bluuebunny/crossref_metadata_2025 huggingface dataset:
High density gradients in the (3×3)R30°-CO layer on Ru(0001)
Authors: Jakob P.
Published: April 2004

The coverage regime just beyond 0.33 ML, representative of a perfectly ordered (∛×∛)R30°-CO layer on Ru(0001), has been investigated using infrared-absorption spectroscopy. Different isotopic mixtures of CO have been employed to derive a profound understanding of structural properties of such layers. It is found that extra CO molecules incorporated into the (∛×∛)R30°-CO layer affect their nearest neighbor molecules only, and the associated density gradient extends over no more than a few angstroms. Contrary to existing belief, the model system CO on Ru(0001) does not represent a case of an unusually shallow adsorption potential corrugation. Rather, CO experiences an exceptionally strong site preference when adsorbed on Ru(0001). Annealing causes the local distortion of the overlattice to propagate laterally, most probably in a density wave-like manner. Incipient motion on the atomic scale thereby has been detected by means of isotopic labeling of inequivalent molecules within the high density areas. All major conclusions are based on observations of (isotopically labeled) minority CO species which feature negligible dynamical lateral coupling. The majority CO species, on the other hand, provide laterally averaged, unspecific information on the status of the layer.
Affinity distribution functions in multicomponent heterogeneous adsorption. Analytical inversion of isotherms to obtain affinity spectra
Authors: Garcés Josep Lluı́s , Mas Francesc , Puy Jaume
Published: April 2004

An analytical approach for the interpretation of multicomponent heterogeneous adsorption or complexation isotherms in terms of multidimensional affinity spectra is presented. Fourier transform, applied to analyze the corresponding integral equation, leads to an inversion formula which allows the computation of the multicomponent affinity spectrum underlying a given competitive isotherm. Although a different mathematical methodology is used, this procedure can be seen as the extension to multicomponent systems of the classical Sips’s work devoted to monocomponent systems. Furthermore, a methodology which yields analytical expressions for the main statistical properties (mean free energies of binding and covariance matrix) of multidimensional affinity spectra is reported. Thus, the level of binding correlation between the different components can be quantified. It has to be highlighted that the reported methodology does not require the knowledge of the affinity spectrum to calculate the means, variances, and covariance of the binding energies of the different components. Nonideal competitive consistent adsorption isotherm, widely used in metal/proton competitive complexation to environmental macromolecules, and Frumkin competitive isotherms are selected to illustrate the application of the reported results. Explicit analytical expressions for the affinity spectrum as well as for the matrix correlation are obtained for the NICCA case.
Cubatic liquid-crystalline behavior in a system of hard cuboids
Authors: John Bettina S. , Stroock Abraham , Escobedo Fernando A.
Published: April 2004

The lyotropic phase behavior of cuboidal particles was investigated via Monte Carlo simulations. Hard cubes were approximated by suitably shaped clusters of hard spheres. Changes in concentration and structure of the system were monitored as a function of osmotic pressure P* (imposed in an isobaric ensemble). As expected, an isotropic phase prevailed at low concentrations (low P*) and a crystalline phase formed at high concentrations (high P*). A third distinct phase was also observed for an intermediate range of concentrations (approximately marked by breaks in the P* versus concentration curve). The structure of this mesophase was characterized both visually and analytically by calculating radial distribution functions and order parameters. It was found that such a mesophase exhibits orientational ordering along three axes (cubatic order) but significant translational disorder, thus having a structure clearly distinct from both isotropic and crystalline phases.
Turning on ribonucleotide reductase by light-initiated amino acid radical generation
Authors: Chang Michelle C. Y. , Yee Cyril S. , Stubbe JoAnne , Nocera Daniel G.
Published: April 2004

Ribonucleotide reductases (RNRs) catalyze the conversion of nucleotides to deoxynucleotides in all organisms, providing the monomeric precursors required for DNA replication and repair. The class I RNRs are composed of two subunits; the R1 subunit contains the active site for nucleotide reduction and allosteric effector binding sites, whereas the R2 subunit houses the essential diirontyrosyl (Y·) radical cofactor. A major unresolved issue is the mechanism by which the tyrosyl radical on R2 (Y122,
Escherichia coli
numbering) reversibly generates the transient thiyl radical (S·) on R1 that initiates nucleotide reduction. This intersubunit radical initiation is postulated to occur through a defined pathway involving conserved aromatic amino acids (R2: Y122, W48, Y356; R1: Y731, Y730) over a long distance of 35 Å. A 20-mer peptide identical to the C-terminal tail of R2 (356–375) and containing Y356 is a competitive inhibitor with respect to R2, and it effectively blocks nucleotide reduction. We now report that a 21-mer peptide, in which a tryptophan has been incorporated at the N terminus of the 20th mer, can replace the R2 subunit and initiate nucleotide reduction by photoinitiated radical generation. The deoxynucleotide generated depends on the presence of allosteric effector and is pathway-dependent. Replacement of Y731 of R2 with phenylalanine prevents deoxynucleotide formation. These results provide direct evidence for the chemical competence of aromatic amino acid radicals and the importance of Y356 in R2 in the radical initiation process of the class I RNRs.
Survey of the market diseases and aflatoxin contamination of tomato (Lycopersicon esculentum MILL) fruits in Sokoto, northwestern Nigeria
Authors: Muhammad S. , Shehu K. , Amusa N.A.
Published: April 2004

