bluuebunny/crossref_metadata_2025 huggingface dataset:
Corticotropin-Releasing Hormone Augments Proinflammatory Cytokine Production from Macrophages In Vitro and in Lipopolysaccharide-Induced Endotoxin Shock in Mice
Authors: Agelaki Sofia , Tsatsanis Christos , Gravanis Achille , Margioris Andrew N.
Published: October 2002

Corticotropin-releasing hormone (CRH) exerts an anti-inflammatory effect indirectly, via cortisole production, and a proinflammatory effect directly on immune cells. The aim of the present work was to examine the effect of CRH on macrophage-derived cytokines both in vitro and in vivo. For the in vitro experiments we used two types of macrophages: (i) the RAW264.7 monocyte/macrophage cell line and (ii) thioglycolate-elicited peritoneal macrophages from BALB/c mice. We have found that CRH enhanced lipopolysaccharide (LPS)-induced tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), and IL-6 production. For the in vivo experiments we have used the LPS-induced endotoxin shock model in BALB/c mice, an established model for systemic inflammation in which macrophages are the major source of the proinflammatory cytokines responsible for the development of the shock. Administration of antalarmin, a synthetic CRH receptor 1 (CRHR1) antagonist, prior to LPS prolonged survival in a statistically significant manner. The effect was more evident at the early stages of endotoxin shock. CRHR1 blockade suppressed LPS-induced elevation of the macrophage-derived cytokines TNF-α, IL-1β, and IL-6, confirming the role of CRH signals in cytokine expression. In conclusion, our data suggest that CRH signals play an early and crucial role in augmenting LPS-induced proinflammatory cytokine production by macrophages. Our data suggest that the diffuse neuroendocrine system via CRH directly affects the immune system at the level of macrophage activation and cytokine production.
Responses of Bovine WC1+γδ T Cells to Protein and Nonprotein Antigens ofMycobacterium bovis
Authors: Welsh Michael D. , Kennedy Hilary E. , Smyth Allister J. , Girvin R. Martyn , Andersen Peter , Pollock John M.
Published: October 2002

WC1+γδ T cells ofMycobacterium bovis-infected cattle are highly responsive toM. bovissonic extract (MBSE). In mycobacterial infections of other species, γδ T cells have been shown to respond to protein and nonprotein antigens, but the bovine WC1+γδ T-cell antigenic targets within MBSE require further definition in terms of the dominance of protein versus nonprotein components. The present study sought to characterize the WC1+γδ T-cell antigenic targets, together with the role of interleukin-2 (IL-2), in the context ofM. bovisinfection. This was achieved by testing crude and defined antigens to assess protein versus nonprotein recognition by WC1+γδ T cells in comparison with CD4+αβ T cells. Both cell types proliferated strongly in response to MBSE, with CD4+T cells being the major producers of gamma interferon (IFN-γ). However, enzymatic digestion of the protein in MBSE removed its ability to stimulate CD4+T-cell responses, whereas some WC1+γδ T-cell proliferation remained. The most antigenic protein inducing proliferation and IFN-γ secretion in WC1+γδ T-cell cultures was found to be ESAT-6, which is a potential novel diagnostic reagent and vaccine candidate. In addition, WC1+γδ T-cell proliferation was observed in response to stimulation with prenyl pyrophosphate antigens (isopentenyl pyrophosphate and monomethyl phosphate). High levels of cellular activation (CD25 expression) resulted from MBSE stimulation of WC1+γδ T cells from infected animals. A similar degree of activation was induced by IL-2 alone, but for WC1+γδ T-cell division IL-2 was found to act only as a costimulatory signal, enhancing antigen-driven responses. Overall, the data indicate that protein antigens are important stimulators of WC1+γδ T-cell proliferation and IFN-γ secretion inM. bovisinfection, with nonprotein antigens inducing significant proliferation. These findings have important implications for diagnostic and vaccine development.
Genetic Analysis and Functional Characterization of the
Streptococcus pneumoniae vic
Operon
Authors: Wagner Christian , Saizieu Antoine de , Schönfeld Hans-Joachim , Kamber Markus , Lange Roland , Thompson Charles J. , Page Malcolm G.
Published: October 2002

The
vic
two-component signal transduction system of
Streptococcus pneumoniae
is essential for growth. The
vic
operon comprises three genes encoding the following: VicR, a response regulator of the OmpR family; VicK, its cognate histidine kinase; and VicX, a putative protein sharing 55% identity to the predicted product (YycJ) of an open reading frame in the
Bacillus subtilis
genome. We show that not only is vic essential for viability but it also influences virulence and competence. A putative transcriptional start site for the
vic
operon was mapped 16 bp upstream of the ATG codon of
vicR
. Only one transcript of 2.9 kb, encoding all three genes, was detected by Northern blot analysis. VicK, an atypical PAS domain-containing histidine kinase, can be autophosphorylated in vitro, and VicR functions in vitro as a phospho-acceptor protein. (PAS is an acronym formed from the names of the proteins in which the domains were first recognized: the Drosophila period clock protein [PER], vertebrate aryl hydrocarbon receptor nuclear translocator [ARNT], and Drosophila single-minded protein [SIM].) PAS domains are commonly involved in sensing intracellular signals such as redox potential, which suggests that the signal for
vic
might also originate in the cytoplasm. Growth rate, competence, and virulence were monitored in strains with mutations in the vic operon. Overexpression of the histidine kinase, VicK, resulted in decreased virulence, whereas the transformability of a null mutant decreased by 3 orders of magnitude.
The
Haemophilus ducreyi
Serum Resistance Antigen DsrA Confers Attachment to Human Keratinocytes
Authors: Cole Leah E. , Kawula Thomas H. , Toffer Kristen L. , Elkins Christopher
Published: October 2002

