Sample records for exploit host hyaluronan

  1. Exploiting host immunity: the Salmonella paradigm (United States)

    Behnsen, Judith; Perez-Lopez, Araceli; Nuccio, Sean-Paul; Raffatellu, Manuela


    Pathogens have evolved clever strategies to evade and in some cases exploit the attacks of an activated immune system. Salmonella enterica is one such pathogen, exploiting multiple aspects of host defense to promote its replication in the host. Here we review recent findings on the mechanisms by which Salmonella establishes systemic and chronic infection, including strategies involving manipulation of innate immune signaling and inflammatory forms of cell death, as well as immune evasion by establishing residency in M2 macrophages. We also examine recent evidence showing that the oxidative environment and the high levels of antimicrobial proteins produced in response to localized Salmonella gastrointestinal infection enable the pathogen to successfully outcompete the resident gut microbiota. PMID:25582038

  2. Characterization of and host response to tyramine substituted-hyaluronan enriched fascia extracellular matrix (United States)

    Chin, LiKang; Calabro, Anthony; Rodriguez, E. Rene; Tan, Carmela D.; Walker, Esteban


    Naturally-occurring biomaterial scaffolds derived from extracellular matrix (ECM) have been previously investigated for soft tissue repair. We propose to enrich fascia ECM with high molecular weight tyramine substituted-hyaluronan (TS-HA) to modulate inflammation associated with implantation and enhance fibroblast infiltration. As critical determinants of constructive remodeling, the host inflammatory response and macrophage polarization to TS-HA enriched fascia were characterized in a rat abdominal wall model. TS-HA treated fascia with cross-linking had a similar lymphocyte (P = 0.11) and plasma cell (P = 0.13) densities, greater macrophage (P = 0.001) and giant cell (P fascia, with or without cross-linking, exhibited a predominantly M2 pro-remodeling macrophage profile similar to water controls (P = 0.82), which is suggestive of constructive tissue remodeling. Our findings demonstrated that HA augmentation can alter the host response to an ECM, but the appropriate concentration and molecular weight needed to minimize chronic inflammation within the scaffold remains to be determined. PMID:21553156

  3. Hyaluronan dermal fillers via crosslinking with 1,4-butandiol diglycidyl ether: Exploitation of heterogeneous reaction conditions. (United States)

    La Gatta, Annalisa; Papa, Agata; Schiraldi, Chiara; De Rosa, Mario


    Most of hyaluronan (HA)-based dermal fillers currently available on the market are produced through biopolymer crosslinking with 1,4-butandiol diglycidyl ether (BDDGE). Chemical modification is usually performed on the biopolymer dissolved in a highly alkaline aqueous medium (homogeneous conditions). Heterogeneous conditions for HA reaction with BDDGE were exploited here to obtain competitive HA fillers and to assess potential improvements in production process. Optimal parameters for effective reaction accomplishment were evaluated (e.g., medium composition, temperature and time of reaction). HA was modified with increasing BDDGE/HA equivalents (7-14%) achieving 66-74% (w/w) biopolymer insolubility. Hydrogels exhibited high swelling extent and outstanding resistance to enzymatic degradation decreasing and improving according to crosslinking degree, respectively. Once suspended in physiological solution (20 mg/mL), these products directly formed easy-to-extrude gels through 27-29 G needles. Gel particle dimensions were in the range 10-1000 µm. Rheological analyses revealed decreasing viscosity with the shear rate and G' values in the range 1200-1700 Pa. Overall, results of the in vitro characterization demonstrated the attainment of crosslinked HA particles suitable for application as dermal fillers. These new gels proved superior to similar commercialized products in terms of stability to enzymatic hydrolysis. Further, the protocol assessed allowed interesting improvements over conventional manufacturing procedures. © 2015 Wiley Periodicals, Inc.

  4. Host exploitation strategies of the social parasite Maculinea alcon

    DEFF Research Database (Denmark)

    Fürst, Matthias Alois

    . Throughout the first instars M. alcon lives on a specific food plant, however, in the last instar before pupation it develops into an obligate social parasite, posing a considerably cost to its host ant colony. I here focus on the different exploitation strategies of M. alcon throughout its lifecycle......  Coevolution is the process where at least two species put some selective pressure on each other, thereby reciprocally influencing each others evolution. To explain co-adaptations invoked by coevolution of interacting species, evolutionary biologists predominantly use host-parasite interactions...... as model systems. These enable the study of adaptations and counter-adaptations that might evolve in the arms-race between a parasite pursuing maximum gain and a host trying to avoid exploitation. One such system is the socially parasitic butterfly Maculinea alcon and its host the ant Myrmica rubra...

  5. Exploiting host compensatory responses: the 'must' of manipulation? (United States)

    Lefèvre, Thierry; Roche, Benjamin; Poulin, Robert; Hurd, Hilary; Renaud, François; Thomas, Frédéric


    Parasite-induced alterations of the host phenotype have been reported in many systems. These changes are traditionally categorized into three kinds of phenomena: secondary outcomes of infection with no adaptive value, host adaptations that reduce the detrimental consequences of infection and parasitic adaptations that facilitate transmission. However, this categorization is a simple view, and host modifications should be considered as co-evolved traits, rather than a total takeover. Here, we present a novel scenario of manipulation, which has considerable potential to resolve issues that are specific to the evolution of behavioural alterations induced by parasites. It is proposed that certain parasites affect fitness-related traits in their hosts to trigger host compensatory responses because these responses can meet the transmission objectives of parasites.

  6. Hiding in Plain Sight: Exploiting Broadcast for Practical Host Anonymity

    Energy Technology Data Exchange (ETDEWEB)

    Shue, Craig A [ORNL; Gupta, Prof. Minaxi [Indiana University


    Users are being tracked on the Internet more than ever before as Web sites and search engines gather pieces of information sufficient to identify and study their behavior. While many existing schemes provide strong anonymity, they are inappropriate when high bandwidth and low latency are required. In this work, we explore an anonymity scheme for end hosts whose performance makes it possible to have it always on. The scheme leverages the natural grouping of hosts in the same subnet and the universally available broadcast primitive to provide anonymity at line speeds. Our scheme is strongly resistant against all active or passive adversaries as long as they are outside the subnet. Even within the subnet, our scheme provides reasonable resistance against adversaries, providing anonymity that is suitable for common Internet applications.

  7. Shining a Light on Exploitative Host Control in a Photosynthetic Endosymbiosis. (United States)

    Lowe, Christopher D; Minter, Ewan J; Cameron, Duncan D; Brockhurst, Michael A


    Endosymbiosis allows hosts to acquire new functional traits such that the combined host and endosymbiont can exploit vacant ecological niches and occupy novel environments [1, 2]; consequently, endosymbiosis affects the structure and function of ecosystems [3, 4]. However, for many endosymbioses, it is unknown whether their evolutionary basis is mutualism or exploitation [5-9]. We estimated the fitness consequences of symbiosis using the interaction between the protist host Paramecium bursaria and the algal symbiont Chlorella sp. [10]. Host fitness was strongly context dependent: whereas hosts benefited from symbiosis at high light intensity, carrying endosymbionts was costly to hosts in the dark and conferred no benefit over growing autonomously at intermediate light levels. Autonomous Chlorella densities increased monotonically with light intensity, whereas per-host symbiont load and symbiont abundance peaked at intermediate light levels and were lowest at high light intensity. This suggests that hosts controlled the costs of symbiosis by manipulating symbiont load according to light intensity. Photosynthetic efficiency was consistently lower for symbiotic compared to autonomous algae, suggesting nutritional constraints upon algae in symbiosis. At intermediate light levels, we observed the establishment of small populations of free-living algae alongside the hosts with endosymbionts, suggesting that symbionts could escape symbiosis, but only under conditions where hosts didn't benefit from symbiosis. Together, these data suggest that hosts exerted strong control over endosymbionts and that there were no conditions where this nutritional symbiosis was mutually beneficial. Our findings support theoretical predictions (e.g., [5, 9]) that controlled exploitation is an important evolutionary pathway toward stable endosymbiosis. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  8. Vision-mediated exploitation of a novel host plant by a tephritid fruit fly. (United States)

    Piñero, Jaime C; Souder, Steven K; Vargas, Roger I


    Shortly after its introduction into the Hawaiian Islands around 1895, the polyphagous, invasive fruit fly Bactrocera (Zeugodacus) cucurbitae (Coquillett) (Diptera: Tephritidae) was provided the opportunity to expand its host range to include a novel host, papaya (Carica papaya). It has been documented that female B. cucurbitae rely strongly on vision to locate host fruit. Given that the papaya fruit is visually conspicuous in the papaya agro-ecosystem, we hypothesized that female B. cucurbitae used vision as the main sensory modality to find and exploit the novel host fruit. Using a comparative approach that involved a series of studies under natural and semi-natural conditions in Hawaii, we assessed the ability of female B. cucurbitae to locate and oviposit in papaya fruit using the sensory modalities of olfaction and vision alone and also in combination. The results of these studies demonstrate that, under a variety of conditions, volatiles emitted by the novel host do not positively stimulate the behavior of the herbivore. Rather, vision seems to be the main mechanism driving the exploitation of the novel host. Volatiles emitted by the novel host papaya fruit did not contribute in any way to the visual response of females. Our findings highlight the remarkable role of vision in the host-location process of B. cucurbitae and provide empirical evidence for this sensory modality as a potential mechanism involved in host range expansion.

  9. Vision-mediated exploitation of a novel host plant by a tephritid fruit fly.

    Directory of Open Access Journals (Sweden)

    Jaime C Piñero

    Full Text Available Shortly after its introduction into the Hawaiian Islands around 1895, the polyphagous, invasive fruit fly Bactrocera (Zeugodacus cucurbitae (Coquillett (Diptera: Tephritidae was provided the opportunity to expand its host range to include a novel host, papaya (Carica papaya. It has been documented that female B. cucurbitae rely strongly on vision to locate host fruit. Given that the papaya fruit is visually conspicuous in the papaya agro-ecosystem, we hypothesized that female B. cucurbitae used vision as the main sensory modality to find and exploit the novel host fruit. Using a comparative approach that involved a series of studies under natural and semi-natural conditions in Hawaii, we assessed the ability of female B. cucurbitae to locate and oviposit in papaya fruit using the sensory modalities of olfaction and vision alone and also in combination. The results of these studies demonstrate that, under a variety of conditions, volatiles emitted by the novel host do not positively stimulate the behavior of the herbivore. Rather, vision seems to be the main mechanism driving the exploitation of the novel host. Volatiles emitted by the novel host papaya fruit did not contribute in any way to the visual response of females. Our findings highlight the remarkable role of vision in the host-location process of B. cucurbitae and provide empirical evidence for this sensory modality as a potential mechanism involved in host range expansion.

  10. First in Vivo Batrachochytrium dendrobatidis Transcriptomes Reveal Mechanisms of Host Exploitation, Host-Specific Gene Expression, and Expressed Genotype Shifts. (United States)

    Ellison, Amy R; DiRenzo, Graziella V; McDonald, Caitlin A; Lips, Karen R; Zamudio, Kelly R


    For generalist pathogens, host species represent distinct selective environments, providing unique challenges for resource acquisition and defense from host immunity, potentially resulting in host-dependent differences in pathogen fitness. Gene expression modulation should be advantageous, responding optimally to a given host and mitigating the costs of generalism. Batrachochytrium dendrobatidis (Bd), a fungal pathogen of amphibians, shows variability in pathogenicity among isolates, and within-strain virulence changes rapidly during serial passages through artificial culture. For the first time, we characterize the transcriptomic profile of Bd in vivo, using laser-capture microdissection. Comparison of Bd transcriptomes (strain JEL423) in culture and in two hosts (Atelopus zeteki and Hylomantis lemur), reveals >2000 differentially expressed genes that likely include key Bd defense and host exploitation mechanisms. Variation in Bd transcriptomes from different amphibian hosts demonstrates shifts in pathogen resource allocation. Furthermore, expressed genotype variant frequencies of Bd populations differ between culture and amphibian skin, and among host species, revealing potential mechanisms underlying rapid changes in virulence and the possibility that amphibian community composition shapes Bd evolutionary trajectories. Our results provide new insights into how changes in gene expression and infecting population genotypes can be key to the success of a generalist fungal pathogen. Copyright © 2017 Ellison et al.

  11. First in Vivo Batrachochytrium dendrobatidis Transcriptomes Reveal Mechanisms of Host Exploitation, Host-Specific Gene Expression, and Expressed Genotype Shifts

    Directory of Open Access Journals (Sweden)

    Amy R. Ellison


    Full Text Available For generalist pathogens, host species represent distinct selective environments, providing unique challenges for resource acquisition and defense from host immunity, potentially resulting in host-dependent differences in pathogen fitness. Gene expression modulation should be advantageous, responding optimally to a given host and mitigating the costs of generalism. Batrachochytrium dendrobatidis (Bd, a fungal pathogen of amphibians, shows variability in pathogenicity among isolates, and within-strain virulence changes rapidly during serial passages through artificial culture. For the first time, we characterize the transcriptomic profile of Bd in vivo, using laser-capture microdissection. Comparison of Bd transcriptomes (strain JEL423 in culture and in two hosts (Atelopus zeteki and Hylomantis lemur, reveals >2000 differentially expressed genes that likely include key Bd defense and host exploitation mechanisms. Variation in Bd transcriptomes from different amphibian hosts demonstrates shifts in pathogen resource allocation. Furthermore, expressed genotype variant frequencies of Bd populations differ between culture and amphibian skin, and among host species, revealing potential mechanisms underlying rapid changes in virulence and the possibility that amphibian community composition shapes Bd evolutionary trajectories. Our results provide new insights into how changes in gene expression and infecting population genotypes can be key to the success of a generalist fungal pathogen.

  12. Production Methods for Hyaluronan

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    Carmen G. Boeriu


    Full Text Available Hyaluronan is a polysaccharide with multiple functions in the human body being involved in creating flexible and protective layers in tissues and in many signalling pathways during embryonic development, wound healing, inflammation, and cancer. Hyaluronan is an important component of active pharmaceutical ingredients for treatment of, for example, arthritis and osteoarthritis, and its commercial value far exceeds that of other microbial extracellular polysaccharides. Traditionally hyaluronan is extracted from animal waste which is a well-established process now. However, biotechnological synthesis of biopolymers provides a wealth of new possibilities. Therefore, genetic/metabolic engineering has been applied in the area of tailor-made hyaluronan synthesis. Another approach is the controlled artificial (in vitro synthesis of hyaluronan by enzymes. Advantage of using microbial and enzymatic synthesis for hyaluronan production is the simpler downstream processing and a reduced risk of viral contamination. In this paper an overview of the different methods used to produce hyaluronan is presented. Emphasis is on the advancements made in the field of the synthesis of bioengineered hyaluronan.

  13. Comparative Genomics of Bacillus thuringiensis Reveals a Path to Specialized Exploitation of Multiple Invertebrate Hosts

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    Jinshui Zheng


    Full Text Available Understanding the genetic basis of host shifts is a key genomic question for pathogen and parasite biology. The Bacillus cereus group, which encompasses Bacillus thuringiensis and Bacillus anthracis, contains pathogens that can infect insects, nematodes, and vertebrates. Since the target range of the essential virulence factors (Cry toxins and many isolates is well known, this group presents a powerful system for investigating how pathogens can diversify and adapt to phylogenetically distant hosts. Specialization to exploit insects occurs at the level of the major clade and is associated with substantial changes in the core genome, and host switching between insect orders has occurred repeatedly within subclades. The transfer of plasmids with linked cry genes may account for much of the adaptation to particular insect orders, and network analysis implies that host specialization has produced strong associations between key toxin genes with similar targets. Analysis of the distribution of plasmid minireplicons shows that plasmids with orf156 and orf157, which carry genes encoding toxins against Lepidoptera or Diptera, were contained only by B. thuringiensis in the specialized insect clade (clade 2, indicating that tight genome/plasmid associations have been important in adaptation to invertebrate hosts. Moreover, the accumulation of multiple virulence factors on transposable elements suggests that cotransfer of diverse virulence factors is advantageous in terms of expanding the insecticidal spectrum, overcoming insect resistance, or through gains in pathogenicity via synergistic interactions between toxins.

  14. Exploiting Cell Death Pathways for Inducible Cell Elimination to Modulate Graft-versus-Host-Disease

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    Corey Falcon


    Full Text Available Hematopoietic stem cell transplantation is a potent form of immunotherapy, potentially life-saving for many malignant hematologic diseases. However, donor lymphocytes infused with the graft while exerting a graft versus malignancy effect can also cause potentially fatal graft versus host disease (GVHD. Our group has previously validated the inducible caspase-9 suicide gene in the haploidentical stem cell transplant setting, which proved successful in reversing signs and symptoms of GVHD within hours, using a non-therapeutic dimerizing agent. Cellular death pathways such as apoptosis and necroptosis are important processes in maintaining healthy cellular homeostasis within the human body. Here, we review two of the most widely investigated cell death pathways active in T-cells (apoptosis and necroptosis, as well as the emerging strategies that can be exploited for the safety of T-cell therapies. Furthermore, such strategies could be exploited for the safety of other cellular therapeutics as well.

  15. Exploiting Cell Death Pathways for Inducible Cell Elimination to Modulate Graft-versus-Host-Disease. (United States)

    Falcon, Corey; Al-Obaidi, Mustafa; Di Stasi, Antonio


    Hematopoietic stem cell transplantation is a potent form of immunotherapy, potentially life-saving for many malignant hematologic diseases. However, donor lymphocytes infused with the graft while exerting a graft versus malignancy effect can also cause potentially fatal graft versus host disease (GVHD). Our group has previously validated the inducible caspase-9 suicide gene in the haploidentical stem cell transplant setting, which proved successful in reversing signs and symptoms of GVHD within hours, using a non-therapeutic dimerizing agent. Cellular death pathways such as apoptosis and necroptosis are important processes in maintaining healthy cellular homeostasis within the human body. Here, we review two of the most widely investigated cell death pathways active in T-cells (apoptosis and necroptosis), as well as the emerging strategies that can be exploited for the safety of T-cell therapies. Furthermore, such strategies could be exploited for the safety of other cellular therapeutics as well.

