bluuebunny/crossref_metadata_2025 huggingface dataset:
NMR study of a membrane protein in detergent-free aqueous solution
Authors: Zoonens Manuela , Catoire Laurent J. , Giusti Fabrice , Popot Jean-Luc
Published: June 2005

One of the major obstacles to membrane protein (MP) structural studies is the destabilizing effect of detergents. Amphipols (APols) are short amphipathic polymers that can substitute for detergents to keep MPs water-soluble under mild conditions. In the present work, we have explored the feasibility of studying the structure of APol-complexed MPs by NMR. As a test MP, we chose the 171-residue transmembrane domain of outer MP A from
Escherichia coli
(tOmpA), whose x-ray and NMR structures in detergent are known.
2
H,
15
N-labeled tOmpA was produced as inclusion bodies, refolded in detergent solution, trapped with APol A8-35, and the detergent removed by adsorption onto polystyrene beads. The resolution of transverse relaxation-optimized spectroscopy–heteronuclear single-quantum correlation spectra of tOmpA/A8-35 complexes was found to be close to that of the best spectra obtained in detergent solutions. The dispersion of chemical shifts indicated that the protein had regained its native fold and retained it during the exchange of surfactants. MP–APol interactions were mapped by substituting hydrogenated for deuterated A8-35. The resulting dipolar broadening of amide proton linewidths was found to be limited to the β-barrel region of tOmpA, indicating that A8-35 binds specifically to the hydrophobic transmembrane surface of the protein. The potential of this approach to MP studies by solution NMR is discussed.
The molecular basis of ferroportin-linked hemochromatosis
Authors: De Domenico Ivana , Ward Diane McVey , Nemeth Elizabeta , Vaughn Michael B. , Musci Giovanni , Ganz Tomas , Kaplan Jerry
Published: June 2005

Mutations in the iron exporter ferroportin (Fpn) (IREG1,
SLC40A1
, and MTP1) result in hemochromatosis type IV, a disorder with a dominant genetic pattern of inheritance and heterogeneous clinical presentation. Most patients develop iron loading of Kupffer cells with relatively low saturation of plasma transferrin, but others present with high transferrin saturation and iron-loaded hepatocytes. We show that known human mutations introduced into mouse Fpn-GFP generate proteins that either are defective in cell surface localization or have a decreased ability to be internalized and degraded in response to hepcidin. Studies using coimmunoprecipitation of epitope-tagged Fpn and size-exclusion chromatography demonstrated that Fpn is multimeric. Both WT and mutant Fpn participate in the multimer, and mutant Fpn can affect the localization of WT Fpn, its stability, and its response to hepcidin. The behavior of mutant Fpn in cell culture and the ability of mutant Fpn to act as a dominant negative explain the dominant inheritance of the disease as well as the different patient phenotypes.
The exocyst component Sec5 is present on endocytic vesicles in the oocyte of Drosophila melanogaster
Authors: Sommer Bernhard , Oprins Adrian , Rabouille Catherine , Munro Sean
Published: June 2005

The exocyst is an octameric complex required for polarized secretion. Some components of the exocyst are found on the plasma membrane, whereas others are recruited to Golgi membranes, suggesting that exocyst assembly tethers vesicles to their site of fusion. We have found that in Drosophila melanogaster oocytes the majority of the exocyst component Sec5 is unexpectedly present in clathrin-coated pits and vesicles at the plasma membrane. In oocytes, the major substrate for clathrin-dependent endocytosis is the vitellogenin receptor Yolkless. A truncation mutant of Sec5 (sec5E13) allows the formation of normally sized oocytes but with greatly reduced yolk uptake. We find that in sec5E13 oocytes Yolkless accumulates aberrantly in late endocytic compartments, indicating a defect in the endocytic cycling of the receptor. An analogous truncation of the yeast SEC5 gene results in normal secretion but a temperature-sensitive defect in endocytic recycling. Thus, the exocyst may act in both Golgi to plasma membrane traffic and endocytic cycling, and hence in oocytes is recruited to clathrin-coated pits to facilitate the rapid recycling of Yolkless.
Heme Regulates Allosteric Activation of the Slo1 BK Channel
Authors: Horrigan Frank T. , Heinemann Stefan H. , Hoshi Toshinori
Published: June 2005

Large conductance calcium-dependent (Slo1 BK) channels are allosterically activated by membrane depolarization and divalent cations, and possess a rich modulatory repertoire. Recently, intracellular heme has been identified as a potent regulator of Slo1 BK channels (Tang, X.D., R. Xu, M.F. Reynolds, M.L. Garcia, S.H. Heinemann, and T. Hoshi. 2003. Nature. 425:531–535). Here we investigated the mechanism of the regulatory action of heme on heterologously expressed Slo1 BK channels by separating the influences of voltage and divalent cations. In the absence of divalent cations, heme generally decreased ionic currents by shifting the channel's G–V curve toward more depolarized voltages and by rendering the curve less steep. In contrast, gating currents remained largely unaffected by heme. Simulations suggest that a decrease in the strength of allosteric coupling between the voltage sensor and the activation gate and a concomitant stabilization of the open state account for the essential features of the heme action in the absence of divalent ions. At saturating levels of divalent cations, heme remained similarly effective with its influence on the G–V simulated by weakening the coupling of both Ca2+ binding and voltage sensor activation to channel opening. The results thus show that heme dampens the influence of allosteric activators on the activation gate of the Slo1 BK channel. To account for these effects, we consider the possibility that heme binding alters the structure of the RCK gating ring and thereby disrupts both Ca2+- and voltage-dependent gating as well as intrinsic stability of the open state.
Initial Coupling of Binding to Gating Mediated by Conserved Residues in the Muscle Nicotinic Receptor
Authors: Mukhtasimova Nuriya , Free Chris , Sine Steven M.
Published: June 2005

