Key Players (key + player)

Distribution by Scientific Domains
Distribution within Medical Sciences

Selected Abstracts

Conservation through buyer-diversity: A key role for not-for-profit land-holding organizations in Australia

Stuart Cowell
,Not-for-profit' nature conservation organizations in Australia are a relatively new and growing phenomenon. Key players discuss the progress of these groups in securing ,in perpetuity' conservation on private land. [source]

Activin/nodal signaling modulates XPAPC expression during Xenopus gastrulation

Xin Lou
Abstract Gastrulation is the first obligatory morphogenesis during vertebrate development, by which the body plan is established. Nodal signaling is a key player in many developmental processes, including gastrulation. XPAPC has been found to exert its biological function through modifying the adhesion property of cells and interacting with other several important molecules in embryos. In this report, we show that nodal signaling is necessary and sufficient for XPAPC expression during Xenopus gastrulation. Furthermore, we isolated 4.8 kb upstream DNA sequence of Xenopus XPAPC, and proved that this 4.8-kb genomic contig is sufficient to recapitulate the expression pattern of XPAPC from gastrula to tail bud stage. Transgene and ChIP assays indicate that Activin/nodal signaling participates in regulation of XPAPC expression through a Smad binding element within the XPAPC promoter. Concomitant investigation suggests that the canonical Wnt pathway-activated XPAPC expression requires nodal signaling. Developmental Dynamics 237:683,691, 2008. © 2008 Wiley-Liss, Inc. [source]

Stearoyl-CoA desaturase: a new therapeutic target of liver steatosis

Pawel Dobrzyn
Abstract Stearoyl-CoA desaturase (SCD) is the rate limiting enzyme catalyzing the biosynthesis of monounsaturated fatty acids, mainly oleate and palmitoleoate, which are used as substrates for the synthesis of triglycerides, wax esters, cholesterol esters, and phospholipids. Recent studies have shown that SCD1, the main SCD isoform expressed in liver, is a key player in the regulation of lipid metabolism. SCD1 deficient mice have increased energy expenditure, reduced body adiposity, increased insulin sensitivity and are resistant to diet-induced obesity and liver steatosis. SCD1 was found to be specifically repressed during leptin-mediated weight loss and leptin-deficient ob/ob mice lacking SCD1 showed markedly reduced adiposity, despite higher food intake. In addition, SCD1 deficiency completely corrects the hypometabolic phenotype and hepatic steatosis of ob/ob mice, and attenuates fasting-induced liver steatosis in peroxisome proliferator-activated receptor-, , deficient mice. Consequently, increased SCD activity has been found in humans and animals which accumulate significant amounts of lipids in liver, whereas SCD1 deficiency ameliorates both high-fat diet induced and genetically induced hepatic steatosis. Much evidence indicates that the direct anti-steatotic effect of SCD1 deficiency stems from increased fatty acid oxidation and reduced lipid synthesis. In this review we discuss our current understanding of the role of SCD1 in regulation of hepatic lipid partitioning and test the hypothesis that pharmacological manipulation of SCD might be of benefit in the treatment of non-alcoholic fatty liver disease. Drug Dev. Res. 67:643,650, 2006. © 2006 Wiley-Liss, Inc. [source]

IL-6: Regulator of Treg/Th17 balance

Akihiro Kimura
Abstract IL-6 is a pleiotropic cytokine involved in the physiology of virtually every organ system. Recent studies have demonstrated that IL-6 has a very important role in regulating the balance between IL-17-producing Th17 cells and regulatory T cells (Treg). The two T-cell subsets play prominent roles in immune functions: Th17 cell is a key player in the pathogenesis of autoimmune diseases and protection against bacterial infections, while Treg functions to restrain excessive effector T-cell responses. IL-6 induces the development of Th17 cells from naïve T cells together with TGF-,; in contrast, IL-6 inhibits TGF-,-induced Treg differentiation. Dysregulation or overproduction of IL-6 leads to autoimmune diseases such as multiple sclerosis (MS) and rheumatoid arthritis (RA), in which Th17 cells are considered to be the primary cause of pathology. Given the critical role of IL-6 in altering the balance between Treg and Th17 cells, controlling IL-6 activities is potentially an effective approach in the treatment of various autoimmune and inflammatory diseases. Here, we review the role of IL-6 in regulating Th17/Treg balance and describe the critical functions of IL-6 and Th17 in immunity and immune-pathology. [source]