Haemophilus ducreyi
is the etiologic agent of the sexually transmitted genital ulcer disease chancroid.
H. ducreyi
serum resistance protein A (DsrA) is a member of a family of multifunctional outer membrane proteins that are involved in resistance to killing by human serum complement. The members of this family include YadA of
Yersinia
species, the UspA proteins of
Moraxella catarrhalis
, and the Eib proteins of
Escherichia coli.
The role of YadA, UspA1, and UspA2H as eukaryotic cell adhesins and the function of UspA2 as a vitronectin binder led to our investigation of the cell adhesion and vitronectin binding properties of DsrA. We found that DsrA was a keratinocyte-specific adhesin as it was necessary and sufficient for attachment to HaCaT cells, a keratinocyte cell line, but was not required for attachment to HS27 cells, a fibroblast cell line. We also found that DsrA was specifically responsible for the ability of
H. ducreyi
to bind vitronectin. We then theorized that DsrA might use vitronectin as a bridge to bind to human cells, but this hypothesis proved to be untrue as eliminating HaCaT cell binding of vitronectin with a monoclonal antibody specific to integrin α
v
β
5
did not affect the attachment of
H. ducreyi
to HaCaT cells. Finally, we wanted to examine the importance of keratinocyte adhesion in chancroid pathogenesis so we tested the wild-type and
dsrA
mutant strains of
H. ducreyi
in our swine models of chancroid pathogenesis. The
dsrA
mutant was less virulent than the wild type in both the normal and immune cell-depleted swine models of chancroid infection.
Transfer of the Cholera Toxin A1 Polypeptide from the Endoplasmic Reticulum to the Cytosol Is a Rapid Process Facilitated by the Endoplasmic Reticulum-Associated Degradation Pathway
Authors: Teter Ken , Allyn Rebecca L. , Jobling Michael G. , Holmes Randall K.
Published: October 2002

The active pool of internalized cholera toxin (CT) moves from the endosomes to the Golgi apparatus en route to the endoplasmic reticulum (ER). The catalytic CTA1 polypeptide is then translocated from the ER to the cytosol, possibly through the action of the ER-associated degradation (ERAD) pathway. Translocation was previously measured indirectly through the downstream effects of CT action. We have developed a direct biochemical assay for CTA1 translocation that is independent of toxin activity. Our assay is based upon the farnesylation of a CVIM motif-tagged CTA1 polypeptide (CTA1-CVIM) after it enters the cytosol. When expressed from a eukaryotic vector in transfected CHO cells, CTA1-CVIM was targeted to the ER, but was not secreted. Instead, it was translocated into the cytosol and degraded in a proteosome-dependent manner. Translocation occurred rapidly and was monitored by the appearance of farnesylated CTA1-CVIM in the detergent phase of cell extracts generated with Triton X-114. Detergent-phase partitioning of CTA1-CVIM resulted from the cytoplasmic addition of a 15-carbon fatty acid farnesyl moiety to the cysteine residue of the CVIM motif. Our use of the CTA1-CVIM translocation assay provided supporting evidence for the ERAD model of toxin translocation and generated new information on the timing of CTA1 translocation.
Acquisition of Regulators of Complement Activation byStreptococcus pyogenesSerotype M1
Authors: Pandiripally Vinod , Gregory Eugene , Cue David
Published: October 2002

Opsonization of bacteria by complement proteins is an important component of the immune response. The pathogenic bacteriumStreptococcus pyogeneshas evolved multiple mechanisms for the evasion of complement-mediated opsonization. One mechanism involves the binding of human regulators of complement activation such as factor H (FH) and FH-like protein 1 (FHL-1). Acquisition of these regulatory proteins can limit deposition of the opsonin C3b on bacteria, thus decreasing the pathogen's susceptibility to phagocytosis. Binding of complement regulatory proteins byS. pyogeneshas previously been attributed to the streptococcal M and M-like proteins. Here, we report that theS. pyogenescell surface protein Fba can mediate binding of FH and FHL-1. We constructed mutant derivatives ofS. pyogenesthat lack Fba, M1 protein, or both proteins and assayed the strains for FH binding, susceptibility to phagocytosis, and C3 deposition. Fba expression was found to be sufficient for binding of purified FH as well as for binding of FH and FHL-1 from human plasma. Plasma adsorption experiments also revealed that M1+Fba+streptococci preferentially bind FHL-1, whereas M1−Fba+streptococci have similar affinities for FH and FHL-1. Fba was found to contribute to the survival of streptococci incubated with human blood and to inhibit C3 deposition on bacterial cells. Streptococci harvested from log-phase cultures readily bound FH, but binding was greatly reduced for bacteria obtained from stationary-phase cultures. Bacteria cultured in the presence of the protease inhibitor E64 maintained FH binding activity in stationary phase, suggesting that Fba is removed from the cell surface via proteolysis. Western analyses confirmed that E64 stabilizes cell surface expression of Fba. These data indicate that Fba is an antiopsonic, antiphagocytic protein that may be regulated by cell surface proteolysis.
Induction of Cytolytic Anti-Gal Antibodies in α-1,3-Galactosyltransferase Gene Knockout Mice by Oral Inoculation withEscherichia coliO86:B7 Bacteria
Authors: Posekany Karla J. , Pittman H. Keith , Bradfield John F. , Haisch Carl E. , Verbanac Kathryn M.
Published: October 2002

