobic moment. The global moment provides a concise measure of the degree and direction of the amphiphilicity or hydrophobic imbalance across the entire protein tertiary structure. Therefore, this measure is a succinct representation of the spatial organization of residue hydrophobicity for each protein. With this measure, a simple comparison of the hydrophobic imbalance or segregation of different protein structures can be made. For example, two structures having the same fold and close in root‐mean‐square deviation may exhibit very different overall hydrophobic organization. Such difference is classified simply by the global moment. Furthermore, the direction of the global moment may point to regions of functional interest. Certain formal issues in the development of such moment are described, and a number of applications to particular protein structures are discussed. Proteins 2003. © 2003 Wiley‐Liss, Inc.
Crystal structures of cephaibols
Authors: Bunkóczi Gábor , Schiell Matthias , Vértesy László , Sheldrick George M.
Published: November 2003

The crystal structures of the peptaibol antibiotics cephaibol A, cephaibol B and cephaibol C have been determined at ca. 0.9 Å resolution. All three adopt a helical conformation with a sharp bend (of about 55° ) at the central hydroxyproline. All isovalines were found to possess the D configuration, superposition of all four models (there are two independent molecules in the cephaibol B structure) shows that the N‐terminal helix is rigid and the C‐terminus is flexible. There are differences in the hydrogen bonding patterns for the three structures that crystallize in different space groups despite relatively similar unit cell dimensions, but only in the case of cephaibol C does the packing emulate the formation of a membrane channel believed to be important for their biological function. Copyright © 2003 European Peptide Society and John Wiley & Sons, Ltd.
Trichogin: a paradigm for lipopeptaibols
Authors: Peggion Cristina , Formaggio Fernando , Crisma Marco , Epand Raquel F. , Epand Richard M. , Toniolo Claudio
Published: November 2003

Lipopeptaibols are members of a novel family of naturally occurring, short peptides with antimicrobial activity, characterized by a lipophilic acyl chain at the N‐terminus, a high content of turn/helix inducing α‐aminoisobutyric acid and a 1,2‐amino alcohol at the C‐terminus. Using solution methods, the prototypical lipopeptaibol trichogin GA IV and a large series of appropriately designed analogues were synthesized, which allow: (i) determination of the minimal lipid chain and peptide main‐chain lengths for the onset of membrane activity, and (ii) exploitation of a number of physico‐chemical techniques aimed at assessing the trichogin preferred conformation under a variety of conditions and at investigating its mechanism of interaction with the phospholipid membranes. Copyright © 2003 European Peptide Society and John Wiley & Sons, Ltd.
Adiabatic potential analysis for some carbon‐containing molecules
Authors: Abarenkov I. V. , Smelkov K. V.
Published: November 2003

In the current article, the procedure to separate a molecule into the ion radicals and bonds, proposed earlier by one of authors within the Hartree–Fock (HF) approach, is used. In this procedure the ion‐radical–occupied orbitals are defined as solutions of HF equations for ion radical in the basis of occupied molecular orbital (MO) of the whole molecule. The bond orbitals are constructed to complete the functional space span by the occupied MO of ion radicals to the functional space span by occupied MO of the whole molecule. In this approach it is easy to calculate the electron density of all ion radicals and bonds, which add up to the total electron density of the whole molecule, the densities overlap being taken into account. Hence, the adiabatic potential of the molecule is expressed as a sum of ion radicals and bonds self‐energies and of various intramolecular interaction energies. The results of ab initio adiabatic potential calculations and its decomposition for several carbon‐containing molecules, such as CH4, CH3Li, CH3F, and C2H6, which can be considered as two ion radicals connected by a single chemical bond, are presented here. The dependence of adiabatic potential components on the bond length is analyzed, and simple approximate equations for them are generated. In addition, the electronic structure of ion‐radical CH, common for all molecules calculated here, is considered, and its dependence on the molecular environment is analyzed. © 2003 Wiley Periodicals, Inc. Int J Quantum Chem, 2004
Modifications to the electronic structure of carbon nanotubes with symmetric and random vacancies
Authors: Belavin V. V. , Bulusheva L. G. , Okotrub A. V.
Published: November 2003