We examined functional consequences of intrasubunit contacts in the nicotinic receptor α subunit using single channel kinetic analysis, site-directed mutagenesis, and structural modeling. At the periphery of the ACh binding site, our structural model shows that side chains of the conserved residues αK145, αD200, and αY190 converge to form putative electrostatic interactions. Structurally conservative mutations of each residue profoundly impair gating of the receptor channel, primarily by slowing the rate of channel opening. The combined mutations αD200N and αK145Q impair channel gating to the same extent as either single mutation, while αK145E counteracts the impaired gating due to αD200K, further suggesting electrostatic interaction between these residues. Interpreted in light of the crystal structure of acetylcholine binding protein (AChBP) with bound carbamylcholine (CCh), the results suggest in the absence of ACh, αK145 and αD200 form a salt bridge associated with the closed state of the channel. When ACh binds, αY190 moves toward the center of the binding cleft to stabilize the agonist, and its aromatic hydroxyl group approaches αK145, which in turn loosens its contact with αD200. The positional changes of αK145 and αD200 are proposed to initiate the cascade of perturbations that opens the receptor channel: the first perturbation is of β-strand 7, which harbors αK145 and is part of the signature Cys-loop, and the second is of β-strand 10, which harbors αD200 and connects to the M1 domain. Thus, interplay between these three conserved residues relays the initial conformational change from the ACh binding site toward the ion channel.
ECONOMICS OF THE “CRITICAL USE” OF METHYL BROMIDE UNDER THE MONTREAL PROTOCOL
Authors: DECANIO STEPHEN J. , NORMAN CATHERINE S.
Published: June 2005

We analyze the economics of granting temporary exceptions to the phaseout of methyl bromide (MeBr) under the Montreal Protocol on Substances that Deplete the Ozone Layer. The protocol allows such exceptions based on technical or economic “feasibility” through a critical use exemption (CUE) process. Data compiled under the protocol make it possible to set forth criteria for the exceptions based on estimation of the benefits of compliance in terms of “willingness to pay” to abate the externality, as well as costs to the users creating the externality. We estimate a political willingness to pay and show that market and supply effects would reduce losses to MeBr users below estimates of such losses provided in CUE nominations. This suggests that the phaseout of MeBr can proceed with considerably fewer CUEs than requested by the parties. (JEL Q1, Q2, Q3, H8)
DEPOSIT INSURANCE AND EXTERNAL FINANCE
Authors: CECCHETTI STEPHEN G. , KRAUSE STEFAN
Published: June 2005

In this article we examine one potential explanation for the cross‐country differences in the importance of banks and capital market financing of investment. We provide both an equilibrium model predicting and empirical evidence showing that countries with explicit deposit insurance and a high degree of state‐owned bank assets have smaller equity markets, a lower number of publicly traded firms, and a smaller amount of bank credit to the private sector. Finally, our results suggest that the effects of deposit guarantees are more important than the origins of national legal systems. (JEL G21, G22, G32)
ON THE INFORMATION CONTENT OF ASYMMETRIC FOMC POLICY STATEMENTS: EVIDENCE FROM A TAYLOR‐RULE PERSPECTIVE
Authors: PAKKO MICHAEL R.
Published: June 2005

For over two decades, the FOMC has included in its policy decisions a statement of bias toward subsequent tightening or easing of policy. This article examines the predictive content of these statements in a Taylor‐rule setting, finding that they convey useful information for forecasting changes in the federal funds rate target, even after controlling for policy responses to inflation and the output gap. Moreover, the evidence suggests that this asymmetry can be represented in terms of shifts to the parameters of the Taylor‐rule equation, indicating a greater or lesser degree of responsiveness to information about inflation and output. (JEL E52, E58)
Autobiography, the dangers of knowledge and Genet's suspect reader
Authors: Boyle Claire
Published: June 2005

Genet's autobiographical work is noticeably resistant to providing its reader with a conventional autobiographical account of the author's life and self.
Notre-Dame-des-Fleurs
writes the self principally through its fantasies;
Journal du voleur
reveals a reluctant autobiographical narrator. My article argues that Genet's determination not to supply the traditional ingredients of autobiography stems from his insights as a prisoner into the means by which deviant, anti-social individuals are made to conform to society's demands. I suggest that Genet is conscious of how the regime of ‘haute surveillance’ in prison aims to correct the unacceptable practices of the prisoner by exposing them knowingly to a constant watchful gaze, which should instil obedience. In this insight, Genet foreshadows Michel Foucault's theorizations in
Surveiller et punir
on the workings of the prison system. Foucault states that the watchful gaze allows knowledge to be amassed about the prisoner: once reduced to the known and the predictable, a prisoner's behaviour is no longer a threat and he can be disciplined and subjectified. I argue that Genet's treatment of his reader and aversion to autobiographical conventions reflect a determination to avoid subjectification, and to continue acting as an irritant to his society.
Algebraic and differential Rainich conditions for symmetric trace-free tensors of higher rank
Authors: Bergqvist Göran , Lankinen Paul
Published: June 2005