Naturally occurring antibodies against [Gal α-1,3-Gal] structures (anti-Gal antibodies) are the primary effectors of human hyperacute rejection (HAR) of nonhuman tissue. Unlike most mammals, humans lack a functional α-1,3-galactosyltransferase (GalT) gene and produce abundant anti-Gal antibodies, putatively in response to GalT+enteric bacteria. GalT knockout (KO) mice have been generated as a small animal model of HAR but inconsistently express anti-Gal antibodies. We hypothesized that enteric exposure of GalT KO mice to live GalT+bacteria would produce cytolytic anti-Gal antibodies. Naive mice lacking anti-Gal antibodies were orally immunized with 1010live GalT+Escherichia coliO86:B7 bacteria and assayed for anti-Gal antibody titer, isotype, and cytolytic activity. Fecal samples were tested forE. coliO86:B7 prior to and after inoculation. In two separate experiments, 77 to 100% (n= 31) of mice developed serum anti-Gal immunoglobulin G (IgG; titer, 1:5 to 1:80) and/or anti-Gal IgM antibodies (titer, 1:5 to 1:1,280) 14 days postinoculation. Induced anti-Gal antibodies caused complement-mediated cytolysis of GalT+target cells, with extensive cytolysis observed consistently at serum IgM titers of ≥1:320. Absorption with synthetic [Gal α-1,3-Gal] inhibited both antibody binding and cytolysis.E. coliO86:B7 was recovered from stool samples from 83 to 94% of inoculated mice but not from naive mice, thus confirming enteric exposure. These findings demonstrate that oral inoculation withE. coliO86:B7 is a novel and effective method to induce cytolytic anti-Gal antibodies in GalT KO mice and support the premise that enteric exposure to GalT+bacteria induces anti-Gal antibodies in humans. These studies also suggest a role for GalT KO mice in elucidating anti-Gal responses in microbial immunity.
Tumor Necrosis Factor Alpha-Induced Interleukin-8 Production via NF-κB and Phosphatidylinositol 3-Kinase/Akt Pathways Inhibits Cell Apoptosis in Human Hepatocytes
Authors: Osawa Yosuke , Nagaki Masahito , Banno Yoshiko , Brenner David A. , Asano Takahiko , Nozawa Yoshinori , Moriwaki Hisataka , Nakashima Shigeru
Published: October 2002

Tumor necrosis factor alpha (TNF-α) not only induces apoptotic signals but also causes antiapoptotic and regenerative responses in the liver. However, the molecular mechanism(s) of the latter events remains unclear. In the present study, we examined TNF-α-induced genes in Hc human normal (unsensitized) hepatocytes by cDNA microarray analysis. Interleukin-8 (IL-8) induction was the most pronounced of the upregulated genes. The IL-8 protein level was also increased. IL-8 belongs to the ELR-CXC chemokine family and appears to exert mitogenic and antiapoptotic functions in other cell systems. IL-8 expression by TNF-α was inhibited when two survival signals, nuclear factor κB (NF-κB) and phosphatidylinositol 3-kinase (PI3K)/Akt, were inhibited by a mutant form of inhibitor of NF-κB (IκB); by dominant negative (kinase-dead) Akt; or by treatment with LY 294002, an inhibitor of PI3K. TNF-α induced apoptosis in Hc cells that were sensitized by inhibition of NF-κB and PI3K activation. IL-8 administration protected mice against concanavalin A-induced hepatitis in vivo. IL-8 also rescued the sensitized Hc cells, at least in part, from TNF-α-induced apoptosis in vitro. TNF-α inhibited DNA synthesis in unsensitized Hc cells in the absence of serum. Exogenous IL-8 reversed, though anti-IL-8 neutralization antibody enhanced, growth inhibition by TNF-α. These results indicate that IL-8, the production of which is stimulated by TNF-α, inhibits apoptosis of sensitized hepatocytes and releases normal (unsensitized) hepatocytes from growth inhibition induced by TNF-α.
Activation of NKT Cells Protects Mice from Tuberculosis
Authors: Chackerian Alissa , Alt Jen , Perera Vaji , Behar Samuel M.
Published: October 2002

The T-cell immune response toMycobacterium tuberculosisis critical in preventing clinical disease. While it is generally accepted that both major histocompatibility complex class I (MHC-I)-restricted CD8+and MHC-II-restricted CD4+T cells are important for the immune response toM. tuberculosis, the role of non-MHC-restricted T cells is still not clearly delineated. We have previously reported that CD1d−/−mice do not differ from CD1d+/+mice in their survival following infection withM. tuberculosis. We now show that, although CD1d-restricted NKT cells are not required for optimum immunity toM. tuberculosis, specific activation of NKT cells by the CD1d ligand α-galactosylceramide protects susceptible mice from tuberculosis. Treatment with α-galactosylceramide reduced the bacterial burden in the lungs, diminished tissue injury, and prolonged survival of mice following inoculation with virulentM. tuberculosis. The capacity of activated NKT cells to stimulate innate immunity and modulate the adaptive immune response to promote a potent antimicrobial immune response suggests that α-galactosylceramide administration could have a role in new strategies for the therapy of infectious diseases.
Genetic Structure and Distribution of Four Pathogenicity Islands (PAI I
536
to PAI IV
536
) of Uropathogenic
Escherichia coli
Strain 536
Authors: Dobrindt Ulrich , Blum-Oehler Gabriele , Nagy Gabor , Schneider György , Johann André , Gottschalk Gerhard , Hacker Jörg
Published: October 2002