A survey of the market diseases and aflatoxin contamination of tomato fruits was conducted in Sokoto in northwestern Nigeria in 2001 and 2002, respectively. Rotten tomato fruits sold at five different markets in Sokoto town, located at Central market, Kasuwar daji, Mabera, Minanata and Arkilla were heavily contaminated with moulds. Eight different fungi were found associated with the rotten tomato fruits sold in the five different markets. The associated fungi were Aspergillus niger, Aspergillus ochraceous, Aspergillus flavus, Aspergillus fumigatus, Penicillium citrinum and Helminthosporim fulvum, Curvularia lunata and Sclerotium rolfsii. A. flavus and A. niger have the highest rate of occurrence among the isolated fungi, while S. rolfsii was the least encountered. Pathogenicity tests revealed that of all the isolated fungi, A. ochraceous, A. flavus, Sclerotium rolfsii and P. citrinum were highly pathogenic with the first three leading to rapid disintegration of treated fruits in 3‐5 days. A. niger was moderately pathogenic, while H. fulvum was least pathogenic on tomato fruits. Aflatoxins were detected from the sampled diseased‐marketed tomato fruits and also from the marketed rotten tomato fruits after autoclaving for 15 minutes at 121°C.
The reality of “new” careers for men and for women
Authors: Ackah Carol , Heaton Norma
Published: April 2004

The research for this paper focused on the career paths and career progression of men and women in management occupations. The study set out to explore the extent to which the traditional career has been replaced by the so‐called “boundaryless” career. In particular it sought to establish whether such new career patterns have been more readily espoused by women than men. The participants in the research were postgraduate, post‐experience students on management courses within the Faculty of Business and Management at the University of Ulster. The findings suggest that both men and women are making more frequent job moves than in the past and that the vast majority of both men and women are assuming responsibility for their career development. Finds a growing similarity in male and female careers but very different perceptions regarding factors influencing career paths and career progression. This has implications for providers of management development and education as it appears that much could be done to convince women they can have control over their own careers.
Training and expectations on job mobility in the call centres sector
Authors: Sieben Inge , de Grip Andries
Published: April 2004

Analyses whether the participation of workers in general, sector‐specific, and firm‐specific training affects their expectations on job mobility within or outside the call centres sector. Distinguishes between the perceived difficulty to find an equally attractive job and the inclination to quit for another job. Employing data on 525 call centre agents working in eight call centres in The Netherlands, finds that training does not significantly affect the perceived labour market perspectives of call centre agents, nor influence expected job mobility inside or outside the sector. The inclination to quit the present job within two years is the same for agents with and without training. There is one exception, however. Agents who followed firm‐specific training significantly less often considered quitting for a job in another call centre. All this is good news for firms offering training. Another finding, however, might be more problematic. The work experience of agents positively affects their labour market perspectives inside the sector. In addition, agents with more experience are more inclined to quit for a job in another call centre. This means that firms need to keep their employees satisfied.
New graduate engagement with “professional development”
Authors: Holden Rick , Harte Victoria
Published: April 2004

If a key purpose of higher education is the development of students into ”critical lifelong learners” then first destination employment for graduates choosing professionally‐oriented careers provides the initial ”testing ground” for its application/practice through ongoing “professional development“. It is principally the workplace that provides the context in which the graduate must now learn and develop. At the heart of the issue is ”professional learning” yet the processes and the complexities of this in respect of new graduates remain unresearched and problematic. The paper reports on the development and design of an exploratory study addressing new graduate engagement with professional development in order to find more adequate ways to conceptualise this process and sharpen the research agenda. It seeks to generate discussion and feedback to assist the further progress of the research project.
Strategic alliances: incorporating the impact of e‐business technological innovations
Authors: Tian Xie Frank , Johnston Wesley J.
Published: April 2004

An extensive, integrated review of literature precedes a new typology of alliances based on participating firms’ relative position in the supply chain (scale or link) and the nature of their cooperation (equity or non‐equity). This typology helps to distinguish among a bewildering array of alliances and to explicate alliance motivations and performance on impact of e‐business technological innovations. Theoretical and managerial implications follow.
Wind‐mediated spread of Rice yellow mottle virus (RYMV) in irrigated rice crops
Authors: Sarra S. , Oevering P. , Guindo S. , Peters D.
Published: April 2004

A study was carried out to demonstrate that Rice yellow mottle virus (RYMV), a virus known to be transmitted by beetles, can spread between rice plants by direct leaf contact caused by wind. Almost all healthy plants surrounding an infected plant became infected when exposed to a fan blowing for 15 min at a distance of 50 cm. Spread of RYMV by plant contact, mediated by wind, was also demonstrated in field experiments, the extent of spread depending on plant density. Infection was almost 10 times higher in plots with a density of 33 plants m−2 than in plots with 16 plants m−2. Less spread was observed in plots protected by 1·5 m high windscreens. It is suggested that wind‐mediated spread of RYMV may result from abrasive contact between leaves of plants.
Characterization of Armillaria heimii from Africa
Authors: Pérez‐Sierra A. , Guillaumin J.‐J. , Spooner B. M. , Bridge P. D.
Published: April 2004