  16. The metabolic costs of fighting and host exploitation in a seed-drilling parasitic wasp. (United States)

    Boisseau, Romain P; Woods, H Arthur; Goubault, Marlène


    Oviposition sites may be challenging and energetically costly to access for females in the presence of competitors contesting that resource. Additionally, oviposition sites may be difficult to reach, and penetrating a hard substrate can raise energy costs. In the seed-drilling parasitic wasp Eupelmus vuilleti, females actively fight with conspecific competitors over access to hosts. They are often observed laying eggs on already parasitized hosts (superparasitism) living inside cowpea seeds despite the resulting larval competition. Using flow-through respirometry, we quantified the metabolic costs of fighting and of drilling through the seed to access the host, to understand the wasp's fighting strategies and the occurrence of superparasitism. Agonistic interactions such as kicks or pushes generated very small instantaneous costs, but the females that won their contests had higher pre-contest metabolic rates, suggesting a potential long-term cost associated with dominance. We also found that drilling holes through the seed accounted for approximately 15% of a wasp's estimated daily energy budget, and that females can reduce these drilling costs by reusing existing holes. Because exploiting new seeds incurs both drilling costs and the risk of fights, it appears cost effective in some situations for females to avoid confrontations and lay eggs in existing holes, on already parasitized hosts. Our study helps explain the evolution of superparasitism in this system. © 2017. Published by The Company of Biologists Ltd.

  17. Exploitation of lipid components by viral and host proteins for hepatitis C virus infection

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    Kohji eMoriishi


    Full Text Available Hepatitis C virus (HCV, which is a major causative agent of blood-borne hepatitis, has chronically infected about 170 million individuals worldwide and leads to chronic infection, resulting in development of steatosis, cirrhosis and eventually hepatocellular carcinoma. Hepatocellular carcinoma associated with HCV infection is not only caused by chronic inflammation, but also by the biological activity of HCV proteins. HCV core protein is known as a main component of the viral nucleocapsid. It cooperates with host factors and possesses biological activity causing lipid alteration, oxidative stress and progression of cell growth, while other viral proteins also interact with host proteins including molecular chaperones, membrane-anchoring proteins and enzymes associated with lipid metabolism to maintain the efficiency of viral replication and production. HCV core protein is localized on the surface of lipid droplets in infected cells. However, the role of lipid droplets in HCV infection has not yet been elucidated. Several groups recently reported that other viral proteins also support viral infection by regulation of lipid droplets and core localization in infected cells. Furthermore, lipid components are required for modification of host factors and the intracellular membrane to maintain or up-regulate viral replication. In this review, we summarize the current status of knowledge regarding the exploitation of lipid components by viral and host proteins in HCV infection.

  18. Chemistry and biology of Hyaluronan

    National Research Council Canada - National Science Library

    Garg, Hari G; Hales, Charles A


    ... rheological properties. They are visco-elastic and the viscosity is strongly shear-dependent. For this reason, hyaluronan can act as a lubricant. It is found in joints and other tissues such as muscles at surfaces which are moving over each other. The human body is a well-oiled machine and hyaluronan seems to be that oil. However, hyaluronan has also ...

  19. Hyaluronan and Stone Disease (United States)

    Asselman, Marino


    Kidney stones cannot be formed as long as crystals are passed in the urine. However, when crystals are retained it becomes possible for them to aggregate and form a stone. Crystals are expected to be formed not earlier than the distal tubules and collecting ducts. Studies both in vitro and in vivo demonstrate that calcium oxalate monohydrate crystals do not adhere to intact distal epithelium, but only when the epithelium is proliferating or regenerating, so that it possesses dedifferentiated cells expressing hyaluronan, osteopontin (OPN) and their mutual receptor CD44 at the apical cell membrane. The polysaccharide hyaluronan is an excellent crystal binding molecule because of its negative ionic charge. We hypothesized that the risk for crystal retention in the human kidney would be increased when tubular cells express hyaluronan at their apical cell membrane. Two different patient categories in which nephrocalcinosis frequently occurs were studied to test this hypothesis (preterm neonates and kidney transplant patients). Hyaluronan (and OPN) expression at the luminal membrane of tubular cells indeed was observed, which preceded subsequent retention of crystals in the distal tubules. Tubular nephrocalcinosis has been reported to be associated with decline of renal function and thus further studies to extend our knowledge of the mechanisms of retention and accumulation of crystals in the kidney are warranted. Ultimately, this may allow the design of new strategies for the prevention and treatment of both nephrocalcinosis and nephrolithiasis in patients.

  20. Ebola Zaire virus blocks type I interferon production by exploiting the host SUMO modification machinery.

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    Tsung-Hsien Chang


    Full Text Available Ebola Zaire virus is highly pathogenic for humans, with case fatality rates approaching 90% in large outbreaks in Africa. The virus replicates in macrophages and dendritic cells (DCs, suppressing production of type I interferons (IFNs while inducing the release of large quantities of proinflammatory cytokines. Although the viral VP35 protein has been shown to inhibit IFN responses, the mechanism by which it blocks IFN production has not been fully elucidated. We expressed VP35 from a mouse-adapted variant of Ebola Zaire virus in murine DCs by retroviral gene transfer, and tested for IFN transcription upon Newcastle Disease virus (NDV infection and toll-like receptor signaling. We found that VP35 inhibited IFN transcription in DCs following these stimuli by disabling the activity of IRF7, a transcription factor required for IFN transcription. By yeast two-hybrid screens and coimmunoprecipitation assays, we found that VP35 interacted with IRF7, Ubc9 and PIAS1. The latter two are the host SUMO E2 enzyme and E3 ligase, respectively. VP35, while not itself a SUMO ligase, increased PIAS1-mediated SUMOylation of IRF7, and repressed Ifn transcription. In contrast, VP35 did not interfere with the activation of NF-kappaB, which is required for induction of many proinflammatory cytokines. Our findings indicate that Ebola Zaire virus exploits the cellular SUMOylation machinery for its advantage and help to explain how the virus overcomes host innate defenses, causing rapidly overwhelming infection to produce a syndrome resembling fulminant septic shock.

  1. HIV Exploits Antiviral Host Innate GCN2-ATF4 Signaling for Establishing Viral Replication Early in Infection. (United States)

    Jiang, Guochun; Santos Rocha, Clarissa; Hirao, Lauren A; Mendes, Erica A; Tang, Yuyang; Thompson, George R; Wong, Joseph K; Dandekar, Satya


    Antiviral innate host defenses against acute viral infections include suppression of host protein synthesis to restrict viral protein production. Less is known about mechanisms by which viral pathogens subvert host antiviral innate responses for establishing their replication and dissemination. We investigated early innate defense against human immunodeficiency virus (HIV) infection and viral evasion by utilizing human CD4 + T cell cultures in vitro and a simian immunodeficiency virus (SIV) model of AIDS in vivo Our data showed that early host innate defense against the viral infection involves GCN2-ATF4 signaling-mediated suppression of global protein synthesis, which is exploited by the virus for supporting its own replication during early viral infection and dissemination in the gut mucosa. Suppression of protein synthesis and induction of protein kinase GCN2-ATF4 signaling were detected in the gut during acute SIV infection. These changes diminished during chronic viral infection. HIV replication induced by serum deprivation in CD4 + T cells was linked to the induction of ATF4 that was recruited to the HIV long terminal repeat (LTR) to promote viral transcription. Experimental inhibition of GCN2-ATF4 signaling either by a specific inhibitor or by amino acid supplementation suppressed the induction of HIV expression. Enhancing ATF4 expression through selenium administration resulted in reactivation of latent HIV in vitro as well as ex vivo in the primary CD4 + T cells isolated from patients receiving suppressive antiretroviral therapy (ART). In summary, HIV/SIV exploits the early host antiviral response through GCN2-ATF4 signaling by utilizing ATF4 for activating the viral LTR transcription to establish initial viral replication and is a potential target for HIV prevention and therapy. IMPORTANCE Understanding how HIV overcomes host antiviral innate defense response in order to establish infection and dissemination is critical for developing prevention and

  2. Hyaluronan Biosynthesis in Prostate Cancer

    National Research Council Canada - National Science Library

    McCarthy, James B


    Despite advances in the diagnosis and treatment of prostate cancer in the last several years metastasis represents the major cause of frustration and failure in the successful treatment of prostate cancer patients. Hyaluronan (HA...

  3. How Toxoplasma and malaria parasites defy first, then exploit host autophagic and endocytic pathways for growth. (United States)

    Coppens, Isabelle


    Infections caused by the apicomplexan parasites Plasmodium and Toxoplasma are wide-spread, life-threatening and therapeutically challenging. These pathogens are obligate intracellular microorganisms that invade mammalian cells by forming a self-made niche, the parasitophorous vacuole that is impervious to host lysosomal fusion. Shortly after invasion, a noncanonical xenophagic pathway resembling LC3-associated phagocytosis is activated by the host cell to control infections. However, Plasmodium and Toxoplasma have elaborated strategies to avoid clearance by the sentinel activities of the host autophagic system. After this initial confrontation, replicating Plasmodium and Toxoplasma adeptly usurp, for their own benefit, host autophagic and endocytic structures by attracting these organelles to their vacuole, likely to access their nutrient-rich content. The pleomorphic function of the autophagy system, from microbial defense to nutrient supply, is reflected by its ambivalent role during the intracellular development of these apicomplexan parasites. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Salmonella exploits the host endolysosomal tethering factor HOPS complex to promote its intravacuolar replication (United States)

    Sindhwani, Aastha; Kaur, Harmeet; Tuli, Amit


    Salmonella enterica serovar typhimurium extensively remodels the host late endocytic compartments to establish its vacuolar niche within the host cells conducive for its replication, also known as the Salmonella-containing vacuole (SCV). By maintaining a prolonged interaction with late endosomes and lysosomes of the host cells in the form of interconnected network of tubules (Salmonella-induced filaments or SIFs), Salmonella gains access to both membrane and fluid-phase cargo from these compartments. This is essential for maintaining SCV membrane integrity and for bacterial intravacuolar nutrition. Here, we have identified the multisubunit lysosomal tethering factor—HOPS (HOmotypic fusion and Protein Sorting) complex as a crucial host factor facilitating delivery of late endosomal and lysosomal content to SCVs, providing membrane for SIF formation, and nutrients for intravacuolar bacterial replication. Accordingly, depletion of HOPS subunits significantly reduced the bacterial load in non-phagocytic and phagocytic cells as well as in a mouse model of Salmonella infection. We found that Salmonella effector SifA in complex with its binding partner; SKIP, interacts with HOPS subunit Vps39 and mediates recruitment of this tethering factor to SCV compartments. The lysosomal small GTPase Arl8b that binds to, and promotes membrane localization of Vps41 (and other HOPS subunits) was also required for HOPS recruitment to SCVs and SIFs. Our findings suggest that Salmonella recruits the host late endosomal and lysosomal membrane fusion machinery to its vacuolar niche for access to host membrane and nutrients, ensuring its intracellular survival and replication. PMID:29084291

  5. The Role of Hyaluronan in Innate Defense Responses of the Intestine

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    Carol A. de la Motte


    Full Text Available Hyaluronan is an abundant extracellular matrix component prevalent in the vertebrate intestinal tract. Here we discuss what is known about hyaluronan distribution during homeostasis and inflammatory diseases of the gut and discuss ways in which this glycosaminoglycan can participate in regulating innate host defense mechanisms. These natural responses include mechanisms promoting rapid leukocyte recruitment after bacterial challenge/colon tissue damage as well as promoting epithelial defense mechanisms in the intestine.

  6. Variation in butterfly larval acoustics as a strategy to infiltrate and exploit host ant colony resources. (United States)

    Sala, Marco; Casacci, Luca Pietro; Balletto, Emilio; Bonelli, Simona; Barbero, Francesca


    About 10,000 arthropods live as ants' social parasites and have evolved a number of mechanisms allowing them to penetrate and survive inside the ant nests. Many of them can intercept and manipulate their host communication systems. This is particularly important for butterflies of the genus Maculinea, which spend the majority of their lifecycle inside Myrmica ant nests. Once in the colony, caterpillars of Maculinea "predatory species" directly feed on the ant larvae, while those of "cuckoo species" are fed primarily by attendance workers, by trophallaxis. It has been shown that Maculinea cuckoo larvae are able to reach a higher social status within the colony's hierarchy by mimicking the acoustic signals of their host queen ants. In this research we tested if, when and how myrmecophilous butterflies may change sound emissions depending on their integration level and on stages of their life cycle. We studied how a Maculinea predatory species (M. teleius) can acoustically interact with their host ants and highlighted differences with respect to a cuckoo species (M. alcon). We recorded sounds emitted by Maculinea larvae as well as by their Myrmica hosts, and performed playback experiments to assess the parasites' capacity to interfere with the host acoustic communication system. We found that, although varying between and within butterfly species, the larval acoustic emissions are more similar to queens' than to workers' stridulations. Nevertheless playback experiments showed that ant workers responded most strongly to the sounds emitted by the integrated (i.e. post-adoption) larvae of the cuckoo species, as well as by those of predatory species recorded before any contact with the host ants (i.e. in pre-adoption), thereby revealing the role of acoustic signals both in parasite integration and in adoption rituals. We discuss our findings in the broader context of parasite adaptations, comparing effects of acoustical and chemical mimicry.

  7. Variation in butterfly larval acoustics as a strategy to infiltrate and exploit host ant colony resources.

    Directory of Open Access Journals (Sweden)

    Marco Sala

    Full Text Available About 10,000 arthropods live as ants' social parasites and have evolved a number of mechanisms allowing them to penetrate and survive inside the ant nests. Many of them can intercept and manipulate their host communication systems. This is particularly important for butterflies of the genus Maculinea, which spend the majority of their lifecycle inside Myrmica ant nests. Once in the colony, caterpillars of Maculinea "predatory species" directly feed on the ant larvae, while those of "cuckoo species" are fed primarily by attendance workers, by trophallaxis. It has been shown that Maculinea cuckoo larvae are able to reach a higher social status within the colony's hierarchy by mimicking the acoustic signals of their host queen ants. In this research we tested if, when and how myrmecophilous butterflies may change sound emissions depending on their integration level and on stages of their life cycle. We studied how a Maculinea predatory species (M. teleius can acoustically interact with their host ants and highlighted differences with respect to a cuckoo species (M. alcon. We recorded sounds emitted by Maculinea larvae as well as by their Myrmica hosts, and performed playback experiments to assess the parasites' capacity to interfere with the host acoustic communication system. We found that, although varying between and within butterfly species, the larval acoustic emissions are more similar to queens' than to workers' stridulations. Nevertheless playback experiments showed that ant workers responded most strongly to the sounds emitted by the integrated (i.e. post-adoption larvae of the cuckoo species, as well as by those of predatory species recorded before any contact with the host ants (i.e. in pre-adoption, thereby revealing the role of acoustic signals both in parasite integration and in adoption rituals. We discuss our findings in the broader context of parasite adaptations, comparing effects of acoustical and chemical mimicry.

  8. Exploiting induced pluripotent stem cell-derived macrophages to unravel host factors influencing Chlamydia trachomatis pathogenesis (United States)

    Yeung, Amy T. Y.; Hale, Christine; Lee, Amy H.; Gill, Erin E.; Bushell, Wendy; Parry-Smith, David; Goulding, David; Pickard, Derek; Roumeliotis, Theodoros; Choudhary, Jyoti; Thomson, Nick; Skarnes, William C.; Dougan, Gordon; Hancock, Robert E. W.


    Chlamydia trachomatis remains a leading cause of bacterial sexually transmitted infections and preventable blindness worldwide. There are, however, limited in vitro models to study the role of host genetics in the response of macrophages to this obligate human pathogen. Here, we describe an approach using macrophages derived from human induced pluripotent stem cells (iPSdMs) to study macrophage–Chlamydia interactions in vitro. We show that iPSdMs support the full infectious life cycle of C. trachomatis in a manner that mimics the infection of human blood-derived macrophages. Transcriptomic and proteomic profiling of the macrophage response to chlamydial infection highlighted the role of the type I interferon and interleukin 10-mediated responses. Using CRISPR/Cas9 technology, we generated biallelic knockout mutations in host genes encoding IRF5 and IL-10RA in iPSCs, and confirmed their roles in limiting chlamydial infection in macrophages. This model can potentially be extended to other pathogens and tissue systems to advance our understanding of host-pathogen interactions and the role of human genetics in influencing the outcome of infections. PMID:28440293

  9. Exploitation of host cell biology and evasion of immunity by Francisella tularensis

    Directory of Open Access Journals (Sweden)

    Yousef eAbu Kwaik


    Full Text Available Francisella tularensis is an intracellular bacterium that infects humans and many small mammals. During infection, F. tularensis replicates predominantly in macrophages but also proliferate in other cell types. Entry into host cells is mediate by various receptors. Complement-opsonized F. tularensis enters into macrophages by looping phagoscytosis. Uptake is mediated in part by Syk, which may activate actin rearrangement in the phagocytic cup resulting in the engulfment of F. tularensis in a lipid raft rich phagosome. Inside the host cells, F. tularensis resides transiently in an acidified late endosome-like compartment before disruption of the phagosomal membrane and escape into the cytosol, where bacterial proliferation occurs. Modulation of phagosome biogenesis and escape into the cytosol is mediated by the Francisella pathogenicity island-encoded type VI-like secretion system. Whilst inside the phagosome, F. tularensis inhibits NADPH oxidase activity but temporarily inducing pro-inflammatory cytokines in PI3K/Akt-dependent manner, which is counteracted by the induction of SHIP that negatively regulates PI3K/Akt activation and promotes bacterial escape into the cytosol. Interestingly, F. tularensis subverts CD4 T cells-mediated killing by inhibiting antigen presentation by activated macrophages through ubiquitin dependent degradation of MHC II molecules on activated macrophages. In the cytosol, F. tularensis is recognized by the host cell AIM2-dependent inflammasome, which is down-regulated by F. tularensis that also inhibits Caspase-1 and ASC activity. During late stages of intracellular proliferation, caspase-3 is activated but apoptosis is delayed through activation of NF-kB and Ras, which ensures cell viability.