For the uropathogenic
Escherichia coli
strain 536 (O6:K15:H31), the DNA sequences of three pathogenicity islands (PAIs) (PAI I
536
to PAI III
536
) and their flanking regions (about 270 kb) were determined to further characterize the virulence potential of this strain. PAI I
536
to PAI III
536
exhibit features typical of PAIs, such as (i) association with tRNA-encoding genes; (ii) G+C content differing from that of the host genome; (iii) flanking repeat structures; (iv) a mosaic-like structure comprising a multitude of functional, truncated, and nonfunctional putative open reading frames (ORFs) with known or unknown functions; and (v) the presence of many fragments of mobile genetic elements. PAI I
536
to PAI III
536
range between 68 and 102 kb in size. Although these islands contain several ORFs and known virulence determinants described for PAIs of other extraintestinal pathogenic
E. coli
(ExPEC) isolates, they also consist of as-yet-unidentified ORFs encoding putative virulence factors. The genetic structure of PAI IV
536
, which represents the core element of the so-called high-pathogenicity island encoding a siderophore system initially identified in pathogenic yersiniae, was further characterized by sample sequencing. For the first time, multiple PAI sequences (PAI I
536
to PAI IV
536
) in uropathogenic
E. coli
were studied and their presence in several wild-type
E. coli
isolates was extensively investigated. The results obtained suggest that these PAIs or at least large fragments thereof are detectable in other pathogenic
E. coli
isolates. These results support our view that the acquisition of large DNA regions, such as PAIs, by horizontal gene transfer is an important factor for the evolution of bacterial pathogens.
Association ofPasteurella multocidaToxin with Vimentin
Authors: Shime Hiroaki , Ohnishi Takahiro , Nagao Kaori , Oka Kiyomasa , Takao Toshifumi , Horiguchi Yasuhiko
Published: October 2002

To help understand the molecular mechanisms ofPasteurella multocidatoxin (PMT) action, we searched for a cellular protein interacting with PMT. The ligand overlay assay revealed a 60-kDa cellular protein that binds to a region from the 840th to 985th amino acids of the toxin. This protein was identified as vimentin by peptide mass fingerprinting. The N-terminal head domain of vimentin was further found to be responsible for the binding to the toxin.
Parenteral Administration of Medium- but Not Long-Chain Lipid Emulsions May Increase the Risk for Infections byCandida albicans
Authors: Wanten Geert J. , Netea Mihai G. , Naber Ton H. , Curfs Jo H. , Jacobs Liesbeth E. , Verver-Jansen Trees J. , Kullberg Bart-Jan
Published: October 2002

Intravenous administration to volunteers of an emulsion of medium-chain lipids, but not of an emulsion of pure long-chain lipids or a placebo, increased the growth ofCandida albicansin serum and modulatedCandida-induced cytokine production by mononuclear cells in a way suggesting that medium-chain, but not long-chain, triglycerides increase the risk for infections byCandida.
COHERENCE OF THE GLASSY STATE
Authors: BUZZACCHI M. , DEL GIUDICE E. , PREPARATA G.
Published: October 2002

Glasses are known to possess some puzzling features among condensed matter systems, as shown by the Kauzmann paradox. We show that if the coherent interaction mechanisms of Quantum Electrodynamics are taken into account, glasses are nothing but molecular liquids in which a large fraction of the molecules enter a collective, coherent state. In this conceptual framework the temperature of glass formation can be identified with the temperature at which the non-coherent fraction vanishes. Using a recently developed treatment of liquid water where QED interactions are not neglected, we suggest a possible interpretation of the surprising finding of two low-temperature water amorphs and of their phase-transition.
THE SECOND VISCOSITY OF SUPERFLUID 6Li
Authors: SHAHZAMANIAN M. A. , YAVARY H.
Published: October 2002

The second viscosity of superfluid 6 Li has been formulated in the scope of Boltzmann equation approach. Due to the isotropy of the energy gap and in the weak coupling limit, calculation of the second viscosity is possible for temperatures near T c and near zero temperature analytically. The value of the second viscosity is temperature independent in the limit of low temperatures, and in the near transition temperature behaves as invers of the gap parameter.
DYNAMICAL LOCALIZATION IN MESOSCOPIC JOSEPHSON JUNCTIONS
Authors: YU KAI-ZHI , GOU BING-CONG , ZOU JIAN
Published: October 2002

In this paper we use numerical method to study the quantum effect of dynamical localization in a mesoscopic Josephson junction driven by a periodically external electromagnetic field. We find that the charge is localized effectively for the case when the ratio of the field magnitude and the field frequency is less than a certain value. In this case too the magnitude of the supercurrent remains a constant.
RESISTIVITY BEHAVIOR OF La0.67Ca0.33MnO3/YBa2Cu3O7-δ EPITAXIAL HETEROSTRUCTURE
Authors: TAN W. S. , WU X. S. , SHA H. , JIANG S. S.
Published: October 2002

The heterostructure La 0.67 Ca 0.33 MnO 3/ YBa 2 Cu 3 O 7-δ (LCMO/YBCO) bilayers with a fixed LCMO thickness and varying YBCO thickness were deposited on (001)-oriented single crystal SrTiO 3 (STO) substrate and its resistivity properties were investigated by standard four-probe technique without magnetic field applied. The X-ray diffraction (XRD) analysis shows that all the bilayers were well c-oriented grown. The resistivity measurement indicated that the bilayer's properties change from superconductivity to magnetism with the decrease of the thickness of the capping layer YBCO. There exists a critical thickness of YBCO, in which case the superconductivity and magnetism coexist in bilayer. We believe that the lattice strain and spin-polarized carriers injection are the main origin of the above-mentioned resistivity behavior.
THE HEATH–JARROW–MORTON DURATION AND CONVEXITY: A GENERALIZED APPROACH
Authors: FRÜHWIRTH MANFRED
Published: October 2002