Armillaria heimii is one of the most widespread Armillaria species recorded in Africa. The species was originally described as Clitocybe (Armillariella) elegans Heim, and was renamed as Armillaria heimii Pegler; this name was subsequently made synonymous with A. fuscipes Petch to represent as a single morphological species. Recent molecular work has suggested that isolates previously identified as A. heimii were distinct and may represent A. fuscipes or another Armillaria species. A collection of isolates that had been identified as A. heimii from different African countries were included in an integrated study that included amplified restriction‐length polymorphism (AFLP) fingerprinting, polymerase chain reaction‐restriction fragment‐length polymorphism (PCR‐RFLP), sequencing, induction of basidiomata in vitro and somatic compatibility, in order to determine their identity. Although the isolates could be assigned to one of two molecular groups, the morphology and somatic compatibility characters suggested that the two groups represent different forms of a single species that closely matches the original description of A. heimii.
A controlled environment test for resistance to Soil‐borne cereal mosaic virus (SBCMV) and its use to determine the mode of inheritance of resistance in wheat cv. Cadenza and for screening Triticum monococcum genotypes for sources of SBCMV resistance
Authors: Kanyuka K. , Lovell D. J. , Mitrofanova O. P. , Hammond‐Kosack K. , Adams M. J.
Published: April 2004

Several wheat genotypes, including eight with known field responses, were evaluated for their reaction to Soil‐borne cereal mosaic virus (SBCMV, genus Furovirus) by growing in naturally infested soil under controlled environment conditions. Virus antigen titres in the foliage 8–9 weeks after sowing mostly reflected the field responses, showing that growth chamber‐based tests can be used to improve the speed and reliability of germplasm screening. Such tests were used to determine the mode of inheritance of the SBCMV resistance in cv. Cadenza, commonly used in UK wheat‐breeding programmes. One hundred and eleven doubled haploid (DH) lines derived from an F1 of a cross between cvs Cadenza (resistant) and Avalon (susceptible) were evaluated. This DH population segregated for the reaction to SBCMV in a ratio of 1 : 1 (resistant : susceptible). This suggests that the SBCMV resistance is controlled by a single gene locus. As a first step towards identification of new sources of improved SBCMV resistance (e.g. immunity) as well as sources of the resistance to the virus vector, Polymyxa graminis, a set of 26 Triticum monococcum lines of diverse geographical origin was also screened. Most lines were susceptible to SBCMV, but one line of Bulgarian origin was resistant to the virus and possibly partially resistant to the virus vector.
Relatives' Affective Style and the Expression of Subclinical Psychopathology in Patients with Schizophrenia
Authors: Woo Stephanie M. , Goldstein Michael J. , Nuechterlein Keith H.
Published: April 2004

High expressed emotion (EE) is a measure of hostile, critical, and emotionally overinvolved attitudes expressed by a family member about a psychiatrically ill relative during an interview conducted in the patient's absence. EE is a robust predictor of relapse in schizophrenia, yet attempts to identify clinical characteristics that differentiate patients from high versus low EE families have mostly yielded negative findings. However, in a previous study, we found that patients with schizophrenia from high EE families exhibited greater levels of subclinical psychopathology when interacting with family members than did patients from low EE families. Patients from high EE families (N=32) also demonstrated considerable heterogeneity in their expression of subclinical psychopathology. The present study extends our previous work by demonstrating that this heterogeneity in patient subclinical psychopathology was associated with the extent to which family members expressed high EE congruent behaviors—as measured by the affective style (AS) coding system—when directly interacting with their patient‐relative. Elevations in anxious/agitated behaviors and hostile/unusual behaviors were observed among patients whose high EE relatives behaved in a manner consistent with their EE status. These findings support a complex, bidirectional model of the role of high EE attitudes in influencing the course of schizophrenia.
The Plant Virus
Tomato Spotted Wilt Tospovirus
Activates the Immune System of Its Main Insect Vector,
Frankliniella occidentalis
Authors: Medeiros Ricardo B. , Resende Renato de O. , de Ávila Antonio Carlos
Published: April 2004

Tospoviruses have the ability to infect plants and their insect vectors.
Tomato spotted wilt virus
(TSWV), the type species in the
Tospovirus
genus, infects its most important insect vector,
Frankliniella occidentalis
, the western flower thrips (WFT). However, no detrimental effects on the life cycle or cytopathological changes have been reported in the WFT after TSWV infection, and relatively few viral particles can be observed even several days after infection. We hypothesized that TSWV infection triggers an immune response in the WFT. Using subtractive cDNA libraries to probe WFT DNA macroarrays, we found that the WFT's immune system is activated by TSWV infection. The activated genes included (i) those encoding antimicrobial peptides, such as defensin and cecropin; (ii) genes involved in pathogen recognition, such as those encoding lectins; (iii) those encoding receptors that activate the innate immune response, such as Toll-3; and (iv) those encoding members of signal transduction pathways activated by Toll-like receptors, such as JNK kinase. Transcriptional upregulation of these genes after TSWV infection was confirmed by Northern analysis, and the kinetics of the immune response was measured over time. Several of the detected genes were activated at the same time that viral replication was first detected by reverse transcription-PCR. To our knowledge, this is the first report of the activation of an insect vector immune response by a plant virus. The results may lead to a better understanding of insects' immune responses against viruses and may help in the future development of novel control strategies against plant viruses, as well as human and animal viruses transmitted by insect vectors.
An Early Stage of Mason-Pfizer Monkey Virus Budding Is Regulated by the Hydrophobicity of the Gag Matrix Domain Core
Authors: Stansell Elizabeth , Tytler Ewan , Walter Mark R. , Hunter Eric
Published: April 2004