Injury-induced neurogenesis in Bax-deficient mice: evidence for regulation by voltage-gated potassium channels

Jian Shi
Abstract Adult neural stem and progenitor cells may help remodel the brain in response to injury. The pro-apoptotic molecule Bax has recently been identified as a key player in adult neural stem cell survival. In Bax-deficient mice that have undergone traumatic brain injury, we find increased numbers of neural progenitor cells in the dentate gyrus and improved remodeling of the hippocampus. Exogenous potassium chloride mimics spreading depression (SD)-like events in vitro, and Bax-deficient neural stem cells proliferate in response to these events more robustly than wild-type neural stem cells. Selective potassium channel blockers interrupt SD-mediated stimulation of stem cells. In addition, the potassium channel Kv4.1 is expressed within neural stem and progenitor cells in the dentate gyrus and is increased in Bax-deficiency. These data suggest that the neuroprotection observed after injury in Bax-deficiency may be due to increased neurogenesis via activation of the Kv4 family of potassium channels. [source]

Human remyelination promoting antibody inhibits apoptotic signaling and differentiation through Lyn kinase in primary rat oligodendrocytes

GLIA, Issue 15 2010
J. Watzlawik
Abstract Purpose: Human remyelination promoting IgM mAbs target oligodendrocytes (OLs) and function in animal models of multiple sclerosis (MS). However, their mechanism of action is unknown. This study seeks to identify the cellular mechanism of action of a recombinant human IgM on OL survival. Methods: Binding of rHIgM22 to the surface of rat OLs was studied by co-localization with various markers. RHIgM22-mediated effects on apoptotic signaling in OLs, differentiation markers, and signaling molecules were detected by Western blotting and immunoprecipitation. Results: RHIgM22 co-localized with integrin ,3 but not other integrin ,-chains in OLs. Downstream of integrin ,3 we identified Src family kinase (SFK) Lyn as a key player of rHIgM22-mediated actions in OLs. Lyn immunoprecipitated in a complex together with integrin ,v,3 and PDGF,R. Lyn expression was 9-fold up-regulated and Lyn activation was 3-fold higher inrHIgM22-treated OL cultures compared with controls. RHIgM22 inhibited apoptotic signaling by greater than 10-fold reduction of caspase-3 and capsase-9 cleavage and reduced by 4-fold expression of differentiation markers MBP and MOG in OLs. SFK inhibitors PP2 and SU6656 inhibited Lyn activity and restored caspase-cleavage in OLs. A human IgM that did not promote remyelination and medium wereused as controls. Conclusions: rHIgM22 prevented apoptotic signaling andinhibited OL differentiation by Lyn implying thatIgM-mediated remyelination is due toprotection of OPC and OLs rather than promotion of OPC differentiation. © 2010 Wiley-Liss, Inc. [source]

A little orphan runs to fat: The orphan receptor small heterodimer partner as a key player in the regulation of hepatic lipid metabolism,,

HEPATOLOGY, Issue 1 2007
Michael Trauner M.D.
First page of article [source]

BUB1 infrequently mutated in human breast carcinomas,,

HUMAN MUTATION, Issue 5 2003
Anita Langerød
Abstract The BUB1 gene is a key player in the mitotic spindle checkpoint machinery that monitors proper segregation of sister chromatides during mitosis. It has been suggested that mutations in BUB1 may disrupt the spindle checkpoint and thereby cause chromosomal instability, which is a hallmark of solid tumors including those from the breast. From a series of breast carcinomas we selected 20 cases with genomic instability, as scored by Comparative Genome Hybridization (CGH), and without somatic TP53 (p53) mutations, and sequenced the entire coding region of the BUB1 gene. Two different constitutional sequence variants were found; a base substitution in exon 5, c.481G>A (CAG>CAA, a synonymous change encoding Gln144) in two samples, and a base substitution 8 bp upstream of exon 10, c.1007-8T>C in two other samples. No somatic mutations were detected. These results indicate that genomic instability scored as copy number alterations by CGH in TP53 wild type breast carcinomas is not caused by somatic mutations in the BUB1 gene. © 2003 Wiley-Liss, Inc. [source]