We present a study of Rainich-like conditions for symmetric and trace-free tensors
T
. For arbitrary even rank we find a necessary and sufficient differential condition for a tensor to satisfy the source-free field equation. For rank 4, in a generic case, we combine these conditions with previously obtained algebraic conditions to gain a complete set of algebraic and differential conditions on
T
for it to be a superenergy tensor of a Weyl candidate tensor, satisfying the Bianchi vacuum equations. By a result of Bell and Szekeres, this implies that in vacuum, generically,
T
must be the Bel–Robinson tensor of the spacetime. For the rank 3 case, we derive a complete set of necessary algebraic and differential conditions for
T
to be the superenergy tensor of a massless spin-3/2 field, satisfying the source-free field equation.
Models of foot-and-mouth disease
Authors: Keeling Matt J
Published: June 2005

During the 2001 foot-and-mouth disease outbreak in the UK, three very different models were used in an attempt to predict the disease dynamics and inform control measures. This was one of the first times that models had been used during an epidemic to support the decision-making process. It is probable that models will play a pivotal role in any future livestock epidemics, and it is therefore important that decision makers, veterinarians and farmers understand the uses and limitations of models. This review describes the utility of models in general before focusing on the three foot-and-mouth disease models used in 2001. Finally, the future of modelling is discussed, analysing the advances needed if models are to be successfully applied during any subsequent epidemics.
Direct assessment of queen quality and lack of worker suppression in a paper wasp
Authors: Liebig Jürgen , Monnin Thibaud , Turillazzi Stefano
Published: June 2005

Assessing a conspecific's potential is often crucial to increase one's fitness, e.g. in female choice, contests with rivals or reproductive conflicts in animal societies. In the latter, helpers benefit from accurately assessing the fertility of the breeder as an indication of inclusive fitness. There is evidence that this can be achieved using chemical correlates of reproductive activity. Here, we show that queen quality can be assessed by directly monitoring her reproductive output. In the paper wasp
Polistes dominulus
, we mimicked a decrease in queen fertility by regularly removing brood. This triggered ovarian development and egg-laying by many workers, which strongly suggests that brood abundance is a reliable cue of queen quality. Brood abundance can be monitored when workers perform regular brood care in small size societies where each brood element is kept in a separate cell. Our results also show that although the queen was not manipulated, and thus remained healthy and fully fertile, she did not control worker egg-laying. Nevertheless, when workers laid eggs, the queen secured a near reproductive monopoly by selectively destroying these eggs, a mechanism known as ‘queen policing’. By contrast, workers destroyed comparatively few queen-laid eggs, but did destroy each other's eggs.
Sex ratio strategies and the evolution of cue use
Authors: Moore Jamie C , Zavodna Monika , Compton Stephen G , Gilmartin Philip M
Published: June 2005

Quantitative tests of sex allocation theory have often indicated that organism strategies deviate from model predictions. In pollinating fig wasps,
Lipporrhopalum tentacularis
, whole fig (brood) sex ratios are generally more female-biased than predicted by local mate competition (LMC) theory where females (foundresses) use density as a cue to assess potential LMC. We use microsatellite markers to investigate foundress sex ratios in
L. tentacularis
and show that they actually use their clutch size as a cue, with strategies closely approximating the predictions of a new model we develop of these conditions. We then provide evidence that the use of clutch size as a cue is common among species experiencing LMC, and given the other predictions of our model argue that this is because their ecologies mean it provides sufficiently accurate information about potential LMC that the use of other more costly cues has not evolved. We further argue that the use of these more costly cues by other species is due to the effect that ecological differences have on cue accuracy. This implies that deviations from earlier theoretical predictions often indicate that the cues used to assess environmental conditions differ from those assumed by models, rather than limits on the ability of natural selection to produce ‘perfect’ organisms.
Episymbiotic microbes as food and defence for marine isopods: unique symbioses in a hostile environment
Authors: Lindquist Niels , Barber Paul H , Weisz Jeremy B
Published: June 2005

Symbioses profoundly affect the diversity of life, often through novel biochemical services that symbionts provide to their hosts. These biochemical services are typically nutritional enhancements and less commonly defensive, but rarely both simultaneously. On the coral reefs of Papua New Guinea, we discovered unique associations between marine isopod crustaceans (
Santia
spp.) and episymbiotic microbes. Transmission electron microscopy and pigment analyses show that episymbiont biomass is dominated by large (20–30 μm) cyanobacterial cells. The isopods consume these photosymbionts and ‘cultivate’ them by inhabiting exposed sunlit substrates, a behaviour made possible by symbionts' production of a chemical defence that is repulsive to fishes. Molecular phylogenetic analyses demonstrated that the symbiotic microbial communities are diverse and probably dominated in terms of population size by bacteria and small unicellular
Synechococcus
-type cyanobacteria. Although largely unknown in the oceans, defensive symbioses probably promote marine biodiversity by allowing niche expansions into otherwise hostile environments.
The Big Flood: North Sea storm surge
Authors: McRobie Allan , Spencer Tom , Gerritsen Herman
Published: June 2005

