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Major Players (major + player)
Selected AbstractsMajor Players: Bureaucracies In American GovernmentPUBLIC ADMINISTRATION REVIEW, Issue 1 2001Herbert Kaufman For more than 50 years, Herbert Kaufman has been an astute observer of public bureaucracies. In this essay, Kaufman draws on his extensive experience in explaining the role of public bureaucracies in the American political system. Kaufman was motivated to write the essay because of his concern that public bureaucracies are not given adequate attention in American government textbooks. We hope that PAR readers will use the essay to educate students and others about the important role of public bureaucracies in American government.,LDT [source] Progenitor cells in liver regeneration: molecular responses controlling their activation and expansion,APMIS, Issue 11-12 2005ERIC SANTONI-RUGIU Although normally quiescent, the adult mammalian liver possesses a great capacity to regenerate after different types of injuries in order to restore the lost liver mass and ensure maintenance of the multiple liver functions. Major players in the regeneration process are mature residual cells, including hepatocytes, cholangiocytes and stromal cells. However, if the regenerative capacity of mature cells is impaired by liver-damaging agents, hepatic progenitor cells are activated and expand into the liver parenchyma. Upon transit amplification, the progenitor cells may generate new hepatocytes and biliary cells to restore liver homeostasis. In recent years, hepatic progenitor cells have been the subject of increasing interest due to their therapeutic potential in numerous liver diseases as alternative or supportive/complementary tools to liver transplantation. While the first investigations on hepatic progenitor cells have focused on their origin and phenotypic characterization, recent attention has focused on the influence of the hepatic microenvironment on their activation and proliferation. This microenvironment comprises the extracellular matrix, epithelial and non-epithelial resident liver cells, and recruited inflammatory cells as well as the variety of growth-modulating molecules produced and/or harboured by these elements. The cellular and molecular responses to different regenerative stimuli seem to depend on the injury inflicted and consequently on the molecular microenvironment created in the liver by a certain insult. This review will focus on molecular responses controlling activation and expansion of the hepatic progenitor cell niche, emphasizing similarities and differences in the microenvironments orchestrating regeneration by recruitment of progenitor cell populations or by replication of mature cells. [source] The ubiquitin-proteasome system and its role in ethanol-induced disordersADDICTION BIOLOGY, Issue 1 2002Terrence M. Donohue Jr The levels of these proteins are controlled by their rates of degradation. Similarly, protein catabolism plays a crucial role in prolonging cellular life by destroying damaged proteins that are potentially cytotoxic. A major player in these catabolic reactions is the ubiquitin-proteasome system, a novel proteolytic system that has become the primary proteolytic pathway in eukaryotic cells. Ubiquitin-mediated proteolysis is now regarded as the major pathway by which most intracellular proteins are destroyed. Equally important, from a toxicological standpoint, is that the ubiquitin-proteasome system is also widely considered to be a cellular defense mechanism, since it is involved in the removal of damaged proteins generated by adduct formation and oxidative stress. This review describes the history and the components of the ubiquitin-proteasome system, its regulation and its role in pathological states, with the major emphasis on ethanol-induced organ injury. The available literature cited here deals mainly with the effects of ethanol consumption on the ubiquitin-proteasome pathway in the liver. However, since this proteolytic system is an essential pathway in all cells it is an attractive experimental model and therapeutic target in extrahepatic organs such as the brain and heart that are also affected by excessive alcohol consumption. [source] Expression and functional characterization of P2Y1 and P2Y12 nucleotide receptors in long-term serum-deprived glioma C6 cellsFEBS JOURNAL, Issue 8 2007Patryk Krzemi We characterized the expression and functional properties of the ADP-sensitive P2Y1 and P2Y12 nucleotide receptors in glioma C6 cells cultured in medium devoid of serum for up to 96 h. During this long-term serum starvation, cell morphology changed from fibroblast-like flat to round, the adhesion pattern changed, cell-cycle arrest was induced, extracellular signal-regulated kinase (ERK1/2) phosphorylation was reduced, Akt phosphorylation was enhanced, and