  10. Mechanisms employed by retroviruses to exploit host factors for translational control of a complicated proteome (United States)

    Bolinger, Cheryl; Boris-Lawrie, Kathleen


    Retroviruses have evolved multiple strategies to direct the synthesis of a complex proteome from a single primary transcript. Their mechanisms are modulated by a breadth of virus-host interactions, which are of significant fundamental interest because they ultimately affect the efficiency of virus replication and disease pathogenesis. Motifs located within the untranslated region (UTR) of the retroviral RNA have established roles in transcriptional trans-activation, RNA packaging, and genome reverse transcription; and a growing literature has revealed a necessary role of the UTR in modulating the efficiency of viral protein synthesis. Examples include a 5' UTR post-transcriptional control element (PCE), present in at least eight retroviruses, that interacts with cellular RNA helicase A to facilitate cap-dependent polyribosome association; and 3' UTR constitutive transport element (CTE) of Mason-Pfizer monkey virus that interacts with Tap/NXF1 and SR protein 9G8 to facilitate RNA export and translational utilization. By contrast, nuclear protein hnRNP E1 negatively modulates HIV-1 Gag, Env, and Rev protein synthesis. Alternative initiation strategies by ribosomal frameshifting and leaky scanning enable polycistronic translation of the cap-dependent viral transcript. Other studies posit cap-independent translation initiation by internal ribosome entry at structural features of the 5' UTR of selected retroviruses. The retroviral armamentarium also commands mechanisms to counter cellular post-transcriptional innate defenses, including protein kinase R, 2',5'-oligoadenylate synthetase and the small RNA pathway. This review will discuss recent and historically-recognized insights into retrovirus translational control. The expanding knowledge of retroviral post-transcriptional control is vital to understanding the biology of the retroviral proteome. In a broad perspective, each new insight offers a prospective target for antiviral therapy and strategic improvement of gene

  11. Enzymatic production of hyaluronan oligo- and polysaccharides

    NARCIS (Netherlands)

    Kooy, F.K.


    Hyaluronan oligo- and polysaccharides are abundant in the human body. Depending on the chain length, hyaluronan is an important structural component or is involved in influencing cell responses during embryonic development, healing processes, inflammation and cancer. Due to these diverse roles of

  12. Hyaluronan: from biomimetic to industrial business strategy. (United States)

    Murano, Erminio; Perin, Danilo; Khan, Riaz; Bergamin, Massimo


    Hyaluronan (hyaluronic acid) is a naturally occurring polysaccharide of a linear repeating disaccharide unit consisting of beta-(1-->4)-linked D-glucopyranuronic acid and beta-(1-->3)-linked 2-acetamido-2-deoxy-D-glucopyranose, which is present in extracellular matrices, the synovial fluid of joints, and scaffolding that comprises cartilage. In its mechanism of synthesis, its size, and its physico-chemical properties, hyaluronan is unique amongst other glycosaminoglycans. The network-forming, viscoelastic and its charge characteristics are important to many biochemical properties of living tissues. It is an important pericellular and cell surface constituent; its interaction with other macromolecules such as proteins, participates in regulating cell behavior during numerous morphogenic, restorative, and pathological processes in the body. The knowledge of HA in diseases such as various forms of cancers, arthritis and osteoporosis has led to new impetus in research and development in the preparation of biomaterials for surgical implants and drug conjugates for targeted delivery. A concise and focused review on hyaluronan is timely. This review will cover the following important aspects of hyaluronan: (i) biological functions and synthesis in nature; (ii) current industrial production and potential biosynthetic processes of hyaluronan; (iii) chemical modifications of hyaluronan leading to products of commercial significance; and (iv) and the global market position and manufacturers of hyaluronan.

  13. Hyaluronan in human deciduous tooth germs in the bell stage. Histochemistry and immunohistochemistry

    DEFF Research Database (Denmark)

    Matthiessen, Martin Ebbe; Garbarsch, Charly; Olsen, Birgitte Engelbrecht


    Anatomy, development, glycosaminoglycans, hyaluronan, tooth germs, histochemistry, immunocytochemistry......Anatomy, development, glycosaminoglycans, hyaluronan, tooth germs, histochemistry, immunocytochemistry...

  14. Smuggling across the border: how arthropod-borne pathogens evade and exploit the host defense system of the skin. (United States)

    Bernard, Quentin; Jaulhac, Benoit; Boulanger, Nathalie


    The skin is a critical barrier between hosts and pathogens in arthropod-borne diseases. It harbors many resident cells and specific immune cells to arrest or limit infections by secreting inflammatory molecules or by directly killing pathogens. However, some pathogens are able to use specific skin cells and arthropod saliva for their initial development, to hide from the host immune system, and to establish persistent infection in the vertebrate host. A better understanding of the initial mechanisms taking place in the skin should allow the development of new strategies to fight these vector-borne pathogens that are spread worldwide and are of major medical importance.

  15. Transcriptome of an entomophthoralean fungus (Pandora formicae) shows molecular machinery adjusted for successful host exploitation and transmission. (United States)

    Małagocka, Joanna; Grell, Morten N; Lange, Lene; Eilenberg, Jørgen; Jensen, Annette B


    Pandora formicae is an obligate entomopathogenic fungus from the phylum Entomophthoromycota, known to infect only ants from the genus Formica. In the final stages of infection, the fungus induces the so-called summit disease syndrome, manipulating the host to climb up vegetation prior to death and fixing the dead cadaver to the surface, all to increase efficient spore dispersal. To investigate this fascinating pathogen-host interaction, we constructed interaction transcriptome libraries from two final infection stages from the material sampled in the field: (1) when the cadavers were fixed, but the fungus had not grown out through the cuticle and (2) when the fungus was growing out from host cadaver and producing spores. These phases mark the switch from within-host growth to reproduction on the host surface, after fungus outgrowth through host integument. In this first de novo transcriptome of an entomophthoralean fungus, we detected expression of many pathogenicity-related genes, including secreted hydrolytic enzymes and genes related to morphological reorganization and nutrition uptake. Differences in expression of genes in these two infection phases were compared and showed a switch in enzyme expression related to either cuticle breakdown or cell proliferation and cell wall remodeling, particularly in subtilisin-like serine protease and trypsin-like protease transcripts. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. How to escape from the host nest: imperfect chemical mimicry in eucharitid parasitoids and exploitation of the ants' hygienic behavior. (United States)

    Pérez-Lachaud, Gabriela; Bartolo-Reyes, Juan Carlos; Quiroa-Montalván, Claudia M; Cruz-López, Leopoldo; Lenoir, Alain; Lachaud, Jean-Paul


    Communication in ants is based to a great extent on chemical compounds. Recognition of intruders is primarily based on cuticular hydrocarbon (CHC) profile matching but is prone to being cheated. Eucharitid wasps are specific parasitoids of the brood of ants; the immature stages are either well integrated within the colony or are protected within the host cocoons, whereas adult wasps at emergence must leave their host nest to reproduce and need to circumvent the ant recognition system to escape unscathed. The behavioral interactions between eucharitid wasps and workers of their host, the Neotropical ant Ectatomma tuberculatum, are characterized. In experimental bioassays, newly emerged parasitoids were not violently aggressed. They remained still and were grabbed by ants upon contact and transported outside the nest; host workers were even observed struggling to reject them. Parasitoids were removed from the nest within five minutes, and most were unharmed, although two wasps (out of 30) were killed during the interaction with the ants. We analyzed the CHCs of the ant and its two parasitoids, Dilocantha lachaudii and Isomerala coronata, and found that although wasps shared all of their compounds with the ants, each wasp species had typical blends and hydrocarbon abundance was also species specific. Furthermore, the wasps had relatively few CHCs compared to E. tuberculatum (22-44% of the host components), and these were present in low amounts. Wasps, only partially mimicking the host CHC profile, were immediately recognized as alien and actively removed from the nest by the ants. Hexane-washed wasps were also transported to the refuse piles, but only after being thoroughly inspected and after most of the workers had initially ignored them. Being recognized as intruder may be to the parasitoids' advantage, allowing them to quickly leave the natal nest, and therefore enhancing the fitness of these very short lived parasitoids. We suggest that eucharitids take advantage

  17. Hyaluronan and phospholipid association in biolubrication. (United States)

    Wang, Min; Liu, Chao; Thormann, Esben; Dėdinaitė, Andra


    It is becoming increasingly clear that the outstanding lubrication of synovial joints is achieved by a sophisticated hierarchical structure of cartilage combined with synergistic actions of surface-active components present in the synovial fluid. In this work we focus on the association of two components of the synovial fluid, hyaluronan and dipalmitoyl phosphatidyl choline (DPPC), in bulk solution and at interfaces. We demonstrate that hyaluronan associates with DPPC vesicles and adsorbs to supported DPPC bilayers. The association structures formed at the interface are sufficiently stable to allow sequential adsorption of DPPC and hyaluronan, whereby promoting the formation of thick composite layers of these two components. The lubricating ability of such composite layers was probed by the AFM colloidal probe technique and found to be very favorable with low friction coefficients and high load bearing capacity. With DPPC as the last adsorbed component, a friction coefficient of 0.01 was found up to pressures significantly above what is encountered in healthy synovial joints. Hyaluronan as the last added component increases the friction coefficient to 0.03 and decreases the load bearing capacity somewhat (but still above what is needed in the synovial joint). Our data demonstrate that self-assembly structures formed by hyaluronan and phospholipids at interfaces are efficient aqueous lubricants, and it seems plausible that such self-assembly structures contribute to the exceptional lubrication of synovial joints.

  18. Transcriptome of an entomophthoralean fungus (Pandora formicae) shows molecular machinery adjusted for successful host exploitation and transmission

    DEFF Research Database (Denmark)

    Malagocka, Joanna; Grell, Morten Nedergaard; Lange, Lene


    and fixing the dead cadaver to the surface, all to increase efficient spore dispersal. To investigate this fascinating pathogen-host interaction, we constructed interaction transcriptome libraries from two final infection stages from the material sampled in the field: (1) when the cadavers were fixed...

  19. Apoptotic-like Leishmania exploit the host´s autophagy machinery to reduce T-cell-mediated parasite elimination (United States)

    Crauwels, Peter; Bohn, Rebecca; Thomas, Meike; Gottwalt, Stefan; Jäckel, Florian; Krämer, Susi; Bank, Elena; Tenzer, Stefan; Walther, Paul; Bastian, Max; van Zandbergen, Ger


    Apoptosis is a well-defined cellular process in which a cell dies, characterized by cell shrinkage and DNA fragmentation. In parasites like Leishmania, the process of apoptosis-like cell death has been described. Moreover upon infection, the apoptotic-like population is essential for disease development, in part by silencing host phagocytes. Nevertheless, the exact mechanism of how apoptosis in unicellular organisms may support infectivity remains unclear. Therefore we investigated the fate of apoptotic-like Leishmania parasites in human host macrophages. Our data showed—in contrast to viable parasites—that apoptotic-like parasites enter an LC3+, autophagy-like compartment. The compartment was found to consist of a single lipid bilayer, typical for LC3-associated phagocytosis (LAP). As LAP can provoke anti-inflammatory responses and autophagy modulates antigen presentation, we analyzed how the presence of apoptotic-like parasites affected the adaptive immune response. Macrophages infected with viable Leishmania induced proliferation of CD4+ T-cells, leading to a reduced intracellular parasite survival. Remarkably, the presence of apoptotic-like parasites in the inoculum significantly reduced T-cell proliferation. Chemical induction of autophagy in human monocyte-derived macrophage (hMDM), infected with viable parasites only, had an even stronger proliferation-reducing effect, indicating that host cell autophagy and not parasite viability limits the T-cell response and enhances parasite survival. Concluding, our data suggest that apoptotic-like Leishmania hijack the host cells´ autophagy machinery to reduce T-cell proliferation. Furthermore, the overall population survival is guaranteed, explaining the benefit of apoptosis-like cell death in a single-celled parasite and defining the host autophagy pathway as a potential therapeutic target in treating Leishmaniasis. PMID:25801301

  20. Apoptotic-like Leishmania exploit the host's autophagy machinery to reduce T-cell-mediated parasite elimination. (United States)

    Crauwels, Peter; Bohn, Rebecca; Thomas, Meike; Gottwalt, Stefan; Jäckel, Florian; Krämer, Susi; Bank, Elena; Tenzer, Stefan; Walther, Paul; Bastian, Max; van Zandbergen, Ger


    Apoptosis is a well-defined cellular process in which a cell dies, characterized by cell shrinkage and DNA fragmentation. In parasites like Leishmania, the process of apoptosis-like cell death has been described. Moreover upon infection, the apoptotic-like population is essential for disease development, in part by silencing host phagocytes. Nevertheless, the exact mechanism of how apoptosis in unicellular organisms may support infectivity remains unclear. Therefore we investigated the fate of apoptotic-like Leishmania parasites in human host macrophages. Our data showed--in contrast to viable parasites--that apoptotic-like parasites enter an LC3(+), autophagy-like compartment. The compartment was found to consist of a single lipid bilayer, typical for LC3-associated phagocytosis (LAP). As LAP can provoke anti-inflammatory responses and autophagy modulates antigen presentation, we analyzed how the presence of apoptotic-like parasites affected the adaptive immune response. Macrophages infected with viable Leishmania induced proliferation of CD4(+) T-cells, leading to a reduced intracellular parasite survival. Remarkably, the presence of apoptotic-like parasites in the inoculum significantly reduced T-cell proliferation. Chemical induction of autophagy in human monocyte-derived macrophage (hMDM), infected with viable parasites only, had an even stronger proliferation-reducing effect, indicating that host cell autophagy and not parasite viability limits the T-cell response and enhances parasite survival. Concluding, our data suggest that apoptotic-like Leishmania hijack the host cells' autophagy machinery to reduce T-cell proliferation. Furthermore, the overall population survival is guaranteed, explaining the benefit of apoptosis-like cell death in a single-celled parasite and defining the host autophagy pathway as a potential therapeutic target in treating Leishmaniasis.

  1. Biology and biotechnology of hyaluronan. (United States)

    Viola, Manuela; Vigetti, Davide; Karousou, Evgenia; D'Angelo, Maria Luisa; Caon, Ilaria; Moretto, Paola; De Luca, Giancarlo; Passi, Alberto


    The hyaluronan (HA) polymer is a critical component of extracellular matrix with a remarkable structure: is a linear and unbranched polymer without sulphate or phosphate groups. It is ubiquitous in mammals showing several biological functions, ranging from cell proliferation and migration to angiogenesis and inflammation. For its critical biological functions the amount of HA in tissues is carefully controlled by different mechanisms including covalent modification of the synthetic enzymes and epigenetic control of their gene expression. The concentration of HA is also critical in several pathologies including cancer, diabetes and inflammation. Beside these biological roles, the structural properties of HA allow it to take advantage of its capacity to form gels even at concentration of 1 % producing scaffolds with very promising applications in regenerative medicine as biocompatible material for advanced therapeutic uses. In this review we highlight the biological aspects of HA addressing the mechanisms controlling the HA content in tissues as well as its role in important human pathologies. In the second part of the review we highlight the different use of HA polymers in the modern biotechnology.

  2. A Novel Two-Component Signaling System Facilitates Uropathogenic Escherichia coli's Ability to Exploit Abundant Host Metabolites (United States)

    Cai, Wentong; Wannemuehler, Yvonne; Dell'Anna, Giuseppe; Nicholson, Bryon; Barbieri, Nicolle L.; Kariyawasam, Subhashinie; Feng, Yaping; Logue, Catherine M.; Nolan, Lisa K.; Li, Ganwu


    Two-component signaling systems (TCSs) are major mechanisms by which bacteria adapt to environmental conditions. It follows then that TCSs would play important roles in the adaptation of pathogenic bacteria to host environments. However, no pathogen-associated TCS has been identified in uropathogenic Escherichia coli (UPEC). Here, we identified a novel TCS, which we termed KguS/KguR (KguS: α-ketoglutarate utilization sensor; KguR: α-ketoglutarate utilization regulator) in UPEC CFT073, a strain isolated from human pyelonephritis. kguS/kguR was strongly associated with UPEC but was found only rarely among other E. coli including commensal and intestinal pathogenic strains. An in vivo competition assay in a mouse UTI model showed that deletion of kguS/kguR in UPEC CFT073 resulted in a significant reduction in its colonization of the bladders and kidneys of mice, suggesting that KguS/KguR contributed to UPEC fitness in vivo. Comparative proteomics identified the target gene products of KguS/KguR, and sequence analysis showed that TCS KguS/KguR and its targeted-genes, c5032 to c5039, are encoded on a genomic island, which is not present in intestinal pathogenic E. coli. Expression of the target genes was induced by α-ketoglutarate (α-KG). These genes were further shown to be involved in utilization of α-KG as a sole carbon source under anaerobic conditions. KguS/KguR contributed to the regulation of the target genes with the direct regulation by KguR verified using an electrophoretic mobility shift assay. In addition, oxygen deficiency positively modulated expression of kguS/kguR and its target genes. Taken altogether, this study describes the first UPEC-associated TCS that functions in controlling the utilization of α-ketoglutarate in vivo thereby facilitating UPEC adaptation to life inside the urinary tract. PMID:23825943

  3. A novel two-component signaling system facilitates uropathogenic Escherichia coli's ability to exploit abundant host metabolites.

    Directory of Open Access Journals (Sweden)

    Wentong Cai

    Full Text Available Two-component signaling systems (TCSs are major mechanisms by which bacteria adapt to environmental conditions. It follows then that TCSs would play important roles in the adaptation of pathogenic bacteria to host environments. However, no pathogen-associated TCS has been identified in uropathogenic Escherichia coli (UPEC. Here, we identified a novel TCS, which we termed KguS/KguR (KguS: α-ketoglutarate utilization sensor; KguR: α-ketoglutarate utilization regulator in UPEC CFT073, a strain isolated from human pyelonephritis. kguS/kguR was strongly associated with UPEC but was found only rarely among other E. coli including commensal and intestinal pathogenic strains. An in vivo competition assay in a mouse UTI model showed that deletion of kguS/kguR in UPEC CFT073 resulted in a significant reduction in its colonization of the bladders and kidneys of mice, suggesting that KguS/KguR contributed to UPEC fitness in vivo. Comparative proteomics identified the target gene products of KguS/KguR, and sequence analysis showed that TCS KguS/KguR and its targeted-genes, c5032 to c5039, are encoded on a genomic island, which is not present in intestinal pathogenic E. coli. Expression of the target genes was induced by α-ketoglutarate (α-KG. These genes were further shown to be involved in utilization of α-KG as a sole carbon source under anaerobic conditions. KguS/KguR contributed to the regulation of the target genes with the direct regulation by KguR verified using an electrophoretic mobility shift assay. In addition, oxygen deficiency positively modulated expression of kguS/kguR and its target genes. Taken altogether, this study describes the first UPEC-associated TCS that functions in controlling the utilization of α-ketoglutarate in vivo thereby facilitating UPEC adaptation to life inside the urinary tract.