The contribution of neurogenic inflammation to sensitive skin: concepts, mechanisms and cosmeceutical intervention

A. Ferrer-Montiel
IFSCC Magazine, 11 (2008) (4) 311,315 This paper was presented as a keynote lecture at the IFSCC Congress 2008, Barcelona, Spain. Cutaneous neurogenic inflammation is emerging as an underlying mechanism for several skin conditions. The intimate cross-talk between the cutaneous immune system and the peripheral nervous system is fundamental for skin biology. However, an imbalance or dysfunction results in the onset of an inflammatory state that is reinforced by the synergic and complementary action of both systems. Cumulative evidence indicates that the thermoreceptor TRPV1 is a key player of neurogenic inflammation. This receptor is activated by both physical and chemical stimuli, and its activity is potentiated by pro-inflammatory mediators. An increase in TRPV1 activity results in an increment of neuronal excitability that leads to the release of proalgesic agents that stimulate the immune system. Therefore, the TRPV1 receptor is being considered as a cosmeceutical target, and agents that reduce its activity will be useful cosmeceuticals. Keywords:, Algogens, epidermis, immune system, nociceptor, sensitization [source]

Trade Politics Ain't What It Used to Be: The European Union in the Doha Round,

The European Union is a key player in the Doha Development Round of multilateral trade negotiations. This article argues that its negotiating position reflects distinctive patterns of politics underlying three aspects of trade policy , traditional trade policy, commercial policy and social trade policy , characterized by different sets of actors and political dynamics. Although there is significant variation in the substance of the EU's position within each aspect of trade policy, their distinctive patterns of politics help to explain why the EU's negotiating position is most liberal in traditional trade policy and least in social trade policy. [source]

,The Day of Burning': Eviction and Reinvention in the Margins of Northwest Zimbabwe

Amanda Hammar
A violent eviction in a remote northwestern corner of Zimbabwe in late 1997 provides a prism through which to explore the changing dynamics of competition over space, power and production in Zimbabwe's agrarian margins, where con?ict over wildlife and agriculture has intensi?ed and the state has become a key player. The article argues that in its quest to (re)gain control over one such location, the state has had to construct it as space of violence in order to de-civilize it and reinvent it as a wilderness zone. The ,day of burning' is taken not only as a signi?er of the violent potential of such competition, but also as a metaphor for the state's increasing loss of legitimacy in the margins: that is, the ,burning away' of any residue of illusion about the state as either the democratic embodiment of the people's will or compassionate provider of services and security. [source]

Phosphate and calcium are required for TGF,-mediated stimulation of ANK expression and function during chondrogenesis

Paulina Oca
The expression of ANK, a key player in biomineralization, is stimulated by treatment with TGF,. The purpose of this study was to determine whether TGF, stimulation of ANK expression during chondrogenesis was dependent upon the influx of calcium and phosphate into cells. Treatment of ATDC5 cells with TGF, increased ANK expression during all phases of chondrogenic differentiation, particularly at day 14 (proliferation) and day 32 (mineralizing hypertrophy) of culture. Phosphate uptake studies in the presence and absence of phosphonoformic acid (PFA), a competitive inhibitor of the type III Na+/Pi channels Pit-1 and Pit-2, indicated that the stimulation of ANK expression by TGF, required the influx of phosphate, specifically by the Pit-1 transporter, at all phases of differentiation. At hypertrophy, when alkaline phosphatase is highly expressed, inhibition of its activity with levamisole also abrogated the stimulatory effect of TGF, on ANK expression, further illustrating that Pi availability and uptake by the cells is necessary for stimulation of ANK expression in response to TGF,. Since previous studies of endochondral ossification in the growth plate have shown that L-type calcium channels are essential for chondrogenesis, we investigated their role in the TGF,-stimulated ANK response in ATDC5 cells. Treatment with nifedipine to inhibit calcium influx via the L-type channel Cav1.2 (,1C) inhibited the TGF, stimulated increase in ANK expression at all phases of chondrogenesis. Our findings indicate that TGF, stimulation of ANK expression is dependent upon the influx of phosphate and calcium into ATDC5 cells at all stages of differentiation. J. Cell. Physiol. 224: 540,548, 2010. © 2010 Wiley-Liss, Inc. [source]

