bluuebunny/crossref_metadata_2025 huggingface dataset:
Regulation of muscle growth by multiple ligands signaling through activin type II receptors
Authors: Lee Se-Jin , Reed Lori A. , Davies Monique V. , Girgenrath Stefan , Goad Mary E. P. , Tomkinson Kathy N. , Wright Jill F. , Barker Christopher , Ehrmantraut Gregory , Holmstrom James , Trowell Betty , Gertz Barry , Jiang Man-Shiow , Sebald Suzanne M. , Matzuk Martin , Li En , Liang Li-fang , Quattlebaum Edwin , Stotish Ronald L. , Wolfman Neil M.
Published: December 2005

Myostatin is a secreted protein that normally functions as a negative regulator of muscle growth. Agents capable of blocking the myostatin signaling pathway could have important applications for treating human muscle degenerative diseases as well as for enhancing livestock production. Here we describe a potent myostatin inhibitor, a soluble form of the activin type IIB receptor (ACVR2B), which can cause dramatic increases in muscle mass (up to 60% in 2 weeks) when injected into wild-type mice. Furthermore, we show that the effect of the soluble receptor is attenuated but not eliminated in
Mstn
-/-
mice, suggesting that at least one other ligand in addition to myostatin normally functions to limit muscle growth. Finally, we provide genetic evidence that these ligands signal through both activin type II receptors, ACVR2 and ACVR2B, to regulate muscle growth
in vivo
.
Premature condensation induces breaks at the interface of early and late replicating chromosome bands bearing common fragile sites
Authors: El Achkar Eliane , Gerbault-Seureau Michelle , Muleris Martine , Dutrillaux Bernard , Debatisse Michelle
Published: December 2005

Various studies suggest a tight relationship between chromosome rearrangements driving tumor progression and breaks at loci called common fragile sites. Most of these sites are induced after perturbation of the replication dynamics, notably by aphidicolin treatment. We have mapped the majority of these sites to the interface of R and G bands, which calls into question the previous assignment of aphidicolin-sensitive sites to R bands. This observation suggests that most of them correspond to loci that ensure the transition between early and late replicating domains. We show that calyculin A, which triggers chromosome condensation at any phase of the cell cycle but does not markedly impair replication, induces damage in the chromosomes of human lymphocytes treated in G
2
but not in G
1
phase. We demonstrate that these lesions colocalize with those induced by aphidicolin treatment. Hence, common fragile site stability is compromised, whether aphidicolin delays replication or calyculin A advances condensation. We also show that, in cells that go through an unperturbed S phase, completion of their replication and/or replication-associated chromatin reorganization occur all along the G
2
phase, which may explain their inability to condense properly after calyculin A treatment during this phase of the cell cycle.
Expression pattern of the transcription factor Olig2 in response to brain injuries: Implications for neuronal repair
Authors: Buffo Annalisa , Vosko Milan R. , Ertürk Dilek , Hamann Gerhard F. , Jucker Mathias , Rowitch David , Götz Magdalena
Published: December 2005

Despite the presence of neural stem cells and ongoing neurogenesis in some regions of the adult mammalian brain, neurons are not replaced in most brain regions after injury. With the aim to unravel factors contributing to the failure of neurogenesis in the injured cerebral cortex, we examined the expression of cell fate determinants after acute brain injuries, such as stab wound or focal ischemia, and in a model of chronic amyloid deposition. Although none of the neurogenic factors, such as Pax6, Mash1, Ngn2, was detected in the injured parenchyma, we observed a strong up-regulation of the bHLH transcription factor Olig2, but not Olig1, upon acute and chronic injury. To examine the function of Olig2 in brain lesion, we injected retroviral vectors containing a dominant negative form of Olig2 into the lesioned cortex 2 days after a stab wound. Antagonizing Olig2 function resulted in a significant number of infected cells generating immature neurons that were not observed after injection of the control virus. These data, therefore, imply Olig2 as a repressor of neurogenesis in cells reacting to brain injury and open innovative perspectives toward evoking endogenous neuronal repair.
Identification of a hyaluronidase, Hyal5, involved in penetration of mouse sperm through cumulus mass
Authors: Kim Ekyune , Baba Daichi , Kimura Masanori , Yamashita Misuzu , Kashiwabara Shin-ichi , Baba Tadashi
Published: December 2005

A glycosylphosphatidylinositol (GPI)-anchored hyaluronidase, PH-20, on the sperm surface has long been believed to assist sperm penetration through the cumulus mass surrounding the eggs. However, mouse sperm lacking PH-20 were still capable of penetrating the cumulus mass despite a delayed dispersal of cumulus cells. Intriguingly, a 55-kDa hyaluronan-hydrolyzing protein was abundantly present in wild-type and PH-20-deficient mouse sperm. In this study, we purified the 55-kDa mouse protein from soluble protein extracts released from epididymal sperm by acrosome reaction and identified as a hyaluronidase, Hyal5.
Hyal5
was exclusively expressed in the testis and formed a 160-kbp gene cluster together with
Hyalp1
,
Hyal4
, and
Ph-20
on mouse chromosome 6. Hyal5 was a single-chain hyaluronidase present on the plasma and acrosomal membranes of sperm presumably as a GPI-anchored protein. Moreover, hyaluronan zymography revealed that Hyal5 is enzymatically active in the pH range 5–7 and inactive at pH 3 and 4. Both Hyal5-enriched PH-20-free soluble protein extracts and PH-20-deficient mouse sperm were capable of dispersing cumulus cells from the cumulus mass. Cumulus cell dispersal was strongly inhibited by the presence of a hyaluronidase inhibitor, apigenin. These results suggest that in the mouse, Hyal5 may function principally as a “cumulus matrix depolymerase” in the sperm penetration through the cumulus mass and in the local hyaluronan hydrolysis near or on the surface of the egg zona pellucida to enable the proximal region of sperm tail to move freely. PH-20 may compensate in part for the functional roles of Hyal5.
Rotation scheme of V
1
-motor is different from that of F
1
-motor
Authors: Imamura Hiromi , Takeda Mizuho , Funamoto Saeko , Shimabukuro Katsuya , Yoshida Masasuke , Yokoyama Ken
Published: December 2005

