bluuebunny/crossref_metadata_2025 huggingface dataset:
The tetraspanin CD9 mediates lateral association of MHC class II molecules on the dendritic cell surface
Authors: Unternaehrer Julia J. , Chow Amy , Pypaert Marc , Inaba Kayo , Mellman Ira
Published: December 2006

We have found that MHC class II (MHC II) molecules exhibit a distinctive organization on the dendritic cell (DC) plasma membrane. Both in DC lysates and on the surface of living cells, I-A and I-E molecules engaged in lateral interactions not observed on other antigen-presenting cells such as B blasts. Because DCs and B blasts express MHC II at comparable surface densities, the interaction was not due to simple mass action. Instead, it reflected the selective expression of the tetraspanin CD9 at the DC surface. I-A and I-E molecules coprecipitated with each other and with CD9. The association of heterologous MHC II molecules was abrogated in DCs from CD9−/−mice. Conversely, expression of exogenous CD9 in B cells induced MHC II interactions. CD9 is thus necessary for the association of heterologous MHC II, a specialization that would facilitate the formation of MHC II multimers expected to enhance T cell receptor stimulation by DCs.
Inhibitory complex of the transmembrane ammonia channel, AmtB, and the cytosolic regulatory protein, GlnK, at 1.96 Å
Authors: Gruswitz Franz , O'Connell Joseph , Stroud Robert M.
Published: December 2006

Ammonia conductance is highly regulated. A P
II
signal transduction protein, GlnK, is the final regulator of transmembrane ammonia conductance by the ammonia channel AmtB in
Escherichia coli
. The complex formed between AmtB and inhibitory GlnK at 1.96-Å resolution shows that the trimeric channel is blocked directly by GlnK and how, in response to intracellular nitrogen status, the ability of GlnK to block the channel is regulated by uridylylation/deuridylylation at Y51. ATP and Mg
2+
augment the interaction of GlnK. The hydrolyzed product, adenosine 5′-diphosphate orients the surface of GlnK for AmtB blockade. 2-Oxoglutarate diminishes AmtB/GlnK association, and sites for 2-oxoglutarate are evaluated.
Herbivore-initiated interaction cascades and their modulation by productivity in an African savanna
Authors: Pringle Robert M. , Young Truman P. , Rubenstein Daniel I. , McCauley Douglas J.
Published: December 2006

Despite conceptual recognition that indirect effects initiated by large herbivores are likely to have profound impacts on ecological community structure and function, the existing literature on indirect effects focuses largely on the role of predators. As a result, we know neither the frequency and extent of herbivore-initiated indirect effects nor the mechanisms that regulate their strength. We examined the effects of ungulates on taxa (plants, arthropods, and an insectivorous lizard) representing several trophic levels, using a series of large, long-term, ungulate-exclusion plots that span a landscape-scale productivity gradient in an African savanna. At each of six sites, lizards, trees, and the numerically dominant order of arthropods (Coleoptera) were more abundant in the absence of ungulates. The effect of ungulates on arthropods was mediated by herbaceous vegetation cover. The effect on lizards was simultaneously mediated by both tree density (lizard microhabitat) and arthropod abundance (lizard food). The magnitudes of the experimental effects on all response variables (trees, arthropods, and lizards) were negatively correlated with two distinct measures of primary productivity. These results demonstrate strong cascading effects of ungulates, both trophic and nontrophic, and support the hypothesis that productivity regulates the strength of these effects. Hence, the strongest indirect effects (and thus, the greatest risks to ecosystem integrity after large mammals are extirpated) are likely to occur in low-productivity habitats.
Long-lasting and transmission-blocking activity of antibodies toPlasmodium falciparumelicited in mice by protein conjugates of Pfs25
Authors: Kubler-Kielb Joanna , Majadly Fathy , Wu Yimin , Narum David L. , Guo Chunyan , Miller Louis H. , Shiloach Joseph , Robbins John B. , Schneerson Rachel
Published: December 2006

Malaria is a leading cause of morbidity and mortality, estimated to cause >1 million childhood deaths annually.Plasmodium falciparumcauses the most severe form of the disease. There is as yet no licensed vaccine for this disease, despite over a half century of research. In this study, we investigated a transmission-blocking vaccine candidate, the ookinete surface protein Pfs25. Antibodies against Pfs25, drawn in during a bite, can block parasite development in the mosquito midgut, preventing transmission to other individuals. Pfs25 is a low-molecular-weight protein, by itself not immunogenic. To increase its immunogenicity, we investigated several methods of conjugating Pfs25 to itself and to other proteins: recombinantPseudomonas aeruginosaexotoxin A, and ovalbumin, using amide, hydrazone, or thioether linkages. All conjugates were immunogenic and induced booster responses in mice. The scheme to form amide bonds between proteins by using adipic acid dihydrizide as a linker produced the most immunogenic conjugates. Adsorption of the conjugates onto aluminum hydroxide further increased the antibody response. Remarkably, the antibody levels 3 or 7 months after the last injection were significantly higher than those 1 wk after that injection. The observed transmission-blocking activity of immune sera correlated with antibody levels measured by ELISA.
Oxygen isotopic composition of carbon dioxide in the middle atmosphere
Authors: Liang Mao-Chang , Blake Geoffrey A. , Lewis Brenton R. , Yung Yuk L.
Published: December 2006