Analyses of Sexual Reproductive Success in Transgenic and/or Mutant Plants

Cristiane P. G. Calixto
The pistil, the female reproductive organ of plants, is a key player in the success of sexual plant reproduction. Ultimately, the production of fruits and seeds depends on the proper pistil development and function. Therefore, the identification and characterization of pistil expressed genes is essential for a better understanding and manipulation of the plant reproduction process. For studying the function of pistil expressed genes, transgenic and/or mutant plants for the genes of interest are used. The present article provides a review of methods already exploited to analyze sexual reproductive success. We intend to supply useful information and to guide future experiments in the study of genes affecting pistil development and function. [source]

Research, policy and practice: why developing countries are different

John Young
Better utilization of research and evidence in development policy and practice can help save lives, reduce poverty and improve the quality of life. However, there is limited systematic understanding of the links between research and policy in international development. The paper reviews existing literature and proposes an analytical framework with four key arenas: external influences, political context, evidence and links. Based on the findings of stakeholder workshops in developing countries around the world, the paper identifies four key issues that characterize many developing countries. These are: (i) troubled political contexts; (ii) problems of research supply; (iii) external interference; and (iv) the emergence of civil society as a key player. Despite these challenges, two institutional models seem to be particularly effective: (i) think tanks and (ii) regional networks. Copyright © 2005 John Wiley & Sons, Ltd. [source]

Nitric oxide regulates BDNF release from nodose ganglion neurons in a pattern-dependent and cGMP-independent manner

Hui-ya Hsieh
Abstract Activity of arterial baroreceptors is modulated by neurohumoral factors, including nitric oxide (NO), released from endothelial cells. Baroreceptor reflex responses can also be modulated by NO signaling in the brainstem nucleus tractus solitarius (NTS), the primary central target of cardiovascular afferents. Our recent studies indicate that brain-derived neurotrophic factor (BDNF) is abundantly expressed by developing and adult baroreceptor afferents in vivo, and released from cultured nodose ganglion (NG) neurons by patterns of baroreceptor activity. Using electrical field stimulation and ELISA in situ, we show that exogenous NO nearly abolishes BDNF release from newborn rat NG neurons in vitro stimulated with single pulses delivered at 6 Hz, but not 2-pulse bursts delivered at the same 6-Hz frequency, that corresponds to a rat heart rate. Application of L-NAME, a specific inhibitor of endogenous NO synthases, does not have any significant effect on activity-dependent BDNF release, but leads to upregulation of BDNF expression in an activity-dependent manner. The latter effect suggests a novel mechanism of homeostatic regulation of activity-dependent BDNF expression with endogenous NO as a key player. The exogenous NO-mediated effect does not involve the cGMP-protein kinase G (PKG) pathway, but is largely inhibited by N-ethylmaleimide and TEMPOL that are known to prevent S-nitrosylation. Together, our current data identify previously unknown mechanisms regulating BDNF availability, and point to NO as a likely regulator of BDNF at baroafferent synapses in the NTS. © 2009 Wiley-Liss, Inc. [source]

Mechanisms of virus-induced asthma exacerbations: state-of-the-art.

ALLERGY, Issue 5 2007
A GA2LEN, InterAirways document
Viral infections of the respiratory tract are the most common precipitants of acute asthma exacerbations. Exacerbations are only poorly responsive to current asthma therapies and new approaches to therapy are needed. Viruses, most frequently human rhinoviruses (RV), infect the airway epithelium, generate local and systemic immune responses, as well as neural responses, inducing inflammation and airway hyperresponsiveness. Using in vitro and in vivo experimental models the role of various proinflammatory or anti-inflammatory mediators, antiviral responses and molecular pathways that lead from infection to symptoms has been partly unravelled. In particular, mechanisms of susceptibility to viral infection have been identified and the bronchial epithelium appeared to be a key player. Nevertheless, additional understanding of the integration between the diverse elements of the antiviral response, especially in the context of allergic airway inflammation, as well as the interactions between viral infections and other stimuli that affect airway inflammation and responsiveness may lead to novel strategies in treating and/or preventing asthma exacerbations. This review presents the current knowledge and highlights areas in need of further research. [source]