expression of the P2Y12 receptor relative to P2Y1 was increased. These processes did not reflect differentiation into astrocytes or oligodendrocytes, as expression of glial fibrillary acidic protein and NG2 proteoglycan (standard markers of glial cell differentiation) was not increased during the serum deprivation. Transfer of the cells into fresh medium containing 10% fetal bovine serum reversed the changes. This demonstrates that serum starvation caused only temporary growth arrest of the glioma C6 cells, which were ready for rapid division as soon as the environment became more favorable. In cells starved for 72 and 96 h, expression of the P2Y1 receptor was low, and the P2Y12 receptor was the major player, responsible for ADP-evoked signal transduction. The P2Y12 receptor activated ERK1/2 kinase phosphorylation (a known cell proliferation regulator) and stimulated Akt activity. These effects were reduced by AR-C69931MX, a specific antagonist of the P2Y12 receptor. On the other hand, Akt phosphorylation increased in parallel with the low expression of the P2Y1 receptor, indicating the inhibitory role of P2Y1 in Akt pathway signaling. The shift in nucleotide receptor expression from P2Y1 to P2Y12 would appear to be a new and important self-regulating mechanism that promotes cell growth rather than differentiation and is a defense mechanism against effects of serum deprivation. [source] HMGA2 and the p19Arf -TP53-CDKN1A axis: A delicate balance in the growth of uterine leiomyomas,GENES, CHROMOSOMES AND CANCER, Issue 8 2010Dominique Nadine Markowski Pathogenetically, uterine leiomyomas (ULs) can be interpreted as the result of a monoclonal abnormal proliferation of myometrial cells. Oncogene-induced senescence (OIS) is a frequent phenomenon in premalignant lesions that leads to a growth arrest mainly by the activation of two potent growth-inhibitory pathways as represented by p16Ink4a and p19Arf. The relevance of OIS for the development of UL has not been addressed, but HMGA2, encoded by a major target gene of recurrent chromosomal abnormalities in UL, has been implicated in the repression of the Ink4a/Arf (CDKN2A) locus. This prompted us to examine if HMGA2 contributes to the growth of leiomyomas by repressing this locus. Contrary to the expectations, we were able to show that generally ULs express significantly higher levels of p19Arf mRNA than myometrium and that UL with 12q14,15 rearrangements showed higher expression levels than UL with other cytogenetic aberrations. Furthermore, the finding of a significant correlation between the expressions of p19Arf and CDKN1A shows that p19Arf triggers senescence rather than apoptosis in UL. Furthermore, the expression levels of HMGA2, p19Arf, and CDKN1A were found to be correlated with the size of the tumors, indicating that an enhanced growth potential is counterbalanced by the p19Arf pathway. Mechanistically, the UL may thus execute a program already present in their cell of origin, where it is activated to protect the genome, for example, in the case of enhanced proliferation. In summary, the results identify the p19Arf -TP53-CDKN1A pathway as a major player in the growth control and genomic stability of uterine fibroids. © 2010 Wiley-Liss, Inc. [source] Development-dependent disappearance of caspase-3 in skeletal muscle is post-transcriptionally regulatedJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 1 2002Louis-Bruno Ruest Abstract Caspase-3, a major player in apoptosis, engages apoptosis-activated cells into an irreversible pathway leading to cell death. In this article, we report that caspase-3 protein is absent from rat and mouse adult skeletal muscles, despite the abundant presence of its mRNA. During skeletal muscle development, caspase-3 protein is present in neonatal animals, but its expression gradually decreases, and disappears completely by 1 month of age, when there is still abundant caspase-3 mRNA. This discordance between caspase-3 message and protein expression is unique to skeletal muscle, as in all other analyzed tissues the protein presence correlates with the presence of the mRNA. The only circumstance in which caspase-3 protein appears in adults is in regenerating muscles; once regeneration is complete, however, it again becomes undetectable in repaired muscles. We conclude that caspase-3 protein in skeletal muscle is uniquely regulated at the post-transcriptional level, unseen in other tissues such as brain, heart, lung, kidney, thymus, spleen, liver, or testis. The post-transcriptional regulation of caspase-3 might serve as a fail-safe mechanism to avoid accidental cell death. J. Cell. Biochem. 