The isotopic composition of long-lived trace molecules provides a window into atmospheric transport and chemistry. Carbon dioxide is a particularly powerful tracer, because its abundance remains >100 parts per million by volume (ppmv) in the mesosphere. Here, we successfully reproduce the isotopic composition of CO
2
in the middle atmosphere, which has not been previously reported. The mass-independent fractionation of oxygen in CO
2
can be satisfactorily explained by the exchange reaction with O(
1
D). In the stratosphere, the major source of O(
1
D) is O
3
photolysis. Higher in the mesosphere, we discover that the photolysis of
16
O
17
O and
16
O
18
O by solar Lyman-α radiation yields O(
1
D) 10–100 times more enriched in
17
O and
18
O than that from ozone photodissociation at lower altitudes. This latter source of heavy O(
1
D) has not been considered in atmospheric simulations, yet it may potentially affect the “anomalous” oxygen signature in tropospheric CO
2
that should reflect the gross carbon fluxes between the atmosphere and terrestrial biosphere. Additional laboratory and atmospheric measurements are therefore proposed to test our model and validate the use of CO
2
isotopic fractionation as a tracer of atmospheric chemical and dynamical processes.
Par4 is required for platelet thrombus propagation but not fibrin generation in a mouse model of thrombosis
Authors: Vandendries Erik R. , Hamilton Justin R. , Coughlin Shaun R. , Furie Bruce , Furie Barbara C.
Published: December 2006

Thrombin, a central mediator of hemostasis and thrombosis, converts fibrinogen to fibrin and is a potent platelet activator. Activated platelets provide a surface for assembly of the tenase and prothrombinase complexes required for thrombin generation. The role of thrombin-induced platelet activation in platelet accumulation and its interplay with fibrin deposition during thrombus assembly has not been fully defined. We studied these processes during laser-induced thrombus formation by using real-time digital fluorescence microscopy in mice lacking protease-activated receptor-4 (Par4), which is necessary for thrombin responsiveness in mouse platelets. Juxtamural platelet accumulation immediately after laser injury was not different in wild-type and
Par4
−/−
mice. However, subsequent growth of platelet thrombi was markedly diminished in
Par4
−/−
mice. At the time of maximal thrombus size in wild type, platelet accumulation was more than 10-fold higher in wild type than in
Par4
−/−
mice. P-selectin expression, a marker of platelet activation, was reduced and delayed in
Par4
−/−
thrombi. In contrast to platelet activation and accumulation, the rate and amount of fibrin deposition, predominantly intramural and juxtamural in this model, were indistinguishable in
Par4
−/−
and wild-type mice. These results suggest that platelet activation by thrombin is necessary for normal propagation of a platelet thrombus at a distance from the injured vessel wall and hence for normal thrombus growth. However, platelet activation by thrombin is unnecessary for initial and limited accumulation of platelets at or near the vessel wall, and this limited accumulation of platelets and/or platelet-independent mechanism(s) of thrombin generation are sufficient for normal fibrin deposition in this model.
Dissociation of estrogen receptor expression and in vivo stem cell activity in the mammary gland
Authors: Sleeman Katherine E. , Kendrick Howard , Robertson David , Isacke Clare M. , Ashworth Alan , Smalley Matthew J.
Published: December 2006

The role of estrogen in promoting mammary stem cell proliferation remains controversial. It is unclear if estrogen receptor (ER)–expressing cells have stem/progenitor activity themselves or if they act in a paracrine fashion to stimulate stem cell proliferation. We have used flow cytometry to prospectively isolate mouse mammary ER-expressing epithelial cells and shown, using analysis of gene expression patterns and cell type–specific markers, that they form a distinct luminal epithelial cell subpopulation that expresses not only the ER but also the progesterone and prolactin receptors. Furthermore, we have used an in vivo functional transplantation assay to directly demonstrate that the ER-expressing luminal epithelial subpopulation contains little in vivo stem cell activity. Rather, the mammary stem cell activity is found within the basal mammary epithelial cell population. Therefore, ER-expressing cells of the mammary epithelium are distinct from the mammary stem cell population, and the effects of estrogen on mammary stem cells are likely to be mediated indirectly. These results are important for our understanding of cellular responses to hormonal stimulation in the normal breast and in breast cancer.
Regulation of activity and localization of the WNK1 protein kinase by hyperosmotic stress
Authors: Zagórska Anna , Pozo-Guisado Eulalia , Boudeau Jérôme , Vitari Alberto C. , Rafiqi Fatema H. , Thastrup Jacob , Deak Maria , Campbell David G. , Morrice Nick A. , Prescott Alan R. , Alessi Dario R.
Published: December 2006