  4. Intracellular Uropathogenic E. coli Exploits Host Rab35 for Iron Acquisition and Survival within Urinary Bladder Cells. (United States)

    Dikshit, Neha; Bist, Pradeep; Fenlon, Shannon N; Pulloor, Niyas Kudukkil; Chua, Christelle En Lin; Scidmore, Marci A; Carlyon, Jason A; Tang, Bor Luen; Chen, Swaine L; Sukumaran, Bindu


    Recurrent urinary tract infections (UTIs) caused by uropathogenic E. coli (UPEC) are common and morbid infections with limited therapeutic options. Previous studies have demonstrated that persistent intracellular infection of bladder epithelial cells (BEC) by UPEC contributes to recurrent UTI in mouse models of infection. However, the mechanisms employed by UPEC to survive within BEC are incompletely understood. In this study we aimed to understand the role of host vesicular trafficking proteins in the intracellular survival of UPEC. Using a cell culture model of intracellular UPEC infection, we found that the small GTPase Rab35 facilitates UPEC survival in UPEC-containing vacuoles (UCV) within BEC. Rab35 plays a role in endosomal recycling of transferrin receptor (TfR), the key protein responsible for transferrin-mediated cellular iron uptake. UPEC enhance the expression of both Rab35 and TfR and recruit these proteins to the UCV, thereby supplying UPEC with the essential nutrient iron. Accordingly, Rab35 or TfR depleted cells showed significantly lower intracellular iron levels and reduced ability to support UPEC survival. In the absence of Rab35, UPEC are preferentially trafficked to degradative lysosomes and killed. Furthermore, in an in vivo murine model of persistent intracellular infection, Rab35 also colocalizes with intracellular UPEC. We propose a model in which UPEC subverts two different vesicular trafficking pathways (endosomal recycling and degradative lysosomal fusion) by modulating Rab35, thereby simultaneously enhancing iron acquisition and avoiding lysosomal degradation of the UCV within bladder epithelial cells. Our findings reveal a novel survival mechanism of intracellular UPEC and suggest a potential avenue for therapeutic intervention against recurrent UTI.

  5. The Role of Hyaluronan and CD44 in the Pathogenesis of Lupus Nephritis

    Directory of Open Access Journals (Sweden)

    Susan Yung


    Full Text Available Systemic lupus erythematosus (SLE is a prototype autoimmune disease that affects multiorgan systems. Lupus nephritis is one of the most severe manifestations of SLE whereby immune-mediated inflammation can lead to permanent damage within the glomerular, tubulo-interstitial, and vascular compartments of the kidney, resulting in acute or chronic renal failure. The mechanisms that regulate host inflammatory responses and tissue injury are incompletely understood. Accumulating evidence suggests that hyaluronan and its interaction with its cell surface receptor CD44 plays an important role in mediating pathogenic mechanisms in SLE. This paper discusses the putative mechanisms through which hyaluronan and CD44 contribute to the pathogenesis of SLE, with particular emphasis on lupus nephritis.

  6. Hyaluronan and calcium carbonate hybrid nanoparticles for colorectal cancer chemotherapy (United States)

    Bai, Jinghui; Xu, Jian; Zhao, Jian; Zhang, Rui


    A hybrid drug delivery system (DDS) composed of hyaluronan and calcium carbonate (CC) was developed. By taking advantage of the tumor-targeting ability of hyaluronan and the drug-loading property of CC, the well-formed hyaluronan-CC nanoparticles were able to serve as a DDS targeting colorectal cancer with a decent drug loading content, which is beneficial in the chemotherapy of colorectal cancer. In this study, hyaluronan-CC nanoparticles smaller than 100 nm were successfully developed to load the wide-range anti-cancer drug adriamycin (Adr) to construct hyaluronan-CC/Adr nanoparticles. On the other hand, we also found that hyaluronan-CC/Adr nanoparticles can possibly increase the uptake ratio of Adr into HT29 colorectal cancer cells when compared with hyaluronan-free nanoparticles (CC/Adr) via the CD44 receptor-mediated endocytosis via competitive uptake and in vivo imaging assays. Note that both in vitro (CCK-8 assay on HT29 cells) and in vivo (anti-cancer assay on HT-29 tumor-bearing nude mice model) experiments revealed that hyaluronan-CC/Adr nanoparticles exhibited stronger anti-cancer activity than free Adr or CC/Adr nanoparticles with minimized toxic side effects and preferable cancer-suppression potential.

  7. Expression of Hyaluronan in human tumor progression

    Directory of Open Access Journals (Sweden)

    Boregowda Rajeev K


    Full Text Available Abstract Background The development and progression of human tumors is accompanied by various cellular, biochemical and genetic alterations. These events include tumor cells interaction with extracellular matrix molecules including hyaluronan (HA. Hyaluronan is a large polysaccharide associated with pericellular matrix of proliferating, migrating cells. Its implication in malignant transformation, tumor progression and with the degree of differentiation in various invasive tumors has well accepted. It has been well known the role HA receptors in tumor growth and metastasis in various cancer tissues. Previously we have observed the unified over expression of Hyaluronic Acid Binding Protein (HABP, H11B2C2 antigen by the tumor cells in various types progressing tumor tissues with different grades. However, the poor understanding of relation between HA and HA-binding protein expression on tumor cells during tumor progression as well as the asymmetric observations of the role of HA expression in tumor progression prompted us to examine the degree of HA expression on tumor cells vs. stroma in various types of human tumors with different grades. Methods In the present study clinically diagnosed tumor tissue samples of different grades were used to screen the histopathological expression of hyaluronan by using b-PG (biotinylated proteoglycan as a probe and we compared the relative HA expression on tumor cells vs. stroma in well differentiated and poorly differentiated tumors. Specificity of the reaction was confirmed either by pre-digesting the tissue sections with hyaluronidase enzyme or by staining the sections with pre-absorbed complex of the probe and HA-oligomers. Results We show here the down regulation of HA expression in tumor cells is associated with progression of tumor from well differentiated through poorly differentiated stage, despite the constant HA expression in the tumor associated stroma. Conclusion The present finding enlighten the

  8. Hyaluronan and the "mushroom" technique: an assessment of hyaluronan injections into the glans. (United States)

    Micheels, Patrick; Saint Hillier, Stéphane; Elias, Badwi; Pujos, Eric


    An Asian technique of injecting collagen below the corona of the glans-the "mushroom" technique-increases the diameter of the penis glans and heightens sexual sensations for the participant and his sexual partner. To improve the physical and aesthetic results of the "mushroom" technique-compared with previous procedures using collagen-by using a new material and alternative injection locations and patterns. The team used a monophasic polydensified hyaluronan (HA) gel for superficial injection into the glans of 12 men aged 28 to 61. Local anesthetic was applied, and one of three injection patterns was tried. Participants self-assessed efficacy and pre- versus postinjection sensitivity using a visual analogue scale and a multiple-choice questionnaire. All participants experienced heightened levels of sensation and increased glans diameter. The hyaluronan gel was well tolerated. Of the three injection patterns tested, one (retrograde contiguous injection) was found to be an improvement over the "mushroom" injection protocol. Injection directly into the glans increases its diameter when the penis is erect, and heightens sexual sensations. The monophasic and polydensified hyaluronan gels are suitable alternatives to collagen. © 2011 by the American Society for Dermatologic Surgery, Inc. Published by Wiley Periodicals, Inc.

  9. Textile structures from hyaluronan based core-shell fibers (United States)

    Pitucha, T.; Lipenska, K.; Kubickova, J.; Zapotocky, V.; Velebny, V.


    Core-shell fibers based on the combination of soluble and insoluble types of hyaluronan were successfully created using wet-spinning method. High swelling of the fibers in synergy with tight textile structures were employed to ensure release of the dissolved fiber core through local cracks in the fiber shell. Thanks to the biocompatibility and resorbability of hyaluronan, the braided or knitted textile structures made from these fibers have a potential to be employed as a drug carrier in medical applications.

  10. The ubiquitous hyaluronan: Functionally implicated in the oviduct? (United States)

    Rodriguez-Martinez, H; Tienthai, P; Atikuzzaman, M; Vicente-Carrillo, A; Rubér, M; Alvarez-Rodriguez, M


    Hyaluronan (hyaluronic acid) is a simple, nonantigenic, nonsulfated glycosaminoglycan present everywhere in the extracellular compartments of the body. Noteworthy, it is highly conserved phylogenetically, from sauropsida to mammals; and plays a plethora of roles from embryonic/fetal development to adult physiological and pathological events, including tumor development. In reproduction, hyaluronan has proven related to initial events as sperm survival, buildup of the sperm reservoir in the oviduct, regulation of sperm capacitation, and prefertilization to later participate in embryo, fetal, and placental development. Synthesis, binding (via the CD44 membrane receptor), and degradation of hyaluronan occur in male and female genital organs, the oviduct being no exception. This review discusses our current knowledge on roles of this ubiquitous glycosaminoglycan on the survival of immunologically foreign spermatozoa in the pig oviduct, a relevant event for fertility. During preovulatory storage in the functional tubal sperm reservoir, spermatozoa are entrapped in a mucus-like tubal fluid. This fluid contains fluctuating levels of hyaluronan, which is synthesized by the lining epithelium by hyaluronan synthase 3. Both hyaluronan and its CD44 receptor are particularly evident in the deep mucosal furrows of the sperm reservoir, in which most spermatozoa are embedded in; kept alive, uncapacitated but also undetected by the immune system of the female. Hyaluronan is also present in the seminal plasma, and evidence points toward an involvement of hyaluronan and its receptor in the local (tubal and possibly uterine) production of antiinflammatory cytokines, such as interleukin-10, pertaining maternal immune tolerance of these foreign cells. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Glial cells assemble hyaluronan-based pericellular matrices in vitro. (United States)

    Maleski, M; Hockfield, S


    The extracellular matrix (ECM) of the brain contains hyaluronan and proteoglycans, as does the ECM of cartilage. Aggrecan, the major proteoglycan of cartilage, forms large aggregates with hyaluronan, which then associate with the chondrocyte cell surface through an interaction with surface hyaluronan binding proteins. In culture, chondrocytes elaborate hyaluronan-proteoglycan aggregates, which form large hydrated pericellular matrices (PCMs) that can be visualized by a particle exclusion assay (Knudson and Toole: Dev Biol 112:308, 1985). It has recently been demonstrated that embryonic glial cells can also elaborate PCMs in culture (Deyst and Toole: Dev Brain Res 28:351, 1995). We demonstrate here that different classes of glial cells elaborate different types of endogenous PCMs in culture. Less differentiated glial cells, as evidenced by their immunoreactivity for nestin, elaborate larger endogenously produced PCMs than differentiated astrocytes, as defined by immunoreactivity for GFAP. This in vitro result may be a reflection of the larger volume of extracellular space present in the embryonic than in the mature brain. We show further that glial cells can incorporate cartilage aggrecan into their PCMs, and that both endogenous and aggrecan-supplemented glial PCMs are dependent on hyaluronan. In contrast, primary neurons from newborn (P0) and P1 rat cortex neither express endogenous matrices nor can assemble exogenous hyaluronan/aggrecan aggregates into PCMs. These results suggest that immature neurons may not have the ability to assemble hyaluronan-based PCMs, and they raise the possibility that neural proteoglycans associate with neuronal surfaces through a mechanism that may not directly involve hyaluronan.

  12. Pulmonary surfactant adsorption is increased by hyaluronan or polyethylene glycol. (United States)

    Taeusch, H William; Dybbro, Eric; Lu, Karen W


    In acute lung injuries, inactivating agents may interfere with transfer (adsorption) of pulmonary surfactants to the interface between air and the aqueous layer that coats the interior of alveoli. Some ionic and nonionic polymers reduce surfactant inactivation in vitro and in vivo. In this study, we tested directly whether an ionic polymer, hyaluronan, or a nonionic polymer, polyethylene glycol, enhanced adsorption of a surfactant used clinically. We used three different methods of measuring adsorption in vitro: a modified pulsating bubble surfactometer; a King/Clements device; and a spreading trough. In addition we measured the effects of both polymers on surfactant turbidity, using this assay as a nonspecific index of aggregation. We found that both hyaluronan and polyethylene glycol significantly increased the rate and degree of surfactant material adsorbed to the surface in all three assays. Hyaluronan was effective in lower concentrations (20-fold) than polyethylene glycol and, unlike polyethylene glycol, hyaluronan did not increase apparent aggregation of surfactant. Surfactant adsorption in the presence of serum was also enhanced by both polymers regardless of whether hyaluronan or polyethylene glycol was included with serum in the subphase or added to the surfactant applied to the surface. Therefore, endogenous polymers in the alveolar subphase, or exogenous polymers added to surfactant used as therapy, may both be important for reducing inactivation of surfactant that occurs with various lung injuries.

  13. Hyaluronan decreases surfactant inactivation in vitro. (United States)

    Lu, Karen W; Goerke, Jon; Clements, John A; Taeusch, H William


    Hyaluronan (HA) is an anionic polymer and a constituent of alveolar fluid that can bind proteins, phospholipids, and water. Previous studies have established that nonionic polymers improve the surface activity of pulmonary surfactants by decreasing inactivation of surfactant. In this work, we investigate whether HA can also have beneficial effects when added to surfactants. We used a modified pulsating bubble surfactometer to measure mixtures of several commercially available pulmonary surfactants or native calf surfactant with and without serum inactivation. Surface properties such as equilibrium surface tension, minimum and maximum surface tensions on compression and expansion of a surface film, and degree of surface area reduction required to reach a surface tension of 10 mN/m were measured. In the presence of serum, addition of HA dramatically improved the surface activities of all four surfactants and in some cases in the absence of serum as well. These results indicate that HA reduces inactivation of surfactants caused by serum and add evidence that endogenous HAs may interact with alveolar surfactant under normal and abnormal conditions.

  14. 4-Methylumbelliferone inhibits hyaluronan synthesis by depletion of cellular UDP-glucuronic acid and downregulation of hyaluronan synthase 2 and 3

    Energy Technology Data Exchange (ETDEWEB)

    Kultti, Anne, E-mail: [Institute of Biomedicine, Anatomy, University of Kuopio, P.O.B. 1627, FIN-70211 Kuopio (Finland); Pasonen-Seppaenen, Sanna [Institute of Biomedicine, Anatomy, University of Kuopio, P.O.B. 1627, FIN-70211 Kuopio (Finland); Jauhiainen, Marjo [Department of Pharmaceutical Chemistry, University of Kuopio, FIN-70211 Kuopio (Finland); Rilla, Kirsi J.; Kaernae, Riikka; Pyoeriae, Emma; Tammi, Raija H.; Tammi, Markku I. [Institute of Biomedicine, Anatomy, University of Kuopio, P.O.B. 1627, FIN-70211 Kuopio (Finland)


    Hyaluronan accumulation on cancer cells and their surrounding stroma predicts an unfavourable disease outcome, suggesting that hyaluronan enhances tumor growth and spreading. 4-Methylumbelliferone (4-MU) inhibits hyaluronan synthesis and retards cancer spreading in experimental animals through mechanisms not fully understood. These mechanisms were studied in A2058 melanoma cells, MCF-7 and MDA-MB-361 breast, SKOV-3 ovarian and UT-SCC118 squamous carcinoma cells by analysing hyaluronan synthesis, UDP-glucuronic acid (UDP-GlcUA) content, and hyaluronan synthase (HAS) mRNA levels. The maximal inhibition in hyaluronan synthesis ranged 22-80% in the cell lines tested. Active glucuronidation of 4-MU produced large quantities of 4-MU-glucuronide, depleting the cellular UDP-GlcUA pool. The maximal reduction varied between 38 and 95%. 4-MU also downregulated HAS mRNA levels: HAS3 was 84-60% lower in MDA-MB-361, A2058 and SKOV-3 cells. HAS2 was the major isoenzyme in MCF-7 cells and lowered by 81%, similar to 88% in A2058 cells. These data indicate that both HAS substrate and HAS2 and/or HAS3 mRNA are targeted by 4-MU. Despite different target point sensitivities, the reduction of hyaluronan caused by 4-MU was associated with a significant inhibition of cell migration, proliferation and invasion, supporting the importance of hyaluronan synthesis in cancer, and the therapeutic potential of hyaluronan synthesis inhibition.

  15. Redefining Exploitation

    DEFF Research Database (Denmark)

    Agarwala, Rina


    -employed workers are organizing as workers. They are fighting labor exploitation by redefining the concept to include additional exploitation axes (from the state and middle class) and forms (including sexual). In doing so, they are redefining potential solutions, including identities and material benefits, to fit...... their unique needs. By expanding the category of “workers” beyond those defined by a narrow focus on a standard employer-employee relationship, these movements are also fighting exclusion from earlier labor protections by increasing the number of entitled beneficiaries. These struggles provide an important...

  16. Atomistic fingerprint of hyaluronan-CD44 binding

    DEFF Research Database (Denmark)

    Vuorio, Joni; Vattulainen, Ilpo; Martinez-Seara, Hector


    that hyaluronan can bind CD44 with three topographically different binding modes that in unison define an interaction fingerprint, thus providing a plausible explanation for the disagreement between the earlier studies. Our results confirm that the known crystallographic mode is the strongest of the three binding...

  17. Lubrication synergy: Mixture of hyaluronan and dipalmitoylphosphatidylcholine (DPPC) vesicles

    DEFF Research Database (Denmark)

    Raj, Akanksha; Wang, Min; Zander, Thomas


    with the outer shell of dipalmitoylphophatidylcholine (DPPC) vesicles in bulk solution. Further, we follow adsorption to silica from mixed hyaluronan/DPPC vesicle solution by Quartz Crystal Microbalance with Dissipation measurements. Atomic Force Microscope imaging visualises the adsorbed layer structure...... and partly removed from between the surfaces under high loads. These layers offer very low friction coefficient (

  18. Hyaluronan-coated nanoparticles: The influence of the molecular weight on CD44-hyaluronan interactions and on the immune response

    NARCIS (Netherlands)

    Mizrahy, S.; Rebe, S.; Hasgaard, M.; Liu, H.; Soffer-tsur, N.; Cohen, K.; Dvash, R.; Landsman, D.; Bremer, M.G.E.G.; Moghimi, S.M.; Peer, D.


    Hyaluronan (HA), a naturally occurring glycosaminoglycan, exerts different biological functions depending on its molecular weight ranging from 4000–10M Da. While high Mw HA (HMw-HA) is considered as anti-inflammatory, low Mw HA (LMw-HA) has been reported to activate an innate immune response. In

  19. Helicobacter pylori exploits a unique repertoire of type IV secretion system components for pilus assembly at the bacteria-host cell interface.