86: 21,28, 2002. © 2002 Wiley-Liss, Inc. [source] Characterization of human liver dendritic cells in liver grafts and perfusatesLIVER TRANSPLANTATION, Issue 3 2006Brenda M. Bosma It is generally accepted that donor myeloid dendritic cells (MDC) are the main instigators of acute rejection after organ transplantation. The aim of the present study was to characterize MDC in human donor livers using liver grafts and perfusates as a source. Perfusates were collected during ex vivo vascular perfusion of liver grafts pretransplantation. MDC, visualized in wedge biopsies by immunohistochemistry with anti-BDCA-1 monoclonal antibody (mAb), were predominantly observed in the portal fields. Liver MDC, isolated from liver wedge biopsies, had an immature phenotype with a low expression of CD80 and CD83. Perfusates were collected from 20 grafts; perfusate mononuclear cells (MNC) contained 1.5% (range, 0.3-6.6%) MDC with a viability of 97 ± 2%. Perfusates were a rich source of hepatic MDC since 0.9 × 106 (range, 0.11-4.5 × 106) MDC detached from donor livers during vascular perfusion pretransplantation. Perfusate MDC were used to further characterize hepatic MDC. Perfusate MDC expressed less DC-LAMP (P = 0.000), CD80 (P = 0.000), CD86 (P = 0.003), and CCR7 (P = 0.014) than mature hepatic lymph node (LN) MDC, and similar CD86 (P = 0.140) and CCR7 (P = 0.262) as and more DC-LAMP (P = 0.007) and CD80 (P = 0.002) than immature blood MDC. Perfusate MDC differed from blood MDC in producing significantly higher amounts of interleukin (IL)-10 in response to lipopolysaccharide (LPS), and in being able to stimulate allogeneic T-cell proliferation. In conclusion, human donor livers contain exclusively immature MDC that detach in high numbers from the liver graft during pretransplantation perfusion. These viable MDC have the capacity to stimulate allogeneic T-cells, and thus may represent a major player in the induction of acute rejection. Liver Transpl 12: 384,393, 2006. © 2006 AASLD. [source] Dietary fat is a major player in obesity , but not the only oneOBESITY REVIEWS, Issue 2 2002Arne Astrup [source] Metastases and multiple myeloma generate distinct transcriptional footprints in osteocytes in vivo,THE JOURNAL OF PATHOLOGY, Issue 5 2008S Eisenberger Abstract Osteocytes are the most abundant bone cells, playing important roles in tissue maintenance. Little is known of how they react in vivo to cancer stress. Here we present a comparative study of the effect of a bone-residing tumour (myeloma) and metastases of bone-remote cancers on osteocytes. While no differences in morphology of the bone are seen, the changes in the transcriptome of osteocytes are specifically related to the tumour stress present. Screening ,22 000 genes in osteocytes prepared from cryosections of native bone using laser-supported microdissection, we observed ,1400 and ,1800 gene expression differences between osteocytes dissected from normal bone compared with those associated with metastases and multiple myeloma, respectively. The genes up-regulated due to the stress exerted by metastases were repressed by multiple myeloma and vice versa, indicating stress-specific footprints in the transcriptome of osteocytes. Functionally, the stressors seem to impose selective pressures on signalling pathways such as that of TGF,, a major player in bone biology. Our data show for the first time that the transcriptome of osteocytes in vivo becomes strongly affected by cancer stress, generating gene expression footprints which, in contrast to comparable morphological changes, appear to relate to the nature of cancer and might thus become helpful in distinguishing different bone diseases. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source] ORIGINAL ARTICLE: HLA-G Expression Is Up-Regulated by Progesterone in Mesenchymal Stem CellsAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 1 2009Ekaterina Ivanova-Todorova Problem, Maternal immune response to fetal tissues is modified in such way that it favors the development of pregnancy. Human leukocyte antigen (HLA)-G, progesterone and mesenchymal stem cells (MSCs) have been identified as potent immunomodulatory agents in different experimental systems and the interactions between these three factors are studies in this paper. Method of study, Human MSCs are isolated from human adipose tissue, bone marrow and decidua are cultured in the presence of progesterone and the expression of HLA-G is followed-up at protein and mRNA levels. Results, The MSCs cultured in the presence of progesterone express increased levels of both cell surface and cytoplasmic HLA-G when compared with the control MSCs. Conclusion, Progesterone up-regulates the expression by MSCs of HLA-G which is a major player in maintenance of the immune balance between the mother and the fetus. MSCs are newly detected targets of progesterone with well documented immunomodulatory activity. [source] Patent Policy for Human Embryonic Stem Cell Research in TaiwanTHE JOURNAL OF WORLD INTELLECTUAL PROPERTY, Issue 4 2010Jerry I.