Mutations within the WNK1 (with-no-K[Lys] kinase-1) gene cause Gordon's hypertension syndrome. Little is known about how WNK1 is regulated. We demonstrate that WNK1 is rapidly activated and phosphorylated at multiple residues after exposure of cells to hyperosmotic conditions and that activation is mediated by the phosphorylation of its T-loop Ser382 residue, possibly triggered by a transautophosphorylation reaction. Activation of WNK1 coincides with the phosphorylation and activation of two WNK1 substrates, namely, the protein kinases STE20/SPS1-related proline alanine–rich kinase (SPAK) and oxidative stress response kinase-1 (OSR1). Small interfering RNA depletion of WNK1 impairs SPAK/OSR1 activity and phosphorylation of residues targeted by WNK1. Hyperosmotic stress induces rapid redistribution of WNK1 from the cytosol to vesicular structures that may comprise trans-Golgi network (TGN)/recycling endosomes, as they display rapid movement, colocalize with clathrin, adaptor protein complex 1 (AP-1), and TGN46, but not the AP-2 plasma membrane–coated pit marker nor the endosomal markers EEA1, Hrs, and LAMP1. Mutational analysis suggests that the WNK1 C-terminal noncatalytic domain mediates vesicle localization. Our observations shed light on the mechanism by which WNK1 is regulated by hyperosmotic stress.
Smurf1 regulates tumor cell plasticity and motility through degradation of RhoA leading to localized inhibition of contractility
Authors: Sahai Erik , Garcia-Medina Raquel , Pouysségur Jacques , Vial Emmanuel
Published: December 2006

Rho GTPases participate in various cellular processes, including normal and tumor cell migration. It has been reported that RhoA is targeted for degradation at the leading edge of migrating cells by the E3 ubiquitin ligase Smurf1, and that this is required for the formation of protrusions. We report that Smurf1-dependent RhoA degradation in tumor cells results in the down-regulation of Rho kinase (ROCK) activity and myosin light chain 2 (MLC2) phosphorylation at the cell periphery. The localized inhibition of contractile forces is necessary for the formation of lamellipodia and for tumor cell motility in 2D tissue culture assays. In 3D invasion assays, and in in vivo tumor cell migration, the inhibition of Smurf1 induces a mesenchymal–amoeboid–like transition that is associated with a more invasive phenotype. Our results suggest that Smurf1 is a pivotal regulator of tumor cell movement through its regulation of RhoA signaling.
Synaptotagmin-12, a synaptic vesicle phosphoprotein that modulates spontaneous neurotransmitter release
Authors: Maximov Anton , Shin Ok-Ho , Liu Xinran , Südhof Thomas C.
Published: December 2006

Central synapses exhibit spontaneous neurotransmitter release that is selectively regulated by cAMP-dependent protein kinase A (PKA). We now show that synaptic vesicles contain synaptotagmin-12, a synaptotagmin isoform that differs from classical synaptotagmins in that it does not bind Ca2+. In synaptic vesicles, synaptotagmin-12 forms a complex with synaptotagmin-1 that prevents synaptotagmin-1 from interacting with SNARE complexes. We demonstrate that synaptotagmin-12 is phosphorylated by cAMP-dependent PKA on serine97, and show that expression of synaptotagmin-12 in neurons increases spontaneous neurotransmitter release by approximately threefold, but has no effect on evoked release. Replacing serine97 by alanine abolishes synaptotagmin-12 phosphorylation and blocks its effect on spontaneous release. Our data suggest that spontaneous synaptic-vesicle exocytosis is selectively modulated by a Ca2+-independent synaptotagmin isoform, synaptotagmin-12, which is controlled by cAMP-dependent phosphorylation.
Prophase I arrest and progression to metaphase I in mouse oocytes are controlled by Emi1-dependent regulation of APCCdh1
Authors: Marangos Petros , Verschuren Emmy W. , Chen Ruby , Jackson Peter K. , Carroll John
Published: December 2006

Mammalian oocytes are arrested in prophase of the first meiotic division. Progression into the first meiotic division is driven by an increase in the activity of maturation-promoting factor (MPF). In mouse oocytes, we find that early mitotic inhibitor 1 (Emi1), an inhibitor of the anaphase-promoting complex (APC) that is responsible for cyclin B destruction and inactivation of MPF, is present at prophase I and undergoes Skp1–Cul1–F-box/βTrCP-mediated destruction immediately after germinal vesicle breakdown (GVBD). Exogenous Emi1 or the inhibition of Emi1 destruction in prophase-arrested oocytes leads to a stabilization of cyclin B1–GFP that is sufficient to trigger GVBD. In contrast, the depletion of Emi1 using morpholino oligonucleotides increases cyclin B1–GFP destruction, resulting in an attenuation of MPF activation and a delay of entry into the first meiotic division. Finally, we show that Emi1-dependent effects on meiosis I require the presence of Cdh1. These observations reveal a novel mechanism for the control of entry into the first meiotic division: an Emi1-dependent inhibition of APCCdh1.
The phosphotyrosine-independent interaction of DLC-1 and the SH2 domain of cten regulates focal adhesion localization and growth suppression activity of DLC-1
Authors: Liao Yi-Chun , Si Lizhen , deVere White Ralph W. , Lo Su Hao
Published: December 2006

The tensin family member cten (C-terminal tensin like) is an Src homology 2 (SH2) and phosphotyrosine binding domain–containing focal adhesion molecule that may function as a tumor suppressor. However, the mechanism has not been well established. We report that cten binds to another tumor suppressor, deleted in liver cancer 1 (DLC-1), and the SH2 domain of cten is responsible for the interaction. Unexpectedly, the interaction between DLC-1 and the cten SH2 domain is independent of tyrosine phosphorylation of DLC-1. By site-directed mutagenesis, we have identified several amino acid residues on cten and DLC-1 that are essential for this interaction. Mutations on DLC-1 perturb the interaction with cten and disrupt the focal adhesion localization of DLC-1. Furthermore, these DLC-1 mutants have lost their tumor suppression activities. When these DLC-1 mutants were fused to a focal adhesion targeting sequence, their tumor suppression activities were significantly restored. These results provide a novel mechanism whereby the SH2 domain of cten-mediated focal adhesion localization of DLC-1 plays an essential role in its tumor suppression activity.
A critical role for the autophagy gene Atg5 in T cell survival and proliferation
Authors: Pua Heather H. , Dzhagalov Ivan , Chuck Mariana , Mizushima Noboru , He You-Wen
Published: December 2006

