bluuebunny/crossref_metadata_2025 huggingface dataset:
mua-3, a gene required for mechanical tissue integrity in Caenorhabditis elegans, encodes a novel transmembrane protein of epithelial attachment complexes
Authors: Bercher Mark , Wahl Jim , Vogel Bruce E. , Lu Charles , Hedgecock Edward M. , Hall David H. , Plenefisch John D.
Published: July 2002

Normal locomotion of the nematode Caenorhabditis elegans requires transmission of contractile force through a series of mechanical linkages from the myofibrillar lattice of the body wall muscles, across an intervening extracellular matrix and epithelium (the hypodermis) to the cuticle. Mutations in mua-3 cause a separation of the hypodermis from the cuticle, suggesting this gene is required for maintaining hypodermal–cuticle attachment as the animal grows in size postembryonically. mua-3 encodes a predicted 3,767 amino acid protein with a large extracellular domain, a single transmembrane helix, and a smaller cytoplasmic domain. The extracellular domain contains four distinct protein modules: 5 low density lipoprotein type A, 52 epidermal growth factor, 1 von Willebrand factor A, and 2 sea urchin-enterokinase-agrin modules. MUA-3 localizes to the hypodermal hemidesmosomes and to other sites of mechanically robust transepithelial attachments, including the rectum, vulva, mechanosensory neurons, and excretory duct/pore. In addition, it is shown that MUA-3 colocalizes with cytoplasmic intermediate filaments (IFs) at these sites. Thus, MUA-3 appears to be a protein that links the IF cytoskeleton of nematode epithelia to the cuticle at sites of mechanical stress.
Transmission of growth cone traction force through apCAM–cytoskeletal linkages is regulated by Src family tyrosine kinase activity
Authors: Suter Daniel M. , Forscher Paul
Published: July 2002

Tyrosine kinase activity is known to be important in neuronal growth cone guidance. However, underlying cellular mechanisms are largely unclear. Here, we report how Src family tyrosine kinase activity controls apCAM-mediated growth cone steering by regulating the transmission of traction forces through receptor–cytoskeletal linkages. Increased levels of tyrosine phosphorylation were detected at sites where beads coated with apCAM ligands were physically restrained to induce growth cone steering, but not at unrestrained bead binding sites. Interestingly, the rate and level of phosphotyrosine buildup near restrained beads were decreased by the myosin inhibitor 2,3-butanedione-2-monoxime, suggesting that tension promotes tyrosine kinase activation. While not affecting retrograde F-actin flow rates, genistein and the Src family selective tyrosine kinase inhibitors PP1 and PP2 strongly reduced the growth cone's ability to apply traction forces through apCAM–cytoskeletal linkages, assessed using the restrained bead interaction assay. Furthermore, increased levels of an activated Src family kinase were detected at restrained bead sites during growth cone steering events. Our results suggest a mechanism by which growth cones select pathways by sampling both the molecular nature of the substrate and its ability to withstand the application of traction forces.
Tropomyosin inhibits ADF/cofilin-dependent actin filament dynamics
Authors: Ono Shoichiro , Ono Kanako
Published: July 2002

Tropomyosin binds to actin filaments and is implicated in stabilization of actin cytoskeleton. We examined biochemical and cell biological properties of Caenorhabditis elegans tropomyosin (CeTM) and obtained evidence that CeTM is antagonistic to ADF/cofilin-dependent actin filament dynamics. We purified CeTM, actin, and UNC-60B (a muscle-specific ADF/cofilin isoform), all of which are derived from C. elegans, and showed that CeTM and UNC-60B bound to F-actin in a mutually exclusive manner. CeTM inhibited UNC-60B–induced actin depolymerization and enhancement of actin polymerization. Within isolated native thin filaments, actin and CeTM were detected as major components, whereas UNC-60B was present at a trace amount. Purified UNC-60B was unable to interact with the native thin filaments unless CeTM and other associated proteins were removed by high-salt extraction. Purified CeTM was sufficient to restore the resistance of the salt-extracted filaments from UNC-60B. In muscle cells, CeTM and UNC-60B were localized in different patterns. Suppression of CeTM by RNA interference resulted in disorganized actin filaments and paralyzed worms in wild-type background. However, in an ADF/cofilin mutant background, suppression of CeTM did not worsen actin organization and worm motility. These results suggest that tropomyosin is a physiological inhibitor of ADF/cofilin-dependent actin dynamics.
Secretory vesicle transport velocity in living cells depends on the myosin-V lever arm length
Authors: Schott Daniel H. , Collins Ruth N. , Bretscher Anthony
Published: July 2002

Myosins are molecular motors that exert force against actin filaments. One widely conserved myosin class, the myosin-Vs, recruits organelles to polarized sites in animal and fungal cells. However, it has been unclear whether myosin-Vs actively transport organelles, and whether the recently challenged lever arm model developed for muscle myosin applies to myosin-Vs. Here we demonstrate in living, intact yeast that secretory vesicles move rapidly toward their site of exocytosis. The maximal speed varies linearly over a wide range of lever arm lengths genetically engineered into the myosin-V heavy chain encoded by the MYO2 gene. Thus, secretory vesicle polarization is achieved through active transport by a myosin-V, and the motor mechanism is consistent with the lever arm model.
Cyclosporin A inhibits caspase-independent death of NGF-deprived sympathetic neurons
Authors: Chang Louis K. , Johnson Eugene M.
Published: July 2002