The influence of different types of atomic vacancies on the electronic structure of carbon nanotubes (20, 0) and (12, 12) was investigated using an empirical tight‐binding method. The models with vacancies randomly and symmetrically arranged in an extended unit cell were constructed. The symmetrical distribution of defects was obtained by rotating a pore, obtained by removing a hexagonal ring from a graphitic shell around the tube axis. The random defects were generated by a specially developed algorithm, which eliminates a given number of atoms from the unit cell so that the remaining carbon atoms have no more than one dangling bond. The presence of vacancies in carbon nanotube causes an enhancement of density of occupied states that is near the Fermi level and whose localization increases with the number of two‐coordinated atoms at the pore boundaries. It was found that the occurrence of atomic vacancies in the carbon nanotube walls might result in the narrow‐gap semiconductors and ferromagnetic materials. © 2003 Wiley Periodicals, Inc. Int J Quantum Chem, 2004
Evolution of liver transplantation in Europe: Report of the European Liver Transplant Registry
Authors: Adam René , McMaster Paul , O’Grady John G. , Castaing Denis , Klempnauer Jurgen L. , Jamieson Neville , Neuhaus Peter , Lerut Jan , Salizzoni Mauro , Pollard Stephen , Muhlbacher Ferdinand , Rogiers Xavier , Valdecasas Juan Carlos Garcia , Berenguer Joaquin , Jaeck Daniel , Gonzalez Enrique Moreno
Published: November 2003

The European Liver Transplant Registry (ELTR) currently allows for the analysis of 44,286 liver transplantations (LTs) performed on 39,196 patients in a 13-year period. After an exponential increase, the number of LTs is plateauing due to a lack of organs. To cope with this, alternatives to cadaveric LT, such as split LT, domino LT, or living-related LT (LRLT) are being used increasingly. They now account for 11% of all procedures. One of the most important findings in the evolution of LT is the considerable improvement of results along time with, for the mean time, a one-year survival of 83%, all indications confounded. The improvement is particularly significant for cancers. This improvement is mainly represented by hepatocellular carcinoma, with a gain of 17% for 5-year survival rate from 1990 to 2000. Increasingly, older donors are used to augment the donor pool and older recipients are transplanted due to improved results and a better selection of patients. More than two thirds of deaths and three quarters of retransplantations occurred within the first year of transplantation. Retransplantation is associated with much less optimal results than first LT. One of the prominent features of recent years is the development of LRLT. LRLT is now performed by almost half of the European centers. As with split LT or domino LT, LRLT aims to provide more patients to be transplanted. Special attention is paid to reducing the risk for the donor, which is now estimated to be 0.5% mortality and 21% postoperative morbidity.
Cerebral glucose and oxygen metabolism in patients with fulminant hepatic failure
Authors: Strauss Gitte Irene , Møller Kirsten , Larsen Fin Stolze , Kondrup Jens , Knudsen Gitte Moos
Published: November 2003

Hyperammonemia and hyperventilation are consistent findings in patients with fulminant hepatic failure (FHF), which may interfere with cerebral glucose and oxygen metabolism. The aim of the present study is to evaluate whether cerebral oxidative metabolism is preserved early in the course of FHF and whether hyperventilation has an influence on this. We included 16 patients with FHF, 5 patients with cirrhosis of the liver, and 8 healthy subjects. Concomitant blood sampling from an arterial catheter and a catheter in the jugular bulb and measurement of cerebral blood flow by the xenon 133 wash-out technique allowed calculation of cerebral uptake of glucose (CMRgluc) and oxygen (CMRo2). Both CMRgluc and CMRo2 were reduced in patients with FHF compared with those with cirrhosis and healthy subjects, i.e., 11.8 ± 2.7 v 18.3 ± 5.5 and 28.5 ± 6.6 μmol/100 g/min (P < .05) and 86 ± 18 v 164 ± 42 and 174 ± 27 μmol/100 g/min (P < .05). Arteriovenous difference in oxygen and oxygen-glucose index were normal in patients with FHF. Institution of mechanical hyperventilation did not affect glucose and oxygen uptake and hyperventilation did not affect lactate-pyruvate ratio or lactate-oxygen index. In conclusion, we found that cerebral glucose and oxygen consumption are proportionally decreased in patients with FHF investigated before clinical signs of cerebral edema. Our data suggest that cerebral oxidative metabolism is retained at this stage of the disease without being compromised by hyperventilation.
Von Willebrand factor-cleaving protease activity in thrombotic microangiopathy after living donor liver transplantation: A case report
Authors: Nakazawa Yuichi , Hashikura Yasuhiko , Urata Koichi , Ikegami Toshihiko , Terada Masaru , Yagi Hideo , Ishizashi Hiromichi , Matsumoto Masanori , Fujimura Yoshihiro , Miyagawa Shinichi
Published: November 2003