In the 50 years since the catastrophic southern North Sea storm surge of 31 January–1 February 1953, there have been technological advances in the engineering of flood protection, increased understanding of physical processes in shallow seas and estuaries, and developments in the mathematical statistics of extreme events. This introductory paper reviews how the scientific understanding of surge events, their impacts and the human responses to them is evolving on many fronts, often across disciplinary boundaries. The question of how the long-term nature of the problem itself will be influenced by possible climate, land use and policy changes is addressed, along with their associated uncertainties.
Bayesian modelling of extreme surges on the UK east coast
Authors: Coles Stuart , Tawn Jonathan
Published: June 2005

The catastrophic surge event of 1953 on the eastern UK and northern European coastlines led to widespread agreement on the necessity of a coordinated response to understand the risk of future oceanographic flood events and, so far as possible, to afford protection against such events. One element of this response was better use of historical data and scientific knowledge in assessing flood risk. The timing of the event also coincided roughly with the birth of extreme value theory as a statistical discipline for measuring risks of extreme events, and over the last 50 years, as techniques have been developed and refined, various attempts have been made to improve the precision of flood risk assessment around the UK coastline. In part, this article provides a review of such developments. Our broader aim, however, is to show how modern statistical modelling techniques, allied with the tools of extreme value theory and knowledge of sea-dynamic physics, can lead to further improvements in flood risk assessment. Our long-term goal is a coherent spatial model that exploits spatial smoothness in the surge process characteristics and we outline the details of such a model. The analysis of the present article, however, is restricted to a site-by-site analysis of high-tide surges. Nonetheless, we argue that the Bayesian methodology adopted for such analysis enables a risk-based interpretation of results that is most natural in this setting, and preferable to inferences that are available from more conventional analyses.
Comparing functional connectivity via thresholding correlations and singular value decomposition
Authors: Worsley Keith J , Chen Jen-I , Lerch Jason , Evans Alan C
Published: June 2005

We compare two common methods for detecting functional connectivity: thresholding correlations and singular value decomposition (SVD). We find that thresholding correlations are better at detecting focal regions of correlated voxels, whereas SVD is better at detecting extensive regions of correlated voxels. We apply these results to resting state networks in an fMRI dataset to look for connectivity in cortical thickness.
A novel simian immunodeficiency virus from black mangabey (Lophocebus aterrimus) in the Democratic Republic of Congo
Authors: Takemura Taichiro , Ekwalanga Michel , Bikandou Blaise , Ido Eiji , Yamaguchi-Kabata Yumi , Ohkura Sadayuki , Harada Hirotada , Takehisa Jun , Ichimura Hiroshi , Parra Henri-Joseph , Nende Monique , Mubwo Eric , Sepole Midingi , Hayami Masanori , Miura Tomoyuki
Published: June 2005

In order to understand primate lentivirus evolution, characterization of additional simian immunodeficiency virus (SIV) strains is essential. Here, an SIV from a black mangabey (Lophocebus aterrimus) originating from the Democratic Republic of Congo was analysed phylogenetically. The monkey had cross-reactive antibodies against human immunodeficiency virus type 1 (HIV-1) and HIV-2. The viral pol region sequence was amplified by nested PCR and sequence analysis confirmed that it was related to known SIV sequences. This is the first report to characterize genetically an SIV from the monkey genus Lophocebus. Phylogenetic analysis of the pol region revealed that this novel SIV, designated SIVbkm, fell into the SIVsyk and SIVgsn virus group, containing viruses isolated from the genus Cercopithecus, and suggests that cross-species transmission has occurred between species of the genera Lophocebus and Cercopithecus.
Mousepox conjunctivitis: the role of Fas/FasL-mediated apoptosis of epithelial cells in virus dissemination
Authors: Krzyzowska Malgorzata , Polanczyk Magdalena , Bas Monika , Cymerys Joanna , Schollenberger Ada , Chiodi Francesca , Niemialtowski Marek
Published: June 2005

BALB/c mice infected with the Moscow strain ofEctromelia virus(ECTV-MOS) show a large number of apoptotic cells, and an influx of lymphoid cells in the epithelium and substantia propria of conjunctivae, respectively. The presence of ECTV-MOS antigens in the epithelium of conjunctivae significantly upregulates Fas in the epithelial layer and FasL in the suprabasal layer of conjunctiva. Inhibition of FasL with blocking antibodies in cultures of conjunctival cells isolated from ECTV-MOS-infected BALB/c mice showed that the Fas/FasL pathway is important in apoptosis of ECTV-MOS-infected cells. The results also showed that the presence of cytokines, in particular interferon (IFN)-γ, upregulated expression of Fas. Interleukin (IL) 2, 4, 10 and IFN-γwere produced at the peak of conjunctivitis (at day 15 of infection) with a predominance of IFN-γand a small, but significant, production of IL4 and IL10 compared with non-infected animals. These results suggest that not only is Fas/FasL expression in conjunctiva involved in elimination of migrating Fas+cells but also plays an important role in the turnover of conjunctival epithelium and thus may be crucial for ECTV spreading to the surrounding environment.
Analysis of a bovine herpesvirus 1 recombinant virus that does not express the bICP0 protein
Authors: Geiser V. , Zhang Y. , Jones C.
Published: June 2005