    Directory of Open Access Journals (Sweden)

    Carrie L Shaffer


    Full Text Available Colonization of the human stomach by Helicobacter pylori is an important risk factor for development of gastric cancer. The H. pylori cag pathogenicity island (cag PAI encodes components of a type IV secretion system (T4SS that translocates the bacterial oncoprotein CagA into gastric epithelial cells, and CagL is a specialized component of the cag T4SS that binds the host receptor α5β1 integrin. Here, we utilized a mass spectrometry-based approach to reveal co-purification of CagL, CagI (another integrin-binding protein, and CagH (a protein with weak sequence similarity to CagL. These three proteins are encoded by contiguous genes in the cag PAI, and are detectable on the bacterial surface. All three proteins are required for CagA translocation into host cells and H. pylori-induced IL-8 secretion by gastric epithelial cells; however, these proteins are not homologous to components of T4SSs in other bacterial species. Scanning electron microscopy analysis reveals that these proteins are involved in the formation of pili at the interface between H. pylori and gastric epithelial cells. ΔcagI and ΔcagL mutant strains fail to form pili, whereas a ΔcagH mutant strain exhibits a hyperpiliated phenotype and produces pili that are elongated and thickened compared to those of the wild-type strain. This suggests that pilus dimensions are regulated by CagH. A conserved C-terminal hexapeptide motif is present in CagH, CagI, and CagL. Deletion of these motifs results in abrogation of CagA translocation and IL-8 induction, and the C-terminal motifs of CagI and CagL are required for formation of pili. In summary, these results indicate that CagH, CagI, and CagL are components of a T4SS subassembly involved in pilus biogenesis, and highlight the important role played by unique constituents of the H. pylori cag T4SS.

  20. Extracellular processing of the cartilage proteoglycan aggregate and its effect on CD44-mediated internalization of hyaluronan. (United States)

    Danielson, Ben T; Knudson, Cheryl B; Knudson, Warren


    In many cells hyaluronan receptor CD44 mediates the endocytosis of hyaluronan and its delivery to endosomes/lysosomes. The regulation of this process remains largely unknown. In most extracellular matrices hyaluronan is not present as a free polysaccharide but often is found in complex with other small proteins and macromolecules such as proteoglycans. This is especially true in cartilage, where hyaluronan assembles into an aggregate structure with the large proteoglycan termed aggrecan. In this study when purified aggrecan was added to FITC-conjugated hyaluronan, no internalization of hyaluronan was detected. This suggested that the overall size of the aggregate prevented hyaluronan endocytosis and furthermore that proteolysis of the aggrecan was a required prerequisite for local, cell-based turnover of hyaluronan. To test this hypothesis, limited C-terminal digestion of aggrecan was performed to determine whether a size range of aggrecan exists that permits hyaluronan endocytosis. Our data demonstrate that only limited degradation of the aggrecan monomer was required to allow for hyaluronan internalization. When hyaluronan was combined with partially degraded, dansyl chloride-labeled aggrecan, blue fluorescent aggrecan was also visualized within intracellular vesicles. It was also determined that sonicated hyaluronan of smaller molecular size was internalized more readily than high molecular mass hyaluronan. However, the addition of intact aggrecan to hyaluronan chains sonicated for 5 and 10 s reblocked their endocytosis, whereas aggregates containing 15-s sonicated hyaluronan were internalized. These data suggest that hyaluronan endocytosis is regulated in large part by the extracellular proteolytic processing of hyaluronan-bound proteoglycan. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  1. Study of interactions between hyaluronan and cationic surfactants by means of calorimetry, turbidimetry, potentiometry and conductometry. (United States)

    Krouská, J; Pekař, M; Klučáková, M; Šarac, B; Bešter-Rogač, M


    The thermodynamics of the micelle formation of the cationic surfactants tetradecyltrimethylammonium bromide (TTAB) and cetyltrimethylammonium bromide (CTAB) with and without the addition of hyaluronan of two molecular weights was studied in aqueous solution by titration calorimetry. Macroscopic phase separation, which was detected by calorimetry and also by conductometry, occurs when charges on the surfactant and hyaluronan are balanced. In contrast, turbidimetry and potentiometry showed hyaluronan-surfactant interactions at very low surfactant concentrations. The observed differences between systems prepared with CTAB and TTAB indicate that besides the electrostatic interactions, which probably predominate, hydrophobic effects also play a significant role in hyaluronan interactions with cationic surfactants. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Hyaluronan-coated extracellular vesicles--a novel link between hyaluronan and cancer. (United States)

    Rilla, Kirsi; Siiskonen, Hanna; Tammi, Markku; Tammi, Raija


    The synthesis of hyaluronan (HA) on the plasma membrane is a unique and still partly mysterious way of macromolecular biosynthesis. HA forms pericellular coats around many cell types and accumulates in the extracellular matrix (ECM) of growing and renewing tissues. It is secreted to high concentrations in body fluids with antifriction properties like pleural, peritoneal, and synovial fluids, but is also detectable in plasma, saliva, and urine. In pathological states, like cancer and inflammation, the amount of HA is increased around cells, in the ECM, and in the body fluids. HA is an indicator of poor prognosis for cancer patients and creates a favorable environment for cellular growth and motility. The recent finding that HA-coated extracellular vesicles act both as a product of HA synthase activity and as special vehicles for HA, and perhaps carry signals important for malignant growth, provides a novel link between HA and cancer. HA could be carried on the surface of these vesicles in tissues and body fluids, creating beneficial environments by itself, or by associated molecules, for the invasion and metastasis of cancer cells. The HA-coated plasma membrane protrusions and vesicles shed from them are potential biomarkers in cancer and other HA-associated disease states. © 2014 Elsevier Inc. All rights reserved.

  3. Hyaluronan Tumor Cell Interactions in Prostate Cancer Growth and Survival (United States)


    hyaluronidase pretreatment or by using RNAi for the hyaluronan synthase enzymes expressed by these cells. The prediction, again, is that limiting HA...vertebrates and is not found in lower organisms or in insects (Fig. 9.2). Given its roles in such important cellular processes as motility and cell division in...cancer. Gut Zlobec, I., et al. (2008b). Node-negative colorectal cancer at high risk of distant metastasis identified by combined analysis of lymph

  4. Quantification and characterization of enzymatically produced hyaluronan with fluorophore-assisted carbohydrate electrophoresis

    NARCIS (Netherlands)

    Kooy, F.K.; Muyuan Ma,; Beeftink, H.H.; Eggink, G.; Tramper, J.; Boeriu, C.G.


    Hyaluronan (HA) is a polysaccharide with high-potential medical applications, depending on the chain length and the chain length distribution. Special interest goes to homogeneous HA oligosaccharides, which can be enzymatically produced using Pasteurella multocida hyaluronan synthase (PmHAS). We

  5. Hyaluronan-mediated aggregation of limb bud mesenchyme and mesenchymal condensation during chondrogenesis. (United States)

    Maleski, M P; Knudson, C B


    Cell condensations are the initial structures in the formation of proper cartilage and skeletal patterning in the developing vertebrate limb. Chondrogenic differentiation is dependent upon the cell-cell and/or cell-matrix interactions which take place during the condensation process. Coincident with the onset of condensation is the expression by limb mesenchyme of specific cell surface binding sites for the extracellular matrix macromolecule hyaluronan. The association of hyaluronan with the cell surface can influence the behavior of cells, especially cell aggregation. In this study the possible involvement of hyaluronan as an extracellular linker molecule in the cell-cell adhesion event during mesenchymal condensation was investigated in the avian limb model. Hyaluronan hexasaccharides were used to prevent the multivalent interactions that occur between native hyaluronan macromolecules and the cell surface. Our studies show that hyaluronan is required for early adhesive cell-cell interactions of limb bud mesenchyme and that perturbations of hyaluronan-cell interactions with hyaluronan hexasaccharides result in a delay in the formation of condensations as well as a delay in chondrogenic differentiation of mesenchymal cells in micromass cultures.

  6. Pertussis Toxin Exploits Host Cell Signaling Pathways Induced by Meningitis-Causing E. coli K1-RS218 and Enhances Adherence of Monocytic THP-1 Cells to Human Cerebral Endothelial Cells. (United States)

    Starost, Laura Julia; Karassek, Sascha; Sano, Yasuteru; Kanda, Takashi; Kim, Kwang Sik; Dobrindt, Ulrich; Rüter, Christian; Schmidt, Marcus Alexander


    Pertussis toxin (PTx), the major virulence factor of the whooping cough-causing bacterial pathogen Bordetella pertussis , permeabilizes the blood-brain barrier (BBB) in vitro and in vivo. Breaking barriers might promote translocation of meningitis-causing bacteria across the BBB, thereby facilitating infection. PTx activates several host cell signaling pathways exploited by the neonatal meningitis-causing Escherichia coli K1-RS218 for invasion and translocation across the BBB. Here, we investigated whether PTx and E. coli K1-RS218 exert similar effects on MAPK p38, NF-κB activation and transcription of downstream targets in human cerebral endothelial TY10 cells using qRT-PCR, Western blotting, and ELISA in combination with specific inhibitors. PTx and E. coli K1-RS218 activate MAPK p38, but only E. coli K1-RS218 activates the NF-κB pathway. mRNA and protein levels of p38 and NF-κB downstream targets including IL-6, IL-8, CxCL-1, CxCL-2 and ICAM-1 were increased. The p38 specific inhibitor SB203590 blocked PTx-enhanced activity, whereas E. coli K1-RS218's effects were inhibited by the NF-κB inhibitor Bay 11-7082. Further, we found that PTx enhances the adherence of human monocytic THP-1 cells to human cerebral endothelial TY10 cells, thereby contributing to enhanced translocation. These modulations of host cell signaling pathways by PTx and meningitis-causing E. coli support their contributions to pathogen and monocytic THP-1 cells translocation across the BBB.

  7. Herbivore exploits chink in armor of host (United States)

    Mites in the genus Raoiella Hirst are obligate plant parasites that feed via stylet-like mouthparts adapted to pierce plant tissues. A species of particular interest in this genus, the red palm mite, R. indica Hirst, is currently spreading aggressively throughout the Americas on species of palm (Ar...

  8. Inhibition of hyaluronan hydrolysis catalysed by hyaluronidase at high substrate concentration and low ionic strength. (United States)

    Astériou, Trias; Vincent, Jean-Claude; Tranchepain, Frédéric; Deschrevel, Brigitte


    Hyaluronidase and high levels of hyaluronan are found together in tumours. It is highly likely that hyaluronidase activity controls the balance between high molecular mass hyaluronan and oligosaccharides, and thus plays an important role in cancer development. The hyaluronan hydrolysis catalysed by bovine testicular hyaluronidase was studied as a model. The kinetics was investigated at pH 5 and 37 degrees C using the colorimetric N-acetyl-d-glucosamine reducing end assay method. While the substrate dependence obtained in the presence of 0.15 mol L(-1) ionic strength exhibited a Michaelis-Menten behaviour, an atypical behaviour was observed under low ionic strength: for increasing hyaluronan concentrations, the initial reaction rate increased, reached a maximum and then decreased to a very low level, close to zero at high substrate concentrations. One of the various hypotheses examined to explain this atypical behaviour is the formation of non-specific complexes between hyaluronan and hyaluronidase based on electrostatic interactions. This hypothesis is the only one that can explain all the experimental results including the variation of the reaction medium turbidity as a function of time and the influence on the initial reaction rate of the hyaluronan concentration over hyaluronidase concentration. However, phenomena such as the high viscosity of highly concentrated hyaluronan solutions or the steric exclusion of hyaluronidase from hyaluronan solutions may contribute to the atypical behaviour. Finally, the biological implications of the non-linear and non-monotonous shape of the hyaluronan-hyaluronidase substrate dependence in the regulation of the hyaluronan chain molecular mass are discussed, in particular in the case of cancer development.

  9. The exploitation of Gestalt principles by magicians. (United States)

    Barnhart, Anthony S


    Magicians exploit a host of psychological principles in deceiving their audiences. Psychologists have recently attempted to pinpoint the most common psychological tendencies exploited by magicians. This paper highlights two co-occurring principles that appear to be the basis for many popular magic tricks: accidental alignment and good continuation.

  10. Hyaluronan synthase 3 (HAS3) overexpression downregulates MV3 melanoma cell proliferation, migration and adhesion

    Energy Technology Data Exchange (ETDEWEB)

    Takabe, Piia, E-mail: [University of Eastern Finland, Institute of Biomedicine, 70211 Kuopio (Finland); Bart, Geneviève [University of Eastern Finland, Institute of Biomedicine, 70211 Kuopio (Finland); Ropponen, Antti [University of Eastern Finland, Institute of Clinical Medicine, 70211 Kuopio (Finland); Rilla, Kirsi; Tammi, Markku; Tammi, Raija; Pasonen-Seppänen, Sanna [University of Eastern Finland, Institute of Biomedicine, 70211 Kuopio (Finland)


    Malignant skin melanoma is one of the most deadly human cancers. Extracellular matrix (ECM) influences the growth of malignant tumors by modulating tumor cells adhesion and migration. Hyaluronan is an essential component of the ECM, and its amount is altered in many tumors, suggesting an important role for hyaluronan in tumorigenesis. Nonetheless its role in melanomagenesis is not understood. In this study we produced a MV3 melanoma cell line with inducible expression of the hyaluronan synthase 3 (HAS3) and studied its effect on the behavior of the melanoma cells. HAS3 overexpression expanded the cell surface hyaluronan coat and decreased melanoma cell adhesion, migration and proliferation by cell cycle arrest at G1/G0. Melanoma cell migration was restored by removal of cell surface hyaluronan by Streptomyces hyaluronidase and by receptor blocking with hyaluronan oligosaccharides, while the effect on cell proliferation was receptor independent. Overexpression of HAS3 decreased ERK1/2 phosphorylation suggesting that inhibition of MAP-kinase signaling was responsible for these suppressive effects on the malignant phenotype of MV3 melanoma cells. - Highlights: • Inducible HAS3-MV3 melanoma cell line was generated using Lentiviral transduction. • HAS3 overexpression inhibits MV3 cell migration via hyaluronan–receptor interaction. • HAS3 overexpression decreases MV3 melanoma cell proliferation and adhesion. • ERK1/2 phosphorylation is downregulated by 50% in HAS3 overexpressing cells. • The results suggest that hyaluronan has anti-cancer like effects in melanoma.

  11. Evaluation of hyaluronan gel (Gengigel(®) ) as a topical applicant in the treatment of gingivitis. (United States)

    Sapna, Nadiger; Vandana, Kharidi Laxman


      To clinically and histopathologically evaluate the anti-inflammatory effect of 0.2% hyaluronan gel alone and with mechanical therapy on gingivitis. The argyrophilic nucleolar organizer region staining technique was attempted to routinely determine its diagnostic and prognostic dependability for periodontal lesions.   In each of the 28 gingivitis patients, the four quadrants were subjected to different treatments: scaling, scaling + topical hyaluronan gel, only topical hyaluronan gel, and topical + intrasulcular hyaluronan gel. Clinical parameters were recorded at baseline, and on days 7, 14, and 21. Biopsies were taken from each quadrant, inflammatory infiltrates were graded, and the argyrophilic nucleolar organizer region count was measured before and after treatment.   A significant reduction was seen in clinical parameters, inflammatory infiltrates, and the argyrophilic nucleolar organizer region count within the groups. The effect of topical + intrasulcular gel was equivalent to scaling (P > 0.05). Topical + intrasulcular hyaluronan gel application demonstrated a better reduction than topical hyaluronan gel alone.   Hyaluronan gel is an effective topical agent for treating gingivitis, along with scaling and intrasulcular application. The argyrophilic nucleolar organizer region count can be used as a histopathological indicator in cases of non-responsive gingivitis to assess the severity of gingival inflammation. © 2011 Blackwell Publishing Asia Pty Ltd.

  12. Effect of Carboxymethylation on the Rheological Properties of Hyaluronan.

    Directory of Open Access Journals (Sweden)

    Rian J Wendling

    Full Text Available Chemical modifications made to hyaluronan to enable covalent crosslinking to form a hydrogel or to attach other molecules may alter the physical properties as well, which have physiological importance. Here we created carboxymethyl hyaluronan (CMHA with varied degree of modification and investigated the effect on the viscosity of CMHA solutions. Viscosity decreased initially as modification increased, with a minimum viscosity for about 30-40% modification. This was followed by an increase in viscosity around 45-50% modification. The pH of the solution had a variable effect on viscosity, depending on the degree of carboxymethyl modification and buffer. The presence of phosphates in the buffer led to decreased viscosity. We also compared large-scale production lots of CMHA to lab-scale and found that large-scale required extended reaction times to achieve the same degree of modification. Finally, thiolated CMHA was disulfide crosslinked to create hydrogels with increased viscosity and shear-thinning aspects compared to CMHA solutions.

  13. Methacrylated gelatin/hyaluronan-based hydrogels for soft tissue engineering (United States)

    Kessler, Lukas; Gehrke, Sandra; Winnefeld, Marc; Huber, Birgit; Hoch, Eva; Walter, Torsten; Wyrwa, Ralf; Schnabelrauch, Matthias; Schmidt, Malte; Kückelhaus, Maximilian; Lehnhardt, Marcus; Hirsch, Tobias; Jacobsen, Frank


    In vitro–generated soft tissue could provide alternate therapies for soft tissue defects. The aim of this study was to evaluate methacrylated gelatin/hyaluronan as scaffolds for soft tissue engineering and their interaction with human adipose–derived stem cells (hASCs). ASCs were incorporated into methacrylated gelatin/hyaluronan hydrogels. The gels were photocrosslinked with a lithium phenyl-2,4,6-trimethylbenzoylphosphinate photoinitiator and analyzed for cell viability and adipogenic differentiation of ASCs over a period of 30 days. Additionally, an angiogenesis assay was performed to assess their angiogenic potential. After 24 h, ASCs showed increased viability on composite hydrogels. These results were consistent over 21 days of culture. By induction of adipogenic differentiation, the mature adipocytes were observed after 7 days of culture, their number significantly increased until day 28 as well as expression of fatty acid binding protein 4 and adiponectin. Our scaffolds are promising as building blocks for adipose tissue engineering and allowed long viability, proliferation, and differentiation of ASCs. PMID:29318000

  14. Electrospun Hyaluronan-Gelatin Nanofibrous Matrix for Nerve Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Hau-Min Liou


    Full Text Available Schwann cells play a critical role in the repair of the peripheral nerve. The goal of this study was to fabricate electrospun gelatin (Gel and hyaluronan-gelatin (HA-Gel composite nanofibers to provide a suitable growth environment for Schwann cells. The fiber diameters of Gel, 0.5 HA-Gel, 1 HA-Gel, and 1.5 HA-Gel were 130 ± 30 nm, 294 ± 87 nm, 362 ± 129 nm, and 224 ± 54 nm, respectively. The biological performance of Gel and HA-Gel was evaluated using an in vitro culture of RT4-D6P2T rat Schwann cells. We found that the cell attachment and proliferation rates were not significantly different on these matrices. However, the Schwann cells displayed better organized F-actin on HA-Gel than on Gel. Moreover, the expression levels of several genes, including Nrg1, GFAP, and P0, were significantly higher on HA-Gel than on Gel. In addition, the levels of Nrg1 and P0 protein expression were also higher on the HA-Gel than on Gel. These results indicate that the hyaluronan-gelatin composite nanofibrous matrix could potentially be used in peripheral nerve repair.