-H. The potential of human embryonic stem cell (ESC) research could prove to provide immense therapeutic value for illnesses not curable under currently existing therapies. However, human ESC research is controversial as it touches the fundamental value of human life. Taiwan has been aiming to become the biotech hub of Asia-Pacific and is becoming a major player in human ESC research. Whether or not the research results from human ESC are patentable could have a profound impact on the progress in this field. In this article, the science of human ESC research is clarified and tested against the existing murky Taiwan patent standards. In particular, this article distinguishes between therapeutic cloning and reproductive cloning techniques, asks questions about the patentability of totipotent human ESCs and explores the meaning of the word embryo. This article draws comparison with the European practice on ethical standards and concludes that patenting human ESC research might not be so controversial, but Taiwan has to make its patent law clearer in this field to fulfill the country's intended goal. [source] ,-Tocopherol counteracts ritonavir-induced proinflammatory cytokines expression in differentiated THP-1 cellsBIOFACTORS, Issue 3-4 2007Weimin Guo Abstract Treatment of HIV-infected individuals with HIV protease inhibitor (HPI) drugs has significantly increased their life span. However, one of the side effects of HPI drugs is the development of premature atherosclerosis, whose molecular pathogenesis remains unclear. Previously we have reported that ,-tocopherol (,-T) normalizes CD36 overexpression induced by ritonavir treatment and reduces oxLDL uptake in THP-1 cells. Since inflammation is a major player in the pathogenesis of atherosclerosis, we hypothesized that HPI drugs, such as ritonavir, increase proinflammatory cytokines synthesis and that ,-T supplementation counteracts this effect by suppressing proinflammatory cytokines levels. Here, we report that after differentiating THP-1 cells to macrophages, ritonavir treatment (10 ,g/mL) significantly increases expression of proinflammatory cytokines, IL-6, MCP-1 and IL-8, at both mRNA and protein levels. This ritonavir-induced effect is significantly suppressed by treatment of THP-1/macrophages with 50 ,M ,-T. We conclude that ritonavir can induce proinflammatory cytokines synthesis in THP-1/macrophages, which might be associated with the development of premature atherosclerosis in ritonavir-treated patients and that this effect is prevented by ,-T. [source] CHARACTERIZATION OF THE ACUTE CARDIOVASCULAR EFFECTS OF INTRAVENOUSLY ADMINISTERED INSULIN-LIKE GROWTH FACTOR-I IN CONSCIOUS SPRAGUE-DAWLEY RATSCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 12 2006Nga Cao SUMMARY 1Insulin-like growth factor (IGF)-I has acute effects on cardiovascular function, including a well-characterized vasodilator response in isolated arteries. In addition to increasing the release of nitric oxide, IGF-I also has effects on a variety of other signalling pathways that affect vascular tone, in particular interactions with the sympathetic nervous system and the renin,angiotensin,aldosterone system. We sought to characterize the effects of intravenous IGF-I on blood pressure and on responses to noradrenaline (NA), angiotensin II, acetylcholine and dobutamine. 2Administration of IGF-I administration caused small decreases in mean arterial pressure (5.4 ± 1.5%) and responsiveness to the prazosin-sensitive vasoconstrictor effects of NA (a 2.1 ± 0.6-fold increase in ED50; n = 40; P < 0.01) and both effects were maximal at 200 µg/kg IGF-I. In addition, IGF-I significantly increased pulse pressure increases induced by low doses of dobutamine (from an increase in pulse pressure of 9.9 ± 1.2 to 13.4 ± 1.9 mmHg; n = 39; P < 0.05). Administration of IGF-I had no significant effect on responses to AngII or ACh. 3Intravenous administration of IGF-I receptor antisense oligonucleotides (400 µg/kg) abolished the effects of IGF-I on NA-induced vasoconstriction (n = 11; P < 0.05), whereas administration of a mismatch oligonucleotide did not. 4These data indicate that the maximal effects of exogenously administered IGF-I include modest direct vasodilation and inhibition of constrictor responses to NA and an increase in the effect of dobutamine on pulse pressure. The magnitude of these effects was less than what previous in vitro studies and those performed in anaesthetized animals may have indicated likely. 