Defective plasma activity of Von Willebrand factor (VWF)-cleaving protease (CP) and/or the inhibitors against this protease has been shown to have a pathological role in several forms of thrombotic microangiopathy (TMA). This report describes a patient for whom a diagnosis of TMA was made immediately after living donor liver transplantation. In this patient, activity of VWF-CP and its inhibitor were analyzed serially. At the onset of the disease, VWF-CP activity was quantified as 17%. Inhibitor against this protease was positive, with a titer of 0.6 Bethesda U/mL, and its inhibitory activity was quantified as 3.8 Bethesda U/mg immunoglobulin G. Laboratory parameters and clinical features were significantly improved after induction of plasma exchange (PE) with fresh frozen plasma and concurrent cessation of tacrolimus therapy. The inhibitors disappeared after one session of PE. However, VWF-CP activity after a transient increase and again decreased to subnormal levels after completion of PE. Nevertheless, this did not result in disease recurrence. In view of sustained VWF-CP activity at disease onset and the absence of definite correlations between levels of this protease and clinical features, abnormality of this enzyme system had no essential role in the pathogenesis of TMA in this case. Clinical findings suggest that TMA was tacrolimus-induced.
Intraoperative red blood cell transfusion in liver transplantation: Influence on patient outcome, prediction of requirements, and measures to reduce them
Authors: Ramos Emilio , Dalmau Antonia , Sabate Antonio , Lama Carmen , Llado Laura , Figueras Juan , Jaurrieta Eduardo
Published: November 2003

Objectives of this study are to quantify the need for blood transfusion during liver transplantation (LT) and confirm the importance of intraoperative blood transfusion as an independent prognostic factor for postoperative outcome. Furthermore, we try to detect useful variables for the preoperative identification of patients likely to require transfusion of packed red blood cell units (PRCUs) and identify measures to reduce transfusion needs. Data were collected prospectively between September 1998 and November 2000. One hundred twenty-two LTs were included in the study. Forty-two patients (34%) did not require transfusion of PRCUs. In multivariate analysis, transfusion of more than three PRCUs was found to be the only significant variable associated with prolonged hospital stay. In addition, excluding perioperative deaths, PRCU transfusion, using a cutoff value of six units, was the only variable to reach statistical significance (P = .008; risk ratio, 4.93; 95% confidence interval, 15 to 15.9) to predict survival in a multivariate analysis that also included Child’s class and United Network for Organ Sharing (UNOS) classification. Moreover, only preoperative hemoglobin (Hb) level was found to significantly predict the need for transfusion of one or more PCRUs. Finally, only UNOS classification and placement of an intraoperative portacaval shunt were found to be statistically significant to predict the need to transfuse more than six PRCUs. We found the requirement of even a moderate number of blood transfusions is associated with longer hospital stay, and transfusion of more than six PRCUs is associated with diminished survival. Preoperative normalization of Hb levels and placement of an intraoperative portacaval shunt can diminish the number of blood transfusions during LT.
AFRICA AND THE AFRICAN DIASPORA: NEW DIRECTIONS OF STUDY Rethinking the African Diaspora: The Making of a Black Atlantic World in the Bight of Benin and Brazil. Edited by KRISTIN MANN and EDNA G. BAY. London: Frank Cass, 2001. Pp. 160. $64.50 (ISBN 0-7146-5129-X); $26.50, paperback (ISBN 0-7146-8158-X). The African Diaspora: African Origins and New World Identities. Edited by ISIDORE OKPEWHO, CAROLE BOYCE DAVIES and ALI A. MAZRUI. Bloomington: Indiana University Press, 2001. Pp. xxviii+566. $59.95 (ISBN 0-253-33425-X); $22.95, paperback (ISBN 0-253-21494-7).
Authors: MANNING PATRICK
Published: November 2003