This paper extends the traditional duration measure for continuous-time Heath–Jarrow–Morton models. The result is a general Heath–Jarrow–Morton duration measure based on a zero-coupon yield for an arbitrary maturity as state variable. A convexity measure compatible to this generalized duration is derived. In addition, closed-form solutions are presented for two popular example models.
THE EFFICIENT FRONTIER OF LONG-SHORT PORTFOLIOS
Authors: CHARPIN FRANÇOISE , LACAZE DOMINIQUE
Published: October 2002

Long-short strategies are now frequently implemented especially by hedge fund managers, or simply by active equity managers. Nevertheless, in the literature, the superiority of long-short strategies on long-only strategies still remains a debated point. A comparison of these strategies requires an efficient-frontier analysis. However such analysis to be relevant must integrate the specific regulation on long-short portfolios which exists on all stock markets. This paper studies the efficient frontier of long-short portfolios taking into account the regulatory constraints. A numerical resolution is proposed using the American regulations. A comparison with leveraged and unleveraged long-only strategies is presented showing the potential benefits of long-short investing.
PERFECT HEDGING OF INDEX DERIVATIVES UNDER A MINIMAL MARKET MODEL
Authors: HEATH DAVID , PLATEN ECKHARD
Published: October 2002

The paper presents a financial market model that generates stochastic volatility using a minimal set of factors. These factors, formed by transformations of square root processes, model the dynamics of different denominations of a benchmark portfolio. Benchmarked prices are assumed to be local martingales. Numerical results for the pricing and hedging of basic derivatives on indices are described for the minimal market model. This includes cases where the standard risk neutral pricing methodology fails because of the presence of a strict local martingale measure. However, payoffs can be perfectly hedged using self-financing strategies and a form of arbitrage exists. This is illustrated by hedge simulations. The different term structure of implied volatilities is documented for calls and puts on an index.
EXTENDING MIRROR CONJECTURE TO CALABI–YAU WITH BUNDLES
Authors: VAFA CUMRUN
Published: October 2002

We define the notion of mirror of a Calabi–Yau manifold with a stable bundle in the context of type II strings in terms of supersymmetric cycles on the mirror. This allows us to relate the variation of Hodge structure for cohomologies arising from the bundle to the counting of holomorphic maps of Riemann surfaces with boundary on the mirror side. Moreover it opens up the possibility of studying bundles on Calabi–Yau manifolds in terms of supersymmetric cycles on the mirror.
HOLOMORPHIC QUANTIZATION FORMULA IN SINGULAR REDUCTION
Authors: ZHANG WEIPING
Published: October 2002

We show that the holomorphic Morse inequalities proved by Tian and the author [8, 9] are in effect equalities by refining the analytic arguments in [8, 9].
TWISTED INDEX THEORY ON GOOD ORBIFOLDS, I: NONCOMMUTATIVE BLOCH THEORY
Authors: MARCOLLI MATILDE , MATHAI VARGHESE
Published: October 2002

We study the twisted index theory of elliptic operators on orbifold covering spaces of compact good orbifolds, which are invariant under a projective action of the orbifold fundamental group. We apply these results to obtain qualitative results on real and complex hyperbolic spaces in two and four dimensions, related to generalizations of the Bethe–Sommerfeld conjecture and the Ten Martini Problem, on the spectrum of self adjoint elliptic operators which are invariant under a projective action of a discrete cocompact group.
Testosterone Diminishes the Proarrhythmic Effects of Dofetilide in Normal Female Rabbits
Authors: Pham Thai V. , Sosunov Eugene A. , Anyukhovsky Evgeny P. , Danilo Peter , Rosen Michael R.
Published: October 2002

Background—

Recent clinical and experimental data suggest that testosterone may protect males against the deleterious effects of repolarization-prolonging drugs. This study tests the hypothesis that 5α-dihydrotestosterone (DHT) protects normal females against drug-induced excessive prolongation of repolarization.

Methods and Results—

We used microelectrode techniques to study isolated preparations of rabbit ventricular endocardium from age-matched normal control female rabbits and female rabbits treated with DHT for 4 weeks. Serum 17β-estradiol levels were identical in the control and DHT-treated animals, whereas DHT levels were high (equaling those in normal males) only in the DHT-treated animals. Basal action potential duration to 90% repolarization (APD
90
) was significantly shorter in DHT-treated (155±7.4 ms, n=32) than control females (178±6.7 ms, n=29;
P
<0.05) at cycle length=1000 ms. The increase in APD
90
induced by 10
−8
mol/L dofetilide at cycle length=1000 ms was significantly less in DHT-treated females than normal females (ΔAPD
90
=8±7 and 29±5 ms, respectively,
P
<0.05). At 10
−6
mol/L dofetilide, the incidence of early afterdepolarizations was 28% in DHT-treated and 55% in normal female rabbits (
P
<0.05).

Conclusions—

Elevating DHT levels diminishes the effects of dofetilide to increase APD and induce early afterdepolarizations in females. Moreover, treatment of females with DHT results in prolongation of APD and an incidence of early afterdepolarization equal to values previously reported by us for dofetilide-treated normal males. That serum levels of 17β-estradiol were the same in DHT-treated and untreated females suggests that estradiol is not involved in the response to dofetilide. Thus, these data suggest that DHT and perhaps other androgenic hormones may protect normal females against the risk of dofetilide-induced arrhythmia.
Thrombin Facilitation of Voltage-Gated Sodium Channel Activation in Human Cardiomyocytes
Authors: Pinet Caroline , Le Grand Bruno , John Gareth W. , Coulombe Alain
Published: October 2002

Background—

Thrombin plays a role in mediating ischemic injury and cardiac arrhythmias, but the mechanisms involved are poorly understood. Because voltage-gated sodium channels (VGSCs) have not previously been considered, putative effects of thrombin on VGSC function were investigated in human isolated cardiomyocytes.