Opening of the permeability transition pore (PTP) has been implicated as an important mitochondrial event that occurs during apoptosis. We examined the role of the PTP in the well-characterized cell death of rat sympathetic neurons deprived of nerve growth factor (NGF) in vitro. Removal of NGF causes these neurons to undergo either a classic apoptotic cell death or, when treated with a broad-spectrum caspase inhibitor such as boc-aspartyl(OMe)-fluoromethylketone (BAF), a delayed, nonapoptotic cell death. The PTP inhibitor, cyclosporin A (CsA), blocked commitment-to-die in the presence of BAF, as defined by the ability of NGF readdition to rescue cells, but had little effect on commitment-to-die in the absence of BAF. CsA did not have trophic effects on BAF-saved cells, but did block the decrease in mitochondrial membrane potential. These data suggest that PTP opening is a critical event in caspase-independent, nonapoptotic (but not caspase-dependent, apoptotic) death of NGF-deprived rat sympathetic neurons.
Transcytosis of Staphylococcal Superantigen Toxins
Authors: Hamad Abdel Rahim A. , Marrack Philippa , Kappler John W.
Published: July 2002

Staphylococcus aureus produces a set of proteins (e.g., staphylococcal enterotoxin A [SEA], SEB, toxic shock syndrome toxin 1 [TSST-1]) which act both as superantigens (SAgs) and toxins. Although their mode of action as SAgs is well understood, little is known about how they enter the body via the intestine and cause food poisoning. To examine this problem we used an in vitro culture system to study the capacity of class II MHC-negative human intestinal epithelial cells (Caco-2) to transcytose several staphylococcal toxins. We found that Caco-2 cells are capable of dosedependent, facilitated transcytosis of SEB and TSST-1, but not SEA. We extended these studies in vivo in mice by showing that ingested SEB appears in the blood more efficiently than SEA. Our data suggest that these toxins can cross the epithelium in an immunologically intact form. These results may have important implications for the pathogenesis of food poisoning.
Antiviral Activity of Tumor Necrosis Factor (TNF) Is Mediated via p55 and p75 TNF Receptors
Authors: Ruby Janet , Bluethmann Horst , Peschon Jacques J.
Published: July 2002

The antiviral nature of tumor necrosis factor (TNF) is generally well accepted. TNF appears to induce multiple antiviral mechanisms, and to synergize with interferon (IFN)-γ in promoting antiviral activities. We infected TNF receptor (TNFR)-deficient mice with the virulent murine pathogen, ectromelia virus (EV), and observed that otherwise resistant mice were susceptible to lethal infection. To study the molecular basis of the antiviral action of TNF, mice were infected with a recombinant vaccinia virus encoding murine TNF (VV-HA-TNF). In normal mice, the replication of VV-HA-TNF was highly attenuated. In contrast, mice in which the TNFR type 1 (p55) or the TNFR type 2 (p75) were genetically disrupted showed a moderate defect in their capacity to clear the TNF-encoding virus. The contribution of both TNF receptors to the control of VV-HA-TNF was confirmed by the enhanced replication of VV-HA-TNF in mice deficient for both p55 and p75. These observations were corroborated by infecting TNFR-deficient mice with EV. For both infections, the p55 and p75 TNFRs were necessary to maintain normal levels of resistance. Thus, the antiviral activity of TNF is mediated via both TNFRs in vivo. Furthermore, these studies establish that TNF is an important component of the host response to a natural virus infection.
Dephosphorylation Targets Bcl-2 for Ubiquitin-dependent Degradation: A Link between the Apoptosome and the Proteasome Pathway
Authors: Dimmeler Stefanie , Breitschopf Kristin , Haendeler Judith , Zeiher Andreas M.
Published: July 2002

Injury of the endothelial cells by the induction of apoptotic cell death may play an important role in the pathophysiology of atherosclerosis and the progression of inflammatory diseases. Here, we demonstrate an essential role for the ubiquitin-dependent proteasome complex in stimulus-induced degradation of the antiapoptotic protein Bcl-2. Bcl-2 is specifically degraded after stimulation of human endothelial cells with tumor necrosis factor (TNF)-α in a process that is inhibited by specific proteasome inhibitors. In addition, the mutation of the potential ubiquitin-acceptor amino acids of Bcl-2 provides protection against TNF-α– and staurosporine-induced degradation in vitro and in vivo. Moreover, mimicking phosphorylation of the putative mitogen-activated protein (MAP) kinase sites of the Bcl-2 protein (Thr 56, Thr 74, and Ser 87) abolishes its degradation, suggesting a link between the MAP kinase pathway to the proteasome pathway. Finally, inhibition of Bcl-2 degradation either by suppressing ubiquitin-dependent proteasomal degradation or by mimicking continuous phosphorylation of the putative MAP kinase sites in the Bcl-2 protein confers resistance against induction of apoptosis. Thus, the degradation of Bcl-2 may unleash the inhibitory function of Bcl-2 over the apoptosome and may thereby amplify the activation of the caspase cascade.
Targeted Inhibition of Intrinsic Coagulation Limits Cerebral Injury in Stroke without Increasing Intracerebral Hemorrhage
Authors: Choudhri Tanvir F. , Hoh Brian L. , Prestigiacomo Charles J. , Huang Judy , Kim Louis J. , Schmidt Ann Marie , Kisiel Walter , Connolly E. Sander , Pinsky David J.
Published: July 2002