V
1
, a water-soluble portion of vacuole-type ATPase (V-ATPase), is an ATP-driven rotary motor, similar to F
1
-ATPase. Hydrolysis of ATP is coupled to unidirectional rotation of the central rotor D and F subunits relative to the A
3
B
3
cylinder. In this study, we analyzed the rotation kinetics of V
1
in detail. At low ATP concentrations, the D subunit rotated stepwise, pausing every 120°. The dwell time between steps revealed that V
1
consumes one ATP per 120° step. V
1
generated torque of ≈35 pN nm, slightly lower than the ≈46 pN nm measured for F
1
. Noticeably, the angles for both ATP cleavage and binding were apparently the same in V
1
, in sharp contrast to F
1
, which cleaves ATP at 80° posterior to the binding of ATP. Thus, the mechanochemical cycle of V
1
has marked differences to that of F
1
.
Protease nexin-2/amyloid β-protein precursor limits cerebral thrombosis
Authors: Xu Feng , Davis Judianne , Miao Jianting , Previti Mary Lou , Romanov Galina , Ziegler Kelly , Van Nostrand William E.
Published: December 2005

The amyloid β-protein precursor (AβPP) is best known as the parent molecule to the amyloid β-peptide that accumulates in the brains of patients with Alzheimer's disease. Secreted isoforms of AβPP that contain the Kunitz proteinase inhibitor domain are analogous to the previously identified cell-secreted proteinase inhibitor known as protease nexin-2 (PN2). Although PN2/AβPP is enriched in brain and in circulating blood platelets, little is understood of its physiological function and potential role in disease processes outside of amyloid β-peptide generation. We hypothesized that the potent inhibition of certain procoagulant proteinases by PN2/AβPP, coupled with its abundance in platelets and brain, indicate that it may function to regulate cerebral thrombosis. Here we show that specific and modest 2-fold overexpression of PN2/AβPP in circulating platelets of transgenic mice caused a marked inhibition of thrombosis
in vivo
. In contrast, deletion of PN2/AβPP in
A
β
PP
gene knockout mice resulted in a significant increase in thrombosis. Similarly, platelet PN2/AβPP transgenic mice developed larger hematomas in experimental intracerebral hemorrhage, whereas
A
β
PP
gene knockout mice exhibited reduced hemorrhage size. These findings indicate that PN2/AβPP plays a significant role in regulating cerebral thrombosis and that modest increases in this protein can profoundly enhance cerebral hemorrhage.
Drosophila
microRNAs exhibit diverse spatial expression patterns during embryonic development
Authors: Aboobaker A. Aziz , Tomancak Pavel , Patel Nipam , Rubin Gerald M. , Lai Eric C.
Published: December 2005

MicroRNAs (miRNAs) are an extensive class of regulatory RNA whose specific functions in animals are generally unknown. Although computational methods have identified many potential targets of miRNAs, elucidating the spatial expression patterns of miRNAs is necessary to identify the sites of miRNA action. Here, we report the spatial patterns of miRNA transcription during
Drosophila
embryonic development, as revealed by
in situ
hybridization to nascent miRNA transcripts. We detect expression of 15 “stand-alone” miRNA loci and 9 intronic miRNA loci, which collectively represent 38 miRNA genes. We observe great variety in the spatial patterns of miRNA transcription, including preblastoderm stripes, in aspects of the central and peripheral nervous systems, and in cellular subsets of the mesoderm and endoderm. We also describe an intronic miRNA (miR-7) whose expression pattern is distinct from that of its host mRNA (
bancal
), which demonstrates that intronic miRNAs can be subject to independent cis-regulatory control. Intriguingly, the expression patterns of several fly miRNAs are analogous to those of their vertebrate counterparts, suggesting that these miRNAs may have ancient roles in animal patterning.
Human stem/progenitor cells from bone marrow promote neurogenesis of endogenous neural stem cells in the hippocampus of mice
Authors: Munoz James R. , Stoutenger Brooke R. , Robinson Andrew P. , Spees Jeffrey L. , Prockop Darwin J.
Published: December 2005