Intracellular capsid transport and release of Mason-Pfizer monkey virus are dependent on myristylation of the Gag matrix domain (MA). A myristylated MA mutant, in which Thr41 and Thr78 are replaced with isoleucines, assembles capsids that are transported to the plasma membrane but are blocked in an early budding step. Since the nuclear magnetic resonance structure of MA showed that these Thr residues point into the hydrophobic core of the protein, it was hypothesized that the T41I/T78I mutant was defective in release of myristic acid from the more hydrophobic core. In order to further investigate whether an increase in the hydrophobicity of the MA core modulates capsid-membrane interactions and viral budding, three tyrosine residues (11, 28, and 67), oriented toward the MA core, were replaced individually or in a pair-wise combination with the more hydrophobic phenylalanine residue(s). As a control, Tyr82, oriented toward the outer surface of MA, was also replaced with phenylalanine. These Tyr-to-Phe substitutions did not alter capsid assembly compared to wild type in a capsid assembly assay. Pulse-chase, immunofluorescence, and electron microscopy studies demonstrated that single substitutions of Tyr11, Tyr28, and Tyr67 recapitulated the T41I/T78I mutant phenotype of decreased budding kinetics and accumulation of capsids at the plasma membrane. MA double mutants with a combination of these Tyr substitutions exhibited a phenotype that was even more defective in budding. In contrast, MA mutants with Tyr82 replaced by Phe resulted in a transport-defective phenotype. These results strongly support the hypothesis that myristic acid is sequestered inside MA prior to capsid-membrane interactions.
θ Defensins Protect Cells from Infection by Herpes Simplex Virus by Inhibiting Viral Adhesion and Entry
Authors: Yasin Bushra , Wang Wei , Pang Mabel , Cheshenko Natalia , Hong Teresa , Waring Alan J. , Herold Betsy C. , Wagar Elizabeth A. , Lehrer Robert I.
Published: April 2004

We tested the ability of 20 synthetic θ defensins to protect cells from infection by type 1 and type 2 herpes simplex viruses (HSV-1 and -2, respectively). The peptides included rhesus θ defensins (RTDs) 1 to 3, originally isolated from rhesus macaque leukocytes, and three peptides (retrocyclins 1 to 3) whose sequences were inferred from human θ-defensin (DEFT) pseudogenes. We also tested 14 retrocyclin analogues, including the retro, enantio, and retroenantio forms of retrocyclin 1. Retrocyclins 1 and 2 and RTD 3 protected cervical epithelial cells from infection by both HSV serotypes, but only retrocyclin 2 did so without causing cytotoxicity or requiring preincubation with the virus. Surface plasmon resonance studies revealed that retrocyclin 2 bound to immobilized HSV-2 glycoprotein B (gB2) with high affinity (Kd, 13.3 nM) and that it did not bind to enzymatically deglycosylated gB2. Temperature shift experiments indicated that retrocyclin 2 and human α defensins human neutrophil peptide 1 (HNP 1) to HNP 3 protected human cells from HSV-2 by different mechanisms. Retrocyclin 2 blocked viral attachment, and its addition during the binding or penetration phases of HSV-2 infection markedly diminished nuclear translocation of VP16 and expression of ICP4. In contrast, HNPs 1 to 3 had little effect on binding but reduced both VP16 transport and ICP4 expression if added during the postbinding (penetration) period. We recently reported that θ defensins are miniature lectins that bind gp120 of human immunodeficiency virus type 1 (HIV-1) with high affinity and inhibit the entry of R5 and X4 isolates of HIV-1. Given its small size (18 residues), minimal cytotoxicity, lack of activity against vaginal lactobacilli, and effectiveness against both HSV-2 and HIV-1, retrocyclin 2 provides an intriguing prototype for future topical microbicide development.
Human Immunodeficiency Virus Type 1 Activates Plasmacytoid Dendritic Cells and Concomitantly Induces the Bystander Maturation of Myeloid Dendritic Cells
Authors: Fonteneau Jean-François , Larsson Marie , Beignon Anne-Sophie , McKenna Kelli , Dasilva Ida , Amara Ali , Liu Yong-Jun , Lifson Jeffrey D. , Littman Dan R. , Bhardwaj Nina
Published: April 2004

In this study, we analyzed the phenotypic and physiological consequences of the interaction of plasmacytoid dendritic cells (pDCs) with human immunodeficiency virus type 1 (HIV-1). pDCs are one cellular target of HIV-1 and respond to the virus by producing alpha/beta interferon (IFN-α/β) and chemokines. The outcome of this interaction, notably on the function of bystander myeloid DC (CD11c+DCs), remains unclear. We therefore evaluated the effects of HIV-1 exposure on these two DC subsets under various conditions. Blood-purified pDCs and CD11c+DCs were exposed in vitro to HIV-1, after which maturation markers, cytokine production, migratory capacity, and CD4 T-cell stimulatory capacity were analyzed. pDCs exposed to different strains of infectious or even chemically inactivated, nonreplicating HIV-1 strongly upregulated the expression of maturation markers, such as CD83 and functional CCR7, analogous to exposure to R-848, a synthetic agonist of toll-like receptor-7 and -8. In addition, HIV-1-activated pDCs produced cytokines (IFN-α and tumor necrosis factor alpha), migrated in response to CCL19 and, in coculture, matured CD11c+DCs, which are not directly activated by HIV. pDCs also acquired the ability to stimulate naïve CD4+T cells, albeit less efficiently than CD11c+DCs. This HIV-1-induced maturation of both DC subsets may explain their disappearance from the blood of patients with high viral loads and may have important consequences on HIV-1 cellular transmission and HIV-1-specific T-cell responses.
Analysis of N-Linked Glycosylation of Hantaan Virus Glycoproteins and the Role of Oligosaccharide Side Chains in Protein Folding and Intracellular Trafficking
Authors: Shi Xiaohong , Elliott Richard M.
Published: April 2004