Agents that restore vascular patency in stroke also increase the risk of intracerebral hemorrhage (ICH). As Factor IXa is a key intermediary in the intrinsic pathway of coagulation, targeted inhibition of Factor IXa–dependent coagulation might inhibit microvascular thrombosis in stroke without impairing extrinsic hemostatic mechanisms that limit ICH. A competitive inhibitor of native Factor IXa for assembly into the intrinsic Factor X activation complex, Factor IXai, was prepared by covalent modification of the Factor IXa active site. In a modified cephalin clotting time assay, in vivo administration of Factor IXai caused a dose-dependent increase in time to clot formation (3.6-fold increase at the 300 μg/kg dose compared with vehicle-treated control animals, P < 0.05). Mice given Factor IXai and subjected to middle cerebral artery occlusion and reperfusion demonstrated reduced microvascular fibrin accumulation by immunoblotting and immunostaining, reduced 111In-labeled platelet deposition (42% decrease, P < 0.05), increased cerebral perfusion (2.6-fold increase in ipsilateral blood flow by laser doppler, P < 0.05), and smaller cerebral infarcts than vehicle-treated controls (70% reduction, P < 0.05) based on triphenyl tetrazolium chloride staining of serial cerebral sections. At therapeutically effective doses, Factor IXai was not associated with increased ICH, as opposed to tissue plasminogen activator (tPA) or heparin, both of which significantly increased ICH. Factor IXai was cerebroprotective even when given after the onset of stroke, indicating that microvascular thrombosis continues to evolve (and may be inhibited) even after primary occlusion of a major cerebrovascular tributary.
Novel Point Mutation in the Extracellular Domain of the Granulocyte Colony-Stimulating Factor (G-Csf) Receptor in a Case of Severe Congenital Neutropenia Hyporesponsive to G-Csf Treatment
Authors: Ward Alister C. , van Aesch Yvette M. , Gits Judith , Schelen Anita M. , de Koning John P. , van Leeuwen Daphne , Freedman Melvin H. , Touw Ivo P.
Published: July 2002

Severe congenital neutropenia (SCN) is a heterogeneous condition characterized by a drastic reduction in circulating neutrophils and a maturation arrest of myeloid progenitor cells in the bone marrow. Usually this condition can be successfully treated with granulocyte colony-stimulating factor (G-CSF). Here we describe the identification of a novel point mutation in the extracellular domain of the G-CSF receptor (G-CSF-R) in an SCN patient who failed to respond to G-CSF treatment. When this mutant G-CSF-R was expressed in myeloid cells, it was defective in both proliferation and survival signaling. This correlated with diminished activation of the receptor complex as determined by signal transducer and activator of transcription (STAT) activation, although activation of STAT5 was more affected than STAT3. Interestingly, the mutant receptor showed normal affinity for ligand, but a reduced number of ligand binding sites compared with the wild-type receptor. This suggests that the mutation in the extracellular domain affects ligand–receptor complex formation with severe consequences for intracellular signal transduction. Together these data add to our understanding of the mechanisms of cytokine receptor signaling, emphasize the role of GCSFR mutations in the etiology of SCN, and implicate such mutations in G-CSF hyporesponsiveness.
B Lymphocytes Regulate Dendritic Cell (Dc) Function in Vivo
Authors: Moulin Véronique , Andris Fabienne , Thielemans Kris , Maliszewski Charlie , Urbain Jacques , Moser Muriel
Published: July 2002

Increasing evidence indicates that dendritic cells (DCs) are the antigen-presenting cells of the primary immune response. However, several reports suggest that B lymphocytes could be required for optimal T cell sensitization. We compared the immune responses of wild-type and B cell-deficient (μMT) mice, induced by antigen emulsified in adjuvant or pulsed on splenic dendritic cells. Our data show that lymph node cells from both control and μMT animals were primed, but each released distinct cytokine profiles. Lymph node T cells from control animals secreted interferon (IFN)-γ, interleukin (IL)-2, and IL-4, whereas those from μMT mice produced IFN-γ and IL-2 but no IL-4. To test whether B cells may influence the T helper cell type 1 (Th1)/Th2 balance by affecting the function of DCs, we immunized mice by transferring antigen-pulsed DCs from wild-type or mutant mice. Injection of control DCs induced the secretion of IL-4, IFN-γ, and IL-2, whereas administration of DCs from μMT animals failed to sensitize cells to produce IL-4. Analysis of IL-12 production revealed that DCs from μMT mice produce higher levels of IL-12p70 than do DCs from wild-type animals. These data suggest that B lymphocytes regulate the capacity of DCs to promote IL-4 secretion, possibly by downregulating their secretion of IL-12, thereby favoring the induction of a nonpolarized immune response.
Acquisition of External Major Histocompatibility Complex Class I Molecules by Natural Killer Cells Expressing Inhibitory Ly49 Receptors
Authors: Sjöström Anna , Eriksson Mikael , Cerboni Cristina , Johansson Maria H. , Sentman Charles L. , Kärre Klas , Höglund Petter
Published: July 2002