Bovine herpesvirus 1 (BHV-1) infected-cell protein 0 (bICP0) stimulates productive infection by activating viral gene expression. In this study, an attempt was made to construct a recombinant virus with point mutations in the C3HC4zinc RING finger of bICP0, as this domain is necessary for activating viral transcription and productive infection. A virus was identified in bovine cells that induced small clusters of infected cells resembling a small plaque. Instead of the expected mutations within the zinc RING finger, this virus contained a point mutation within the initiating ATG of bICP0, a point mutation two bases downstream from the ATG mutation and deletion of flanking plasmid sequences used for homologous recombination. The bICP0 mutant was rescued with wild-type (wt) bICP0 sequences and the bICP0-rescued virus produced wt plaques. The bICP0-rescued virus and wt BHV-1, but not the mutant, expressed the bICP0 protein during productive infection of bovine cells, suggesting that the mutant virus was a null mutant. Consequently, the mutant was designated the bICP0 null mutant. Infection of bovine cells with the bICP0 null mutant resulted in at least 100-fold lower virus titres, indicating that bICP0 protein expression is important, but not required, for virus production. When bovine cells infected with the bICP0 null mutant virus were subcultured, the cells continued to divide, but viral DNA could be detected after more than 35 passages, suggesting that the bICP0 null mutant induced a persistent-like infection in bovine cells and that it may be useful for generating additional bICP0 mutants.
Identification of the Borna disease virus (BDV) proteins required for the formation of BDV-like particles
Authors: Perez Mar , de la Torre Juan Carlos
Published: June 2005

Borna disease virus (BDV) is an enveloped virus with a non-segmented, negative-strand RNA genome that has an organization characteristic of Mononegavirales. However, based on its unique genetics and biological features BDV is considered to be the prototypic member of a new virus family,Bornaviridae. Here, the use of a reverse genetic approach to identify the viral proteins required for packaging of BDV RNA analogues (MG) into infectious virus-like particles (VLPs) was described. Plasmids encoding individual BDV proteins under the control of a RNA polymerase II promoter were co-transfected with a plasmid that allows for intracellular synthesis of a BDV MG mediated by the cellular RNA polymerase I. Clarified lysates from transfected cells were passaged onto fresh cells that were previously transfected with plasmids expressing the minimal BDVtrans-acting factors L, N and P required for RNA synthesis mediated by the BDV polymerase. Reconstitution of BDV MG-specific packaging and passage of infectious VLP was monitored by expression of the chloramphenicol acetyl transferase reporter gene present in the BDV MG. BDV M and G, in addition to L, N and P, were sufficient for the passage of chloramphenicol acetyl transferase activity, which could be blocked by BDV neutralizing antibodies to G, indicating that VLP infectivity was fully mediated by BDV G. Passage of BDV MG was abrogated by omission of either M or G.
Functional characterization of the Beet necrotic yellow vein virus RNA-5-encoded p26 protein: evidence for structural pathogenicity determinants
Authors: Link Didier , Schmidlin Laure , Schirmer Audrey , Klein Elodie , Erhardt Mathieu , Geldreich Angèle , Lemaire Olivier , Gilmer David
Published: June 2005

A Beet necrotic yellow vein virus isolate containing a fifth RNA is present in the Pithiviers area of France. A full-length cDNA clone of RNA-5 was obtained and placed under the control of a T7-RNA-pol promoter that allowed the production of infectious transcripts. ‘Pithiviers' isolate-specific necrotic symptoms were obtained on Chenopodium quinoa when RNA-5-encoded p26 was expressed either from RNA-5 or from an RNA-3-derived replicon. By using haemagglutinin- and green fluorescent protein-tagged constructs, virally expressed p26-fusion proteins induced the same necrotic local lesions on host plants and were localized mainly in the nucleus of infected cells. Deletion mutagenesis permitted identification of two domains, responsible respectively for nuclear export and cytoplasmic retention of the p26 mutated proteins. By using a yeast two-hybrid system, Gal4DB–p26 protein self-activated transcription of the His3 reporter gene. The p26 transcription-activation domain was located within its first 55 aa and has been studied by alanine scanning. Resulting p26 mutants were tested for their capability to induce necrotic symptoms and to localize in the nuclear compartment.
US3 protein kinase of herpes simplex virus type 2 is required for the stability of the UL46-encoded tegument protein and its association with virus particles
Authors: Matsuzaki Akio , Yamauchi Yohei , Kato Akihisa , Goshima Fumi , Kawaguchi Yasushi , Yoshikawa Tetsushi , Nishiyama Yukihiro
Published: June 2005

The herpes simplex virus (HSV) US3 gene encodes a serine/threonine protein kinase (PK). Although US3 PK is not essential for virus replication in cell culture, it plays an important role in the regulation of apoptosis in infected cells. However, the role of US3 PK in virus replication and pathogenicity is not well understood. The UL46 gene encodes virion tegument phosphoproteins, the properties and functions of which are poorly understood. In this study, it is shown that the UL46 protein of HSV type 2 (HSV-2) is affected strikingly by the presence of US3 PK. In the absence of US3 PK, UL46 protein was quite unstable, being much more susceptible to degradation. UL46 protein was undetectable in the extracellular virions of US3-deficient virus. Moreover, in vitro kinase assays using recombinant US3 PK show that UL46 protein is phosphorylated by the US3 PK, suggesting that UL46 can be a direct substrate for US3 PK in infected cells. Together, these findings shed new light on the physiological functions of US3 PK.
High birthweight and shoulder dystocia: the strongest risk factors for obstetrical brachial plexus palsy in a Swedish population‐based study
Authors: Margareta Mollberg , Henrik Hagberg , Börje Bager , Håkan Lilja , Lars Ladfors
Published: June 2005

Background.  Obstetrical brachial plexus palsy (OBPP) is a serious form of neonatal morbidity.