Stem/progenitor cells from bone marrow and other sources have been shown to repair injured tissues by differentiating into tissue-specific phenotypes, by secreting chemokines, and, in part, by cell fusion. Here we prepared the stem/progenitor cells from human bone marrow (MSCs) and implanted athem into the dentate gyrus of the hippocampus of immunodeficient mice. The implanted human MSCs markedly increased the proliferation of endogenous neural stem cells that expressed the stem cell marker Sox2. Labeling of the mice with BrdUrd demonstrated that, 7 days after implantation of the human MSCs, BrdUrd-labeled endogenous cells migrated throughout the dorsal hippocampus (positive for doublecortin) and expressed markers for astrocytes and for neural or oligodendrocyte progenitors. Subpopulations of BrdUrd-labeled cells exhibited short cytoplasmic processes immunoreactive for nerve growth factor and VEGF. By 30 days after implantation, the newly generated cells expressed markers for more mature neurons and astrocytes. Also, subpopulations of BrdUrd-labeled cells exhibited elaborate processes immunoreactive for ciliary neurotrophic factor, neurotrophin-4/5, nerve growth factor, or VEGF. Therefore, implantation of human MSCs stimulated proliferation, migration, and differentiation of the endogenous neural stem cells that survived as differentiated neural cells. The results provide a paradigm to explain recent observations in which MSCs or related stem/progenitor cells were found to produce improvements in disease models even though a limited number of the cells engrafted.
Combining chemical genetics and proteomics to identify protein kinase substrates
Authors: Dephoure Noah , Howson Russell W. , Blethrow Justin D. , Shokat Kevan M. , O'Shea Erin K.
Published: December 2005

Phosphorylation is a ubiquitous protein modification important for regulating nearly every aspect of cellular biology. Protein kinases are highly conserved and constitute one of the largest gene families. Identifying the substrates of a kinase is essential for understanding its cellular role, but doing so remains a difficult task. We have developed a high-throughput method to identify substrates of yeast protein kinases that employs a collection of yeast strains each expressing a single epitope-tagged protein and a chemical genetic strategy that permits kinase reactions to be performed in native, whole-cell extracts. Using this method, we screened 4,250 strains expressing epitope-tagged proteins and identified 24 candidate substrates of the Pho85–Pcl1 cyclin-dependent kinase, including the known substrate Rvs167. The power of this method to identify true kinase substrates is strongly supported by functional overlap and colocalization of candidate substrates and the kinase, as well as by the specificity of Pho85–Pcl1 for some of the substrates compared with another Pho85-cyclin kinase complex. This method is readily adaptable to other yeast kinases.
A genome-wide visual screen reveals a role for sphingolipids and ergosterol in cell surface delivery in yeast
Authors: Proszynski Tomasz J. , Klemm Robin W. , Gravert Maike , Hsu Peggy P. , Gloor Yvonne , Wagner Jan , Kozak Karol , Grabner Hannes , Walzer Karen , Bagnat Michel , Simons Kai , Walch-Solimena Christiane
Published: December 2005

Recently synthesized proteins are sorted at the trans-Golgi network into specialized routes for exocytosis. Surprisingly little is known about the underlying molecular machinery. Here, we present a visual screen to search for proteins involved in cargo sorting and vesicle formation. We expressed a GFP-tagged plasma membrane protein in the yeast deletion library and identified mutants with altered marker localization. This screen revealed a requirement of several enzymes regulating the synthesis of sphingolipids and ergosterol in the correct and efficient delivery of the marker protein to the cell surface. Additionally, we identified mutants regulating the actin cytoskeleton (Rvs161p and Vrp1p), known membrane traffic regulators (Kes1p and Chs5p), and several unknown genes. This visual screening method can now be used for different cargo proteins to search in a genome-wide fashion for machinery involved in post-Golgi sorting.
Tissue plasminogen activator and plasminogen mediate stress-induced decline of neuronal and cognitive functions in the mouse hippocampus
Authors: Pawlak Robert , Rao B. S. Shankaranarayana , Melchor Jerry P. , Chattarji Sumantra , McEwen Bruce , Strickland Sidney
Published: December 2005

Repeated stress can impair function in the hippocampus, a brain structure essential for learning and memory. Although behavioral evidence suggests that severe stress triggers cognitive impairment, as seen in major depression or posttraumatic stress disorder, little is known about the molecular mediators of these functional deficits in the hippocampus. We report here both pre- and postsynaptic effects of chronic stress, manifested as a reduction in the number of NMDA receptors, dendritic spines, and expression of growth-associated protein-43 in the cornu ammonis 1 region. Strikingly, the stress-induced decrease in NMDA receptors coincides spatially with sites of plasminogen activation, thereby predicting a role for tissue plasminogen activator (tPA) in this form of stress-induced plasticity. Consistent with this possibility, tPA-/- and plasminogen-/- mice are protected from stress-induced decrease in NMDA receptors and reduction in dendritic spines. At the behavioral level, these synaptic and molecular signatures of stress-induced plasticity are accompanied by impaired acquisition, but not retrieval, of hippocampal-dependent spatial learning, a deficit that is not exhibited by the tPA-/- and plasminogen-/- mice. These findings establish the tPA/plasmin system as an important mediator of the debilitating effects of prolonged stress on hippocampal function at multiple levels of neural organization.
Peripheral B cells latently infected with Epstein–Barr virus display molecular hallmarks of classical antigen-selected memory B cells
Authors: Souza Tatyana A. , Stollar B. David , Sullivan John L. , Luzuriaga Katherine , Thorley-Lawson David A.
Published: December 2005