Murine natural killer (NK) cells express inhibitory Ly49 receptors specific for major histocompatibility complex (MHC) class I molecules. We report that during interactions with cells in the environment, NK cells acquired MHC class I ligands from surrounding cells in a Ly49-specific fashion and displayed them at the cell surface. Ligand acquisition sometimes reached 20% of the MHC class I expression on surrounding cells, involved transfer of the entire MHC class I protein to the NK cell, and was independent of whether or not the NK cell expressed the MHC class I ligand itself. We also present indirect evidence for spontaneous MHC class I acquisition in vivo, as well as describe an in vitro coculture system with transfected cells in which the same phenomenon occurred. Functional studies in the latter model showed that uptake of H-2Dd by Ly49A+ NK cells was accompanied by a partial inactivation of cytotoxic activity in the NK cell, as tested against H-2Dd-negative target cells. In addition, ligand acquisition did not abrogate the ability of Ly49A+ NK cells to receive inhibitory signals from external H-2Dd molecules. This study is the first to describe ligand acquisition by NK cells, which parallels recently described phenomena in T and B cells.
Structure of a Complex of the Human α/β T Cell Receptor (TCR) HA1.7, Influenza Hemagglutinin Peptide, and Major Histocompatibility Complex Class II Molecule, HLA-DR4 (DRA0101 and DRB10401)
Authors: Hennecke Jens , Wiley Don C.
Published: July 2002

The α/β T cell receptor (TCR) HA1.7 specific for the hemagglutinin (HA) antigen peptide from influenza A virus is HLA-DR1 restricted but cross-reactive for the HA peptide presented by the allo-major histocompatibility complex (MHC) class II molecule HLA-DR4. We report here the structure of the HA1.7/DR4/HA complex, determined by X-ray crystallography at a resolution of 2.4 Å. The overall structure of this complex is very similar to the previously reported structure of the HA1.7/DR1/HA complex. Amino acid sequence differences between DR1 and DR4, which are located deep in the peptide binding groove and out of reach for direct contact by the TCR, are able to indirectly influence the antigenicity of the pMHC surface by changing the conformation of HA peptide residues at position P5 and P6. Although TCR HA1.7 is cross-reactive for HA presented by DR1 and DR4 and tolerates these conformational differences, other HA-specific TCRs are sensitive to these changes. We also find a dependence of the width of the MHC class II peptide-binding groove on the sequence of the bound peptide by comparing the HA1.7/DR4/HA complex with the structure of DR4 presenting a collagen peptide. This structural study of TCR cross-reactivity emphasizes how MHC sequence differences can affect TCR binding indirectly by moving peptide atoms.
Fast Inactivation in Shaker K+ Channels
Authors: Roux Michel J. , Olcese Riccardo , Toro Ligia , Bezanilla Francisco , Stefani Enrico
Published: July 2002

Fast inactivating Shaker H4 potassium channels and nonconducting pore mutant Shaker H4 W434F channels have been used to correlate the installation and recovery of the fast inactivation of ionic current with changes in the kinetics of gating current known as “charge immobilization” (Armstrong, C.M., and F. Bezanilla. 1977. J. Gen. Physiol. 70:567–590.). Shaker H4 W434F gating currents are very similar to those of the conducting clone recorded in potassium-free solutions. This mutant channel allows the recording of the total gating charge return, even when returning from potentials that would largely inactivate conducting channels. As the depolarizing potential increased, the OFF gating currents decay phase at −90 mV return potential changed from a single fast component to at least two components, the slower requiring ∼200 ms for a full charge return. The charge immobilization onset and the ionic current decay have an identical time course. The recoveries of gating current (Shaker H4 W434F) and ionic current (Shaker H4) in 2 mM external potassium have at least two components. Both recoveries are similar at −120 and −90 mV. In contrast, at higher potentials (−70 and −50 mV), the gating charge recovers significantly more slowly than the ionic current. A model with a single inactivated state cannot account for all our data, which strongly support the existence of “parallel” inactivated states. In this model, a fraction of the charge can be recovered upon repolarization while the channel pore is occupied by the NH2-terminus region.
The Influence of Sarcoplasmic Reticulum Ca2+ Concentration on Ca2+ Sparks and Spontaneous Transient Outward Currents in Single Smooth Muscle Cells
Authors: ZhuGe Ronghua , Tuft Richard A. , Fogarty Kevin E. , Bellve Karl , Fay Fredric S. , Walsh John V.
Published: July 2002