  15. Splanchnic and renal extraction of circulating hyaluronan in patients with alcoholic liver disease

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik; Bentsen, K D; Laurent, T C


    Splanchnic and renal extraction of hyaluronan was determined in patients with alcoholic cirrhosis (n = 9), non-cirrhotic alcoholic liver disease (n = 5), and controls without liver disease (n = 19) in the supine fasting condition. Arterial plasma concentration of hyaluronan was significantly...... increased in patients with cirrhosis (mean 480 micrograms/l) as compared to non-cirrhotic patients (29 micrograms/l, P less than 0.001) and controls (25 micrograms/l, P less than 0.001), whereas no difference was present between the two last-mentioned groups. In patients with liver disease, circulating...... pressure. In patients with alcoholic liver disease no significant renal hyaluronan extraction was found as compared to an extraction ratio of 0.17 in controls (P less than 0.05). Our results suggest that the increased level of circulating endogenous hyaluronan found in patients with cirrhosis is caused...

  16. Influence of serum albumin on intracellular delivery of drug-loaded hyaluronan polymeric micelles

    Czech Academy of Sciences Publication Activity Database

    Nešporová, K.; Sogorková, J.; Smejkalova, D.; Kulhánek, J.; Huerta-Angeles, G.; Kubala, Lukáš; Velebný, V.


    Roč. 511, č. 1 (2016), s. 638-647 ISSN 0378-5173 Institutional support: RVO:68081707 Keywords : Polymeric micelle * Hyaluronan * Fatty acid Subject RIV: BO - Biophysics Impact factor: 3.649, year: 2016

  17. Hyaluronan with dextran added to therapeutic lung surfactants improves effectiveness in vitro and in vivo. (United States)

    Lu, Karen W; Taeusch, H William; Clements, John A


    Surfactants in current clinical use are largely ineffective in treating acute lung injury (ALI)/ acute respiratory distress syndrome. In part, this ineffectiveness is due to inactivation of surfactant by serum leakage into the alveoli. Previously, we reported that adding hyaluronan and some nonionic polymers to synthetic lipids combined with native SP-B and SP-C enhanced surface activity. In this study, we first tested two therapeutic lung surfactants and then retested after adding hyaluronan, polyethylene glycol or dextran alone or in two-polymer combinations including hyaluronan in the absence or presence of serum. Surface activities were measured in a modified bubble surfactometer. Results indicate that the inhibition threshold (defined as the amount of serum required to produce a minimum surface tension above 10 mN/m after 5 minutes of cycling) was 35 times higher with hyaluronan plus dextran added to Infasurf than with Infasurf alone, and better than all other mixtures tested. The threshold for Survanta with hyaluronan plus polyethylene glycol was 7 times higher than Survanta alone. We next tested selected surfactant mixtures in an animal model that mimicked ALI. All measurements of lung function showed significant improvement (P ≤ .05) with hyaluronan, or with hyaluronan and dextran added to Infasurf compared to Infasurf alone. Also, for these two groups, lung function was still improving at the end of the experiment. We conclude that certain polymers added to clinical surfactants can greatly increase resistance to inactivation in vitro, while in vivo, both Infasurf mixtures containing hyaluronan tended to normalize measures of lung function unlike other mixtures tested.

  18. A Hyaluronan-Based Scaffold for the in Vitro Construction of Dental Pulp-Like Tissue

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    Letizia Ferroni


    Full Text Available Dental pulp tissue supports the vitality of the tooth, but it is particularly vulnerable to external insults, such as mechanical trauma, chemical irritation or microbial invasion, which can lead to tissue necrosis. In the present work, we present an endodontic regeneration method based on the use of a tridimensional (3D hyaluronan scaffold and human dental pulp stem cells (DPSCs to produce a functional dental pulp-like tissue in vitro. An enriched population of DPSCs was seeded onto hyaluronan-based non-woven meshes in the presence of differentiation factors to induce the commitment of stem cells to neuronal, glial, endothelial and osteogenic phenotypes. In vitro experiments, among which were gene expression profiling and immunofluorescence (IF staining, proved the commitment of DPSCs to the main components of dental pulp tissue. In particular, the hyaluronan-DPSCs construct showed a dental pulp-like morphology consisting of several specialized cells growing inside the hyaluronan fibers. Furthermore, these constructs were implanted into rat calvarial critical-size defects. Histological analyses and gene expression profiling performed on hyaluronan-DPSCs grafts showed the regeneration of osteodentin-like tissue. Altogether, these data suggest the regenerative potential of the hyaluronan-DPSC engineered tissue.

  19. Priming Adipose-Derived Mesenchymal Stem Cells with Hyaluronan Alters Growth Kinetics and Increases Attachment to Articular Cartilage

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    Peter Succar


    Full Text Available Background. Biological therapeutics such as adipose-derived mesenchymal stem cell (MSC therapy are gaining acceptance for knee-osteoarthritis (OA treatment. Reports of OA-patients show reductions in cartilage defects and regeneration of hyaline-like-cartilage with MSC-therapy. Suspending MSCs in hyaluronan commonly occurs in animals and humans, usually without supporting data. Objective. To elucidate the effects of different concentrations of hyaluronan on MSC growth kinetics. Methods. Using a range of hyaluronan concentrations, we measured MSC adherence and proliferation on culture plastic surfaces and a novel cartilage-adhesion assay. We employed time-course and dispersion imaging to assess MSC binding to cartilage. Cytokine profiling was also conducted on the MSC-secretome. Results. Hyaluronan had dose-dependent effects on growth kinetics of MSCs at concentrations of entanglement point (1 mg/mL. At higher concentrations, viscosity effects outweighed benefits of additional hyaluronan. The cartilage-adhesion assay highlighted for the first time that hyaluronan-primed MSCs increased cell attachment to cartilage whilst the presence of hyaluronan did not. Our time-course suggested patients undergoing MSC-therapy for OA could benefit from joint-immobilisation for up to 8 hours. Hyaluronan also greatly affected dispersion of MSCs on cartilage. Conclusion. Our results should be considered in future trials with MSC-therapy using hyaluronan as a vehicle, for the treatment of OA.

  20. Hyaluronan-Inorganic Nanohybrid Materials for Biomedical Applications. (United States)

    Cai, Zhixiang; Zhang, Hongbin; Wei, Yue; Cong, Fengsong


    Nanomaterials, including gold, silver, and magnetic nanoparticles, carbon, and mesoporous materials, possess unique physiochemical and biological properties, thus offering promising applications in biomedicine, such as in drug delivery, biosensing, molecular imaging, and therapy. Recent advances in nanotechnology have improved the features and properties of nanomaterials. However, these nanomaterials are potentially cytotoxic and demonstrate a lack of cell-specific function. Thus, they have been functionalized with various polymers, especially polysaccharides, to reduce toxicity and improve biocompatibility and stability under physiological conditions. In particular, nanomaterials have been widely functionalized with hyaluronan (HA) to enhance their distribution in specific cells and tissues. This review highlights the most recent advances on HA-functionalized nanomaterials for biotechnological and biomedical applications, as nanocarriers in drug delivery, contrast agents in molecular imaging, and diagnostic agents in cancer therapy. A critical evaluation of barriers affecting the use of HA-functionalized nanomaterials is also discussed, and insights into the outlook of the field are explored.

  1. Hyaluronan synthases (HAS1-3 and hyaluronidases (HYAL1-2 in the accumulation of hyaluronan in endometrioid endometrial carcinoma

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    Kosma Veli-Matti


    Full Text Available Abstract Background Hyaluronan accumulation correlates with the degree of malignancy in many solid tumor types, including malignant endometrial carcinomas. To elucidate the mechanism of hyaluronan accumulation, we examined the expression levels of the hyaluronan synthases (HAS1, HAS2 and HAS3 and hyaluronidases (HYAL1 and HYAL2, and correlated them with hyaluronan content and HAS1-3 immunoreactivity. Methods A total of 35 endometrial tissue biopsies from 35 patients, including proliferative and secretory endometrium (n = 10, post-menopausal proliferative endometrium (n = 5, complex atypical hyperplasia (n = 4, grade 1 (n = 8 and grade 2 + 3 (n = 8 endometrioid adenocarcinomas were divided for gene expression by real-time RT-PCR, and paraffin embedded blocks for hyaluronan and HAS1-3 cytochemistry. Results The mRNA levels of HAS1-3 were not consistently changed, while the immunoreactivity of all HAS proteins was increased in the cancer epithelium. Interestingly, HAS3 mRNA, but not HAS3 immunoreactivity, was increased in post-menopausal endometrium compared to normal endometrium (p = 0.003. The median of HYAL1 mRNA was 10-fold and 15-fold lower in both grade 1 and grade 2+3 endometrioid endometrial cancers, as compared to normal endometrium (p = 0.004-0.006, and post-menopausal endometrium (p = 0.002, respectively. HYAL2 mRNA was also reduced in cancer (p = 0.02 and correlated with HYAL1 (r = 0.8, p = 0.0001. There was an inverse correlation between HYAL1 mRNA and the epithelial hyaluronan staining intensity (r = -0.6; P = 0.001. Conclusion The results indicated that HYAL1 and HYAL2 were coexpressed and significantly downregulated in endometrioid endometrial cancer and correlated with the accumulation of hyaluronan. While immunoreactivity for HASs increased in the cancer cells, tumor mRNA levels for HASs were not changed, suggesting that reduced turnover of HAS protein may also have contributed to the accumulation of hyaluronan.

  2. Human Milk Hyaluronan Enhances Innate Defense of the Intestinal Epithelium* (United States)

    Hill, David R.; Rho, Hyunjin K.; Kessler, Sean P.; Amin, Ripal; Homer, Craig R.; McDonald, Christine; Cowman, Mary K.; de la Motte, Carol A.


    Breast-feeding is associated with enhanced protection from gastrointestinal disease in infants, mediated in part by an array of bioactive glycan components in milk that act through molecular mechanisms to inhibit enteric pathogen infection. Human milk contains hyaluronan (HA), a glycosaminoglycan polymer found in virtually all mammalian tissues. We have shown that synthetic HA of a specific size range promotes expression of antimicrobial peptides in intestinal epithelium. We hypothesize that hyaluronan from human milk also enhances innate antimicrobial defense. Here we define the concentration of HA in human milk during the first 6 months postpartum. Importantly, HA isolated from milk has a biological function. Treatment of HT-29 colonic epithelial cells with human milk HA at physiologic concentrations results in time- and dose-dependent induction of the antimicrobial peptide human β-defensin 2 and is abrogated by digestion of milk HA with a specific hyaluronidase. Milk HA induction of human β-defensin 2 expression is also reduced in the presence of a CD44-blocking antibody and is associated with a specific increase in ERK1/2 phosphorylation, suggesting a role for the HA receptor CD44. Furthermore, oral administration of human milk-derived HA to adult, wild-type mice results in induction of the murine Hβ D2 ortholog in intestinal mucosa and is dependent upon both TLR4 and CD44 in vivo. Finally, treatment of cultured colonic epithelial cells with human milk HA enhances resistance to infection by the enteric pathogen Salmonella typhimurium. Together, our observations suggest that maternally provided HA stimulates protective antimicrobial defense in the newborn. PMID:23950179

  3. Human mesenchymal stem cells secrete hyaluronan-coated extracellular vesicles. (United States)

    Arasu, Uma Thanigai; Kärnä, Riikka; Härkönen, Kai; Oikari, Sanna; Koistinen, Arto; Kröger, Heikki; Qu, Chengjuan; Lammi, Mikko J; Rilla, Kirsi


    Extracellular vesicles (EVs) secreted by stem cells are potential factors mediating tissue regeneration. They travel from bone marrow stem cells into damaged tissues, suggesting that they can repair tissue injuries without directly replacing parenchymal cells. We have discovered that hyaluronan (HA) synthesis is associated with the shedding of HA-coated EVs. The aim of this study was to test whether bone marrow-derived hMSCs secrete HA-coated EVs. The EVs secreted by MSCs were isolated by differential centrifugation and characterized by nanoparticle tracking analysis. Their morphology and budding mechanisms were inspected by confocal microscopy and correlative light and electron microscopy. Hyaluronan synthesis of hMSCs was induced by lipopolysaccharide and inhibited by RNA interference and 4-methylumbelliferone. It was found that the MSCs have extremely long apical and lateral HA-coated filopodia, typical for cells with an active HA secretion. Additionally, they secreted HA-coated EVs carrying mRNAs for CD44 and all HAS isoforms. The results show that stem cells have a strong intrinsic potential for HA synthesis and EV secretion, and the amount of HA carried on EVs reflects the HA content of the original cells. These results show that the secretion of HA-coated EVs by hMSCs is a general process, that may contribute to many of the mechanisms of HA-mediated tissue regeneration. Additionally, an HA coat on EVs may regulate their interactions with target cells and participate in extracellular matrix remodeling. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. The Ethics of Exploitation

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    Paul McLaughlin


    Full Text Available Philosophical inquiry into exploitation has two major deficiencies to date: it assumes that exploitation is wrong by definition; and it pays too much attention to the Marxian account of exploitation. Two senses of exploitation should be distinguished: the ‘moral’ or pejorative sense and the ‘non-moral’ or ‘non-prejudicial’ sense. By demonstrating the conceptual inadequacy of exploitation as defined in the first sense, and by defining exploitation adequately in the latter sense, we seek to demonstrate the moral complexity of exploitation. We contend, moreover, that moral evaluation of exploitation is only possible once we abandon a strictly Marxian framework and attempt, in the long run, to develop an integral ethic along Godwinian lines.

  5. Synthesis of ¹³C-labeled and functionalized Hyaluronan derivatives for biophysical studies and surface modifications. (United States)

    Rigol, Stephan; Xia, Liang; Giannis, Athanassios


    A convergent synthesis of a tetrasaccharide partial sequence of (13)C-labeled Hyaluronan is presented. This tetrasaccharide can be used for biophysical studies as well as for surface modifications. Furthermore, tetrasaccharide 7 can be employed for the synthesis of additionally labeled higher oligomers of Hyaluronan on the basis of the presented methodology. Copyright © 2012 Elsevier Ltd. All rights reserved.

  6. Modulation of Hyaluronan Synthesis by the Interaction between Mesenchymal Stem Cells and Osteoarthritic Chondrocytes

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    Eliane Antonioli


    Full Text Available Bone marrow mesenchymal stem cells (BM-MSCs are considered a good source for cellular therapy in cartilage repair. But, their potential to repair the extracellular matrix, in an osteoarthritic environment, is still controversial. In osteoarthritis (OA, anti-inflammatory action and extracellular matrix production are important steps for cartilage healing. This study examined the interaction of BM-MSC and OA-chondrocyte on the production of hyaluronan and inflammatory cytokines in a Transwell system. We compared cocultured BM-MSCs and OA-chondrocytes with the individually cultured controls (monocultures. There was a decrease in BM-MSCs cell count in coculture with OA-chondrocytes when compared to BM-MSCs alone. In monoculture, BM-MSCs produced higher amounts of hyaluronan than OA-chondrocytes and coculture of BM-MSCs with OA-chondrocytes increased hyaluronan production per cell. Hyaluronan synthase-1 mRNA expression was upregulated in BM-MSCs after coculture with OA-chondrocytes, whereas hyaluronidase-1 was downregulated. After coculture, lower IL-6 levels were detected in BM-MSCs compared with OA-chondrocytes. These results indicate that, in response to coculture with OA-chondrocytes, BM-MSCs change their behavior by increasing production of hyaluronan and decreasing inflammatory cytokines. Our results indicate that BM-MSCs per se could be a potential tool for OA regenerative therapy, exerting short-term effects on the local microenvironment even when cell:cell contact is not occurring.

  7. Hyaluronan-positive plasma membrane protrusions exist on mesothelial cells in vivo. (United States)

    Koistinen, Ville; Jokela, Tiina; Oikari, Sanna; Kärnä, Riikka; Tammi, Markku; Rilla, Kirsi


    Previous observations of our research group showed that HAS2 and HAS3 overexpression in cultured cells induces the formation of long and numerous microvillus-like cell protrusions, which are present also in cultured cell types with naturally high hyaluronan secretion and the cell protrusions resemble those found in mesothelial cells. The aim of this study was to investigate whether these hyaluronan secreting, actin-dependent protrusions exist also in vivo. It was found that rat mesothelium in vivo is positive for hyaluronan and Has1-3. Also microvilli in rat mesothelium and live primary cultures of mesothelial cells were found to be hyaluronan positive, and the cells expressed all Has isoforms. Furthermore, ultrastructure of the cell protrusions in rat mesothelium was similar to that induced by overexpression of HAS2 and HAS3, and the number and orientation of actin filaments supporting the cell protrusions was identical. The results of this study show that HA-positive protrusions exist in vivo and support the idea that hyaluronan secretion from plasma membrane protrusions is a general process. This mechanism is potentially crucial for the normal function and maintenance of tissues and body fluids and may be utilized in many therapeutic applications.

  8. Mechanical Properties of Tyramine Substituted-Hyaluronan Enriched Fascia Extracellular Matrix (United States)

    Chin, LiKang; Calabro, Anthony; Walker, Esteban; Derwin, Kathleen A.