RECENT studies addressing the ‘African diaspora’ have sought to provide global context for the experience of people of African descent. The two books under review – each a major contribution to studies of the African diaspora – provide an opportunity to take stock of the emerging genre of historical and cultural studies of which they are a part. The perspective of the African diaspora has the advantage of locating movements and connections of Africans around the world, and in so doing has the power to inform and sometimes surprise. From such a perspective, for instance, Alberto da Costa e Silva notes that during the 1860s a French bookseller in Rio de Janeiro sold a hundred copies of the Qur'an each year, mainly as clandestine sales to slaves and ex-slaves. This evidence confirms the continuing significance of Islam in Brazil, and raises the possibility that the religious practice was sustained through continuing contacts with West Africa. Over a century later, novelist Alice Walker launched a headline-grabbing campaign against female circumcision in Africa. As Joseph McLaren shows, Walker's campaign reflected not the shock of an African-American's initial encounter with the complex social practices of the African continent, but her considered judgment after decades of visits to East Africa. These examples suggest the range and interest of linkages across wide distances that may be elicited through studies of the African diaspora. They reflect the contributions of an academic enterprise that is apparently settling into a permanent place on the scholarly and curricular scene.
Crustal structure of the ocean‐continent transition at Flemish Cap: Seismic refraction results
Authors: Funck Thomas , Hopper John R. , Larsen Hans Christian , Louden Keith E. , Tucholke Brian E. , Holbrook W. Steven
Published: November 2003

We conducted a seismic refraction experiment across Flemish Cap and into the deep basin east of Newfoundland, Canada, and developed a velocity model for the crust and mantle from forward and inverse modeling of data from 25 ocean bottom seismometers and dense air gun shots. The continental crust at Flemish Cap is 30 km thick and is divided into three layers with P wave velocities of 6.0–6.7 km/s. Across the southeast Flemish Cap margin, the continental crust thins over a 90‐km‐wide zone to only 1.2 km. The ocean‐continent boundary is near the base of Flemish Cap and is marked by a fault between thinned continental crust and 3‐km‐thick crust with velocities of 4.7–7.0 km/s interpreted as crust from magma‐starved oceanic accretion. This thin crust continues seaward for 55 km and thins locally to ∼1.5 km. Below a sediment cover (1.9–3.1 km/s), oceanic layer 2 (4.7–4.9 km/s) is ∼1.5 km thick, while layer 3 (6.9 km/s) seems to disappear in the thinnest segment of the oceanic crust. At the seawardmost end of the line the crust thickens to ∼6 km. Mantle with velocities of 7.6–8.0 km/s underlies both the thin continental and thin oceanic crust in an 80‐km‐wide zone. A gradual downward increase to normal mantle velocities is interpreted to reflect decreasing degree of serpentinization with depth. Normal mantle velocities of 8.0 km/s are observed ∼6 km below basement. There are major differences compared to the conjugate Galicia Bank margin, which has a wide zone of extended continental crust, more faulting, and prominent detachment faults. Crust formed by seafloor spreading appears symmetric, however, with 30‐km‐wide zones of oceanic crust accreted on both margins beginning about 4.5 m.y. before formation of magnetic anomaly M0 (∼118 Ma).
Direction finding of AKR sources with three orthogonal antennas
Authors: Panchenko M.
Published: November 2003