Localized, transient elevations in cytosolic Ca2+, known as Ca2+ sparks, caused by Ca2+ release from sarcoplasmic reticulum, are thought to trigger the opening of large conductance Ca2+-activated potassium channels in the plasma membrane resulting in spontaneous transient outward currents (STOCs) in smooth muscle cells. But the precise relationships between Ca2+ concentration within the sarcoplasmic reticulum and a Ca2+ spark and that between a Ca2+ spark and a STOC are not well defined or fully understood. To address these problems, we have employed two approaches using single patch-clamped smooth muscle cells freshly dissociated from toad stomach: a high speed, wide-field imaging system to simultaneously record Ca2+ sparks and STOCs, and a method to simultaneously measure free global Ca2+ concentration in the sarcoplasmic reticulum ([Ca2+]SR) and in the cytosol ([Ca2+]CYTO) along with STOCs. At a holding potential of 0 mV, cells displayed Ca2+ sparks and STOCs. Ca2+ sparks were associated with STOCs; the onset of the sparks coincided with the upstroke of STOCs, and both had approximately the same decay time. The mean increase in [Ca2+]CYTO at the time and location of the spark peak was ∼100 nM above a resting concentration of ∼100 nM. The frequency and amplitude of spontaneous Ca2+ sparks recorded at −80 mV were unchanged for a period of 10 min after removal of extracellular Ca2+ (nominally Ca2+-free solution with 50 μM EGTA), indicating that Ca2+ influx is not necessary for Ca2+sparks. A brief pulse of caffeine (20 mM) elicited a rapid decrease in [Ca2+]SR in association with a surge in [Ca2+]CYTO and a fusion of STOCs, followed by a fast restoration of [Ca2+]CYTO and a gradual recovery of [Ca2+]SR and STOCs. The return of global [Ca2+]CYTO to rest was an order of magnitude faster than the refilling of the sarcoplasmic reticulum with Ca2+. After the global [Ca2+]CYTO was fully restored, recovery of STOC frequency and amplitude were correlated with the level of [Ca2+]SR, even though the time for refilling varied greatly. STOC frequency did not recover substantially until the [Ca2+]SR was restored to 60% or more of resting levels. At [Ca2+]SR levels above 80% of rest, there was a steep relationship between [Ca2+]SR and STOC frequency. In contrast, the relationship between [Ca2+]SR and STOC amplitude was linear. The relationship between [Ca2+]SR and the frequency and amplitude was the same for Ca2+ sparks as it was for STOCs. The results of this study suggest that the regulation of [Ca2+]SR might provide one mechanism whereby agents could govern Ca2+ sparks and STOCs. The relationship between Ca2+ sparks and STOCs also implies a close association between a sarcoplasmic reticulum Ca2+ release site and the Ca2+-activated potassium channels responsible for a STOC.
Allosteric Voltage Gating of Potassium Channels I
Authors: Horrigan Frank T. , Cui Jianmin , Aldrich Richard W.
Published: July 2002

Activation of large conductance Ca2+-activated K+ channels is controlled by both cytoplasmic Ca2+ and membrane potential. To study the mechanism of voltage-dependent gating, we examined mSlo Ca2+-activated K+ currents in excised macropatches from Xenopus oocytes in the virtual absence of Ca2+ (<1 nM). In response to a voltage step, IK activates with an exponential time course, following a brief delay. The delay suggests that rapid transitions precede channel opening. The later exponential time course suggests that activation also involves a slower rate-limiting step. However, the time constant of IK relaxation [τ(IK)] exhibits a complex voltage dependence that is inconsistent with models that contain a single rate limiting step. τ(IK) increases weakly with voltage from −500 to −20 mV, with an equivalent charge (z) of only 0.14 e, and displays a stronger voltage dependence from +30 to +140 mV (z = 0.49 e), which then decreases from +180 to +240 mV (z = −0.29 e). Similarly, the steady state GK–V relationship exhibits a maximum voltage dependence (z = 2 e) from 0 to +100 mV, and is weakly voltage dependent (z ≅ 0.4 e) at more negative voltages, where Po = 10−5–10−6. These results can be understood in terms of a gating scheme where a central transition between a closed and an open conformation is allosterically regulated by the state of four independent and identical voltage sensors. In the absence of Ca2+, this allosteric mechanism results in a gating scheme with five closed (C) and five open (O) states, where the majority of the channel's voltage dependence results from rapid C–C and O–O transitions, whereas the C–O transitions are rate limiting and weakly voltage dependent. These conclusions not only provide a framework for interpreting studies of large conductance Ca2+-activated K+ channel voltage gating, but also have important implications for understanding the mechanism of Ca2+ sensitivity.
Biotechnology in Switzerland: high on the public agenda, but only moderate support
Authors: Bonfadelli Heinz , Dahinden Urs , Leonarz Martina
Published: July 2002

In Switzerland, there have been intensive public debates about biotechnology because of the specific Swiss political system of direct democracy that led, in 1992 and 1998, to two national referenda on biotechnology regulation. As a result, the Swiss population is well informed but skeptical about this technology. These findings contrast with the deficit model of public understanding of science, which predicts a positive correlation between knowledge of, and support for, a specific technology. What role did the media play in the development of public opinion? This question is discussed because of a content analysis (time series) of national newspapers. In addition, representative surveys and focus groups yield insights into the public perception of biotechnology and the influence of mass communication for opinion formation.
Amenability and weak amenability of second conjugate Banach algebras
Authors: Ghahramani F. , Loy R. , Willis G.
Published: July 2002

For a Banach algebra

A

\mathfrak {A}

, amenability of

A

∗
∗

\mathfrak {A}^{**}

necessitates amenability of

A

\mathfrak {A}

, and similarly for weak amenability provided

A

\mathfrak {A}

is a left ideal in

A

∗
∗

\mathfrak {A}^{**}

. For

G

\mathfrak {G}

a locally compact group, indeed more generally,

L
1

(

G

)

∗
∗

L^1(\mathfrak {G})^{**}

is amenable if and only if

G

\mathfrak {G}

is finite. If

L
1

(

G

)

∗
∗

L^1(\mathfrak {G})^{**}

is weakly amenable, then

M
(

G

)

M(\mathfrak {G})

is weakly amenable.
A visit to the Erdös problem
Authors: Humke Paul , Laczkovich Miklós
Published: July 2002