5The modest magnitude of the dilator effects of IGF-I observed in conscious rats in vivo in the present study suggests that IGF-I is unlikely to be a major player in regulating vascular tone in normotensive animals. [source] Contribution of Chloroflexus respiration to oxygen cycling in a hypersaline microbial mat from Lake Chiprana, SpainENVIRONMENTAL MICROBIOLOGY, Issue 8 2007Lubos Polerecky Summary In dense stratified systems such as microbial mats, photosynthesis and respiration are coupled due to a tight spatial overlap between oxygen-producing and -consuming microorganisms. We combined microsensors and a membrane inlet mass spectrometer with two independent light sources emitting in the visible (VIS) and near infrared (NIR) regions to study this coupling in more detail. Using this novel approach, we separately quantified the activity of the major players in the oxygen cycle in a hypersaline microbial mat: gross photosynthesis of cyanobacteria, NIR light-dependent respiration of Chloroflexus -like bacteria (CLB) and respiration of aerobic heterotrophs. Illumination by VIS light induced oxygen production in the top ,1 mm of the mat. In this zone CLB were found responsible for all respiration, while the contribution of the aerobic heterotrophs was negligible. Additional illumination of the mat with saturating NIR light completely switched off CLB respiration, resulting in zero respiration in the photosynthetically active zone. We demonstrate that microsensor-based quantification of gross and net photosyntheses in dense stratified systems should carefully consider the NIR light-dependent behaviour of CLB and other anoxygenic phototrophic groups. [source] Shire: a specialty global biopharmaceutical companyFUTURE PRESCRIBER, Issue 3 2009Article first published online: 13 AUG 200 This series of company profiles looks at some of the major players in the UK pharmaceutical industry, their current areas of expertise, and forthcoming products and initiatives that will have an impact on therapeutics and prescribing in the near future. In this article we provide an overview of Shire and its current portfolio, and look at its current pipeline and areas of research interest. Copyright © 2009 John Wiley & Sons, Ltd. [source] Servier: establishing research and education partnershipsFUTURE PRESCRIBER, Issue 3 2008Article first published online: 19 JAN 200 This series of company profiles looks at some of the major players in the UK pharmaceutical industry, their current areas of expertise and forthcoming products and initiatives that will have an impact on therapeutics and prescribing in the near future. In this article we provide an overview of Servier Laboratories and its top products, as well as Servier's ongoing development of research and education partnerships. Copyright © 2008 John Wiley & Sons, Ltd. [source] Immunological basis of the development of necrotic lesions following Mycobacterium avium infectionIMMUNOLOGY, Issue 4 2002Manuela Flórido Summary Normal C57BL/6 mice infected with 106 colony-forming units of a highly virulent strain of Mycobacterium avium developed a progressive infection characterized by loss of T cells from the tissues and infiltration with high numbers of heavily infected macrophages. In contrast, when C57BL/6 mice were infected with 102 colony-forming units of the same strain they retained T cells and T-cell reactivity in the tissues, and granulomas evolved into large masses that, at 4 months of infection, exhibited central necrosis. The development of these necrotic lesions did not occur in nude mice, nor in mice genetically deficient in CD4, interleukin-12 (IL-12) p40, interferon-, (IFN-,) and CD40 and were reduced in mice deficient in CD54 or IL-6. They were less numerous but bigger in mice deficient in IL-10 or the inducible nitric oxide synthase, correlating with the increased resistance to mycobacterial proliferation of these strains as compared to control mice. The appearance of necrosis was not affected in mice deficient in CD8,, T-cell receptor ,, tumour necrosis factor receptor p55, and perforin, nor was it affected in mice over-expressing bcl2. The appearance of necrosis could be prevented by administering antibodies specific for CD4, IL-12p40, or IFN-, from the second month of infection when organized granulomas were already found. Our results show that the immunological mediators involved in the induction of protective immunity are also major players in the immunopathology associated with mycobacteriosis. [source] Volatility linkages among interest rates: implications for global monetary policyINTERNATIONAL JOURNAL OF FINANCE & ECONOMICS, Issue 3 2002Nikiforos T. Laopodis Abstract This paper explores the effects of a greater integration among major capital markets from 1984 to 2001 on the conduct of global monetary policy. The methodological design is a multivariate vector moving average GARCH model which is suitable for examining the nature of the volatility spillover mechanism of long-term interest rates across markets. The empirical findings indicate that there have been stronger linkages among major bond markets since 1990 at the volatility level. The more synchronized behaviour of long-term interest rates across countries is evidenced by the speed and persistence with which disturbances in a