A method of the direction finding of auroral kilometric radiation (AKR) sources from board of a spinning spacecraft is presented. It uses relative power densities of radiation received on three orthogonal antennas with the assumption that the AKR is circularly polarized. The method is checked for a case of AKR source location provided by Polrad radio‐spectro‐polarimeter on board the Interball‐2 satellite. Projection of the source location along magnetic field lines coincides with the active auroral arc observed by the Polar UV imager.
Spatio-temporal propagation of Ca2+ signals by cyclic ADP-ribose in 3T3 cells stimulated via purinergic P2Y receptors
Authors: Bruzzone Santina , Kunerth Svenja , Zocchi Elena , De Flora Antonio , Guse Andreas H.
Published: November 2003

The role of cyclic ADP-ribose in the amplification of subcellular and global Ca2+ signaling upon stimulation of P2Y purinergic receptors was studied in 3T3 fibroblasts. Either (1) 3T3 fibroblasts (CD38− cells), (2) 3T3 fibroblasts preloaded by incubation with extracellular cyclic ADP-ribose (cADPR), (3) 3T3 fibroblasts microinjected with ryanodine, or (4) 3T3 fibroblasts transfected to express the ADP-ribosyl cyclase CD38 (CD38+ cells) were used. Both preincubation with cADPR and CD38 expression resulted in comparable intracellular amounts of cyclic ADP-ribose (42.3 ± 5.2 and 50.5 ± 8.0 pmol/mg protein). P2Y receptor stimulation of CD38− cells yielded a small increase of intracellular Ca2+ concentration and a much higher Ca2+ signal in CD38-transfected cells, in cADPR-preloaded cells, or in cells microinjected with ryanodine. Confocal Ca2+ imaging revealed that stimulation of ryanodine receptors by cADPR or ryanodine amplified localized pacemaker Ca2+ signals with properties resembling Ca2+ quarks and triggered the propagation of such localized signals from the plasma membrane toward the internal environment, thereby initiating a global Ca2+ wave.
Autoregulation of E-cadherin expression by cadherin–cadherin interactions
Authors: Conacci-Sorrell Maralice , Simcha Inbal , Ben-Yedidia Tamar , Blechman Janna , Savagner Pierre , Ben-Ze'ev Avri
Published: November 2003

Transcriptional repression of E-cadherin, characteristic of epithelial to mesenchymal transition, is often found also during tumor cell invasion. At metastases, migratory fibroblasts sometimes revert to an epithelial phenotype, by a process involving regulation of the E-cadherin–β-catenin complex. We investigated the molecular basis of this regulation, using human colon cancer cells with aberrantly activated β-catenin signaling. Sparse cultures mimicked invasive tumor cells, displaying low levels of E-cadherin due to transcriptional repression of E-cadherin by Slug. Slug was induced by β-catenin signaling and, independently, by ERK. Dense cultures resembled a differentiated epithelium with high levels of E-cadherin and β-catenin in adherens junctions. In such cells, β-catenin signaling, ErbB-1/2 levels, and ERK activation were reduced and Slug was undetectable. Disruption of E-cadherin–mediated contacts resulted in nuclear localization and signaling by β-catenin, induction of Slug and inhibition of E-cadherin transcription, without changes in ErbB-1/2 and ERK activation. This autoregulation of E-cadherin by cell–cell adhesion involving Slug, β-catenin and ERK could be important in tumorigenesis.
The Endoplasmic Reticulum Membrane Is Permeable to Small Molecules
Authors: Le Gall Sylvie , Neuhof Andrea , Rapoport Tom
Published: November 2003