Erdős asked if for every infinite set,

A
A

, of real numbers there exists a measurable subset of the reals having positive measure that does not contain a subset similar to

A
A

. In this note we transform this question to a finite combinatorial problem. Using this translation we extend some results of Eigen and Falconer concerning slow sequences for which the answer to Erdős’ question is positive.
Linear isometries between subspaces of continuous functions
Authors: Araujo Jesús , Font Juan
Published: July 2002

We say that a linear subspaceAAofC0(X)C_0 (X)is strongly separating if given any pair of distinct pointsx1,x2x_1, x_2of the locally compact spaceXX, then there existsf∈Af \in Asuch that|f(x1)|≠|f(x2)|\left | f(x_1 ) \right | \neq \left | f(x_2 ) \right |. In this paper we prove that a linear isometryTTofAAonto such a subspaceBBofC0(Y)C_0(Y)induces a homeomorphismhhbetween two certain singular subspaces of the Shilov boundaries ofBBandAA, sending the Choquet boundary ofBBonto the Choquet boundary ofAA. We also provide an example which shows that the above result is no longer true if we do not assumeAAto be strongly separating. Furthermore we obtain the following multiplicative representation ofTT:(Tf)(y)=a(y)f(h(y))(Tf)(y)=a(y)f(h(y))for ally∈∂By \in \partial Band allf∈Af \in A, whereaais a unimodular scalar-valued continuous function on∂B\partial B. These results contain and extend some others by Amir and Arbel, Holsztyński, Myers and Novinger. Some applications to isometries involving commutative Banach algebras without unit are announced.
Infinite families of solutions of the equation \binom{𝑛}𝑘=2\binom{𝑎}𝑏
Authors: Goetgheluck P.
Published: July 2002

We give explicit formulas providing two new infinite families of couples of binomial coefficients whose ratio is 2.
Bases in equivariant 𝐾-theory. II
Authors: Lusztig G.
Published: July 2002

In this paper we establish a connection between the “bases" inBases in equivariantKK-theory, Represent. Theory2(1999), 298-369 and the periodicWW-graphs introduced inPeriodicWW-graphs, Represent. Theory1(1997), 207–279.
A Phosphorylated Cytoplasmic Autoantigen, GW182, Associates with a Unique Population of Human mRNAs within Novel Cytoplasmic Speckles
Authors: Eystathioy Theophany , Chan Edward K. L. , Tenenbaum Scott A. , Keene Jack D. , Griffith Kevin , Fritzler Marvin J.
Published: July 2002

A novel human cellular structure has been identified that contains a unique autoimmune antigen and multiple messenger RNAs. This complex was discovered using an autoimmune serum from a patient with motor and sensory neuropathy and contains a protein of 182 kDa. The gene and cDNA encoding the protein indicated an open reading frame with glycine-tryptophan (GW) repeats and a single RNA recognition motif. Both the patient's serum and a rabbit serum raised against the recombinant GW protein costained discrete cytoplasmic speckles designated as GW bodies (GWBs) that do not overlap with the Golgi complex, endosomes, lysosomes, or peroxisomes. The mRNAs associated with GW182 represent a clustered set of transcripts that are presumed to reside within the GW complexes. We propose that the GW ribonucleoprotein complex is involved in the posttranscriptional regulation of gene expression by sequestering a specific subset of gene transcripts involved in cell growth and homeostasis.
Use of stepwise subtraction to comprehensively isolate mouse genes whose transcription is up‐regulated during spermiogenesis
Authors: Fujii Takayuki , Tamura Kazutoshi , Masai Kumiko , Tanaka Hiromitsu , Nishimune Yoshitake , Nojima Hiroshi
Published: July 2002

We report the isolation of 153 mouse genes whose expression is dramatically up‐regulated during spermiogenesis. We used a novel variation of the subtractive hybridization technique called stepwise subtraction, wherein the subtraction process is systematically repeated in a stepwise manner. We named the genes thus identified as TISP genes (transcript induced in spermiogenesis). The transcription of 80 of these TISP genes is almost completely specific to the testis. This transcription is abruptly turned on after 17 days of age, when the mice enter puberty and spermiogenesis is initiated. Considering that the most advanced cells present at these stages of spermatogenesis are the spermatids, it is likely that we could isolate most of the spermatid‐specific genes. DNA sequencing revealed that about half the TISP genes are novel and uncharacterized genes, confirming the utility of the stepwise subtraction approach for gene discovery.
Rationalizing Consumption: Lejaren à Hiller and the Origins of American Advertising Photography, 1913–1924
Authors: Brown Elspeth H.
Published: July 2002

The reasons why photographic illustration was generally avoided by American print advertisers before 1913, even though halftone technology had made such illustration economically advantageous, have not been adequately explored. This article explains that art directors initially avoided the medium because of its slavish dependence on material reality. Photography offered too much detail; it seemed incapable of the abstraction or idealization necessary for “capitalist realism.” The change in this outlook can be dated from the work of Lejaren à Hiller, who, borrowing fine art aesthetics and techniques from pictorialist photography, established the medium as suitable for the complex visual and narrative strategies required by the social tableaux advertising of the period.
In-vitro activity of levofloxacin against Streptococcus pneumoniae with various levels of penicillin resistance
Authors: Thomson K. S. , Chartrand S. A. , Sanders C. C. , Block S. L.
Published: July 2002