Epstein–Barr virus (EBV) establishes a lifelong persistent infection within peripheral blood B cells with the surface phenotype of memory cells. To date there is no proof that these cells have the genotype of true germinal-center-derived memory B cells. It is critical to understand the relative contribution of viral mimicry versus antigen signaling to the production of these cells because EBV encodes proteins that can affect the surface phenotype of infected cells and provide both T cell help and B cell receptor signals in the absence of cognate antigen. To address these questions we have developed a technique to identify single EBV-infected cells in the peripheral blood and examine their expressed Ig genes. The genes were all isotype-switched and somatically mutated. Furthermore, the mutations do not cause stop codons and display the pattern expected for antigen-selected memory cells based on their frequency, type, and location within the Ig gene. We conclude that latently infected peripheral blood B cells display the molecular hallmarks of classical antigen-selected memory B cells. Therefore, EBV does not disrupt the normal processing of latently infected cells into memory, and deviations from normal B cell biology are not tolerated in the infected cells. This article provides definitive evidence that EBV in the peripheral blood persists in true memory B cells.
Forest response to elevated CO2is conserved across a broad range of productivity
Authors: Norby Richard J. , DeLucia Evan H. , Gielen Birgit , Calfapietra Carlo , Giardina Christian P. , King John S. , Ledford Joanne , McCarthy Heather R. , Moore David J. P. , Ceulemans Reinhart , De Angelis Paolo , Finzi Adrien C. , Karnosky David F. , Kubiske Mark E. , Lukac Martin , Pregitzer Kurt S. , Scarascia-Mugnozza Giuseppe E. , Schlesinger William H. , Oren Ram
Published: December 2005

Climate change predictions derived from coupled carbon-climate models are highly dependent on assumptions about feedbacks between the biosphere and atmosphere. One critical feedback occurs if C uptake by the biosphere increases in response to the fossil-fuel driven increase in atmospheric [CO2] (“CO2fertilization”), thereby slowing the rate of increase in atmospheric [CO2]. Carbon exchanges between the terrestrial biosphere and atmosphere are often first represented in models as net primary productivity (NPP). However, the contribution of CO2fertilization to the future global C cycle has been uncertain, especially in forest ecosystems that dominate global NPP, and models that include a feedback between terrestrial biosphere metabolism and atmospheric [CO2] are poorly constrained by experimental evidence. We analyzed the response of NPP to elevated CO2(≈550 ppm) in four free-air CO2enrichment experiments in forest stands. We show that the response of forest NPP to elevated [CO2] is highly conserved across a broad range of productivity, with a stimulation at the median of 23 ± 2%. At low leaf area indices, a large portion of the response was attributable to increased light absorption, but as leaf area indices increased, the response to elevated [CO2] was wholly caused by increased light-use efficiency. The surprising consistency of response across diverse sites provides a benchmark to evaluate predictions of ecosystem and global models and allows us now to focus on unresolved questions about carbon partitioning and retention, and spatial variation in NPP response caused by availability of other growth limiting resources.
An Equilibrium Assembly Model Applied to Murine Polyomavirus
Authors: Keef T.
Published: December 2005

In Keef et al., Assembly Models for Papovaviridae based on Tiling Theory (submitted to J. Phys. Biol.), 2005 [1] we extended an equilibrium assembly model to the (pseudo–)T = 7 viral capsids in the family of Papovaviridae providing assembly pathways for the most likely or primary intermediates and computing their concentrations. Here this model is applied to Murine Polyomavirus based on the association energies provided by the VIPER web page Reddy et al.“Virus particle explorer (VIPER), a website for virus capsid structures and their computational analyses”, J. Virol., 75, pp. 11943–11947, 2001.
The Architecture of Viral Capsids Based on Tiling Theory
Authors: Twarock R.
Published: December 2005

A vital constituent of a virus is its protein shell, called the viral capsid, that encapsulates and hence protects the viral genome. The surface structures of a large number of icosahedral viruses can be modelled via Caspar‐Klug Theory, which has hence become one of the fundamental concepts in virology. However, growing experimental evidence have shown that a significant fraction of viruses falls out of the remit of this theory. Among them are the Papovaviridae, which are of particular interest for the medical sector as they contain cancer causing viruses. A novel approach for the prediction of the protein stoichiometry and bonding structure of icosahedral viruses based on tiling theory is discussed here. It generalises Caspar‐Klug Theory, and is in particular applicable also to Papovaviridae. Besides describing the surface structures of the viruses, this approach also provides a tool for the classification of cross‐linking structures and the construction of assembly models.
A Model of N‐Terminal Cyclin T1 Based on FRET Experiments
Authors: Pantano Sergio , Marcello Alessandro , Sabò Arianna , Ferrari Aldo , Pellegrini Vittorio , Beltram Fabio , Giacca Mauro , Carloni Paolo
Published: December 2005

Human Cyclin T1 is the cyclin partner of kinase CDK9 in the positive transcription elongation factor b (P‐TEFb). P‐TEFb is recruited by Tat, the transactivator of the human immunodeficiency virus type 1 (HIV‐1), to the viral promoter by direct interactions between Tat, Cyclin T1 and the cis‐acting transactivation‐responsive region (TAR) present at the 5′‐end of each viral mRNA. At present, no structural data for Cyclin T1 are available. Here, we build a structural model of an N‐terminus portion of Cyclin T1 (aa 27–263) based on the X‐ray structure of Cyclin H. The model is compared with site directed mutagenesis data from the literature and validated by fluorescence resonance energy transfer (FRET) using Tat as a probe in living cells. This model provides a first step towards the structural characterization of the CDK9–CycT1–Tat‐TAR complex, which is crucial for HIV‐1 replication and may constitute a promising target for pharmaceutical intervention.
A Stochastic Model of Icosahedral Capsid Growth
Authors: Kerner R.
Published: December 2005

A model of growth of icosahedral capsids is proposed. It is similar to the stochastic model of fullerene growth, but takes into account variations in the composition of pentamers and hexamers that are responsible for the final capsid size. We show that the observed high yield of capsid production implies a high level of self‐organization of the elementary building blocks.
Energy Landscapes, Self‐Assembly and Viruses
Authors: Wales D. J.
Published: December 2005