Macroautophagy (hereafter referred to as autophagy) is a well-conserved intracellular degradation process. Recent studies examining cells lacking the autophagy genes Atg5 and Atg7 have demonstrated that autophagy plays essential roles in cell survival during starvation, in innate cell clearance of microbial pathogens, and in neural cell maintenance. However, the role of autophagy in T lymphocyte development and survival is not known. Here, we demonstrate that autophagosomes form in primary mouse T lymphocytes. By generating Atg5−/− chimeric mice, we found that Atg5-deficient T lymphocytes underwent full maturation. However, the numbers of total thymocytes and peripheral T and B lymphocytes were reduced in Atg5 chimeras. In the periphery, Atg5−/− CD8+ T lymphocytes displayed dramatically increased cell death. Furthermore, Atg5−/− CD4+ and CD8+ T cells failed to undergo efficient proliferation after TCR stimulation. These results demonstrate a critical role for Atg5 in multiple aspects of lymphocyte development and function and suggest that autophagy may be essential for both T lymphocyte survival and proliferation.
Convergence of TCR and cytokine signaling leads to FOXO3a phosphorylation and drives the survival of CD4+ central memory T cells
Authors: Riou Catherine , Yassine-Diab Bader , Van grevenynghe Julien , Somogyi Roland , Greller Larry D. , Gagnon Dominic , Gimmig Sylvain , Wilkinson Peter , Shi Yu , Cameron Mark J. , Campos-Gonzalez Roberto , Balderas Robert S. , Kelvin David , Sekaly Rafick-Pierre , Haddad Elias K.
Published: December 2006

The molecular events involved in the establishment and maintenance of CD4+ central memory and effector memory T cells (TCM and TEM, respectively) are poorly understood. In this study, we demonstrate that ex vivo isolated TCM are more resistant to both spontaneous and Fas-induced apoptosis than TEM and have an increased capacity to proliferate and persist in vitro. Using global gene expression profiling, single cell proteomics, and functional assays, we show that the survival of CD4+ TCM depends, at least in part, on the activation and phosphorylation of signal transducer and activator of transcription 5a (STAT5a) and forkhead box O3a (FOXO3a). TCM showed a significant increase in the levels of phosphorylation of STAT5a compared with TEM in response to both IL-2 (P < 0.04) and IL-7 (P < 0.002); the latter is well known for its capacity to enhance T cell survival. Moreover, ex vivo TCM express higher levels of the transcriptionally inactive phosphorylated forms of FOXO3a and concomitantly lower levels of the proapoptotic FOXO3a target, Bim. Experiments aimed at blocking FOXO3a phosphorylation confirmed the role of this phosphoprotein in protecting TCM from apoptosis. Our results provide, for the first time in humans, an insight into molecular mechanisms that could be responsible for the longevity and persistence of CD4+ TCM.
DNA polymerase η is the sole contributor of A/T modifications during immunoglobulin gene hypermutation in the mouse
Authors: Delbos Frédéric , Aoufouchi Said , Faili Ahmad , Weill Jean-Claude , Reynaud Claude-Agnès
Published: December 2006

Mutations at A/T bases within immunoglobulin genes have been shown to be generated by a repair pathway involving the DNA-binding moiety of the mismatch repair complex constituted by the MSH2–MSH6 proteins, together with DNA polymerase η (pol η). However, residual A/T mutagenesis is still observed upon inactivation in the mouse of each of these factors, suggesting that the panel of activities involved might be more complex. We reported previously (Delbos, F., A. De Smet, A. Faili, S. Aoufouchi, J.-C. Weill, and C.-A. Reynaud. 2005. J. Exp. Med. 201:1191–1196) that residual A/T mutagenesis in pol η–deficient mice was likely contributed by another enzyme not normally involved in hypermutation, DNA polymerase κ, which is mobilized in the absence of the normal polymerase partner. We report the complete absence of A/T mutations in MSH2–pol η double-deficient mice, thus indicating that the residual A/T mutagenesis in MSH2-deficient mice is contributed by pol η, now recruited by uracil N-glycosylase, the second DNA repair pathway involved in hypermutation. We propose that this particular recruitment of pol η corresponds to a profound modification of the function of uracil glycosylase in the absence of the mismatch repair complex, suggesting that MSH2–MSH6 actively prevent uracil glycosylase from error-free repair during hypermutation. pol η thus appears to be the sole contributor of A/T mutations in the normal physiological context.
Open Channel Block by Ca2+ Underlies the Voltage Dependence of Drosophila TRPL Channel
Authors: Parnas Moshe , Katz Ben , Minke Baruch
Published: December 2006