    Naturally-occurring biomaterial scaffolds derived from extracellular matrix (ECM) have been the topic of recent investigation in the context of rotator cuff tendon repair. We previously reported a method to treat fascia ECM with high molecular weight tyramine substituted-hyaluronan (TS-HA) for use as a tendon augmentation scaffold. The presence of cross-linked TS-HA in fascia was associated with an increased macrophage and giant cell response compared to water treated controls after implantation in a rat abdominal wall model. The objective of this study was to determine the extent to which TS-HA treatment was associated with mechanical property changes of fascia after implantation in the rat model. Fascia samples in all groups demonstrated time-dependent decreases in mechanical properties. TS-HA treated fascia with cross-linking exhibited a lower toe modulus, a trend toward lower toe stiffness, and a higher transition strain than water treated controls not only after implantation, but also at time zero. TS-HA treatment, with or without cross-linking, had no significant effect on time-zero or post-implantation load relaxation ratio, load relaxation rate, linear-region stiffness, or linear-region modulus. Our findings demonstrated that the particular TS-HA treatment employed in this study decreased the low-load elastic mechanical properties of fascia ECM, in keeping with the heightened macrophage and giant cell host response seen previously. This work provides a starting point and guidance for investigating alternative HA treatment strategies. PMID:22238019

  9. Reductions of phospholipase A(2) inhibition of pulmonary surfactant with hyaluronan. (United States)

    Iwanicki, Janetta L; Lu, Karen W; Taeusch, H William


    In acute lung injuries, secretory phospholipase A(2) (sPLA(2)) inhibits surfactants by hydrolyzing phospholipids. Because hyaluronan (HA) reduces hydrolysis of phospholipids by sPLA(2), and because sPLA(2) inhibits surfactant in vitro, the authors hypothesized HA would reduce sPLA(2) inhibition. Surfactants were used alone or mixed with HA and/or sPLA(2) then tested for surface activity in 2 separate assays, or for sPLA(2) activity. Equilibrium surface pressures were identical for surfactant with or without HA. sPLA(2) inhibited surface activity but this inhibitory effect was reduced with HA by 14% in the spreading trough and by 63% in a modified bubble surfactometer. Hyaluronan caused a modest reduction (39%) of sPLA(2) breakdown of labeled phospholipid. Therefore hyaluronan reduces inhibition of surfactants by sPLA(2) in vitro, and reduces the activity of the enzyme.

  10. Splanchnic and renal extraction of circulating hyaluronan in patients with alcoholic liver disease

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik Sahl; Bentsen, K D; Laurent, T C


    extraction ratio (arterio-hepatic venous extraction ratio) had a mean value of 0.14 in patients with cirrhosis as compared to 0.36 in non-cirrhotic patients (P less than 0.05) and 0.34 in controls (P less than 0.025). Splanchnic hyaluronan extraction was not correlated to liver function tests or portal......Splanchnic and renal extraction of hyaluronan was determined in patients with alcoholic cirrhosis (n = 9), non-cirrhotic alcoholic liver disease (n = 5), and controls without liver disease (n = 19) in the supine fasting condition. Arterial plasma concentration of hyaluronan was significantly...... increased in patients with cirrhosis (mean 480 micrograms/l) as compared to non-cirrhotic patients (29 micrograms/l, P less than 0.001) and controls (25 micrograms/l, P less than 0.001), whereas no difference was present between the two last-mentioned groups. In patients with liver disease, circulating...

  11. The Rise and Fall of Hyaluronan in Respiratory Diseases

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    Mark E. Lauer


    Full Text Available In normal airways, hyaluronan (HA matrices are primarily located within the airway submucosa, pulmonary vasculature walls, and, to a lesser extent, the alveoli. Following pulmonary injury, elevated levels of HA matrices accumulate in these regions, and in respiratory secretions, correlating with the extent of injury. Animal models have provided important insight into the role of HA in the onset of pulmonary injury and repair, generally indicating that the induction of HA synthesis is an early event typically preceding fibrosis. The HA that accumulates in inflamed airways is of a high molecular weight (>1600 kDa but can be broken down into smaller fragments (<150 kDa by inflammatory and disease-related mechanisms that have profound effects on HA pathobiology. During inflammation in the airways, HA is often covalently modified with heavy chains from inter-alpha-inhibitor via the enzyme tumor-necrosis-factor-stimulated-gene-6 (TSG-6 and this modification promotes the interaction of leukocytes with HA matrices at sites of inflammation. The clearance of HA and its return to normal levels is essential for the proper resolution of inflammation. These data portray HA matrices as an important component of normal airway physiology and illustrate its integral roles during tissue injury and repair among a variety of respiratory diseases.

  12. Hyaluronan Immobilized Polyurethane as a Blood Contacting Material

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    Feirong Gong


    Full Text Available Hyaluronan (hyaluronic acid, HA was immobilized onto the surface of amino-functionalized polyurethane films with the goal of obtaining a novel kind of biomaterial which had the potential in blood-contacting applications. The amino-functionalized polyurethane was prepared by synthesized acidic polyurethane whose pendant carboxyl groups were treated with an excess amount of 1,3-diaminopropane in the presence of N,N-carbonyldiimidazole (CDI. Attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR, Raman spectroscopy (RS, scanning electron microscopy (SEM, and water contact angle measurement were used to confirm the surface changes at each step of treatment, both in morphologies and chemical compositions. APTT and PT results showed that HA immobilization could prolong the blood coagulation time, thus HA-immobilized polyurethane (PU-HA exhibited improved blood compatibility. Cytotoxicity analysis showed that the PU-HA films synthesized in this study were cytocompatible and could support human vein endothelial cells (HUVECs adhesion and proliferation.

  13. Hydration of hyaluronan: effects on structural and thermodynamic properties. (United States)

    Albèr, Cathrine; Engblom, Johan; Falkman, Peter; Kocherbitov, Vitaly


    Hyaluronan (HA) is a frequently occurring biopolymer with a large variety of functions in nature. During the past 60 years, there have been numerous reports on structural and dynamic behavior of HA in water. Nevertheless, studies covering a wider concentration range are still lacking. In this work, we use isothermal scanning sorption calorimetry for the first time to investigate hydration-induced transitions in HA (sodium hyaluronate, 17 kDa). From this method, we obtain the sorption isotherm and the enthalpy and the entropy of hydration. Thermotropic events are evaluated by differential scanning calorimetry (DSC), and structure analysis is performed with X-ray scattering (SWAXS) and light and scanning electron microscopy. During isothermal hydration, HA exhibits a glass transition, followed by crystallization and subsequent dissolution of HA crystals and formation of a one-phase solution. Structural analysis reveals that the crystal may be indexed on an orthorhombic unit cell with space group P212121. Crystallization of HA was found to occur either through endothermic or exothermic processes, depending on the temperature and water content. We propose a mechanism of crystallization that explains this phenomenon based on the interplay between the hydrophobic effect and strengthening of hydrogen bonds during formation of crystals. The combined results were used to construct a binary phase diagram for the HA-water system.

  14. Regulation and roles of the hyaluronan system in mammalian reproduction. (United States)

    Fouladi-Nashta, Ali A; Raheem, Kabir A; Marei, Waleed F; Ghafari, Fataneh; Hartshorne, Geraldine M


    Hyaluronan (HA) is a non-sulphated glycosaminoglycan polymer naturally occurring in many tissues and fluids of mammals, including the reproductive system. Its biosynthesis by HA synthase (HAS1-3) and catabolism by hyaluronidases (HYALs) are affected by ovarian steroid hormones. Depending upon its molecular size, HA functions both as a structural component of tissues in the form of high-molecular-weight HA or as a signalling molecule in the form of small HA molecules or HA fragments with effects mediated through interaction with its specific cell-membrane receptors. HA is produced by oocytes and embryos and in various segments of the reproductive system. This review provides information about the expression and function of members of the HA system, including HAS, HYALs and HA receptors. We examine their role in various processes from folliculogenesis through oocyte maturation, fertilisation and early embryo development, to pregnancy and cervical dilation, as well as its application in assisted reproduction technologies. Particular emphasis has been placed upon the role of the HA system in pre-implantation embryo development and embryo implantation, for which we propose a hypothetical sequential model. © 2017 Society for Reproduction and Fertility.

  15. Hyaluronan induces odontoblastic differentiation of dental pulp stem cells via CD44. (United States)

    Umemura, Naoki; Ohkoshi, Emika; Tajima, Masamichi; Kikuchi, Hirotaka; Katayama, Tadashi; Sakagami, Hiroshi


    Dental pulp tissue contains many undifferentiated mesenchymal cells, which retain the ability to differentiate into mature cells. Induced pluripotent stem cells have been developed from various cell sources, including dental pulp-derived stem cells, and evaluated for potential application to regenerative therapy. Dental pulp tissues overexpress CD44, a cell-adhesion factor involved in the induction of mineralization. In this study, we investigated the effects of hyaluronan-a known CD44 ligand-on dental pulp stem cells (DPSCs). DPSC CD44 expression was analyzed using immunofluorescence staining, flow cytometry, and western blotting. Cell proliferation was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Effects of hyaluronan on the cell cycle were analyzed by flow cytometry. Alkaline phosphatase activity was employed as marker of mineralization and measured by fluorometric quantification and western blotting. Bone morphogenetic protein (BMP)-2, BMP-4, dentin sialophosphoprotein (DSPP), and dentin matrix acidic phosphoprotein 1 (DMP-1) levels were measured using real-time polymerase chain reaction. Odontoblastic differentiation and the close cell signaling examination of DPSC differentiation were determined using western blotting. Hyaluronan induced expression of the odontoblastic differentiation markers DMP-1 and DSPP. Moreover, the odontoblastic differentiation induced by hyaluronan was mediated by CD44-but not by Akt, Smad1 or MAPK signaling. Our results indicate that hyaluronan induces odontoblastic differentiation of DPSCs via CD44. This suggests that hyaluronan plays a crucial role in the induction of odontoblastic differentiation from DPSCs. Our findings may aid the development of new, inexpensive, and effective conservative treatments for dental pulp repair.

  16. Exploitability Assessment with TEASER (United States)


    exploits. We saw this as an advantage of our dataset because we had to confirm that either a bug was exploitable or not exploitable. For the 28 CHAPTER 5...corruption which demonstrates that there is very little activity within c-ares to take advantage of after the heap corruption. This idea is in line with the...remote code execution POCs. 42 Bibliography [1] Analyze crashes to find security vulnerabilities in your apps . https: //

  17. Anthropology of sexual exploitation

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    Lalić Velibor


    Full Text Available In this paper, the authors observe sexual exploitation from an anthropological perspective. They analyze the rational, ethical, emotional and mythological dimensions of human sexuality. Consequently, after setting the phenomenon in a social and historical context, sexual exploitation is closely observed in the contemporary age. Based on thoughts of relevant thinkers, they make the conclusion that the elimination of sexual exploitation is not an utterly legal issue, but political and economical issues as well. Namely, legal norms are not sufficient to overcome sexual exploitation, but, political and economical relationships in contemporary societies, which will be based on sincere equal opportunities must be established.


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    Ivan Cotman


    Full Text Available The processes of forming, petrography, features, properties and exploitation of granite boulders are described. The directional drilling and black powder blasting is the succesful method in exploitation of granite boulders (boulder technology (the paper is published in Croatian.

  19. Hyaluronan Does Not Affect Bupivacaine’s Inhibitory Action on Voltage-Gated Potassium Channel Activities in Bovine Articular Chondrocytes

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    William Hester


    Full Text Available Objectives. The objective of this paper is to determine if hyaluronan affects bupivacaine’s anesthetic function. Methods. Whole cell patch clamp recordings were performed on bovine articular chondrocytes cultured in 60 mm dishes. The chondrocytes were treated with phosphate-buffered saline (control group, 7.5 mg/mL hyaluronan (Orthovisc, 0.25% bupivacaine, or a mixture of 7.5 mg/mL hyaluronan and 0.25% bupivacaine. Outward currents were elicited by step depolarization from −90 mV to 150 mV with 5 mV increments and holding for 200 ms. Results. The amplitude of outward currents elicited at 150 mV was 607.1±135.4 pA (mean ± standard error in the chondrocytes treated with phosphate buffered saline, 550.0±194.9 pA in the chondrocytes treated with hyaluronan, 18.4±8.3 pA in the chondrocytes treated with bupivacaine, and 12.8±2.6 pA in the chondrocytes treated with a mixture of hyaluronan and bupivacaine. Conclusion. Hyaluronan does not affect bupivacaine’s inhibitory action on the potassium channel activities in bovine articular chondrocytes. This finding suggests that intra-articular injection of a mixture of hyaluronan and bupivacaine may not affect the anesthetic effects of bupivacaine.

  20. The Roles of Hyaluronan/RHAMM/CD44 and Their Respective Interactions along the Insidious Pathways of Fibrosarcoma Progression (United States)

    Nikitovic, Dragana; Kouvidi, Katerina; Karamanos, Nikos K.; Tzanakakis, George N.


    Fibrosarcomas are rare malignant mesenchymal tumors originating from fibroblasts. Importantly, fibrosarcoma cells were shown to have a high content and turnover of extracellular matrix (ECM) components including hyaluronan (HA), proteoglycans, collagens, fibronectin, and laminin. ECMs are complicated structures that surround and support cells within tissues. During cancer progression, significant changes can be observed in the structural and mechanical properties of the ECM components. Importantly, hyaluronan deposition is usually higher in malignant tumors as compared to benign tissues, predicting tumor progression in some tumor types. Furthermore, activated stromal cells are able to produce tissue structure rich in hyaluronan in order to promote tumor growth. Key biological roles of HA result from its interactions with its specific CD44 and RHAMM (receptor for HA-mediated motility) cell-surface receptors. HA-receptor downstream signaling pathways regulate in turn cellular processes implicated in tumorigenesis. Growth factors, including PDGF-BB, TGFβ2, and FGF-2, enhanced hyaluronan deposition to ECM and modulated HA-receptor expression in fibrosarcoma cells. Indeed, FGF-2 through upregulation of specific HAS isoforms and hyaluronan synthesis regulated secretion and net hyaluronan deposition to the fibrosarcoma pericellular matrix modulating these cells' migration capability. In this paper we discuss the involvement of hyaluronan/RHAMM/CD44 mediated signaling in the insidious pathways of fibrosarcoma progression. PMID:24083250

  1. Hyaluronan degrading silica nanoparticles for skin cancer therapy (United States)

    Scodeller, P.; Catalano, P. N.; Salguero, N.; Duran, H.; Wolosiuk, A.; Soler-Illia, G. J. A. A.


    We report the first nanoformulation of Hyaluronidase (Hyal) and its enhanced adjuvant effect over the free enzyme. Hyaluronic acid (HA) degrading enzyme Hyal was immobilized on 250 nm silica nanoparticles (SiNP) maintaining specific activity of the enzyme via the layer-by-layer self-assembly technique. This process was characterized by dynamic light scattering (DLS), zeta potential, infrared and UV-Vis spectroscopy, transmission electron microscopy (TEM) and enzymatic activity measurements. The nanoparticles were tested in vivo as adjuvants of carboplatin (CP), peritumorally injected in A375 human melanoma bearing mice and compared with the non-immobilized enzyme, on the basis of equal enzymatic activity. Alcian Blue staining of A375 tumors indicated large overexpression of hyaluronan. At the end of the experiment, tumor volume reduction with SiNP-immobilized Hyal was significantly enhanced compared to non-immobilized Hyal. Field emission scanning electron microscopy (FE-SEM) images together with energy dispersive X-ray spectroscopy (EDS) spectra confirmed the presence of SiNP on the tumor. We mean a proof of concept: this extracellular matrix (ECM) degrading enzyme, immobilized on SiNP, is a more effective local adjuvant of cancer drugs than the non-immobilized enzyme. This could prove useful in future therapies using other or a combination of ECM degrading enzymes.We report the first nanoformulation of Hyaluronidase (Hyal) and its enhanced adjuvant effect over the free enzyme. Hyaluronic acid (HA) degrading enzyme Hyal was immobilized on 250 nm silica nanoparticles (SiNP) maintaining specific activity of the enzyme via the layer-by-layer self-assembly technique. This process was characterized by dynamic light scattering (DLS), zeta potential, infrared and UV-Vis spectroscopy, transmission electron microscopy (TEM) and enzymatic activity measurements. The nanoparticles were tested in vivo as adjuvants of carboplatin (CP), peritumorally injected in A375 human

  2. Synthesis of a hexasaccharide partial sequence of hyaluronan for click chemistry and more

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    Marina Bantzi


    Full Text Available In the present work, the synthesis of a hexasaccharide partial sequence of hyaluronan equipped with a terminal azido moiety is reported. This hexasaccharide can be used for the attachment on surfaces by means of click chemistry and after suitable deprotection for biophysical studies.

  3. Synthesis of a hexasaccharide partial sequence of hyaluronan for click chemistry and more. (United States)

    Bantzi, Marina; Rigol, Stephan; Giannis, Athanassios


    In the present work, the synthesis of a hexasaccharide partial sequence of hyaluronan equipped with a terminal azido moiety is reported. This hexasaccharide can be used for the attachment on surfaces by means of click chemistry and after suitable deprotection for biophysical studies.