Methods and Results—

Sodium current (I
Na
) was recorded by the whole-cell patch-clamp method. Thrombin increased peak I
Na
amplitude in an activity-dependent manner, from 1 to 100 U/mL, with an apparent EC
50
of 91±16 U/mL. When tested at 32 U/mL, thrombin-increased I
Na
was abolished by tetrodotoxin (50 μmol/L). Thrombin effects on I
Na
were reversible and repeatable, and 100 U/mL doubled peak I
Na
amplitude. Thrombin (32 U/mL) shifted I
Na
activation to hyperpolarized potentials without affecting steady-state inactivation, producing unusually large increases in window current. Hirudin (320 U/mL) or haloenol lactone suicide substrate (10 μmol/L) failed to significantly affect these effects of thrombin. In current-clamped cardiomyocytes, thrombin (32 U/mL) depolarized resting membrane potential by 10 mV.

Conclusions—

Facilitation of VGSC activation causing large increases in window current is a major mechanism by which thrombin may promote ischemic sodium loading and injury.
PAUL'S APPROPRIATION OF THE ROLE OF THE FOOL IN 1 CORINTHIANS 1–4
Authors: Welborn Laurence
Published: October 2002

This essay suggests that Paul's acceptance of the role of the "fool," and, arising out of this, his evaluation of the message of the cross as "folly," are best understood against the background of the popular theater and the fool's role in mime. The interpretation is, therefore, a corrective to the traditional view that the proclamation of the crucified Christ was an absurdity to the people of the ancient world. The essay also offers an alternative to the attempt, in some recent monographs and commentaries, to subsume Paul's "foolishness" under the category of the anti-rhetorical. The essay argues that the term "folly" was generally understood as a designation of the attitude and behavior of a particular social type, the lower class buffoon. As a source of amusement, these lower class types were widely represented on the stage in the vulgar and realistic comedy known as the mime. The essay suggests that Paul's Corinthian detractors labeled him as a "fool," in contrast to the eloquent and sophisticated Apollos. Paul's acceptance of the role of the fool mirrors the strategy of a number of intellectuals in the early Empire, who exploited the paradoxical freedom which the role permitted for the utterance of a dangerous truth.
Application of X‐ray microscopy in analysis of living hydrated cells
Authors: Yamamoto Yoshimasa , Shinohara Kunio
Published: October 2002

Because there is a limit for analysis of fine hydrophilic cell structures of living cells in medium by ordinary techniques, including electron microscopy, the development of a new technology to overcome such limitation is highly desirable. In this regard, soft X‐ray microscopy (high‐resolution X‐ray imaging of structures), which does not require any special procedures for sample preparation, has been developed and applied to analyze structures of biological specimens. In this article, application of two types of X‐ray microscopes, which use laser‐produced plasma X‐rays or synchrotron radiation to image the structure of macrophage cells, is introduced as an example of a novel approach to analysis of biological specimens. Both types of X‐ray microscopy show the network of fine fibrillar surface structures on macrophages in medium. Ordinary transmission and scanning electron microscopy and light microscopy also show the presence of such structures, but electron microscopy showed alterations due to sample processing and light microscopy did not show a clear image due to low resolution. Thus, X‐ray microscopy has the potential capability to analyze structures of live cells in a hydrated condition and may reveal a function‐related structural alignment of cells in their natural form. Anat Rec (New Anat) 269:217–223, 2002. © 2002 Wiley‐Liss, Inc.
The use of brainstorming for teaching human anatomy
Authors: Geuna S. , Giacobini‐Robecchi M.G.
Published: October 2002

Interactive teaching techniques have been used mainly in clinical teaching, with little attention given to their use in basic science teaching. With the aim of partially filling this gap, this study outlines an interactive approach to teaching anatomy based on the use of “brainstorming.” The results of the students' critique of the teaching techniques are also included. Seventy‐five students from the first‐year nursing curriculum were tested by a structured questionnaire after three brainstorming sessions. The overall response to these sessions was very positive, indicating that students perceived this interactive technique as both interesting and useful. Furthermore, this approach may provide a useful strategy when learning the clinical courses of the upcoming academic years. Anat Rec (New Anat) 269:214–216, 2002. © 2002 Wiley‐Liss, Inc.
Intracellular signaling in M‐CSF‐induced microglia activation: Role of Iba1
Authors: Imai Yoshinori , Kohsaka Shinichi
Published: October 2002

Microglia are reactively activated by various environmental stimulations caused by brain injury or disease. Activated microglia exhibit morphological transformation, proliferation, migration, phagocytosis, and the production of bioactive molecules. Various molecules are reported and suggested to activate microglia. Among them, macrophage‐colony‐stimulating factor (M‐CSF) is considered one of the most convincing candidates responsible for maintaining activation properties of microglia. Therefore, the focus of the present study is on intracellular molecular events that arise downstream of M‐CSF stimulation. M‐CSF activates its receptor, Fms tyrosine kinase, and Fms sequentially activates a number of signaling molecules, including PI3K or phospholipase Cγ (PLCγ). Stimulation of continuing signaling cascades results in the activation of a small GTPase, Rac, the key molecule in microglia activation. Rac is known to be activated downstream of receptor tyrosine kinases and to regulate reorganization of the actin cytoskeleton, which profoundly underlies the above‐mentioned properties of activated microglia. Iba1, a macrophage/microglia‐specific calcium‐binding protein, was identified by our group and was shown to be involved in the Rac signaling pathway. Further, we introduce a novel signaling pathway in which Rac is activated, dependent on PLCγ and Iba1. However, to understand the molecular details of microglia activation, future work is required. GLIA 40:164–174, 2002. © 2002 Wiley‐Liss, Inc.
Calcium signaling in microglial cells
Authors: Möller Thomas
Published: October 2002