The light-activated channels of Drosophila photoreceptors transient receptor potential (TRP) and TRP-like (TRPL) show voltage-dependent conductance during illumination. Recent studies implied that mammalian members of the TRP family, which belong to the TRPV and TRPM subfamilies, are intrinsically voltage-gated channels. However, it is unclear whether the Drosophila TRPs, which belong to the TRPC subfamily, share the same voltage-dependent gating mechanism. Exploring the voltage dependence of Drosophila TRPL expressed in S2 cells, we found that the voltage dependence of this channel is not an intrinsic property since it became linear upon removal of divalent cations. We further found that Ca2+ blocked TRPL in a voltage-dependent manner by an open channel block mechanism, which determines the frequency of channel openings and constitutes the sole parameter that underlies its voltage dependence. Whole cell recordings from a Drosophila mutant expressing only TRPL indicated that Ca2+ block also accounts for the voltage dependence of the native TRPL channels. The open channel block by Ca2+ that we characterized is a useful mechanism to improve the signal to noise ratio of the response to intense light when virtually all the large conductance TRPL channels are blocked and only the low conductance TRP channels with lower Ca2+ affinity are active.
Depolarization-induced Calcium Responses in Sympathetic Neurons: Relative Contributions from Ca2+ Entry, Extrusion, ER/Mitochondrial Ca2+ Uptake and Release, and Ca2+ Buffering
Authors: Patterson Michael , Sneyd James , Friel David D.
Published: December 2006

Many models have been developed to account for stimulus-evoked [Ca2+] responses, but few address how responses elicited in specific cell types are defined by the Ca2+ transport and buffering systems that operate in the same cells. In this study, we extend previous modeling studies by linking the time course of stimulus-evoked [Ca2+] responses to the underlying Ca2+ transport and buffering systems. Depolarization-evoked [Ca2+]i responses were studied in sympathetic neurons under voltage clamp, asking how response kinetics are defined by the Ca2+ handling systems expressed in these cells. We investigated five cases of increasing complexity, comparing observed and calculated responses deduced from measured Ca2+ handling properties. In Case 1, [Ca2+]i responses were elicited by small Ca2+ currents while Ca2+ transport by internal stores was inhibited, leaving plasma membrane Ca2+ extrusion intact. In Case 2, responses to the same stimuli were measured while mitochondrial Ca2+ uptake was active. In Case 3, responses were elicited as in Case 2 but with larger Ca2+ currents that produce larger and faster [Ca2+]i elevations. Case 4 included the mitochondrial Na/Ca exchanger. Finally, Case 5 included ER Ca2+ uptake and release pathways. We found that [Ca2+]i responses elicited by weak stimuli (Cases 1 and 2) could be quantitatively reconstructed using a spatially uniform model incorporating the measured properties of Ca2+ entry, removal, and buffering. Responses to strong depolarization (Case 3) could not be described by this model, but were consistent with a diffusion model incorporating the same Ca2+ transport and buffering descriptions, as long as endogenous buffers have low mobility, leading to steep radial [Ca2+]i gradients and spatially nonuniform Ca2+ loading by mitochondria. When extended to include mitochondrial Ca2+ release (Case 4) and ER Ca2+ transport (Case 5), the diffusion model could also account for previous measurements of stimulus-evoked changes in total mitochondrial and ER Ca concentration.
Pharmacological Dissection and Distribution of NaN/Nav1.9, T-type Ca2+ Currents, and Mechanically Activated Cation Currents in Different Populations of DRG Neurons
Authors: Coste Bertrand , Crest Marcel , Delmas Patrick
Published: December 2006

Low voltage–activated (LVA) T-type Ca2+ (ICaT) and NaN/Nav1.9 currents regulate DRG neurons by setting the threshold for the action potential. Although alterations in these channels have been implicated in a variety of pathological pain states, their roles in processing sensory information remain poorly understood. Here, we carried out a detailed characterization of LVA currents in DRG neurons by using a method for better separation of NaN/Nav1.9 and ICaT currents. NaN/Nav1.9 was inhibited by inorganic ICa blockers as follows (IC50, μM): La3+ (46) > Cd2+ (233) > Ni2+ (892) and by mibefradil, a non-dihydropyridine ICaT antagonist. Amiloride, however, a preferential Cav3.2 channel blocker, had no effects on NaN/Nav1.9 current. Using these discriminative tools, we showed that NaN/Nav1.9, Cav3.2, and amiloride- and Ni2+-resistant ICaT (AR-ICaT) contribute differentially to LVA currents in distinct sensory cell populations. NaN/Nav1.9 carried LVA currents into type-I (CI) and type-II (CII) small nociceptors and medium-Aδ–like nociceptive cells but not in low-threshold mechanoreceptors, including putative Down-hair (D-hair) and Aα/β cells. Cav3.2 predominated in CII-nociceptors and in putative D-hair cells. AR-ICaT was restricted to CII-nociceptors, putative D-hair cells, and Aα/β-like cells. These cell types distinguished by their current-signature displayed different types of mechanosensitive channels. CI- and CII-nociceptors displayed amiloride-sensitive high-threshold mechanical currents with slow or no adaptation, respectively. Putative D-hair and Aα/β-like cells had low-threshold mechanical currents, which were distinguished by their adapting kinetics and sensitivity to amiloride. Thus, subspecialized DRG cells express specific combinations of LVA and mechanosensitive channels, which are likely to play a key role in shaping responses of DRG neurons transmitting different sensory modalities.
Quasi-metric and metric spaces
Authors: Schroeder Viktor
Published: December 2006