This in-vitro study was designed to compare the activity of levofloxacin with that of ciprofloxacin, ofloxacin, erythromycin, penicillin, amoxycillin, loracarbef, cefaclor, cefpodoxime, ceftriaxone, trimethoprim–sulphamethoxazole, clindamycin and vancomycin against a collection of 202 Streptococcus pneumoniae isolates (56% susceptible to penicillin, 34% intermediate, 10% resistant). The isolates (60% nasopharyngeal, 40% middle ear) were obtained from otherwise healthy children at child care centres in urban and rural Nebraska, and at a paediatric clinic in rural Kentucky. MICs were determined by NCCLS agar dilution methodology using an inoculum of 10 4 cfu/spot. Using NCCLS breakpoints, the percentage of penicillin- intermediate and -resistant strains susceptible to the evaluable agents were, respectively, as follows: levofloxacin (99%, 100%), ofloxacin (87%, 100%), erythromycin (52%, 65%), ceftriaxone (93%, 25%), trimethoprim–sulphamethoxazole (7%, 0%), clindamycin (93%, 100%) and vancomycin (100%, 100%). Without NCCLS interpretive criteria, no conclusions could be made concerning the susceptibility of penicillin-intermediate and -resistant strains to the other study drugs. All β-lactam antibiotics, erythromycin and trimethoprim–sulphamethoxazole were less active against penicillin-resistant strains, indicating that these may be suboptimal agents for empirical therapy for suspected S. pneumoniae infections in these patient populations. However, levofloxacin, ofloxacin, clindamycin and vancomycin were equally active against penicillin-susceptible and -resistant strains. These data suggest that the efficacy of levofloxacin should be examined in both adult and paediatric S. pneumoniae infections involving body sites where levofloxacin concentrations >2 mg/L can be achieved safely.
A Fast, Easy, and Efficient Estimator for Multiparty Electoral Data
Authors: Honaker James , Katz Jonathan N. , King Gary
Published: July 2002

Katz and King have previously developed a model for predicting or explaining aggregate electoral results in multiparty democracies. Their model is, in principle, analogous to what least-squares regression provides American political researchers in that two-party system. Katz and King applied their model to three-party elections in England and revealed a variety of new features of incumbency advantage and sources of party support. Although the mathematics of their statistical model covers any number of political parties, it is computationally demanding, and hence slow and numerically imprecise, with more than three parties. In this paper we produce an approximate method that works in practice with many parties without making too many theoretical compromises. Our approach is to treat the problem as one of missing data. This allows us to use a modification of the fast EMis algorithm of King, Honaker, Joseph, and Scheve and to provide easy-to-use software, while retaining the attractive features of the Katz and King model, such as thetdistribution and explicit models for uncontested seats.
The evolution of diversity in ancient ecosystems: a review
Authors: Morris S. Conway
Published: July 2002

On a perfect planet, such as might be acceptable to a physicist, one might predict that from its origin the diversity of life would grow exponentially until the carrying capacity, however defined, was reached. The fossil record of the Earth, however, tells a very different story. One of the most striking aspects of this record is the apparent evolutionary longueur, marked by the Precambrian record of prokaryotes and primitive eukaryotes, although our estimates of microbial diversity may be seriously incomplete. Subsequently there were various dramatic increases in diversity, including the Cambrian ‘explosion’ and the radiation of Palaeozoic–style faunas in the Ordovician. The causes of these events are far from resolved. It has also long been appreciated that the history of diversity has been punctuated by important extinctions. The subtleties and nuances of extinction as well as the survival of particular clades have to date, however, received rather too little attention, and there is still a tendency towards blanket assertions rather than a dissection of these extraordinary events. In addition, some but perhaps not all mass extinctions are characterized by long lag–times of recovery, which may reflect the slowing waning of extrinsic forcing factors or alternatively the incoherence associated with biological reassembly of stable ecosystems. The intervening periods between the identified mass extinctions may be less stable and benign than popularly thought, and in particular the frequency of extraterrestrial impacts leads to predictions of recurrent disturbance on timescales significantly shorter than the intervals separating the largest extinction events. Even at times of quietude it is far from clear whether biological communities enjoy stability and interlocked stasis or are dynamically reconstituted at regular intervals. Finally, can we yet rely on the present depictions of the rise and falls in the levels of ancient diversity? Existing data is almost entirely based on Linnean taxa, and the application of phylogenetic systematics to this problem is still in its infancy. Not only that, but even more intriguingly the pronounced divergence in estimates of origination times of groups as diverse as angiosperms, diatoms and mammals in terms of the fossil record as against molecular data point to the possibilities of protracted intervals of geological time with a cryptic diversity. If this is correct, and there are alternative explanations, then some of the mystery of adaptive radiations may be dispelled, in as much as the assembly of key features in the stem groups could be placed in a gradualistic framework of local adaptive response punctuated by intervals of opportunity.
The early Triassic rhynchosaur Mesosuchus browni and the interrelationships of basal archosauromorph reptiles
Authors: Dilkes David W.
Published: July 2002