The membrane glycoproteins Gn and Gc of Hantaan virus (HTNV) (family
Bunyaviridae
) are modified by N-linked glycosylation. The glycoproteins contain six potential sites for the attachment of N-linked oligosaccharides, five sites on Gn and one on Gc. The properties of the N-linked oligosaccharide chains were analyzed by treatment with endoglycosidase H, peptide:
N
-glycosidase F, tunicamycin, and deoxynojirimycin and were confirmed to be completely of the high-mannose type. Ten glycoprotein gene mutants were constructed by site-directed mutagenesis, including six single N glycosylation site mutants and four double-site mutants. We determined that four sites (N134, -235, -347, and -399) on Gn and the only site (N928) on Gc in their ectodomains are utilized, whereas the fifth site on Gn (N609), which faces the cytoplasm, is not glycosylated. The importance of individual N-oligosaccharide chains varied with respect to folding and intracellular transport. The oligosaccharide chain on residue N134 was found to be crucial for protein folding, whereas single mutations at the other glycosylation sites were better tolerated. Mutation at glycosylation sites N235 and N399 together resulted in Gn misfolding. The endoplasmic reticulum chaperones calnexin and calreticulin were found to be involved in HTNV glycoprotein folding. Our data demonstrate that N-linked glycosylation of HTNV glycoproteins plays important and differential roles in protein folding and intracellular trafficking.
CD4-Induced T-20 Binding to Human Immunodeficiency Virus Type 1 gp120 Blocks Interaction with the CXCR4 Coreceptor
Authors: Yuan Wen , Craig Stewart , Si Zhihai , Farzan Michael , Sodroski Joseph
Published: April 2004

The synthetic peptide T-20, which corresponds to a sequence within the C-terminal heptad repeat region (HR2) of the human immunodeficiency virus type 1 (HIV-1) gp41 envelope glycoprotein, potently inhibits viral membrane fusion and entry. Although T-20 is thought to bind the N-terminal heptad repeat region (HR1) of gp41 and interfere with gp41 conformational changes required for membrane fusion, coreceptor specificity determined by the V3 loop of gp120 strongly influences the sensitivity of HIV-1 variants to T-20. Here, we show that T-20 binds to the gp120 glycoproteins of HIV-1 isolates that utilize CXCR4 as a coreceptor in a manner determined by the sequences of the gp120 V3 loop. T-20 binding to gp120 was enhanced in the presence of soluble CD4. Analysis of T-20 binding to gp120 mutants with variable loop deletions and the reciprocal competition of T-20 and particular anti-gp120 antibodies suggested that T-20 interacts with a gp120 region near the base of the V3 loop. Consistent with the involvement of this region in coreceptor binding, T-20 was able to block the interaction of gp120-CD4 complexes with the CXCR4 coreceptor. These results help to explain the increased sensitivity of CXCR4-specific HIV-1 isolates to the T-20 peptide. Interactions between the gp41 HR2 region and coreceptor-binding regions of gp120 may also play a role in the function of the HIV-1 envelope glycoproteins.
Comparison of the Rta/Orf50 Transactivator Proteins of Gamma-2-Herpesviruses
Authors: Damania Blossom , Jeong Joseph H. , Bowser Brian S. , DeWire Scott M. , Staudt Michelle R. , Dittmer Dirk P.
Published: April 2004

The viral immediate-early transactivator Rta/Orf50 is necessary and sufficient to initiate Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8 (KSHV/HHV-8) reactivation from latently infected cells. Since Rta/Orf50 is conserved among all known gamma-2-herpesviruses, we investigated whether the murine gamma-68-herpesvirus (MHV-68) and rhesus monkey rhadinovirus (RRV) homologs can functionally substitute for KSHV Rta/Orf50. (i) Our comparison of 12 KSHV promoters showed that most responded to all three Rta/Orf50proteins, but three promoters (vGPCR, K8, and gB) responded only to the KSHV Rta/Orf50 transactivator. Overall, the activation of KSHV promoters was higher with KSHV Rta than with the RRV and MHV-68 Rta. (ii) Only the primate Rta/Orf50 homologs were able to interfere with human p53-depedent transcriptional activation. (iii) Transcriptional profiling showed that the KSHV Rta/Orf50 was more efficient than it's homologs in inducing KSHV lytic transcription from the latent state. These results suggest that the core functionality of Rta/Orf50 is conserved and independent of its host, but the human protein has evolved additional, human-specific capabilities.
Trans-Endocytosis via Spinules in Adult Rat Hippocampus
Authors: Spacek Josef , Harris Kristen M.
Published: April 2004