Receptor‐mediated Ca2+ signals are a common signal transduction mechanism in all living cells, including microglia. Recent years have brought major advances in our understanding of microglial Ca2+ signaling. More than 20 receptor/ligand interactions leading to Ca2+ signals in microglia have been described so far, and it seems that this is just the beginning. The literature has grown rapidly during the past few years, especially in regard to chemokine and ATP/UTP receptor signaling. This article presents a brief overview of the basics of Ca2+ signaling, reviews the current literature on microglial Ca2+ signaling, and discusses the current challenges and possible future directions of this emerging field. GLIA 40:184–194, 2002. © 2002 Wiley‐Liss, Inc.
Microglia and inflammatory mechanisms in the clearance of amyloid β peptide
Authors: Rogers Joseph , Strohmeyer Ron , Kovelowski C.J. , Li Rena
Published: October 2002

There is now abundant evidence that brain microglia, when activated, have the lineage, receptors, and synthetic capacity to participate in both potentially neurotoxic inflammatory responses and potentially beneficial phagocytic responses. Amyloid β peptide (Aβ) forms highly insoluble, β‐pleated aggregates that are widely deposited in the Alzheimer's disease (AD) cortex and limbic system. Aggregated Aβ also activates the classical and alternative complement cascades. These properties make Aβ an excellent target for microglial phagocytosis, a view supported by multiple reports, through well established mechanisms of phagocyte clearance. GLIA 40:260–269, 2002. © 2002 Wiley‐Liss, Inc.
A model of broker's trading, with applications to order flow internalization
Authors: Chakravarty Sugato , Sarkar Asani
Published: October 2002

Although brokers' trading is endemic in securities markets, the form of this trading differs between markets. Whereas in some securities markets, brokers may trade with their customers in the same transaction (simultaneous dual trading or SDT), in other markets, brokers are only allowed to tradeaftertheir customers in a separate transaction (consecutive dual trading or CDT). We show theoretically that informed and noise traders are worse off and brokers are better off while market depth is lower in the SDT market. Thus, given a choice, traders prefer fewer brokers in the SDT market compared to the CDT market. With free entry, however, market depth may be higher in the SDT market provided its entry cost is sufficiently low relative to the CDT market. We study order flow internalization by broker‐dealers, and show that, in the free entry equilibrium, internalization hurts retail customers and market quality.
Membership growth, multiple membership groups and agency control at credit unions
Authors: Leggett Keith J , Strand Robert W
Published: October 2002

Starting in 1982, the federal credit union regulator allowed credit unions to add multiple membership groups. The policy was disallowed by the U.S. Supreme Court in 1998, but revalidated by the U.S. Congress later that year. Allowing credit unions to attach multiple membership groups has contributed significantly to rapid growth in the industry. As credit unions add unrelated groups and expand, the prospects for separation between ownership and control increases, creating potential agency control problems. This potential is compounded by the one member, one vote governance structure of credit unions. This research finds empirical evidence that agency problems grow as credit unions add membership groups and members. If a credit union takes on more than one membership group, and as membership increases, management is apparently able to channel residual earnings away from members (in the form of higher net interest margins) toward itself (higher salaries and operating expenses).
The authority of human nature: the Schädellehre of Franz Joseph Gall
Authors: VAN WYHE JOHN
Published: October 2002

This essay is the first account in English to examine Franz Joseph Gall and the origins of phrenology. In doing so a host of legends about Gall and the beginnings of phrenology, which exist only in the English-language historiography, are dispelled. An understanding of the context of phrenology's origins is essential to the historicization of the movement as a whole. The first of two sections in the essay, therefore, introduces Gall's biography and the context in which his provocative science emerged. It is shown to what extent Gall borrowed from other thinkers of his time. I show that Gall's system was meant to be a certain science of human nature. In the second section I analyse the reactions of contemporaries to Gall's important two-year lecture tour of Europe. I conclude that although many critics dismissed Gall as a charlatan, there was no consensus about the proper way to disseminate scientific knowledge or the attributes necessary for the gentleman of science. For example, it was not clear whether science could be profitable, whether it should be shared with lay audiences or whether it could in fact be science at all if it was also entertaining. I argue that in any case Gall's aim was never really to impart science or to disseminate his system. His science and early means of disseminating it were meant to generate elite intellectual status. In this Gall was quite successful.
Alfred Russel Wallace, Robert Owen and the theory of natural selection
Authors: JONES GRETA
Published: October 2002

Whereas there has been considerable debate about the social context of Darwin's theory of natural selection, much less focus has been placed upon Alfred Russel Wallace. This article looks at Wallace's socialism and, in particular, the influence upon his thought of the early nineteenth-century socialist Robert Owen. It argues that a case can be made for seeing Wallace's thought about nature and natural selection in the years up to 1858 in the context of Owenism. Three aspects of his thought are singled out for examination. These are, first, Wallace's views on the role of instinct in animal and human behaviour; second, the idea of colonization in human society and in nature; and third, a re-examination of the role of Malthus in Wallace's thought, emphasizing the influence upon him of the early nineteenth-century socialist critique of Malthusianism.
THE LEGALITY OF THE MANDATORY LIFE SENTENCE
Authors: Padfield Nicola
Published: October 2002