Restudy of the unique diapsid reptileMesosuchus browniWatson, from theCynognathusAssemblage Zone (late Early Triassic to early Middle Triassic) of the Burgersdorp Formation (Tarkastad Subgroup; Beaufort Group) of South Africa, confirms that it is the most plesiomorphic known member of the Rhynchosauria. A new phylogenetic analysis of basal taxa of Archosauromorpha indicates that Choristodera falls outside of the Sauria, Prolacertiformes is a paraphyletic taxon withProlacertasharing a more recent common ancestor with Archosauriformes than with any other clade,MegalancosaurusandDrepanosaurusare sister taxa in the clade Drepanosauridae within Archosauromorpha, and are the sister group to the clade Tanystropheidae composed ofTanystropheus,Macrocnemus, andLangobardisaurus. Combination of the phylogenetic relationships of basal archosauromorphs and their known stratigraphic ranges reveals significant gaps in the fossil records of Late Permian and Triassic diapsids. Extensions of the temporal ranges of several lineages of diapsids into the Late Permian suggests that more groups of terrestrial reptiles survived the end-Permian mass extinction than thought previously.
Studying and approximating spatio–temporal models for epidemic spread and control
Authors: Filipe J. A. N. , Gibson G. J.
Published: July 2002

A class of simple spatio–temporal stochastic models for the spread and control of plant disease is investigated. We consider a lattice–based susceptible–infected model in which the infection of a host occurs through two distinct processes: a background infective challenge representing primary infection from external sources, and a short–range interaction representing the secondary infection of susceptibles by infectives within the population. Recent data–modelling studies have suggested that the above model may describe the spread of aphid–borne virus diseases in orchards. In addition, we extend the model to represent the effects of different control strategies involving replantation (or recovery). The Contact Process is a particular case of this model. The behaviour of the model has been studied using Cellular–Automata simulations. An alternative approach is to formulate a set of deterministic differential equations that captures the essential dynamics of the stochastic system. Approximate solutions to this set of equations, describing the time evolution over the whole parameter range, have been obtained using the pairwise approximation (PA) as well as the most commonly used mean–field approximation (MF). Comparison with simulation results shows that PA is significantly superior to MF, predicting accurately both transient and long–run, stationary behaviour over relevant parts of the parameter space. The conditions for the validity of the approximations to the present model and extensions thereof are discussed.
Stochastic dynamics and a power law for measles variability
Authors: Keeling Matt , Grenfell Bryan
Published: July 2002

Since the discovery of a power law scaling between the mean and variance of natural populations, this phenomenon has been observed for a variety of species. Here, we show that the same form of power law scaling also occurs in measles case reports in England and Wales. Remarkably this power law holds over four orders of magnitude. We consider how the natural experiment of vaccination affects the slope of the power law. By examining simple generic models, we are able to predict the effects of stochasticity and coupling and we propose a new phenomenon associated with the critical community size.
Malaria epidemiology and economics: the effect of delayed immune acquisition on the cost–effectiveness of insecticide–treated bednets
Authors: Guyatt H. L. , Snow R. W. , Evans D. B.
Published: July 2002

An understanding of the epidemiology of a disease is central in evaluating the health impact and cost–effectiveness of control interventions. The epidemiology of life–threatening malaria is receiving renewed interest, with concerns that the implementation of preventive measures such as insecticide–treated bednets (ITNs) while protecting young children might in fact increase the risks of mortality and morbidity in older ages by delaying the acquisition of functional immunity. This paper aims to illustrate how a combined approach of epidemiology and economics can be used to (i) explore the long–term impact of changes in epidemiological profiles, and (ii) identify those variables that are critical in determining whether an intervention will be an efficient use of resources. The key parameters for determining effectiveness are the protective efficacy of ITNs (reduction in all–cause mortality), the malaria attributable mortality and the increased malaria–specific mortality risk due to delays in the acquisition of functional immunity. In particular, the analysis demonstrates that delayed immune acquisition is not a problemper se, but that the critical issue is whether it occurs immediately following the implementation of an ITN programme or whether it builds up slowly over time. In the ‘worst case’ scenario where ITNs immediately increase malaria–specific mortality due to reduced immunity, the intervention might actually cost lives. In other words, it might be better to not use ITNs. On the other hand, if reduced immunity takes two years to develop, ITNs would still fall into the category of excellent value for money compared to other health interventions, saving a year of life (YLL) at a cost of between US$25–30. These types of calculations are important in identifying the parameters which field researchers should be seeking to measure to address the important question of the net impact of delaying the acquisition of immunity through preventive control measures.
Self-assembly, self-organization and division of labour
Authors: Sendova-Franks Ana B. , Franks Nigel R.
Published: July 2002

The prospect of generic principles of biological organization being uncovered through the increasingly broad use of the concepts of ‘self–assembly’ and ‘self–organization’ in biology will only be fulfilled if students of different levels of biological organization use the same terms with the same meanings. We consider the different ways the terms ‘self–assembly’ and ‘self–organization’ have been used, from studies of molecules to studies of animal societies. By linking ‘self–assembly’ and ‘self–organization’ with division of labour, we not only put forward a distinction between the underlying concepts but we are also able to relate them to the question: Why has a certain structure been favoured by natural selection? Using the particularly instructive case of social resilience in ant colonies, we demonstrate that the principle of self–organizing self–assembly may apply to higher levels of biological organization than previously considered. We predict that at the level of interactions among organisms within the most advanced animal societies, specialization through learning has a crucial role to play in re–assembly processes. This review may also help important commonalities and differences to be recognized between ordering mechanisms up to the social level and those further up the biological hierarchy, at the level of ecological communities.