The role of the pathologist in translational and personalized medicine

Daniel P. Perl MD
Abstract Over the years, pathologists have served to make morphologic diagnoses for clinicians when provided with a biopsy or surgically resected tissue specimen. Traditionally, pathologists have used a series of morphologic techniques and relied on the microscopic appearance of resected tissues to determine a pathologic diagnosis and, with respect to neoplastic lesions, provide predictions of the potential growth pattern that might be anticipated. With the introduction of the techniques of molecular biology in medicine, the role of the pathologist has changed as have the tools available for characterizing pathologic specimens. With the pathologist's unique perspective on disease processes and access to tissue specimens from the operating room, he has become a key player in the area of translational and personalized medicine and the development of new approaches to diagnosis and translational research. Mt Sinai J Med 74:22,26, 2007. © 2007 Mount Sinai School of Medicine [source]

Evidence that the terms of petroleum contracts influence the rate of development of oil fields

Mustafa Bakar Mahmud
This paper presents evidence that the main determinant of the rate of development of Libya's crude oil upstream activities, from 1961 to 1999, was the terms of the petroleum contractual agreements, which existed between the state and the international oil industry during that period, and that US sanctions against the Socialist People's Libyan Arab Jamahiriya failed to affect this rate of development. In keeping with other Members of the Organisation of the Petroleum Exporting Countries (OPEC), Libya has, over three decades, been a key player in helping to regulate global production levels of oil and gas. However, the economic and political strengths and weaknesses of individual Members of OPEC vary widely and it is inevitable that the stresses arising from adherence to OPEC policies will vary proportionately to these strengths and weaknesses. It is instructive, therefore, to analyse how successfully Libya has exploited its own petroleum resources. The results are thought-provoking and send signals to the superpowers of the futility of economic sanctions against countries whose political policies they find distasteful. Further, the analysis highlights the need for OPEC Members to be fully informed of the significance of the terms of the petroleum agreements they employ in their countries. [source]

The impact of the introduction of web information systems (WIS) on information policies: An analysis of the Canadian federal government policies related to WIS,

Christine Dufour
This communication presents the results of an analysis of the Canadian federal government information policies that govern its Web information systems (WIS). The goal of this study was to better understand how the Canadian federal government has adapted its information policies to the WIS. A side-by-side analysis of 53 policy instruments was done. The results indicate that the Canadian federal government has crafted new instruments to take into account the WIS context. These policies build upon generic information management and information technologies policy instruments. These policy instruments have a good coverage of the tasks underlying the WIS life-cycle. Among the many players present in the policy instruments, one of the key player is the Treasury Board Secretariat that plays an important coordination and evaluation role. [source]

Quantitative proteomics and phosphoproteomics reveal novel insights into complexity and dynamics of the EGFR signaling network

Sandra Morandell
Abstract The epidermal growth factor receptor (EGFR/ErbB1/Her1) belongs to the ErbB family of receptor tyrosine kinases (RTKs) and is a key player in the regulation of cell proliferation, differentiation, survival, and migration. Overexpression and mutational changes of EGFR have been identified in a variety of human cancers and the regulation of EGFR signaling plays a critical role in tumor development and progression. Due to its biological significance the EGFR signaling network is a widely used model system for the development of analytical techniques. Novel quantitative proteomics and phosphoproteomics approaches play an important role in the characterization of signaling pathways in a time and stimulus dependent manner. Recent studies discussed in this review provide new insights into different aspects of EGFR signal transduction, such as regulation and dynamics of its phosphorylation sites, association with interaction partners and identification of regulated phosphoproteins. Correlation of data from functional proteomics studies with results from other fields of signal transduction research by systems biology will be necessary to integrate and translate these findings into successful clinical applications. [source]

Ultrastructure and Estrogen Regulation of the Lymphatic Stomata of Ovarian Bursa in Mice