We give a short review of a construction of Frink to obtain a metric space from a quasi-metric space. By an example we illustrate the limits of the construction.
Thatcherism and the Conservative Party
Authors: Whiteley Paul F. , Seyd Patrick , Richardson Jeremy , Bissell Paul
Published: December 2006

Neither spatial models of party competition nor the ‘Westminster’ model of British politics explain the phenomenon of Thatcherism. One explanation of its success, examined by Crewe and Searing, suggests that Mrs Thatcher sought to convert the Conservative party and the wider electorate to her distinctive brand of liberal Whiggism and traditional Toryism. They found little evidence of the success of this, however, among the British electorate as a whole. In this paper, data from the first national survey of Conservative party members demonstrates that she had little success in converting the Conservative party to these ideas either, although she did have a secure ideological base within the party. The results also suggest that her successor, John Major, has a rather different support base within the party from that of Mrs Thatcher. The implications of these findings for spatial models of party competition and the Westminster model of British politics are discussed.
British Conservatism and the Problem of Ideology
Authors: Vincent Andrew
Published: December 2006

This essay is concerned with one key problem, namely, whether traditionalist conservatism (mainly in the British tradition) can be considered as an ideology. Some conservative theorists and commentators, have clearly been at pains to distance it from the ideological domain. They argue that conservatism is a natural disposition which embodies the historical tradition, customs and prejudices of a society and cannot, in consequence, be articulated as a body of ideas and values. In this sense, conservatism cannot be considered to be an ideology like liberalism or socialism. Despite the attraction of such a claim for many of its proponents there are a number of fatal flaws. After unpacking the argument behind the claim the paper contends that the dispositional interpretation (which is a central plank of much traditionalist conservatism) remains inchoate and unsubstantiated.
International Constraints and Domestic Choices: Economic Convergence and Exchange Rate Policy in France and Italy
Authors: Walsh James I.
Published: December 2006

As tensions in the European Monetary System demonstrate, international capital flows can have a decisive influence on countries' economic policies. The external constraint of high international capital mobility led the countries of Western Europe in the 1980s to attempt to stabilize their exchange rates and converge toward low levels of inflation. Yet this process was not uniform: French governments pursued a rigorous anti-inflationary policy of high interest rates and a strengthening currency, while Italian governments had difficulty controlling inflation and maintaining the lira in the European Monetary System. This difference is best explained by comparing political institutions and policymaking processes in the two countries. Particular attention is given to political leaders' access to economic policy tools and their capacity to design and implement long-term goals.
Policy Convergence in Banking: A Comparative Study
Authors: Coleman William D.
Published: December 2006

The relationship between global economic integration and policy convergence in banking is examined in five countries: Canada, France, Germany, the United Kingdom and the United States. Focusing upon policy styles and modes of policy-making, considerable convergence in membership of policy communities and some convergence in the organization of state agencies is found. When it comes to policy networks, there is more limited convergence on a corporatist mode of policy-making in banking. Policy style may not be as responsive to international economic changes as policy goals, policy content, and policy instruments.
LECTINS*
Authors: Boyd William C.
Published: December 2006

Blood group specific plant agglutinins (named lectins by the present author) were discovered in 1945, first mentioned in 1947, and described in detail by Renkonen in 1948 and by Boyd in 1949. Similar agglutinins have since been found in some invertebrates. Thousands of species have now been screened for such activity. The commonest activities are anti‐A, anti‐H, anti‐N, and someimes anti‐B and anti‐M. A specificity apparently new was found in Arachis hypogaea, and a report of a specificity pertaining to the Rh‐system has appeared. Lectins have been used in routine blood grouping, in the determination of the subgroups of A and AB, in the diagnosis of secretors, and in various theoretical investigations. They have been used to estimate the minimum number of moleules per red cell required for agglutination and in attempts to determine the number of molecules that can combine with a red cell. Lectins have been purified and characterized. Their quantitative precipitin behavior with blood‐group subtances has been studied. It has been possible to alter the specificity of lectins by selective inhibition and by chemical modification.
THE EFFECT OF ISOANTIBODIES ON RED‐CELL SURVIVAL
Authors: Mollison P. L.
Published: December 2006

This paper reviews the progress in relating in vitro characteristics of isoanti‐bodies, such as Ig class, ability to bind complement, and serum concentration, to the rate of destruction of incompatible red cells that they bring about in vivo.

In man, those IgG antibodies that do not bind complement, e.g. anti‐Rh, bring about clearance predominantly in the spleen; in the absence of the spleen, the cells are cleared 100 times more slowly. In the rabbit, with a relatively smaller and evidently less efficient spleen, the minimum concentration of IgG, noncomplement‐binding antibody (anti‐HgA) required for clearance of a dose of 0.02 ml red cells/kg is about 100 times greater than in man.

In detecting the presence of low concentrations of anti‐Rh, estimation of the rate of clearance of a small dose (0.02 ml/kg of red cells) is about ten times more sensitive than the indirect antiglobulin test, even after modifying this test to increase its sensitivity.

Those IgG antibodies that bind complement bring about far more rapid clearance than those that do not, and IgM antibodies are more efficient still. If noncomplement‐binding antibodies are compared, the ratio of IgM:IgG molecules required for a given rate of clearance is less than 1:100.