Objective.  The aim of this work was to study the incidence of OBPP and to analyze its risk factors.

Methods.  This is a population‐based retrospective case–control study. All deliveries recorded in the Swedish Medical Birth Registry between 1987 and 1997 (n = 1 213 987) were investigated. Cases (n = 2399) with OBPP were compared to all other cases.

Results.  The incidence of OBPP increased from 0.17 in 1987 to 0.27% in 1997 (p = 0.002). During the same time period, the mean birthweight increased from 3483 to 3525 g. Birthweight increasing from 4000 g was associated with a progressive rise in OBPP risk. Other significant risk factors associated with the injury were shoulder dystocia, breech presentation in vaginal delivery, operative vaginal delivery, diabetes mellitus, induction of labor, protracted active phase, secondary arrest of dilatation, and epidural anesthesia. Cesarean section was associated with a decreased risk of OBPP. If 5000 g is chosen as cut‐off for cesarean section, 85% of the infants in this weight class are underestimated using ultrasonography. Approximately, 331 abdominal deliveries have to be performed to avoid one case of OBPP.

Conclusions.  Shoulder dystocia and infant birthweight of 4500 g and more are the strongest risk factors for OBPP in a Swedish population.
Tumor suppressor and growth regulatory genes are overexpressed in severe early‐onset preeclampsia – an array study on case‐specific human preeclamptic placental tissue
Authors: Annaleena Heikkilä , Tiina Tuomisto , Sanna‐Kaisa Häkkinen , Leea Keski‐Nisula , Seppo Heinonen , Seppo Ylä‐Herttuala
Published: June 2005

Background.  Preeclampsia is an important clinical condition with unknown etiology. We used DNA array technique to compare placental gene expression profile in severe early‐onset preeclampsia from 25 to 27 gestational weeks with strictly non‐affected placental samples from similar gestational weeks.

Method.  DNA arrays were validated by showing the up‐regulation of several genes typical for preeclampsia such as chorionic gonadotrophin beta‐chain, tissue factor pathway inhibitor, and intercellular adhesion molecule‐1. In DNA array, 5% of genes displayed less than or equal to twofold increase in expression level and only 0.2% of genes showed ≤0.5‐fold decrease in expression in preeclampsia versus control. Signs of immunological factors, hypoxia, apoptosis, oxidative stress and altered thrombosis, coagulation as well as endothelial injury were seen in the gene expression profile.

Results.  As a new finding, we identified a group of 13 genes with a function in tumor suppression and growth regulation which were significantly up‐regulated in preeclampsia. Three out of the five most highly up‐regulated genes belonged to this group which included genes, such as protein phosphatase 2, phospholipid scramblase 1, transcription elongation factor, melanoma adhesion molecule, retinoic acid receptor responder 3, and RANTES.

Conclusions.  It is concluded that up‐regulation of tumor suppressor and growth regulatory genes may play an important role in the pathogenesis of severe early‐onset preeclampsia.
Expression, production and excretion of Bla g 1, a major human allergen, in relation to food intake in the German cockroach,Blattella germanica
Authors: Gore J. Chad , Schal C.
Published: June 2005

Abstract. The German cockroach,Blattella germanica(Linnaeus) (Dictyoptera: Blattellidae), produces several potent human allergens, one of which,Blattella germanicaallergen 1 (Bla g 1), is produced in the midgut and excreted in faeces. We tested with descriptive and experimental approaches the hypothesis that Bla g 1 production is related to food intake in adult males and females of the German cockroach. Bla g 1 mRNA expression in the female midgut (assayed by real time quantitative polymerase chain reaction), her Bla g 1 content (assayed by enzyme‐linked immunosorbent assay), and the female's faeces production and its Bla g 1 content tracked a cyclic pattern in relation to the gonadotrophic cycle. All four measures rose as food intake increased, declined before oviposition in relation to diminishing food intake, and remained low while the female carried an egg case for 20 days. After her first clutch of embryos hatched, the female resumed feeding, and faeces and Bla g 1 production increased concomitantly. Both Bla g 1 mRNA expression and Bla g 1 protein levels remained low in experimentally starved females. However, when starved females were allowed to feed, Bla g 1 production elevated and the gonadotrophic cycle resumed. Bla g 1 mRNA expression also increased six‐fold in response to feeding compared to starved females. By contrast, there were no apparent cycles in the pattern of Bla g 1 production in males, reflecting their low and non‐cyclic food intake. Our results therefore demonstrate that Bla g 1 production inB. germanicais modulated in relation to food intake.
Six new species of the Anopheles leucosphyrus group, reinterpretation of An. elegans and vector implications
Authors: Sallum M. A. M. , Peyton E. L. , Wilkerson R. C.
Published: June 2005