CHALLENGES to the mandatory life sentence by way of judicial review continue to hit the courts. Among the most dramatic are R. v. Lichniak and R. v. Pyrah [2001] EWHC Admin 294, [2001] 3 W.L.R. 933, where it was argued that the mandatory sentence violated Article 3 of the European Convention on Human Rights (prohibition of torture or degrading treatment or punishment) because it was disproportionate, and that it violated Article 5 of the Convention (right to liberty and security) because it was arbitrary. When Scott Baker J. granted leave to apply for judicial review he ordered that the court should sit both as a Divisional Court and as the Court of Appeal (Criminal Division). Kennedy L.J., giving the judgment of the Court of Appeal, held that “the most attractive route” was for the Court to sit as a division of the Court of Appeal.
INCORPORATING PARTICULARLY ONEROUS OR UNUSUAL TERMS
Authors: Elvin Jesse
Published: October 2002

INO’Brien v. MGN Ltd. [2001] EWCA Civ 1279, the Court of Appeal gave a significant decision dealing with the issue of incorporation of onerous or unusual terms.
China's New Scientific Elite: Distinguished Young Scientists, the Research Environment and Hopes for Chinese Science
Authors: Cao Cong , Suttmeier Richard P.
Published: October 2002

Based on interviews with scientists who have received the Distinguished Young Scientist award from the National Natural Science Foundation of China, the paper examines the backgrounds, experiences, and attitudes of China's rising scientific elite, and explores how this new generation of scientists thinks about the conditions necessary for scientific distinction. The new elite scientists in China show signs of having mastered the institutional environment for research; individually, they seem to be able to find the resources and autonomy to build successful research enterprises. At the same time, as the elite seeks to bridge the norms and practices of the best of international science and Chinese realities, their collective lives are subject to tensions, uncertainties, and contradictions which make the building of a dynamic scientific community especially challenging. As the institutional environment within China changes, scientists receive mixed signals as to the balance between professional and commercial values of research.
Hegemony and Workers' Politics in China
Authors: Blecher Marc J.
Published: October 2002

Workers' protests in the 1980s and 1990s, numerous and widely distributed though they may be, remain spasmodic, spontaneous and unco-ordinated. While the reasons are numerous, this article focuses on the role of workers' hegemonic acceptance of the core values of the market and the state. Data from interviews in Tianjin from 1995 to 1999 are used to explicate the existence of this hegemony. Several of its sources, some general, some specific to China, are then discussed. The findings are situated within recent scholarship on labour politics in China, and the prospects are discussed.
Chinatown and Transnationalism: Ethnic Chinese in Europe and Southeast Asia. By Gregor Benton and Edmund Terence Gomez. [Canberra: Australian National University, 2001. 40 pp. ISBN 0-909524-44-0.]
Authors: Alves Ana Cristina Dias
Published: October 2002

This occasional paper is a revised version of a paper presented in February 2000 at a symposium on “The Chinese transnational communities” and the first result of a wider research project currently being developed by Gregor Benton and Edmund Terence Gomez. In this succinct comparative study, the authors analyse the topic of trans-nationalism within the Chinese communities of the UK and South-East Asia, focusing on two main aspects: business style and political consciousness.
Legacies of the Comfort Women of World War II. Edited by Margaret D. Stetz and Bonnie B. C. Oh. [Armonk, NY: M. E. Sharpe, 2001. 230+xvi pp. Hard cover ISBN 0-7656-0543-0; paperback ISBN 0-7656-0544-9.]
Authors: Howard Keith
Published: October 2002

Accounts of the comfort women, including this one, suggest that up to 200,000 women were involved. Women were designated as without value. They lost all claim on their bodies, which were confiscated as war matériel. They became sexual slaves, raped, for the Japanese imperial army. Many died at the front line, or were murdered for sport or to ensure nobody would live to tell the tale. Penniless, displaced and dispossessed, many of those who survived could never return home. Few married, and few could have children.
The Chinese Lexicon: A Comprehensive Survey. By Yip Po-Ching. [London and New York: Routledge, 2000. ISBN 0-415-15174-0.]
Authors: Baker Hugh D. R.
Published: October 2002

The simple definition of “lexicon” in the Concise Oxford English Dictionary is “dictionary.” Unlike a dictionary, though, the words in this work cannot be consulted through an alphabetical index, the only access being afforded by the chapter headings and subheadings of the three-page Contents list at the front. It does not pretend to be nor is it a dictionary, it is a systematic attempt to classify and in part to explain the typology and functions of the word stock of Chinese. The Index is a guide to the descriptors rather than to the material described.
AFRICAN RICE IN THE COLUMBIAN EXCHANGE
Authors: CARNEY JUDITH A.
Published: October 2002

Most studies of the Columbian Exchange have not appreciated the significance of Africans in establishing plant domesticates in the Americas. African plants traversed the Atlantic as provisions aboard slave ships and slaves proved instrumental in their establishment in the New World as preferred food staples. This paper identifies the diverse crops domesticated in Africa, the intercontinental plant exchanges between Africa and Asia that occurred in the millennia before the Columbian Exchange and the role of African indigenous knowledge in establishing rice in the Americas.
WRITING HISTORIES OF CONTEMPORARY AFRICA
Authors: ELLIS STEPHEN
Published: October 2002

This essay argues that historians need to engage with the history of contemporary Africa both as a way of throwing new light on Africa's more remote past and as a way of understanding the present. The paper discusses two types of problem involved in such an enterprise. The first is the identification of the most fruitful themes for investigation. The second is the sources that may be used.