When small amounts of incompatible red cells are injected into recipients whose serum contains a low concentration of IgM antibody, two‐component curves of destruction are observed. There is evidence that this is due partly to heterogeneity of antigen within the red‐cell population, but that probably the major factor is the limited amount of antibody available.

In man, when relatively small volumes (1‐10 ml) of red cells are transfused to previously untransfused subjects, evidence of primary immunization in the form of accelerated destruction of red cells, beginning at 10‐20 days after transfusion and leading to virtually complete clearance of the cells within 30 days, is observed in approximately 30% of recipients. Although it is postulated that this kind of red‐cell‐survival curve (collapse curve) is due to the production of small amounts of isoantibody, no antibody can, as a rule, be detected serologically, and its specificity is a matter for speculation. Experiments in rabbits show that, as in man, collapse curves are less frequently observed when relatively large volumes of red cells are transfused.
Some Old and Some New Results on Combinatorial Properties of Fixed‐point Free Maps
Authors: BLSASZCZYK ALEKSANDER , VERMEER JOHANNES
Published: December 2006

ABSTRACT: For a fixed‐point free continuous map f: X → X there is studied the minimal size of an open (closed) cover P of X with f(A) → A =Ø for any A → P. Topological versions of some classical results of combinatorics are proved.
Resolvability in Topology and in Topological Groups
Authors: COMFORT W. W. , MASAVEU OSCAR , ZHOU HAO
Published: December 2006

ABSTRACT: A space is resolvable if it contains complementary dense subsets. Among the results proved here, are these. Let Gi (1 ≤i≤ 6) be nondiscrete Hausdorff topological groups with Gi Abelian (1 ≤i≤ 4), G3 locally bounded, G4 a Baire group, and G5 totally bounded and uncountable. Then G1×G2, G3, G4, G5, and G6×G6 are resolvable.
On Hausdorff Spaces via Topological Ideals and I‐irresolute Functions
Authors: DONTCHEV JULIAN
Published: December 2006

ABSTRACT: In this paper I‐open sets are used to introduce a new weak separation axiom and a new type of function. Some of the basic properties of I‐Hausdorff spaces and I‐irresolute functions, as well as the connections between them are investigated.
A Note on Distal Functions
Authors: FILALI M.
Published: December 2006

ABSTRACT: The function f(n)= exp(ip(n)) is known to be distal on the group of the integers whenever p is a real polynomial. We establish a simple criterion from which we deduce the following generalization:

Let R be a discrete ring, X a character of the additive group of R, and p a polynomial function on R and with coefficients in R. Then the function f(s) =X(p(s)) is distal on the additive group of R.
The Space of Maximal Complete Subgraphs of a Graph
Authors: FRIEDLER LOUIS M. , MARTIN HAROLD W.
Published: December 2006

ABSTRACT: M(G) is the set of all maximal complete subgraphs of a graph G with a topology as a subset of the power set 2G. We characterize those Hausdorff spaces homeomorphic to M(G) for some graph G and call such spaces graph spaces. It follows from this characterization that every completely metrizable, zero dimensional space is a graph space. We characterize those graphs G for which M(L(G)) is compact, where L(G) is the line graph of G. It is also shown that the topological product of graph spaces is a graph space.
B‐spaces
Authors: HUNG H. H.
Published: December 2006

ABSTRACT: The recently formulated concept of B‐spaces lies halfway between those of Morita's M‐spaces and Ishii's M*‐spaces on the one hand, and Nagami's Σ‐spaces on the other, and shares with them most of the properties that have come to be expected of generalized metric spaces. We are to look into its stability with respect to the formation of countable products, sums, quasi‐perfect images and pre‐images and subspaces; the preservation of paracompactness over countable products within its confines and of course its metrization.
Uniform Separation and a Theorem of Katětov
Authors: ITZKOWITZ GERALD
Published: December 2006

ABSTRACT: In 1951, Katětov, in an article appearing in Fundamenta Mathematica, showed that each bounded uniformly continuous real‐valued function defined on a subspace (Y𝒰Y) of a uniform space (X,𝒰), can be extended to all of X so as to be uniformly continuous without increase in sup norm. The original proof made use of an intertwining lemma that tends to obscure the proof and its motivation. We define the notions of uniformly separated sets and functionally uniformly separated sets. It then follows from a classical and folklore theorem that two sets are uniformly separated iff they are functionally uniformly separated. Furthermore, it turns out that two sets are uniformly separated in Y iff they are uniformly separated in X. This allows us to apply an elementary Urysohn extension procedure argument to prove Katětov's theorem.
On Completions of Filter Spaces
Authors: KENT D. C. , RATH NANDITA
Published: December 2006

ABSTRACT: Completion theory is established for T2 filter spaces by adapting methods previously developed for Cauchy spaces.
Connectednesses and Disconnectednesses
Authors: LORD HARRIET
Published: December 2006

ABSTRACT: This is the first of two survey articles on Connectednesses and Disconnectednesses. While this paper deals mainly with topological spaces, we do investigate topological categories in order to determine those properties of connectednesses and disconnectednesses in topological spaces that also hold in all topological categories. In addition, we look at the problem of characterizing connectednesses and disconnectednesses both in topological spaces and in topological categories.
Topological Nearrings on the Euclidean Plane
Authors: MAGILL K. D.
Published: December 2006