Meng Li
Abstract The ovarian bursa is a key player in maintaining adaptive ovarian microenvironment for ovulation. The lymphatic stomata are believed to be a major contributor to execute the function of the ovarian bursa, whereas little is known about their ultrastructure and regulation. Here, we examined the ultrastructure of lymphatic stomata in mouse ovarian bursa by scanning electron microscopy and transmission electron microscopy and investigated its regulation by estrogen. We found that the mesothelium on the visceral layer of mouse ovarian bursa was composed of the cuboidal and flattened cells. The lymphatic stomata with round and oval shapes were mainly among the cuboidal cells. The particles, cells, and fluid passed through the stomata and entered into the lymphatic drainage unit composed of connective tissue and lymphatic endothelial cells beneath the stomata. We also used trypan blue as a tracer and found that the absorption of trypan blue through the lymphatic stomata was increased by estrogen that enlarged the average opening area of lymphatic stomata. Furthermore, we detected that there existed estrogen receptors in the nuclei of the mesothelial cells on the visceral ovarian bursa by using immunoelectron microscopy. Taken together, these data suggest that both the absorption and opening area of the lymphatic stomata in mouse ovarian bursa may be influenced by estrogen. Anat Rec, 290:1195-1202, © 2007 Wiley-Liss, Inc. [source]

The emerging role of ACE2 in physiology and disease,

I Hamming
Abstract The renin,angiotensin,aldosterone system (RAAS) is a key regulator of systemic blood pressure and renal function and a key player in renal and cardiovascular disease. However, its (patho)physiological roles and its architecture are more complex than initially anticipated. Novel RAAS components that may add to our understanding have been discovered in recent years. In particular, the human homologue of ACE (ACE2) has added a higher level of complexity to the RAAS. In a short period of time, ACE2 has been cloned, purified, knocked-out, knocked-in; inhibitors have been developed; its 3D structure determined; and new functions have been identified. ACE2 is now implicated in cardiovascular and renal (patho)physiology, diabetes, pregnancy, lung disease and, remarkably, ACE2 serves as a receptor for SARS and NL63 coronaviruses. This review covers available information on the genetic, structural and functional properties of ACE2. Its role in a variety of (patho)physiological conditions and therapeutic options of modulation are discussed. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source]

Protein kinase A-dependent enhanced NMDA receptor function in pain-related synaptic plasticity in rat amygdala neurones

Gary C. Bird
Mechanisms of pain-related plasticity in the amygdala, a key player in emotionality, were studied at the cellular and molecular levels in a model of arthritic pain. The influence of the arthritis pain state induced in vivo on synaptic transmission and N -methyl- d -aspartate (NMDA) receptor function was examined in vitro using whole-cell voltage-clamp recordings of neurones in the latero-capsular part of the central nucleus of the amygdala (CeA), which is now defined as the ,nociceptive amygdala'. Synaptic transmission was evoked by electrical stimulation of afferents from the pontine parabrachial area (part of the spino-parabrachio-amygdaloid pain pathway) in brain slices from control rats and from arthritic rats. This study shows that pain-related synaptic plasticity is accompanied by protein kinase A (PKA)-mediated enhanced NMDA-receptor function and increased phosphorylation of NMDA-receptor 1 (NR1) subunits. Synaptic plasticity in the arthritis pain model, but not normal synaptic transmission in control neurones, was inhibited by a selective NMDA receptor antagonist. Accordingly, an NMDA receptor-mediated synaptic component was recorded in neurones from arthritic animals, but not in control neurones, and was blocked by inhibition of PKA but not protein kinase C (PKC). Exogenous NMDA evoked a larger inward current in neurones from arthritic animals than in control neurones, indicating a postsynaptic effect. Paired-pulse facilitation, a measure of presynaptic mechanisms, was not affected by an NMDA-receptor antagonist. Increased levels of phosphorylated NR1 protein, but not of total NR1, were measured in the CeA of arthritic rats compared to controls. Our results suggest that pain-related synaptic plasticity in the amygdala involves a critical switch of postsynaptic NMDA receptor function through PKA-dependent NR1 phosphorylation. [source]