Abstract.  Among Oriental anopheline mosquitoes (Diptera: Culicidae), several major vectors of forest malaria belong to the group of Anopheles (Cellia) leucosphyrus Dönitz. We have morphologically examined representative material (> 8000 specimens from seven countries) for taxonomic revision of the Leucosphyrus Group. Six new species are here described from adult, pupal and larval stages (with illustrations of immature stages) and formally named as follows: An. latens n. sp. (= An. leucosphyrus species A of Baimai et al., 1988b), An. cracens n. sp., An. scanloni n. sp., An. baimaii n. sp. (formerly An. dirus species B, C, D, respectively), An. mirans n. sp. and An. recens n. sp. Additionally, An. elegans (James) is redescribed and placed in the complex of An. dirus Peyton & Harrison (comprising An. baimaii, An. cracens, An. dirus, An. elegans, An. nemophilous Peyton & Ramalingam, An. scanloni and An. takasagoensis Morishita) of the Leucosphyrus Subgroup, together with An. baisasi Colless and the An. leucosphyrus complex (comprising An. balabacensis Baisas, An. introlatus Baisas, An. latens and An. leucosphyrus). Hence, the former Elegans Subgroup is renamed the Hackeri Subgroup (comprising An. hackeri Edwards, An. pujutensis Colless, An. recens and An. sulawesi Waktoedi).

Distribution data and bionomics of the newly defined species are given, based on new material and published records, with discussion of morphological characters for species distinction and implications for ecology and vector roles of such species. Now these and other members of the Leucosphyrus Group are identifiable, it should be possible to clarify the medical importance and distribution of each species. Those already regarded as vectors of human malaria are: An. baimaii[Bangladesh, China (Yunnan), India (Andamans, Assam, Meghalaya, West Bengal), Myanmar, Thailand]; An. latens[Borneo (where it also transmits Bancroftian filariasis), peninsular Malaysia, Thailand]; probably An. cracens (Sumatra, peninsular Malaysia, Thailand); presumably An. scanloni (Thailand); perhaps An. elegans (the Western Ghat form of An. dirus, restricted to peninsular India); but apparently not An. recens (Sumatra) nor An. mirans[Sri Lanka and south‐west India (Karnataka, Kerala, Tamil Nadu)], which is a natural vector of simian malarias. Together with typical An. balabacensis, An. dirus and An. leucosphyrus, therefore, the Leucosphyrus Group includes about seven important vectors of forest malaria, plus at least a dozen species of no known medical importance, with differential specific distributions collectively spanning > 5000 km from India to the Philippines.
Seasonality of Old World screwworm myiasis in the Mesopotamia valley in Iraq
Authors: Siddig A. , Al Jowary S. , Al Izzi M. , Hopkins J. , Hall M. J. R. , Slingenbergh J.
Published: June 2005

Abstract.  Following the first recorded introduction of the Old World screwworm fly (OWS), Chrysomya bezziana Villeneuve (Diptera: Calliphoridae), into the Mesopotamia valley in Iraq in September 1996, cases of livestock myiasis caused by OWS developed a distinctly seasonal pattern. The annual cycle of clinical OWS cases is explained here on the basis of environmental variables that affect the different life‐cycle stages of C. bezziana. This analysis suggests that low temperatures restricted pupal development during the winter, whereas the dispersal of adult flies was constrained by hot/dry summer conditions. A restricted number of OWS foci persisted throughout the year. In these foci, pupal development was fastest during the autumn months. In autumn, rapid multiplication, lasting several OWS generations, allowed subsequent adult fly dispersal across the valley floor during the winter. Hence, the monthly incidence of clinical OWS cases in livestock peaked during December–January and was lowest during July–August. In addition to temperature and humidity, vegetation cover played a role in OWS distribution. Hence the majority of OWS cases were clustered in the medium density type of vegetation [normalized difference vegetation index (NDVI) values of 0.2–0.4] along the main watercourses in the marshy Mesopotamia valley. Although sheep were the host most commonly infested by C. bezziana, local sheep density was not found to be a major factor in disease spread. Satellite imagery and the application of Geographical Information System (GIS) tools were found to be valuable in understanding the distribution of OWS in relation to vegetation and watercourses. The presence of screwworm in Iraq, at the perimeter of the intercontinental OWS distribution, may give rise to major seasonal flare‐ups.
Amazonian malaria vector anopheline relationships interpreted from ITS2 rDNA sequences
Authors: Marrelli M. T. , Floeter‐Winter L. M. , Malafronte R. S. , Tadei W.P. , Lourenço‐de‐oliveira R. , Flores‐Mendoza C. , Marinotti O.
Published: June 2005

Abstract.  Species identification of anopheline mosquitoes (Diptera: Culicidae) can be problematic because many of them belong to complexes of morphologically similar species, often with contrasted ecology, behaviour and vectorial importance. The application of DNA‐based diagnostics has proved to be useful for distinguishing between such species. We determined ribosomal DNA sequences of the second internal transcribed spacer (ITS2) from samples of 16 species of Anopheles captured in the Amazon Basin, Brazil. Length of the ITS2 varied from 323 to 410 base pairs, with GC content ranging from 50.7% to 66.5% and sequence identity from 25% to 99% between species. Maximum‐likelihood paup analysis separated two distinct groups of species conforming with the recognized subgenera Anopheles (represented by eiseni, mattogrossensis, mediopunctatus and peryassui) and Nyssorhynchus (represented by 12 spp.). For the latter group, the neighbour‐joining tree generated from rDNA sequence ITS2 relationships is compatible with the morphological taxonomic key established for these Amazonian species: albitarsis, aquasalis, benarrochi, braziliensis, darlingi, deaneorum, dunhami, evansae, nuneztovari, oswaldoi, rangeli and triannulatus. These ITS2 sequence data proved to be a useful tool for species identification and, potentially, to solve taxonomic problems.
Towards a more coherent oil policy in Russia?
Authors: Boussena Sadek , Locatelli Catherine
Published: June 2005