Phenomena such as protein folding, crystallisation, self‐assembly, and the observation of magic number clusters in molecular beams are all the result of non‐random searches. Analysis of the underlying potential energy surface may provide a unifying framework to explain how such events occur as the result of a guided exploration of the landscape. In particular, icosahedral shells composed of 12 pentagonal pyramids are found to be thermodynamically favourable and kinetically accessible when the pyramids are not too spiky and not too flat. Hence, viruses with icosahedral capsids not only minimise the genetic material required to encode the repeated subunits, but may also utilise the favourable properties of a potential energy surface that effectively directs self‐assembly.
Simple Models and Simple Analyses of Virus Capsid Assembly
Authors: Zlotnick A.
Published: December 2005

Assembly of even a simple virus is a complex reaction. Yet, in many cases, the capsids of isometric viruses assemble spontaneously and with high fidelity in vitro. In vitro reactions can be used as the basis for interpreting assembly in vivo, searching for assembly‐directed small molecules, or subverting normal assembly to generate novel structures. A model is required to interpret experimental observation of any complex reaction. To this end, we developed a thermodynamickinetic (master equation) model, in which assembly is described in terms of a cascade of low order reactions. The resulting model can readily be adjusted to match the specific features of a biological system. Simulations replicate experimental observations of assembly and lead to experimentally testable predictions. Analyses based on a basic model, in which only a single path from monomer to capsid was posited, are equally applicable to sparse and complete models that include selected intermediates and every possible intermediate, respectively.
HIF-1–dependent repression of equilibrative nucleoside transporter (ENT) in hypoxia
Authors: Eltzschig Holger K. , Abdulla Parween , Hoffman Edgar , Hamilton Kathryn E. , Daniels Dionne , Schönfeld Caroline , Löffler Michaela , Reyes German , Duszenko Michael , Karhausen Jorn , Robinson Andreas , Westerman Karen A. , Coe Imogen R. , Colgan Sean P.
Published: December 2005

Extracellular adenosine (Ado) has been implicated as central signaling molecule during conditions of limited oxygen availability (hypoxia), regulating physiologic outcomes as diverse as vascular leak, leukocyte activation, and accumulation. Presently, the molecular mechanisms that elevate extracellular Ado during hypoxia are unclear. In the present study, we pursued the hypothesis that diminished uptake of Ado effectively enhances extracellular Ado signaling. Initial studies indicated that the half-life of Ado was increased by as much as fivefold after exposure of endothelia to hypoxia. Examination of expressional levels of the equilibrative nucleoside transporter (ENT)1 and ENT2 revealed a transcriptionally dependent decrease in mRNA, protein, and function in endothelia and epithelia. Examination of the ENT1 promoter identified a hypoxia inducible factor 1 (HIF-1)–dependent repression of ENT1 during hypoxia. Using in vitro and in vivo models of Ado signaling, we revealed that decreased Ado uptake promotes vascular barrier and dampens neutrophil tissue accumulation during hypoxia. Moreover, epithelial Hif1α mutant animals displayed increased epithelial ENT1 expression. Together, these results identify transcriptional repression of ENT as an innate mechanism to elevate extracellular Ado during hypoxia.
Innate NKT lymphocytes confer superior adaptive immunity via tumor-capturing dendritic cells
Authors: Liu Kang , Idoyaga Juliana , Charalambous Anna , Fujii Shin-ichiro , Bonito Anthony , Mordoh Jose , Wainstok Rosa , Bai Xue-Feng , Liu Yang , Steinman Ralph M.
Published: December 2005

If irradiated tumor cells could be rendered immunogenic, they would provide a safe, broad, and patient-specific array of antigens for immunotherapies. Prior approaches have emphasized genetic transduction of live tumor cells to express cytokines, costimulators, and surrogate foreign antigens. We asked if immunity could be achieved by delivering irradiated, major histocompatibility complex–negative plasmacytoma cells to maturing mouse dendritic cells (DCs) within lymphoid organs. Tumor cells injected intravenously (i.v.) were captured by splenic DCs, whereas subcutaneous (s.c.) injection led only to weak uptake in lymph node or spleen. The natural killer T (NKT) cells mobilizing glycolipid α-galactosyl ceramide, used to mature splenic DCs, served as an effective adjuvant to induce protective immunity. This adjuvant function was mimicked by a combination of poly IC and agonistic αCD40 antibody. The adjuvant glycolipid had to be coadministered with tumor cells i.v. rather than s.c. Specific resistance was generated both to a plasmacytoma and lymphoma. The resistance afforded by a single vaccination lasted >2 mo and required both CD4+ and CD8+ T cells. Mature tumor capturing DCs stimulated the differentiation of P1A tumor antigen-specific, CD8+ T cells and uniquely transferred tumor resistance to naive mice. Therefore, the access of dying tumor cells to DCs that are maturing to activated NKT cells efficiently induces long-lived adaptive resistance.
International Trade Theory and Policy: What is Left of the Free Trade Paradigm?
Authors: Sen Sunanda
Published: December 2005

Free trade doctrines have been questioned from the angle of their logical validity as well as relevance. Their replacement by New Trade Theories has been matched by important policy moves on strategic trade and industrial policy in advanced countries. These are defended by the advanced nations, both at inter‐governmental levels and in multilateral institutions, largely in the interest of big capital in industry and finance. However, the theoretically discarded principles of free trade are still in use to push trade liberalization in developing countries. An uneven power relation between the rich and poor nations of the world has generated this asymmetric combination of policies in the world economy. Neglect of the macroeconomic issues relating to the national as well as the world economy has led these theories and the related policies to ignore the concerns for growth as well as development.
Strategic Factors in Economic Development: East Asian Industrialization 1950–2003
Authors: Storm Servaas , Naastepad C. W. M.
Published: December 2005