Locations of a distinctive mode of trans-endocytosis involving dendrites, axons, and glia were quantified through serial section electron microscopy. Short vesicular or long vermiform evaginations emerged from dendrites and axons and were engulfed by presynaptic or neighboring axons, astrocytes, and, surprisingly, a growth cone to form double-membrane structures called spinules. In total, 254 spinules were evaluated in 326 μm3of stratum radiatum in area CA1 of mature rat hippocampus. Spinules emerged from spine heads (62%), necks (24%), axons (13%), dendritic shafts (1%), or nonsynaptic protrusions (<1%) and invaginated into axons (∼90%), astrocytic processes (∼8%), or a growth cone (∼1%). Coated pits occurred on the engulfing membrane at the tips of most spinules (69%), and double-membrane structures occurred freely in axonal and astrocytic cytoplasm, suggesting trans-endocytosis. Spinule locations differed among mushroom and thin spines. For mushroom spines, most (84%) of the spinules were engulfed by presynaptic axons, 16% by neighboring axons, and none by astrocytic processes. At thin spines, only 17% of the spinules were engulfed by presynaptic axons, whereas 67% were engulfed by neighboring axons and 14% by astrocytic processes. Spinules engulfed by astrocytic processes support the growing evidence that perisynaptic glia interact directly with synapses at least on thin spines. Spinules with neighboring axons may provide a mechanism for synaptic competition in the mature brain. Trans-endocytosis of spinules by presynaptic axons suggest retrograde signaling or coordinated remodeling of presynaptic and postsynaptic membranes to remove transient perforations and assemble the postsynaptic density of large synapses on mushroom spines.
Neuronal Pentraxin 1: A Novel Mediator of Hypoxic-Ischemic Injury in Neonatal Brain
Authors: Hossain Mir Ahamed , Russell Juliet C. , O'Brien Richard , Laterra John
Published: April 2004

Neonatal hypoxic-ischemic brain injury is a major cause of neurological disability and mortality. Its therapy will likely require a greater understanding of the discrete neurotoxic molecular mechanism(s) triggered by hypoxia-ischemia (HI). Here, we investigated the role of neuronal pentraxin 1 (NP1), a member of a newly recognized subfamily of “long pentraxins,” in the HI injury cascade. Neonatal brains developed marked infarcts in the ipsilateral cerebral hemisphere at 24 hr and showed significant loss of ipsilateral striatal, cortical, and hippocampal volumes at 7 d after HI compared with the contralateral hemisphere and sham controls. Immunofluorescence analyses revealed elevated neuronal expression of NP1 in the ipsilateral cerebral cortex from 6 hr to 7 d and in the hippocampal CA1 and CA3 regions from 24 hr to 7 d after HI. These same brain areas developed infarcts and terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling-positive cells within 24-48 hr of HI. In primary cortical neurons, NP1 protein was induced >2.5-fold (p< 0.001) after their exposure to hypoxia that caused ∼30-40% neuronal death. Transfecting cortical neurons with antisense oligodeoxyribonucleotides directed against NP1 mRNA (NP1AS) significantly inhibited (p< 0.01) hypoxia-induced NP1 protein induction and neuronal death (p< 0.001), demonstrating a specific requirement of NP1 in hypoxic neuronal injury. NP1 protein colocalized and coimmunoprecipitated with the fast excitatory AMPA glutamate receptor subunit (GluR1) in primary cortical neurons, and hypoxia induced a time-dependent increase in NP1-GluR1 interactions. NPIAS also protected against AMPA-induced neuronal death (p< 0.05), implicating a role for NP1 in the excitotoxic cascade. Our results show that NP1 induction mediates hypoxic-ischemic injury probably by interacting with and modulating GluR1 and potentially other excitatory glutamate receptors.
Bone Morphogenetic Protein-2 and -4 Limit the Number of Enteric Neurons But Promote Development of a TrkC-Expressing Neurotrophin-3-Dependent Subset
Authors: Chalazonitis Alcmène , D'Autréaux Fabien , Guha Udayan , Pham Tuan D. , Faure Christophe , Chen Jason J. , Roman Daniel , Kan Lixin , Rothman Taube P. , Kessler John A. , Gershon Michael D.
Published: April 2004

The hypothesis that BMPs (bone morphogenetic proteins), which act early in gut morphogenesis, also regulate specification and differentiation in the developing enteric nervous system (ENS) was tested. Expression of BMP-2 and BMP-4, BMPR-IA (BMP receptor subunit), BMPR-IB, and BMPR-II, and the BMP antagonists, noggin, gremlin, chordin, and follistatin was found when neurons first appear in the primordial bowel at embryonic day 12 (E12). Agonists, receptors, and antagonists were detected in separated populations of neural crest- and noncrest-derived cells. When applied to immunopurified E12 ENS precursors, BMP-2 and BMP-4 induced nuclear translocation of phosphorylated Smad-1 (Sma and Mad-related protein). The number of neurons developing from these cells was increased by low concentrations and decreased by high concentrations of BMP-2 or BMP-4. BMPs induced the precocious appearance of TrkC-expressing neurons and their dependence on neurotrophin-3 for survival. BMP-4 interacted with glial cell line-derived neurotrophic factor (GDNF) to enhance neuronal development but limited GDNF-driven expansion of the precursor pool. BMPs also promoted development of smooth muscle from mesenchymal cells immunopurified at E12. To determine the physiological significance of these observations, the BMP antagonist noggin was overexpressed in the developing ENS of transgenic mice under the control of the neuron-specific enolase promoter. Neuronal numbers in both enteric plexuses and smooth muscle were increased throughout the postnatal small intestine. These increases were already apparent by E18. In contrast, TrkC-expressing neurons decreased in both plexuses of postnatal noggin-overexpressing animals, again an effect detectable at E18. BMP-2 and/or BMP-4 thus limit the size of the ENS but promote the development of specific subsets of enteric neurons, including those that express TrkC.
FE65 Constitutes the Functional Link between the Low-Density Lipoprotein Receptor-Related Protein and the Amyloid Precursor Protein
Authors: Pietrzik Claus U. , Yoon Il-Sang , Jaeger Sebastian , Busse Tracy , Weggen Sascha , Koo Edward H.
Published: April 2004