CCR5 is involved in resolution of inflammation in proteoglycan-induced arthritis

Paul D. Doodes
Objective CCR5 and its ligands (CCL3, CCL4, and CCL5) may play a role in inflammatory cell recruitment into the joint. However, it was recently reported that CCR5 on T cells and neutrophils acts as a decoy receptor for CCL3 and CCL5 to assist in the resolution of inflammation. The aim of this study was to determine whether CCR5 functions as a proinflammatory or antiinflammatory mediator in arthritis, by examining the role of CCR5 in proteoglycan (PG),induced arthritis (PGIA). Methods Arthritis was induced by immunizing wild-type (WT) and CCR5-deficient (CCR5,/,) BALB/c mice with human PG in adjuvant. The onset and severity of PGIA were monitored over time. Met-RANTES was used to block CCR5 in vivo. Arthritis was transferred to SCID mice, using spleen cells from arthritic WT and CCR5,/, mice. The expression of cytokines and chemokines was measured by enzyme-linked immunosorbent assay. Results In CCR5,/, mice and WT mice treated with the CCR5 inhibitor Met-RANTES, exacerbated arthritis developed late in the disease course. The increase in arthritis severity in CCR5,/, mice correlated with elevated serum levels of CCL5. However, exacerbated arthritis was not intrinsic to the CCR5,/, lymphoid cells, because the arthritis that developed in SCID mouse recipients was similar to that in WT and CCR5,/, mice. CCR5 expression in the SCID mouse was sufficient to clear CCL5, because serum levels of CCL5 were the same in SCID mouse recipients receiving cells from either WT or CCR5,/, mice. Conclusion These data demonstrate that CCR5 is a key player in controlling the resolution of inflammation in experimental arthritis. [source]

Fibroblast growth factor 2: A new key player in osteoarthritis

Jelena Gavrilovic
First page of article [source]

Natural killer T cell-mediated antitumor immune responses and their clinical applications

CANCER SCIENCE, Issue 9 2006
Ken-ichiro Seino
A unique lymphocyte population, CD1d-restricted NKT cells, has been revealed to be a key player in both the innate and acquired immune responses, including antitumor effects. Recent studies revealed that at least two subsets of CD1d-restricted NKT cells exist: type I, having invariant V,14 receptor; and type II, having heterogeneous non-V,14 receptor. The specific glycolipid ligand, ,-GalCer, effectively stimulates mouse and human type I NKT cells. The activation of type I NKT cells substantially influences function of other various cell types, particularly DC, NK cells, CD4 Th1 cells, and CD8 cytotoxic T cells, all contributing to the antitumor immune responses. Recent studies also indicated that, unlike type I NKT cells, type II NKT cells have a potential to repress antitumor immune responses. In this review, we summarize the characteristics of the antitumor immune responses mediated by both mouse and human CD1d-restricted NKT cells and discuss their potential in clinical applications against cancer. (Cancer Sci 2006; 97: 807,812) [source]

Essential roles of Gli3 and sonic hedgehog in pattern formation and developmental anomalies caused by their dysfunction

Jun Motoyama
ABSTRACT Pattern formation along the body axis directs the proportion of different types of cells required for functional tissue structures. The secreted protein sonic hedgehog (Shh) and zinc finger transcription factor Gli3 are key players in pattern formation during brain and limb development; the antagonistic action of Shh towards Gli3 may be crucial for pattern formation. Recent findings from Shh/Gli3 double homozygous mutants suggest that a balance of both activities is required for the production of the normal proportion of different cell types during organogenesis. This conclusion contrasts with the alternative hypothesis that a Shh gradient directs the specification of several different cell types. The observations reviewed here offer a new perspective on understanding the pathogenesis of human birth defects caused by mutations of the Shh and Gli3 genes. [source]

Making the Leap from Researcher to Planner: Lessons from Avian Conservation Planning in the Dominican Republic