East Asia's newly industrializing economies are the paragon of successful industrialization. This article investigates what lies behind this success by identifying seven ‘stylized facts’, which concern the contributions to industrialization and growth of structural change and technological change; and the role played by investment, savings and exports. Based on these stylized facts, the authors offer a new formulation of East Asian growth in terms of a cumulative‐causation growth model. They discuss the impact on industrial diversification and upgrading of industrial and trade policies (including import substitution), and labour‐market policies in the context of East Asia's authoritarian political regimes. Important specific factors are highlighted and the particular kinds of policies and institutions used in East Asia to finance accumulation are reviewed, before briefly considering the transferability of the East Asian growth regime.
Phenotype of early cardiomyopathic changes induced by active immunization of rats with a synthetic peptide corresponding to the second extracellular loop of the human β1-adrenergic receptor
Authors: Buvall L , Bollano E , Chen J , Shultze W , Fu M
Published: December 2005

In the failing human heart, due to idiopathic dilated cardiomyopathy, it has been suggested that the β1-adrenergic receptor (β1AR) is a potential pathogenic autoantigen. The aim of the present study was to investigate whether immunization of rats with a synthetic peptide corresponding to the second extracellular loop of the β1AR (β1AR ECII) was able to induce the early stage of cardiomyopathy and also to investigate immunological and receptor functional parameters at a transcriptional level to permit insights into the autoimmune mechanism in cardiomyopathy. Eleven Whistar Fur rats were immunized with a β1AR ECII peptide (H26R) once a month during 12 months and seven control rats were injected with vehicle according to the same procedure used for the immunized group. Cardiac function, β1AR autoantibodies and their functional effects on cardiomyocytes were analysed. β1AR receptor signalling, immunological and cardiomyocyte stretch markers were determined on transcriptional level. In H26R immunized rats, β1AR autoantibodies were shown to be present and functionally active, cardiac functions in terms of fractional shortening were decreased and β1-adrenergic receptor kinase (GRK2) mRNA were increased compared with the control group. These data have shown that immunization of rats with a putative antigenic peptide was able to induce an early stage phenotype of cardiomyopathy in the form of cardiac dysfunction and up-regulation of GRK2 as the first step in the desensitization process of the β1AR, implying the pathological importance of the β1AR autoantibody.
Recurrent infections in partial complement factor I deficiency: evaluation of three generations of a Brazilian family
Authors: Grumach A S , Leitão M F , Arruk V G , Kirschfink M , Condino-Neto A
Published: December 2005

We report here on the evaluation of a factor I-deficient Brazilian family (three generations, 39 members) with strong consanguinity. The complete factor I-deficient patients (n = 3) presented recurrent respiratory infections, skin infections and meningitis; one of them died after sepsis. They presented an impaired total haemolytic activity (CH50), low C3, low factor H and undetectable C3dg/C3d. Partial factor I deficiency was detected in 16 family members (normal low cut-off value was 25 µg/ml). Respiratory infections were the most common clinical occurrence among partial factor I-deficient relatives. Two of them were submitted to nephrectomy following recurrent urinary tract infections. An additional two heterozygous relatives presented with arthritis and rheumatic fever. Apparently, patients with partial factor I deficiency are also at higher risk for recurrent infections. Vaccination against capsulated bacteria and the eventual use of prophylactic antibiotics should be considered individually in this patient group.
A phyto‐sociological analysis of the distribution of riverine tsetse flies in Burkina Faso
Authors: Bouyer J. , Guerrini L. , Cesar J. , De La Rocque S. , Cuisance D.
Published: December 2005

Abstract.  In Burkina Faso, Glossina palpalis gambiensis Vanderplank and G. tachinoides Westwood (Diptera: Glossinidae) are the main cyclic vectors of trypanosomiasis. The vegetation type along river banks is an important factor determining the distribution and abundance of these tsetse. The following work investigated the relation between the plant species present (including the disturbance level) and tsetse distribution and abundance, using three ecotypes, described by P.C. Morel in 1978. These were the Guinean, Sudano‐Guinean and Sudanese gallery forests. In the Mouhoun River basin, these three ecotypes are found successively from upstream to downstream. Berlinia grandiflora, Syzygium guineense and Cola laurifolia and finally Acacia seyal and Mitragyna inermis were the best indicators for the Guinean, Sudano‐Guinean and Sudanese gallery forest ecotypes, respectively, as suggested by Morel. However, other species such as Pterocarpus santalinoides and Mimosa pigra were not ecotype specific. Trap catches confirmed that G. palpalis and G. tachinoides are predominant in Guinean and Sudanese gallery forests, respectively, and that both species are well represented in the Sudano‐Guinean ecotype. Tsetse densities dropped significantly in disturbed Sudano‐Guinean and Sudanese gallery forest sites. However, this was not the case for both species in Guinean or for G. tachinoides in half‐disturbed Sudanese gallery forest sites, confirming their high resilience to human‐made changes. The importance of a detailed consideration of riverine ecotypes when predicting tsetse densities is discussed.
Morphological and molecular comparison of host‐derived populations of parasitic Psoroptes mites
Authors: Pegler K. R. , Evans L. , Stevens J. R. , Wall R.
Published: December 2005