Increasing evidence has implicated the low density lipoprotein receptor-related protein (LRP) and the adaptor protein FE65 in Alzheimer's disease pathogenesis. We have shown previously that LRP mediates β-amyloid precursor protein (APP) processing and affects amyloid β-protein and APP secretion and APP-c-terminal fragment generation. Furthermore, LRP mediates APP processing through its intracellular domain. Here, we set out to examine whether this interaction is of direct or indirect nature. Specifically, we asked whether adaptor proteins such as FE65 influence the LRP-mediated effect on APP processing by forming a protein complex. In coimmunoprecipitation experiments, we confirmed the postulated APP-FE65 and the LRP-FE65 interaction. However, we also showed an LRP-FE65-APP trimeric complex using pull-down techniques. Because FE65 alters APP processing, we investigated whether this effect is LRP dependent. Indeed, FE65 was only able to increase APP secretion in the presence of LRP. In the absence of LRP, APP secretion was unchanged compared with the LRP knock-out phenotype. Using RNA short interference techniques against FE65, we demonstrated that a reduction in FE65 protein mimics the LRP knock-out phenotype on APP processing. These results clearly demonstrate that FE65 acts as a functional linker between APP and LRP.
Enantioselective Reduction of Ketones
Authors: Itsuno Shinichi
Published: April 2004

Enantioselective reduction of prochiral ketones is among the most important methods for preparing enantioenriched secondary alcohols, which are important starting materials for a number of enantiopure compounds, including natural products. Various methods for enantioselective reduction of ketones have been developed for producing enantioenriched alcohols. These methods involve the use of both stoichiometric reagents and catalytic reductions. Metal hydride reagents such as lithium aluminum hydride (LAH) and sodium borohydride (NaBH4) are easily modified by enantiopure compounds. For example, binaphthol‐modified aluminum hydride reagent (BINAL‐H) is a derivative of LAH in which the enantiopure diol 1,1′‐bi‐2‐naphthol and one other alcohol replace three of the hydrogens. This reagent achieves high selectivity in many ketone reductions. The other impressive area of success is the use of enantiopure alkylboranes. The β hydride of enantiopure alkylboranes is delivered selectively, often exclusively, to one face of the carbonyl group of a ketone.

Despite remarkable success with stoichiometric reagents, their important drawback is that at least one equivalent of reagent is required for reduction of the ketone. Thus catalytic processes are desirable for enantioselective ketone reduction as well as for other asymmetric transformations. Hydrogenation and hydrosilylation of ketones are catalyzed by transition metal catalysts. Enantiopure ligand‐transition metal complexes can be used as asymmetric catalysts for these reactions. Recent research makes it possible to achieve high enantioselectivity, not only for the reduction of functionalized ketones in which a transition metal can coordinate to an adjacent functional group, but also for simple ketones such as acetophenone. One of the most remarkable catalytic systems described in recent years is borane reduction in the presence of an oxazaborolidine, which contains adjacent donor (nitrogen) and acceptor (boron) sites. Many biologically active compounds have been synthesized by using oxazaborolidine‐catalyzed borane reductions of ketones as the key step. Asymmetric reduction with enzymes is another important method. Some baker's yeast mediated ketone reductions have practical applicability.

This chapter addresses the enantioselective reduction of ketones by various methods including chirally modified hydride reductions, oxazaborolidine catalyzed reductions, Meerwein‐Ponndorf‐Verley (MPV) reductions, hydrogenations, hydrosilylations, and enzymatic reductions.
Intermolecular Metal‐Catalyzed Carbenoid Cyclopropanations
Authors: Davies Huw M. L. , Antoulinakis Evan G.
Published: April 2004

The metal‐catalyzed decomposition of diazo compounds in the presence of alkenes is a well‐established reaction. Since the originalOrganic Reactionsreview on the reaction of ethyl diazoacetate with alkenes and aromatic compounds in 1970, several new developments have revolutionized this area of chemistry. Most notably, major advances have been made in catalyst design such that highly chemoselective, diastereoselective and enantioselective carbenoid transformations can now be achieved. Furthermore, it has been recognized that a wide array of carbenoid structures can be utilized in this chemistry, leading to a broad range of synthetic applications.

This chapter comprises coverage of the metal‐catalyzed intermolecular cyclopropanations of diazo compounds containing at least one adjacent electron‐withdrawing group. The coverage of diazoacetate chemistry will be limited to material since 1970 because the previousOrganic Reactionsreview covers the earlier literature. The alkene component is limited to alkenes, dienes, furans, and pyrroles because these are the systems that have resulted in the greatest developments since the 1970 review. Metal‐carbenoid intermediates derived from diazo compounds undergo a variety of useful reactions, including cyclopropanation, insertion, and ylide formation. In recent years several excellent reviews have appeared on various aspects of this chemistry. Three recent reviews have focused on asymmetric intermolecular cyclopropanations. Several books and reviews on carbenoid chemistry have major sections on intermolecular cyclopropanations. Because of the historical central prominence of carbenoids derived from diazoacetates, most reviews have tended to focus on this class of carbenoids. In this chapter, a comparison is presented of the chemical differences that exist among the major classes of carbenoids that contain adjacent electron‐withdrawing groups. The extensive nature of the topic precludes coverage of related reactions such as the metal‐catalyzed decomposition of diazoalkanes, phenyldiazoalkanes, or vinyldiazoalkanes that lack adjacent electron‐withdrawing functionality. Other cyclopropanation reactions such as the Simmons‐Smith reaction, photochemical or thermal decomposition of diazo compounds in the presence of alkenes, and cyclopropanation using stoichiometric metal carbenes are not covered.
Oxidation of Phenolic Compounds with Organohypervalent Iodine Reagents
Authors: Moriarty Robert M. , Om Prakash
Published: April 2004