The lumen of the endoplasmic reticulum (ER) differs from the cytosol in its content of ions and other small molecules, but it is unclear whether the ER membrane is as impermeable as other membranes in the cell. Here, we have tested the permeability of the ER membrane to small, nonphysiological molecules. We report that isolated ER vesicles allow different chemical modification reagents to pass from the outside into the lumen with little hindrance. In permeabilized cells, the ER membrane allows the passage of a small, charged modification reagent that is unable to cross the plasma membrane or the lysosomal and trans-Golgi membranes. A larger polar reagent of ∼5 kDa is unable to pass through the ER membrane. Permeation of the small molecules is passive because it occurs at low temperature in the absence of energy. These data indicate that the ER membrane is significantly more leaky than other cellular membranes, a property that may be required for protein folding and other functions of the ER.
Involvement of the AP-1 Adaptor Complex in Early Steps of Phagocytosis and Macropinocytosis
Authors: Lefkir Yaya , Malbouyres Marilyne , Gotthardt Daniel , Ozinsky Adrian , Cornillon Sophie , Bruckert Franz , Aderem Alan A. , Soldati Thierry , Cosson Pierre , Letourneur François
Published: November 2003

The best described function of the adaptor complex-1 (AP-1) is to participate in the budding of clathrin-coated vesicles from the trans-Golgi network and endosomes. Here, we show that AP-1 is also localized to phagocytic cups in murine macrophages as well as in Dictyostelium amoebae. AP-1 is recruited to phagosomal membranes at this early stage of phagosome formation and rapidly dissociates from maturing phagosomes. To establish the role of AP-1 in phagocytosis, we made used of Dictyostelium mutant cells (apm1-cells) disrupted for AP-1 medium chain. In this mutant, phagocytosis drops by 60%, indicating that AP-1 is necessary for efficient phagocytosis. Furthermore, phagocytosis in apm1-cells is more affected for large rather than small particles, and cells exhibiting incomplete engulfment are then often observed. This suggests that AP-1 could participate in the extension of the phagocytic cup. Interestingly, macropinocytosis, a process dedicated to fluid-phase endocytosis and related to phagocytosis, is also impaired in apm1-cells. In summary, our data suggest a new role of AP-1 at an early stage of phagosome and macropinosome formation.
The Functions of Klarsicht and Nuclear Lamin in Developmentally Regulated Nuclear Migrations of Photoreceptor Cells in theDrosophilaEye
Authors: Patterson Kristin , Molofsky Ari B. , Robinson Christina , Acosta Shelley , Cater Courtney , Fischer Janice A.
Published: November 2003

Photoreceptor nuclei in the Drosophila eye undergo developmentally regulated migrations. Nuclear migration is known to require the perinuclear protein Klarsicht, but the function of Klarsicht has been obscure. Here, we show that Klarsicht is required for connecting the microtubule organizing center (MTOC) to the nucleus. In addition, in a genetic screen for klarsicht-interacting genes, we identified Lam Dm0, which encodes nuclear lamin. We find that, like Klarsicht, lamin is required for photoreceptor nuclear migration and for nuclear attachment to the MTOC. Moreover, perinuclear localization of Klarsicht requires lamin. We propose that nuclear migration requires linkage of the MTOC to the nucleus through an interaction between microtubules, Klarsicht, and lamin. The Klarsicht/lamin interaction provides a framework for understanding the mechanistic basis of human laminopathies.
A General Role for Rab27a in Secretory Cells
Authors: Tolmachova Tanya , Anders Ross , Stinchcombe Jane , Bossi Giovanna , Griffiths Gillian M. , Huxley Clare , Seabra Miguel C.
Published: November 2003

Vesicular transport is a complex multistep process regulated by distinct Rab GTPases. Here, we show for the first time that an EGFP-Rab fusion protein is fully functional in a mammalian organism. We constructed a PAC-based transgenic mouse, which expresses EGFP-Rab27a under the control of endogenous Rab27a promoter. The EGFP-Rab27a transgene was fully functional and rescued the two major defects of the ashen Rab27a knockout mouse. We achieved cell-specific expression of EGFP-Rab27a, which faithfully followed the pattern of expression of endogenous Rab27a. We found that Rab27a is expressed in an exceptionally broad range of specialized secretory cells, including exocrine (particularly in mucin- and zymogen-secreting cells), endocrine, ovarian, and hematopoietic cells, most of which undergo regulated exocytosis. We suggest that Rab27a acts in concert with Rab3 proteins in most regulated secretory events. The present strategy represents one way in which the complex pattern of expression and function of proteins involved in specialized cell types may be unraveled.