particular market transmit to other markets. Such volatile behaviour affects the conduct of global monetary policy which now has to be done interactively among the world's major players. Copyright © 2002 John Wiley & Sons, Ltd. [source] Two-way interactions between ocean biota and climate mediated by biogeochemical cyclesISRAEL JOURNAL OF CHEMISTRY, Issue 1 2002Hezi Gildor Some of the two-way interactions between ocean biota and climate are mediated by biogeochemical cycles that link the different components of the climate system. As suggested by proxy records extracted from ice and ocean cores, by recent measurements, and by numerical models, such two-way interactions were likely major players in past climate variability on glacial,interglacial timescales, and may act to amplify or moderate an anthropogenically induced climate change in the near future. At present, our lack of understanding of these interactions hampers our ability to anticipate the consequences of possible anthropogenic climate change. In this article, we highlight some of the possible feedbacks between ocean biota and climate, reviewing some key biogeochemical processes and discussing mechanisms of two-way interactions. We also outline the need and strategies for continuing research aimed at advancing our understanding of these feedbacks and discuss their significance. [source] Changes in the serum levels of interleukin-17/interleukin-23 during acute rejection in liver transplantationLIVER TRANSPLANTATION, Issue 6 2009Emilio Fábrega Interleukin-23 (IL-23) and T helper 17 (Th17) cells have been cast as major players in autoimmunity, but their role in transplantation immunity remains to be specified. The aim of our study was to investigate the time course of serum levels of IL-23 and IL-17 during hepatic allograft rejection. Serum levels of IL-23 and IL-17 were determined in 20 healthy subjects and 50 hepatic transplant recipients. These patients were divided into 2 groups: group I was composed of 15 patients with acute rejection, and group II was composed of 35 patients without acute rejection. Samples were collected on days 1 and 7 after liver transplantation and on the day of liver biopsy. The concentrations of IL-23 were similar for the rejection group and nonrejection group at early postoperative times. We observed a significant increase in serum IL-23 levels in the rejection group when a diagnosis of acute rejection had been established. Similarly to IL-23, at the diagnosis of acute rejection, the concentration of IL-17 was significantly higher in the rejection group versus the nonrejection group. The whole transplant group, including those with stable graft function, had higher serum levels of IL-23 and IL-17 than the controls during the entire postoperative period. In conclusion, IL-23 and IL-17 are up-regulated during acute hepatic rejection. These findings suggest a role for Th17 cells in human liver allograft rejection. Liver Transpl 15:629,633, 2009. © 2009 AASLD. [source] Nationalism, international factors and the ,Irish question' in the era of the First World WarNATIONS AND NATIONALISM, Issue 1 2005Karen Stanbridge The ,Irish question' encompassed negotiations leading to the partition of Ireland in 1921. The paper considers factors that contributed to the growing tendency for the major players involved in the struggle , Irish nationalists, unionists and British officials , to adopt postures that were mutually irreconcilable. Conceptualising the problem in terms of Rogers Brubaker's ,triadic nexus' model of nationalisms reveals that the rigidity was encouraged by the dynamic interaction of nationalist representations employed by the three parties in response to the postures adopted by their rivals. Further, international factors , specifically, the prevailing international definition of nation and the position taken by the authority in place to adjudicate claims of nationhood , combined with regional pressures to consolidate Irish, Ulster and British nationalisms in such forms that militated against a compromise solution. By amending Brubaker's model to include international as well as regional forces, the analysis shows how understanding of the Irish contest can be enhanced if conceived as issuing from the continuous and reflexive interaction of three distinct nationalisms with and within an international context that itself was structured with respect to questions of nation. [source] Mosquito midguts and malaria: cell biology, compartmentalization and immunologyPARASITE IMMUNOLOGY, Issue 4 2006M. M. A. WHITTEN SUMMARY The malaria parasite Plasmodium has an absolute requirement for both a vertebrate and a mosquito host in order to complete its life cycle, and its interactions with the latter provide the focus for this review. The mosquito midgut represents one of the most challenging environments for the survival and