The oxidation of phenols is a key biochemical process in oxidative phosphorylation, and it is also important in numerous biosynthetic pathways. Controlled oxidative transformations of substituted phenols are found in many synthetic organic sequences. Accordingly, a large number of oxidizing agents for phenols have been developed. Useful reagents include Fremy's salt (KSO3)2NO,and a wide variety of other redox metal‐based oxidants such as Pb(IV), Mn(III), Tl(III), Cu(II), and Fe(III). Recently, organohypervalent iodine reagents have emerged as particularly useful agents for oxidizing phenols. In the area of natural product synthesis, organohypervalent iodine reagents have been used extensively to effect oxidative intramolecular bicyclization and spirocyclization. The focus of this chapter is on synthetic applications. The chapter also covers formation and applications of phenolic iodonium ylides.

The processes that occur during the oxidation of phenols with organohypervalent iodine reagents can be divided into two categories. The first category involves ligand exchange of the phenolic proton with the hypervalent iodine reagent to generate the O‐I(III) intermediate, which is subsequently transformed to various products, depending upon the reaction conditions.

These transformations include oxidation of phenols to quinones and related compounds, formation of spirocyclic and oxygen heterocyclic compounds via oxidative intramolecular participation reactions, and intramolecular carbon‐carbon bond formation via phenolic oxidative coupling. All of these reactions are driven by the reduction of iodine(III) [or iodine(V)] to iodine(I) (iodobenzene).

A second class of reactions that is discussed in this chapter includes formation of stable iodonium salts and ylides, which are important intermediates in organic synthesis. These reactions occur via carbon‐I(III) bond formation without loss of iodobenzene.
Effect of imidization conditions on the morphology of polyimide
Authors: Huang Jiann‐Wen , Kang Chiun‐Chia
Published: April 2004

A poly(amic acid) derived from pyromellitic dianhydride and oxydianiline was imidized under different conditions. The sample imidized in solution (PI‐1) showed the X‐ray diffraction pattern of a crystalline material, whereas that of the sample imidized in the solid state was essentially amorphous. Both samples were further characterized by 13C‐NMR spectroscopy, IR spectroscopy, electron paramagnetic resonance, and thermogravimetric analysis. The orders of polyimide in both the crystalline and amorphous states are discussed. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 93: 1065–1070, 2004
Conductivity of layer and matrix polyaniline–silver–copper composites by plasma
Authors: Cruz G. J. , Palacios J. C. , Olayo M. G. , Morales J. , Olayo R.
Published: April 2004

This work presents a study on the formation of polymer–metal composites by means of plasma, combining silver and copper alloys with semiconducting polymer films. The objective is to improve the electric conductivity of polyanilines by forming layer and matrix composites. In this way, it is possible to increase the superficial and/or volumetric conductivity of the polymers. Electronic variables as the electronic density and energy along the reactor and their influence on the chemical composition, deposition rate, and the morphology of plasma polymer–metal composites are taken into consideration in the course of this study, as the shower of the most energetic particles in the plasma can produce multiple bonds between the metals and the polymers. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 93: 1031–1036, 2004
Laser dye diffusion in polymer solutions studied by spectrophotometry
Authors: Marigoudar Prabhugouda , Lagare Mahaveer T. , Mallikarjuna Nadagouda N. , Aminabhavi Tejraj M.
Published: April 2004

A mathematical approach based on the combined application of Fick's law of diffusion and the Beer–Lambert law was used to measure the diffusion coefficient of dyes viz., coumarin 515 [3‐(1‐methylbenzimidazol‐2‐yl)‐7‐diethylaminocoumarin], POPOP [1,4‐bis (5‐phenyloxazolyl‐2‐yl) benzene], and exalite 416 {1,1,1′,1′‐tetraethyl‐5,5′‐diparaanisyl‐[2,3:5,6] diindanobenzene} in solutions of polystyrene and poly(methyl methacrylate) in 1,4‐dioxane. Diffusion data agreed well with the published results obtained using other techniques. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 93: 1157–1165, 2004
Electros: Development of an educational software for simulations in electrostatic
Authors: Martínez‐Jiménez P. , Casado E.
Published: April 2004

This is an introduction to the main design features of a computer‐aided educational package addressed to students of the first years of sciences and engineering. The package includes interrelated tutorials, computer simulation, and self‐evaluators, in which graphical output, hypertext, and animations are widely used. The package is devoted to the study of electrostatic fields and potentials produced by charged dielectrics arbitrarily located by the user in three‐dimensional space. It provides instant numerical evaluation and a graphical display of the electric field and potentials of the charge distribution created by the user, and permits its investigation with probe charges. The software presented in this paper has all the features we consider important for any educational software of physical phenomena simulation: an integrative character, self‐evaluation tests, personalized and active learning process, adaptability to teacher's aims, versatility as a teaching tool, multimedia resources, and simplicity. All these features will be explained in the following sections. © 2004 Wiley Periodicals, Inc. Comput Appl Eng Educ 12: 65–73, 2004; Published online in Wiley InterScience (www.interscience.wiley.com); DOI 10.1002/cae.10050