Two recent trends have rekindled the debate concerning the place and strategy of Russia on the world oil scene. The first is the development of its oil production and the second is the gradual resumption of control of the country's oil policy by President Vladimir Putin's government. Will Russia be a key variable in world energy balances and could the nation, as some suggest and even desire, become an alternative supply to OPEC and/or challenge Saudi Arabia's position? If so, is that what Russia actually wants? In this study, we attempt to answer some of these important questions by assessing and comparing the capabilities of the producing countries, while studying Russia's aims and objectives for the petroleum sector in the future, when demand for energy supplies is forecast to rise considerably.
The immunobiology of Guillain‐Barré syndromes
Authors: Willison Hugh J.
Published: June 2005

Abstract  This presentation highlights aspects of the immunobiology of the Guillain‐Barré syndromes (GBS), the world's leading cause of acute autoimmune neuromuscular paralysis. Understanding the key pathophysiological pathways of GBS and developing rational, specific immunotherapies are essential steps towards improving the clinical outcome of this devastating disorder. Much of the research into GBS over the last decade has focused on the forms mediated by anti‐ganglioside antibodies, and we have made substantial progress in our understanding in several related areas. Particular highlights include (a) the emerging correlations between anti‐ganglioside antibodies and specific clinical phenotypes, notably between anti‐GM1/anti‐GD1a antibodies and the acute motor axonal variant and anti‐GQ1b/anti‐GT1a antibodies and the Miller Fisher syndrome; (b) the identification of molecular mimicry between GBS‐associated Campylobacter jejuni oligosaccharides and GM1, GD1a, and GT1a gangliosides as a mechanism for anti‐ganglioside antibody induction; (c) the development of rodent models of GBS with sensory ataxic or motor phenotypes induced by immunisation with GD1b or GM1 gangliosides, respectively. Our work has particularly studied the motor nerve terminal as a model site of injury, and through combined active and passive immunisation paradigms, we have developed murine neuropathy phenotypes mediated by anti‐ganglioside antibodies. This has been achieved through use of glycosyltransferase and complement regulator knock‐out mice, both for cloning anti‐ganglioside antibodies and inducing disease. Through such studies, we have proven a neuropathogenic role for murine anti‐ganglioside antibodies and human GBS‐associated antisera and identified several determinants that influence disease expression including (a) the level of immunological tolerance to microbial glycans that mimic self‐gangliosides; (b) the ganglioside density in target tissue; (c) the level of complement activation and the neuroprotective effects of endogenous complement regulators; and (d) the role of calcium influx through complement pores in mediating axonal injury. Such studies provide us with clear information on an antibody‐mediated pathogenesis model for GBS and should lead to rational therapeutic testing of agents that are potentially suitable for use in humans.
Japanese multicenter phase II study of CHOP followed by radiotherapy in stage I–II1, diffuse large B‐cell lymphoma of the stomach
Authors: Ishikura Satoshi , Tobinai Kensei , Ohtsu Atsushi , Nakamura Shigeo , Yoshino Tadashi , Oda Ichiro , Takagi Toshiyuki , Mera Kiyomi , Kagami Yoshikazu , Itoh Kuniaki , Tamaki Yoshio , Suzumiya Junji , Taniwaki Masafumi , Yamamoto Seiichiro
Published: June 2005

CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) followed by radiotherapy is regarded as standard care for localized aggressive lymphoma; however, prospective confirmation of its applicability to localized primary gastric lymphoma is inadequate, and most patients in Japan have been initially treated with gastrectomy. We conducted a multicenter phase II study to evaluate the feasibility and efficacy of the non‐surgical treatment. Eligibility criteria required primary gastric diffuse large B‐cell lymphoma, stage I–II1, age 20–75, performance status 0–1 and adequate organ function. Treatment consisted of three cycles of CHOP followed by radiotherapy 40.5 Gy. Fifty‐five patients were enrolled between December 1999 and February 2003, and 52 eligible patients were analyzed. Patient characteristics were as follows: median age, 61 years; 28 men, 24 women; 36 with stage I, 16 with stage II1; 47 with a low International Prognostic Index (IPI) and five with a low–intermediate IPI. All but one patient completed planned treatment. No serious complications including massive hemorrhage or perforation were observed. A complete response was achieved in 48 of the 52 patients (92%, 95% confidence interval: 82–98%) and progressive disease in three. Two patients underwent salvage gastrectomy due to disease persistence or recurrence. With a median follow‐up period of 28 months, 2‐year progression‐free and overall survivals were 88 and 94%, respectively. CHOP followed by radiotherapy is safe and highly effective in localized gastric diffuse large B‐cell lymphoma. This organ‐preserving treatment should be considered as a very reasonable therapeutic option. (Cancer Sci 2005; 96: 349–352)