development of Plasmodium, and is thus also one of the most attractive sites for novel targeted malaria control strategies. During their attempts to cross the midgut epithelium en route to the salivary glands, motile ookinetes are swiftly detected and labelled by mosquito recognition factors and targeted for destruction by a variety of immune responses that recruit killing factors both from the midgut and from other tissues in the surrounding body cavity. The exact interplay between these factors and the parasite is highly species- and strain-specific, as are the timing and the route of parasite invasion. These features are paramount to determining the success of the infection and the vector competence of the mosquito. Here we discuss recent advances in genomic analyses, coupled with detailed microscopical investigations, which are helping to unravel the identity and roles of the major players of these complex systems. [source] Unravelling control freakery: redefining central-local government relationsBRITISH JOURNAL OF POLITICS & INTERNATIONAL RELATIONS, Issue 3 2003David Wilson Central-local relations have been of particular interest since the Labour government came to power in 1997. Both academics and practitioners have pointed to tensions within the Labour government's reform agenda,between a ,top-down' and ,bottom-up' approach; between a drive for national standards and the encouragement of local learning and innovation; and between strengthening executive leadership and enhancing public participation. It is argued that while Labour's modernisation strategy has clear elements of a top-down approach (legislation, inspectorates, white papers, etc) there is also a significant bottom-up dimension (a variety of zones, experiments and pilots, albeit with different degrees of freedom). This article utilises a multi-level governance framework of analysis and argues that, while much of the research using such frameworks has hitherto focused on the EU, recent developments in governance at neighbourhood, local authority, sub-regional and regional levels facilitate its application within a nation state. The central thesis is that, while there is extensive interaction between actors at sub-national level, this should not be seen as a proxy for policy influence. The local political arena is characterised less by multi-level governance than by multi-level dialogue. Sub-national actors participate but they are rarely major players in shaping policy outcomes: the plurality which characterises sub-central governance does not reflect a pluralist power structure. [source] Rhoptries are major players in Toxoplasma gondii invasion and host cell interactionCELLULAR MICROBIOLOGY, Issue 4 2007Jean François Dubremetz Summary Rhoptries are unique secretory organelles shared by all Apicomplexan invasive stages. They are exocytosed upon host cell invasion and their contents are involved in creating the moving junction that propels the parasite in the cell and in building the parasitophorous vacuole in which the parasite will develop. In addition, some rhoptry proteins are targeted to the host cell nucleus. The array of roles played by these organelles has considerably expanded in the recent years, making them a major clue to the understanding of the early interaction between these parasites and their host. Yet, our knowledge on these organelles is still very poor and much has to be done before we get a clear view of the part they play in Apicomplexan biology. [source] Long-Chain Polyamines (LCPAs) from Marine Sponge: Possible Implication in Spicule FormationCHEMBIOCHEM, Issue 14 2007Satoko Matsunaga Abstract Two distinct marine organisms, diatoms and sponges, deposit dissolved silicates to construct highly architectural and species-specific body supports. Several factors such as proteins, long-chain polyamines (LCPAs), or polypeptides modified with LCPAs are known to be involved in this process. The LCPAs contained in the silica walls of diatoms are thought to play pivotal roles in the silica deposition. In sponges, however, a protein called silicatein and several other proteins have been reported to be the factors involved in the silica deposition. However, no other factors involved in this process have been reported. We have identified the LCPAs from the marine sponge Axinyssa aculeata and present here some evidence that sponge-derived LCPAs can deposit silica and that the LCPA derivatives are associated with spicules. The results indicate a common chemistry between sponges and diatoms, the two major players in the biological circulation of silicon in the marine environment. A wide variety of organisms are known to utilize silica in their biological processes. Polyamines or other functional molecules might be involved, in combination with proteins, in their biosilicification process. [source] | ||||||||||||||||||||||