Abstract.  Infestation by parasitic Psoroptes mites (Acari: Psoroptidae) is an important cause of economic loss and welfare problems in livestock in many areas of the world. At least five species within this genus have been recognized, based on the host infested, the infestation site and differences in length of the opisthosomal setae of adult male mites. Here the integrity of these species is considered by subjecting populations of mites from a range of host species and geographical locations to simultaneous morphological and molecular genetic analyses. Morphological analysis showed that there were significant differences in shape and size between mite populations from different hosts, and that length of the outer opisthosomal setae in males and the homologous seta in females were the most important distinguishing character in adults. However, considerable variation in outer opisthosomal seta length was evident within and between populations of mites, and differences were not clearly related to host‐species or geographical origin and did not support the accepted species differences. Molecular characterization using sequence data from the mitochondrial second internal transcribed spacer (ITS‐2) region and microsatellite markers found little or no consistent host‐related variation between the mite population samples. The results suggest that there is no case for considering the Psoroptes mites from the different hosts examined as separate species and that the morphological variation observed therefore may represent phenotypic adaptation to the local microenvironment on particular species of host.
Ovipositional site selection by Anopheles gambiae: influences of substrate moisture and texture
Authors: Huang J. , Walker E. D. , Giroux P. Y. , Vulule J. , Miller J. R.
Published: December 2005

Abstract.  The influence of substrate moisture (hydration) and grain size (texture) on oviposition was quantified in choice tests using Anopheles gambiae sensu stricto Giles (Diptera: Culicidae) laboratory strains and gravid An. gambiae sensu lato from a natural population in Western Kenya. A strong, positive correlation was found between moisture content and the degree of egg‐laying, which peaked at saturation with standing water. Soil moisture quantified as surface conductivity, was measured with an electronic leaf‐wetness sensor slightly modified from a unit available commercially. Although An. gambiae females were sensitive to measurable differences in substrate moisture, they distributed eggs on both fully hydrated and less hydrated substrates. In contrast, An. gambiae females showed little response to substrate texture: they oviposited with equal frequency on all silica substrates of eight particle size classes, ranging from small pebbles (850 µm diameter) to very fine grains (< 38 µm diameter), when all were moist. Female An. gambiae laid more eggs on dark than white substrates against a light background, but did not discriminate between moist, pulverized black soapstone and moist black Kenyan soil taken from typical An. gambiae larval habitats. We conclude that hydration and visual contrast are critical ovipositional site qualities for An. gambiae, but substrate texture is not.
Plant tissues: the frugal diet of mosquitoes in adverse conditions
Authors: Müller G. , Schlein Y.
Published: December 2005

Abstract.  The plant tissue feeding of Anopheles sergentii Theobald, An. claviger Meigen, Culex pipiens Forskål and Aedes caspius Pallas (Diptera: Culicidae) was investigated. The relative frequency of plant feeding was compared to the general intake of sugar in different seasons and in different habitats in Israel. The study shows that mosquitoes feed on sugar‐poor plant tissue in the lack of better options. Optimal conditions were in the sugar‐rich En Fesha oasis, where plant tissue was found in only 0.3% of An. sergentii females, and, except for the winter, about 80% of females were sugar positive and the gut content was equivalent to 72.3 ± 1.6 µg sucrose. By contrast, in the dry season in the desert, guts of 46.3% An. sergentii females contained plant tissue residues, only 46.0% were sugar positive, and the gut‐content was less than a tenth, the equivalent of 5.6 ± 0.9 µg sucrose. Age grouping of contemporary, desert An. sergentii showed that the growing population consisted mostly of newly emerged adults, as 80.2% of the females were nulliparous and only 12.1% of them survived one gonotrophic cycle.
Chromosomal evidence of incipient speciation in the Afrotropical malaria mosquito Anopheles funestus
Authors: Guelbeogo W. M. , Grushko O. , Boccolini D. , Ouédraogo P. A. , Besansky N. J. , Sagnon N. F. , Costantini C.
Published: December 2005

Abstract.  The analysis of chromosomal polymorphism of paracentric inversions in anopheline mosquitoes has often been instrumental to the discovery of sibling species complexes and intraspecific genetic heterogeneities associated with incipient speciation processes. To investigate the population structure of Anopheles funestus Giles (Diptera: Culicidae), one of the three most important vectors of human malaria in sub‐Saharan Africa, a three‐year survey of chromosomal polymorphism was carried out on 4638 karyotyped females collected indoors and outdoors from two villages of central Burkina Faso. Large and temporally stable departures from Hardy–Weinberg equilibrium due to significant deficits of heterokaryotypes were found irrespective of the place of capture, and of the spatial and temporal units chosen for the analysis. Significant linkage disequilibrium was observed among inversion systems on independently assorting chromosomal arms, indicating the existence of assortative mating phenomena. Results were consistent with the existence of two chromosomal forms characterized by contrasting degrees of inversion polymorphism maintained by limitations to gene flow. This hypothesis was supported by the reestablishment of Hardy–Weinberg and linkage equilibria when individual specimens were assigned to each chromosomal form according to two different algorithms. This pattern of chromosomal variability is suggestive of an incipient speciation process in An. funestus populations from Burkina Faso.
Sex pheromone of the tsetse species, Glossina austeni: isolation and identification of natural hydrocarbons, and bioassay of synthesized compounds
Authors: Carlson D. A. , Mramba F. , Sutton B. D. , Bernier U. R. , Geden C. J. , K. Mori
Published: December 2005