ABSTRACT:Every continuous binary operation* which is right distributive over (R2, +), the two‐dimensional topological Euclidean group, is induced by four continuous functions from R2to the reals, R. We choose two of these functions to map everything onto zero, we let one be an arbitrary constant function and we let the remaining function be arbitrary. We then find necessary and sufficient conditions on the constant function and the remaining function so that the induced multiplication is associative and, hence, (R2, +, *) is a topological nearring. This allows us to completely describe all the induced multiplications which result in topological nearrings with additive group (R2, +). In addition, we determine the ideals of each of these nearrings as well as its automorphism group.
Inverse Compactness Versus Compactness
Authors: MALYKHIN VIACHESLAV I. , MATVEEV MICHAEL V.
Published: December 2006

ABSTRACT: The problem when an inversely compact space must or must not be compact is considered.
Cardinality and Structure of Semilattices of Ordered Compactifications
Authors: MOONEY DOUGLAS D. , RICHMOND THOMAS A.
Published: December 2006

ABSTRACT: Cardinalities and lattice structures which are attainable by semilattices of ordered compactifications of completely regular ordered spaces are examined. Visliseni and Flachsmeyer have shown that every infinite cardinal is attainable as the cardinality of a semilattice of compactifications of a Tychonoff space. Among the finite cardinals, however, only the Bell numbers are attainable as cardinalities of semilattices of compactifications. It is shown here that all cardinals, both finite and infinite, are attainable as the cardinalities of semilattices of ordered compactifications of completely regular ordered spaces. The last section examines lattice structures which are realizable as semilattices of ordered compactifications, such as chains and power sets.
A Note on Ordered Power Associative (Topological) Groupoids
Authors: ROBBIE DESMOND
Published: December 2006

ABSTRACT: Compact, connected, totally ordered, (Hausdorff) topological groupoids in which each element is power associative are considered. Some conditions are proved to be sufficient for such a groupoid to be (order iseomorphic to) [0, 1/2] with the usual multiplication. Also, an example is given which establishes that a particular condition may not be omitted.
mRNA Regulation by Puf Domain Proteins
Authors: Wharton Robin P. , Aggarwal Aneel K.
Published: December 2006

Puf domain proteins bind specific sequences in mRNAs to regulate their translation or stability, or both. Neither the mechanism of their action nor the identities of targeted mRNAs have been well defined. Recent work suggests that Puf proteins generally act by recruiting Pop2, a deadenylation enzyme that is part of a large complex. Recent work from a separate group defines a subset of the
Drosophila
transcriptome that is bound by the fly Puf protein, Pumilio. Together, these papers substantially increase our understanding of the biology of the Puf family of mRNA regulators.
Pore-Forming Pathogens Activate the Inflammasome
Authors: Gough Nancy R.
Published: December 2006

Pathogenic microbes introduce pores in the host plasma membrane as part of the infectious process. Gurcel
et al
. determined that pore-forming toxins, such as aerolysin from
Aeromonas
and α-toxin from
Staphylococcus aureus
, stimulate the SREBP (sterol response element–binding protein) transcription factors to promote membrane repair. RNA differential display analysis suggested that aerolysin increased the expression of the gene encoding SREBP-2. Indeed, exposure of cells to either aerolysin or α-toxin increased the activity of SREBP-2. In Chinese hamster ovary cells, exposure to aerolysin stimulated proteolytic processing of SREBP-1 and SREBP-2 to release these membrane-bound transcription factors from the endoplasmic reticulum and allowed translocation to the nucleus of the transcriptionally active fragment. The increase in the activity of the SREBPs was verified by an increase in the expression of target genes and an increase in total cellular cholesterol through both increased biosynthesis and uptake (the low-density lipoprotein receptor is encoded by a SREBP-responsive gene). Mutant aerolysin subunits that could not form pores were incapable of stimulating SREBP-2 activity, and SREBP-2 activation required K
+
efflux but did not require an increase in intracellular calcium concentration. Indeed, exposure of cells to a K
+
, but not a Na
+
, ionophore, triggered SREBP-2 activation. Decreased intracellular K
+
concentration is known to activate caspase 1 through activation of inflammasomes with either the IPAF or NALP3 subunits, which are intracellular pattern recognition receptors. When RNA interference was used to knock down subunits of the IPAF or NALP3 inflammasome, the activation of caspase 1 and SREBP-2 in response to aerolysin was diminished. Pharmacological inhibition or knockdown of caspase 1 also prevented SREBP-2 activation. SREBP-2 was not directly cleaved by caspase 1; instead, caspase 1 activated the known SREBP-activating pathway that involves SCAP (an escort protein) and S1P and S2P (the two enzymes responsible for SREBP proteolysis and release). Using various pharmacological and RNAi approaches, the authors showed that activation of the inflammasome caspase 1 and the SREBPs was required for cell survival after exposure to aerolysin. Saleh discusses these findings.

L. Gurcel, L. Abrami, S. Girardin, J. Tschopp, F. G. van der Goot, Caspase-1 activation of lipid metabolic pathways in response to bacterial pore-forming toxins promotes cell survival.
Cell
126
, 1135-1145 (2006).
[Online Journal]

M. Saleh, Caspase-1 builds a new barrier to infection.
Cell
126
, 1028-1030 (2006).
[Online Journal]