Steven C. Latta
Published accounts of national, multidisciplinary planning efforts and priority setting for avian conservation are not common. I describe the process and results of a broad-based, grassroots-oriented avian conservation planning workshop held in the Dominican Republic in which we designed a coordinated strategy for avian conservation in the country. The planning process sought to (1) increase communication and cooperation among conservationists; (2) familiarize participants with resources pertinent to avian conservation; (3) encourage the transfer of information between researchers and managers; (4) promote the concepts of long-term avian monitoring, avian conservation plans, and species management plans; and (5) develop a common, multidisciplinary strategy to promote the conservation of birds in the Dominican Republic. The workshop highlighted group discussions among research biologists, managers, educators, and public policy specialists to assess avian conservation needs and priorities with respect to each discipline and has since galvanized a significant portion of the conservation community around several cooperative projects involving diverse segments of the community. Avian biologists can play a significant role in conservation efforts through a willingness to work with key players in diverse fields and to envision holistic, multidisciplinary approaches to conservation issues. Resumen: Cuando los biologícos investigadores incursionan en la biología de la conservación enfrentan nuevos desafíos, especialmente en países extranjeros, al intentar prestar apoyo para esfuerzos de planificación de la conservación. Los informes publicados de esfuerzos de planificación nacional, multidisciplinaria y de establecimiento de prioridades para la conservación de aves no son comunes. Describo el proceso y los resultados de un taller nacional de planificación para conservación de aves en la República Dominicana que utilizaba un proceso fundamental de base amplia donde creamos una estrategia coordinada para la conservación de aves del país. El proceso de planeación buscaba (1) aumentar comunicación y cooperación entre conservacionistas, (2) familiarizar a los participantes con los recursos disponibles para la conservación de aves, (3) estimular la transferencia de información entre investigadores y manejadores, (4) promover los conceptos del monitoreo de aves a largo plazo, planes de conservación de especies y planes de manejo de especies y (5) desarrollar una estrategia multidisciplinaria común para promover la conservación de aves en la República Dominicana. El taller puso a relieve discusiones de grupo entre investigadores, manejadores, educadores y especialistas en política pública para evaluar las necesidaes y prioridades para la conservación de aves con respecto a cada disciplina, desde entonces se ha estimulado a una porción significativa de la comunidad conservacionista alrededor de proyectos de cooperación que involucran a diversos segmentos de la comunidad. Los ornitólogos pueden jugar un papel significativo en los esfuerzos de conservación mediante una buena disposición para trabajar con personas clave en diversas disciplinas y visualizar de una manera integral y multidisciplinaria las estrategias para abordar asuntos de conservación. [source]

Cardiovascular metabolic syndrome , an interplay of, obesity, inflammation, diabetes and coronary heart disease

J. S. Rana
Cardiovascular disease is currently one of the biggest causes of morbidity and mortality facing humanity. Such a paradigm shift of disease pattern over the last century has only worsened due to the alarming global prevalence of obesity and type 2 diabetes. In recent years there is increasing focus on inflammation as one of the key players in the patho-physiology of these disorders. In addition to these overt risk factors new research is unraveling the significance of a constellation of early metabolic abnormalities that include weight gain, insulin resistance, prehypertension and a specific pattern of dyslipidaemia. There exists a complex interrelationship of these various metabolic disorders and their effect on cardiovascular system. Simplified explanation can be that inflammation increases insulin resistance, which in turn leads to obesity while perpetuating diabetes, high blood pressure, prothrombotic state and dyslipidaemia. While inflammation and insulin resistance have direct adverse effects on cardiac muscle, these metabolic abnormalities as a whole cause causes cardiovascular complications; warranting a multi pronged therapeutic and preventive approach for the ,Cardiovascular Metabolic Syndrome' as an entity. [source]

New insights into the pathophysiology of diabetic nephropathy: from haemodynamics to molecular pathology

G. Wolf
Abstract Although debated for many years whether haemodynamic or structural changes are more important in the development of diabetic nephropathy, it is now clear that these processes are interwoven and present two sides of one coin. On a molecular level, hyperglycaemia and proteins altered by high blood glucose such as Amadori products and advanced glycation end-products (AGEs) are key players in the development of diabetic nephropathy. Recent evidence suggests that an increase in reactive oxygen species (ROS) formation induced by high glucose-mediated activation of the mitochondrial electron-transport chain is an early event in the development of diabetic complications. A variety of growth factors and cytokines are then induced through complex signal transduction pathways involving protein kinase C, mitogen-activated protein kinases, and the transcription factor NF-,B. High glucose, AGEs, and ROS act in concert to induce growth factors and cytokines. Particularly, TGF-, is important in the development of renal hypertrophy and accumulation of extracellular matrix components. Activation of the renin-angiotensin system by high glucose, mechanical stress, and proteinuria with an increase in local formation of angiotensin II (ANG II) causes many of the pathophysiological changes associated with diabetic nephropathy. In fact, it has been shown that angiotensin II is involved in almost every pathophysiological process implicated in the development of diabetic nephropathy (haemodynamic changes, hypertrophy, extracellular matrix accumulation, growth factor/cytokine induction, ROS formation, podocyte damage, proteinuria, interstitial inflammation). Consequently, blocking these deleterious effects of ANG II is an essential part of every therapeutic regiment to prevent and treat diabetic nephropathy. Recent evidence suggests that regression of diabetic nephropathy could be achieved under certain circumstances. [source]