Abstract.  Copulatory responses of male Glossina austeni (Newstead) (Diptera: Glossinidae), that were elicited after contact with frozen female tsetse, were not observed after solvent washing of cuticular lipids. Chromatographic analysis of extracts from laboratory‐reared and field‐collected G. austeni females yielded natural hydrocarbons that were highly stimulatory to males. Most of this activity was produced by compounds in the alkene fraction. Gas chromatograms (GC) contained five natural alkenes; these were separated by preparative GC for bioassays conducted in Tanzania. The two major alkenes were identified using gas chromatography–mass spectrometry (GC–MS) to be 13,17‐dimethyltritriacont‐1‐ene and 13,17‐dimethylpentatriacont‐1‐ene, after the samples had undergone derivatization using dimethyl disulphide and saturation with deuterium. These alkenes and natural alkanes were quantified from G. austeni of both sexes from laboratory and field samples to confirm that their presence was consistent in this species. Trials of synthetic samples resulted in the order of biological activity for the stereoisomers of 13,17‐dimethyltritriacont‐1‐ene as follows: S,R‐33:1 > R,S‐ 33:1 > S,S‐33:1 > R,R‐33:1. Dose–response data showed an ED50 at 5 µg per treated, solvent‐washed male decoy. Of the four stereoisomers of 13,17‐dimethylpentatriacont‐1‐ene, R,R‐35:1 showed the most activity. This is the first report of alkene‐induced sexual activity in males of the genus Glossina.
Tomato Pto encodes a functional N‐myristoylation motif that is required for signal transduction in Nicotiana benthamiana
Authors: de Vries Jeroen S. , Andriotis Vasilios M.E. , Wu Ai‐Jiuan , Rathjen John P.
Published: December 2005

Pto kinase of tomato (Lycopersicon esculentum) confers resistance to bacterial speck disease caused by Pseudomonas syringae pv. tomato expressing avrPto or avrPtoB. Pto interacts directly with these type‐III secreted effectors, leading to induction of defence responses including the hypersensitive response (HR). Signalling by Pto requires the nucleotide‐binding site–leucine‐rich repeat (NBS–LRR) protein Prf. Little is known of how Pto is controlled prior to or during stimulation, although kinase activity is required for Avr‐dependent activation. Here we demonstrate a role for the N‐terminus in signalling by Pto. N‐terminal residues outside the kinase domain were required for induction of the HR in Nicotiana benthamiana. The N‐terminus also contributed to both AvrPto‐binding and phosphorylation abilities. Pto residues 1–10 comprise a consensus motif for covalent attachment of myristate, a hydrophobic 14‐carbon saturated fatty acid, to the Gly‐2 residue. Several lines of evidence indicate that this motif is important for Pto function. A heterologous N‐myristoylation motif complemented N‐terminal deletion mutants of Pto for Prf‐dependent signalling. Signalling by wild‐type and mutant forms of Pto was strictly dependent on the Gly‐2 residue. The N‐myristoylation motif of Pto complemented the cognate motif of AvrPto for avirulence function and membrane association. Furthermore, Pto was myristoylated in vivo dependent on the presence of Gly‐2. The subcellular localization of Pto was independent of N‐myristoylation, indicating that N‐myristoylation is required for some function other than membrane affinity. Consistent with this idea, AvrPtoB was also found to be a soluble protein. The data indicate an important role(s) for the myristoylated N‐terminus in Pto signalling.
L’économie Social e et Coopérative Des Associationnistes: De La Critique Des Fondements De L’économie Politique à La Régulation Sociale Du Marché
Authors: Demoustier Danièle , Rousseliere Damien
Published: December 2005

Resume**:  Cet article propose une présentation et une discussion des principales thèses défendues par un courant fondateur de l’économie sociale et coopérative en France, les associationnistes. Ces théoriciens (Louis Blanc, Auguste Ott, Philippe Buchez) développent une critique du fonctionnement de leur société, à partir d’une réflexion sur les fondements de l’économie politique classique. L’actualité de la pensée de ces auteurs se trouve à trois niveaux: d’une part sur la méthode de l’économie politique avec la séparation discutée entre science positive et normative, d’autre part sur le droit au travail par l’association et la question de la propriété collective, enfin sur la nature de la régulation sociale du marché.
Caractérisation Des Rapports Entre L’état et Le Tiers Secteur Associatif Au Sein Du Système Sociosanitaire Québécois: L’émergence De Nouveaux Modes De Coordination
Authors: Jetté Christian
Published: December 2005

Résumé**:  La reconnaissance progressive acquise au cours des années 1970 et 1980 par le tiers secteur associatif oeuvrant en santé et services sociaux au Québec ne peut être dissociée, d’une part, d’une prise de conscience par les acteurs politiques et administratifs, des limites du providentialisme et, d’autre part, des luttes menées par les acteurs de ce tiers secteur pour imposer leurs principes d’action au sein du système sociosanitaire. Cette reconnaissance s’est cristallisée autour d’une structure institutionnelle particulière: le Programme de soutien aux organismes communautaires (PSOC), un programme de financement permettant aux associations d’obtenir des subventions sur la base d’un financement pour leur mission globale. Les modalités originales de ce programme ont ainsi permis l’articulation, au sein du système sociosanitaire québécois, de modes de coordination axés sur le principe de l’efficacité technocratique avec d’autres principes tels la réciprocité, la participation et l’innovation. Cet agencement de différents modes de coordination et des dispositifs institutionnels qui le soutiennent constituent un élément important de l’originalité du modèle québécois de développement social en Amérique du Nord.