  4. Hyaluronan hydrogels with a low degree of modification as scaffolds for cartilage engineering. (United States)

    La Gatta, Annalisa; Ricci, Giulia; Stellavato, Antonietta; Cammarota, Marcella; Filosa, Rosanna; Papa, Agata; D'Agostino, Antonella; Portaccio, Marianna; Delfino, Ines; De Rosa, Mario; Schiraldi, Chiara


    In the field of cartilage engineering, continuing efforts have focused on fabricating scaffolds that favor maintenance of the chondrocytic phenotype and matrix formation, in addition to providing a permeable, hydrated, microporous structure and mechanical support. The potential of hyaluronan-based hydrogels has been well established, but the ideal matrix remains to be developed. This study describes the development of hyaluronan sponges-based scaffolds obtained by lysine methyl-ester crosslinking. The reaction conditions are optimized with minimal chemical modifications to obtain materials that closely resemble elements in physiological cellular environments. Three hydrogels with different amounts of crosslinkers were produced that show morphological, water-uptake, mechanical, and stability properties comparable or superior to those of currently available hyaluronan-scaffolds, but with significantly fewer hyaluronan modifications. Primary human chondrocytes cultured with the most promising hydrogel were viable and maintained lineage identity for 3 weeks. They also secreted cartilage-specific matrix proteins. These scaffolds represent promising candidates for cartilage engineering. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Hyaluronan hydrogels modified by glycinated Kraft lignin: Morphology, swelling, viscoelastic properties and biocompatibility. (United States)

    Musilová, Lenka; Mráček, Aleš; Kovalcik, Adriana; Smolka, Petr; Minařík, Antonín; Humpolíček, Petr; Vícha, Robert; Ponížil, Petr


    Effects of the addition of water soluble glycinated Kraft lignin (WS/KL) on the mechanical stability and biocompatibility of hyaluronan (NaHy) hydrogels were evaluated in this work. Water soluble lignin was obtained by the modification of Kraft lignin via a Mannich reaction. It was found that WS/KL is highly compatible with hyaluronan due to its improved water solubility, which favours its use in designing new advanced composite hydrogels. The effects of the concentration of WS/KL on morphological, swelling and creep/recovery behaviours of hyaluronan hydrogels were investigated. It was detected that the creep resistance and creep recovery of NaHy hydrogels was improved by the incorporation of up to 3% (w/w) of WS/KL. In contrast, the swelling capacity of hydrogels was decreased. The cytotoxicity tests proved that glycinated KL lignin limits the viability of cells only slightly, and the final hyaluronan/lignin hydrogels were non-toxic materials. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Effect of hyaluronan on osteogenic differentiation of porcine bone marrow stromal cells in vitro

    DEFF Research Database (Denmark)

    Zou, Lijin; Zou, Xuenong; Chen, Li


    Hyaluronan (HA) plays a predominant role in tissue morphogenesis, cell migration, proliferation, and cell differentiation. The aims of the present study were to investigate whether (i) prolonged presence of high concentration (4.0 mg/mL) 800 KDa HA and (ii) pretreatment with HA can modify osteoge...

  7. Increased Levels of Type I and III Collagen and Hyaluronan in Scleroderma Skin

    DEFF Research Database (Denmark)

    Søndergaard, Klaus; Heickendorff, Lene; L, Risteli


    The aminoterminal propeptide of type III procollagen (PIIINP) and the carboxyterminal propeptide of type I procollagen (PICP) and hyaluronan (HA) were measured in plasma and suction blister fluid from 13 systemic sclerosis patients and 11 healthy volunteers. Suction blisters and skin biopsies were...

  8. Stimulation of porcine bone marrow stromal cells by hyaluronan, dexamethasone and rhBMP-2

    DEFF Research Database (Denmark)

    Zou, Xuenong; Li, Haisheng; Chen, Li


    In the interest of optimizing osteogenesis in in vitro, the present study sought to determine how porcine bone marrow stromal cell (BMSc) would respond to different concentrations of hyaluronan (HY) and its different combinations with dexamethasone (Dex) and recombinant human bone morphogenic pro...

  9. The role of hyaluronan produced by Has2 gene expression in development of the spine. (United States)

    Roughley, Peter J; Lamplugh, Lisa; Lee, Eunice R; Matsumoto, Kazu; Yamaguchi, Yu


    Histologic analysis of spine development in cartilage-specific knockout mice. To evaluate the role hyaluronan produced by hyaluronan synthase-2 (Has2) in spine development. The Has2 gene is responsible for most hyaluronan production throughout the body, including the skeleton. However, it is not possible to study the involvement of hyaluronan in skeletal development using constitutive Has2 knockout mice, as the embryonic mice die early before skeletal development has occurred. This problem can be overcome by the use of cartilage-specific knockout mice. Mice possessing floxed Has2 genes were crossed with mice expressing Cre recombinase under control of the type II collagen promoter to generate cartilage-specific Has2 knockout mice. Spine development was studied by histology. Knockout mice died near birth and displayed severe abnormality in skeletal development. The spine showed defects in vertebral body size and the formation of the intervertebral discs. There was no evidence for the formation of an organized primary center of ossification within the vertebrae, and the appearance and organization of the hypertrophic chondrocytes was abnormal. Although no organized endochondral ossification appeared to be taking place, there was excessive bone formation at the center of the vertebrae. There was also a generalized increased cellularity of the vertebral cartilage and a corresponding decrease in the abundance of extracellular matrix. The nucleus pulposus of the intervertebral discs were less flattened than in the control mice and possessed an increased amount of large vacuolated cells. Remnants of the notochord could also be seen between adjacent discs. Hyaluronan production by Has2 is essential for normal vertebral and intervertebral disc development within the spine, and the absence of this synthase impairs the organization of both soft and hard tissue elements.

  10. The Control and Importance of Hyaluronan Synthase Expression in Palatogenesis

    Directory of Open Access Journals (Sweden)

    Jennifer eGalloway


    Full Text Available Development of the lip and palate involves a complex series of events that requires the close co-ordination of cell migration, growth, differentiation and apoptosis. Palatal shelf elevation is considered to be driven by regional accumulation and hydration of glycosoaminoglycans, principally hyaluronan (HA, which provides an intrinsic shelf force, directed by components of the extracellular matrix (ECM. During embryogenesis, the extracellular and pericellular matrix surrounding migrating and proliferating cells is rich in HA. This would suggest that HA may be important in both shelf growth and fusion. TGFβ3 plays an important role in palatogenesis and the corresponding homozygous null (TGFβ3 -/- mouse, exhibits a defect in the fusion of the palatal shelves resulting in clefting of the secondary palate. TGFβ3 is expressed at the future medial edge epithelium (MEE and at the actual edge epithelium during E14.5, suggesting a role for TGFβ3 in fusion. This is substantiated by experiments showing that addition of exogenous TGFβ3 can ‘rescue’ the cleft palate phenotype in the null mouse. In addition, TGFβ1 and TGFβ2 can rescue the null mouse palate (in vitro to near normal fusion. In vivo a TGFβ1 knock-in mouse, where the coding region of the TGFβ3 gene was replaced with the full-length TGFβ1 cDNA, displayed complete fusion at the mid portion of the secondary palate, whereas the anterior and posterior regions failed to fuse appropriately. We present experimental data indicating that the three Has enzymes are differentially expressed during palatogenesis. Using immunohistochemistry and embryo sections from the TGFβ3 null mouse at days E13.5 and E14.5, it was established that there was a decrease in expression of Has2 in the mesenchyme and an increase in expression of Has3 in comparison to the wild type mouse. In vitro data indicate that HA synthesis is affected by addition of exogenous TGFβ3. Preliminary data suggests that this increase

  11. Hybrid Complexes of High and Low Molecular Weight Hyaluronans Highly Enhance HASCs Differentiation: Implication for Facial Bioremodelling

    Directory of Open Access Journals (Sweden)

    Antonietta Stellavato


    Full Text Available Background/Aims: Adipose-derived Stem Cells (ASCs are used in Regenerative Medicine, including fat grafting, recovery from local tissue ischemia and scar remodeling. The aim of this study was to evaluate hyaluronan based gel effects on ASCs differentiation and proliferation. Methods: Comparative analyses using high (H and low (L molecular weight hyaluronans (HA, hyaluronan hybrid cooperative complexes (HCCs, and high and medium cross-linked hyaluronan based dermal fillers were performed. Human ASCs were characterized by flow cytometry using CD90, CD34, CD105, CD29, CD31, CD45 and CD14 markers. Then, cells were treated for 7, 14 and 21 days with hyaluronans. Adipogenic differentiation was evaluated using Oil red-O staining and expression of leptin, PPAR-γ, LPL and adiponectin using qRT-PCR. Adiponectin was analyzed by immunofluorescence, PPAR-γ and adiponectin were analyzed using western blotting. ELISA assays for adiponectin and leptin were performed. Results: HCCs highly affected ASCs differentiation by up-regulating adipogenic genes and related proteins, that were also secreted in the culture medium. H-HA and L-HA induced a lower level of ASCs differentiation. Conclusion: HCCs-based formulations clearly enhance adipogenic differentiation and proliferation, when compared with linear HA and cross-linked hyaluronans. Injection of HCCs in subdermal fat compartment may recruit and differentiate stem cells in adipocytes, and considerably improving fat tissue renewal.

  12. A hexadecylamide derivative of hyaluronan (HYMOVIS®) has superior beneficial effects on human osteoarthritic chondrocytes and synoviocytes than unmodified hyaluronan (United States)


    Background Intra-articular hyaluronan (HA) injection provides symptomatic benefit in the treatment of osteoarthritis (OA). Previously we found superior beneficial effects in a large animal OA model of a hexadecylamide derivative compared with unmodified HA of the same initial molecular weight. The current study sought to define possible molecular mechanisms whereby this enhanced relief of symptoms was occurring. Methods Chondrocytes and synovial fibroblasts were isolated from tissues of patients undergoing arthroplasty for knee OA. Monolayer cultures of cells were treated with 0, 0.5, 1.0 or 1.5 mg/mL of unmodified HA (500–730 kDa) or a hexadecylamide derivative of HA of the same initial molecular weight (HYADD4®-G; HYMOVIS®) simultaneously or 1 hour before incubation with interleukin (IL)-1beta (2 ng/mL). Cultures were terminated 15 or 30 minutes later (chondrocytes and synovial fibroblasts, respectively) for quantitation of phosphorylated-(p)-JNK, p-NFkappaB, p-p38, or at 24 hours for quantitation of gene expression (MMP1 &13, ADAMTS4 &5, TIMP1 &3, CD44, COL1A1 &2A1, ACAN, PTGS2, IL6, TNF) and matrix metalloproteinase (MMP)-13 activity. Results The hexadecylamide derivative of HA had significantly better amelioration of IL-1beta-induced gene expression of key matrix degrading enzymes (MMP1, MMP13, ADAMTS5), and inflammatory mediators (IL6, PTGS2) by human OA chondrocytes and synovial fibroblasts. Pre-incubation of cells with the derivatized HA for 1 hour prior to IL-1beta exposure significantly augmented the inhibition of MMP1, MMP13, ADAMTS4 and IL6 expression by chondrocytes. The reduction in MMP13 mRNA by the amide derivative of HA was mirrored in reduced MMP-13 protein and enzyme activity in IL-1beta-stimulated chondrocytes. This was associated in part with a greater inhibition of phosphorylation of the cell signalling molecules JNK, p38 and NF-kappaB. Conclusions The present studies have demonstrated several potential key mechanisms whereby the

  13. Multivalent dendrimers presenting spatially controlled clusters of binding epitopes in thermoresponsive hyaluronan hydrogels. (United States)

    Seelbach, Ryan J; Fransen, Peter; Peroglio, Marianna; Pulido, Daniel; Lopez-Chicon, Patricia; Duttenhoefer, Fabian; Sauerbier, Sebastian; Freiman, Thomas; Niemeyer, Philipp; Semino, Carlos; Albericio, Fernando; Alini, Mauro; Royo, Miriam; Mata, Alvaro; Eglin, David


    The controlled presentation of biofunctionality is of key importance for hydrogel applications in cell-based regenerative medicine. Here, a versatile approach was demonstrated to present clustered binding epitopes in an injectable, thermoresponsive hydrogel. Well-defined multivalent dendrimers bearing four integrin binding sequences and an azido moiety were covalently grafted to propargylamine-derived hyaluronic acid (Hyal-pa) using copper-catalyzed alkyne-azide cycloaddition (CuAAC), and then combined with pN-modified hyaluronan (Hyal-pN). The dendrimers were prepared by synthesizing a bifunctional diethylenetriamine pentaacetic acid core with azido and NHBoc oligo(ethylene glycol) aminoethyl branches, then further conjugated with solid-phase synthesized RGDS and DGRS peptides. Azido terminated pN was synthesized by reversible addition-fragmentation chain transfer polymerization and reacted to Hyal-pa via CuAAC. Nuclear magnetic resonance (NMR), high performance liquid chromatography, size exclusion chromatography and mass spectroscopy proved that the dendrimers had well-defined size and were disubstituted. NMR and atomic absorption analysis confirmed the hyaluronan was affixed with dendrimers or pN. Rheological measurements demonstrated that dendrimers do not influence the elastic or viscous moduli of thermoresponsive hyaluronan compositions at a relevant biological concentration. Finally, human mesenchymal stromal cells were encapsulated in the biomaterial and cultured for 21days, demonstrating the faculty of this dendrimer-modified hydrogel as a molecular toolbox for tailoring the biofunctionality of thermoresponsive hyaluronan carriers for biomedical applications. Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  14. Impaired reparative processes in particular related to hyaluronan in various cutaneous disorders : a structural analysis


    Bertheim, Ulf


    Cutaneous reparative processes, including wound healing, are highly developed procedures in which a chain of actions occurs to reconstitute the function of the wounded tissue. To prevent a delayed or excessive reparative process it is important to understand how this procedure develops and is maintained. One of the major extracellular matrix components of the skin is the glycosaminoglycan hyaluronan (HA). HA contributes to an extracellular environment, which is permissive for cell motility an...

  15. Hyaluronan suppresses lidocaine-induced apoptosis of human chondrocytes in vitro by inhibiting the p53-dependent mitochondrial apoptotic pathway (United States)

    Lee, Yoon-Jin; Kim, Soo A; Lee, Sang-Han


    Aim: Intra-articular injection of local anesthetics (LAs) is a common procedure for therapeutic purposes. However, LAs have been found toxic to articular cartilage, and hyaluronan may attenuate this toxicity. In this study we investigated whether hyaluronan attenuated lidocaine-induced chondrotoxicity, and if so, to elucidate the underlying mechanisms. Methods: Human chondrocyte cell line SW1353 and newly isolated murine chondrocytes were incubated in culture medium containing hyaluronan and/or lidocaine for 72 h. Cell viability was evaluated using MTT assay. Cell apoptosis was detected with DAPI staining, caspase 3/7 activity assay and flow cytometry. Cell cycle distributions, ROS levels and mitochondrial membrane potential (ΔΨm) were determined using flow cytometry. The expression of p53 and p53-regulated gene products was measured with Western blotting. Results: Lidocaine (0.005%−0.03%) dose-dependently decreased the viability of SW1353 cells. This local anesthetic (0.015%, 0.025%) induced apoptosis, G2/M phase arrest and loss of ΔΨm, and markedly increased ROS production in SW1353 cells. Hyaluronan (50−800 μg/mL) alone did not affect the cell viability, but co-treatment with hyaluronan (200 μg/mL) significantly attenuated lidocaine-induced apoptosis and other abnormalities in SW1353 cells. Furthermore, co-treatment with lidocaine and hyaluronan significantly decreased the levels of p53 and its transcription targets Bax and p21 in SW1353 cells, although treatment with lidocaine alone did not significantly change these proteins. Similar results were obtained in ex vivo cultured murine chondrocytes. Conclusion: Hyaluronan suppresses lidocaine-induced apoptosis of human chondrocytes in vitro through inhibiting the p53-dependent mitochondrial apoptotic pathway. PMID:27041463

  16. Bimodal tumor-targeting from microenvironment responsive hyaluronan layer-by-layer (LbL) nanoparticles. (United States)

    Dreaden, Erik C; Morton, Stephen W; Shopsowitz, Kevin E; Choi, Jae-Hyeok; Deng, Zhou J; Cho, Nam-Joon; Hammond, Paula T


    Active targeting of nanoscale drug carriers can improve tumor-specific delivery; however, cellular heterogeneity both within and among tumor sites is a fundamental barrier to their success. Here, we describe a tumor microenvironment-responsive layer-by-layer (LbL) polymer drug carrier that actively targets tumors based on two independent mechanisms: pH-dependent cellular uptake at hypoxic tumor pH and hyaluronan-directed targeting of cell-surface CD44 receptor, a well-characterized biomarker for breast and ovarian cancer stem cells. Hypoxic pH-induced structural reorganization of hyaluronan-LbL nanoparticles was a direct result of the nature of the LbL electrostatic complex, and led to targeted cellular delivery in vitro and in vivo, with effective tumor penetration and uptake. The nanoscale drug carriers selectively bound CD44 and diminished cancer cell migration in vitro, while co-localizing with the CD44 receptor in vivo. Multimodal targeting of LbL nanoparticles is a powerful strategy for tumor-specific cancer diagnostics and therapy that can be accomplished using a single bilayer of polyamine and hyaluronan that, when assembled, produce a dynamic and responsive cell-particle interface.

  17. Mechanical Stretch Induces Epithelial-Mesenchymal Transition in Alveolar Epithelia via Hyaluronan Activation of Innate Immunity* (United States)

    Heise, Rebecca L.; Stober, Vandy; Cheluvaraju, Chaitra; Hollingsworth, John W.; Garantziotis, Stavros


    Epithelial injury is a central event in the pathogenesis of many inflammatory and fibrotic lung diseases like acute respiratory distress syndrome, pulmonary fibrosis, and iatrogenic lung injury. Mechanical stress is an often underappreciated contributor to lung epithelial injury. Following injury, differentiated epithelia can assume a myofibroblast phenotype in a process termed epithelial to mesenchymal transition (EMT), which contributes to aberrant wound healing and fibrosis. We demonstrate that cyclic mechanical stretch induces EMT in alveolar type II epithelial cells, associated with increased expression of low molecular mass hyaluronan (sHA). We show that sHA is sufficient for induction of EMT in statically cultured alveolar type II epithelial cells and necessary for EMT during cell stretch. Furthermore, stretch-induced EMT requires the innate immune adaptor molecule MyD88. We examined the Wnt/β-catenin pathway, which is known to mediate EMT. The Wnt target gene Wnt-inducible signaling protein 1 (wisp-1) is significantly up-regulated in stretched cells in hyaluronan- and MyD88-dependent fashion, and blockade of WISP-1 prevents EMT in stretched cells. In conclusion, we show for the first time that innate immunity transduces mechanical stress responses through the matrix component hyaluronan, and activation of the Wnt/β-catenin pathway. PMID:21398522

  18. Viruses exploiting peroxisomes. (United States)

    Lazarow, Paul B


    Viruses that are of great importance for global public health, including HIV, influenza and rotavirus, appear to exploit a remarkable organelle, the peroxisome, during intracellular replication in human cells. Peroxisomes are sites of lipid biosynthesis and catabolism, reactive oxygen metabolism, and other metabolic pathways. Viral proteins are targeted to peroxisomes (the spike protein of rotavirus) or interact with peroxisomal proteins (HIV's Nef and influenza's NS1) or use the peroxisomal membrane for RNA replication. The Nef interaction correlates strongly with the crucial Nef function of CD4 downregulation. Viral exploitation of peroxisomal lipid metabolism appears likely. Mostly, functional significance and mechanisms remain to be elucidated. Recently, peroxisomes were discovered to play a crucial role in the innate immune response by signaling the presence of intracellular virus, leading to the first rapid antiviral response. This review unearths, interprets and connects old data, in the hopes of stimulating new and promising research. Copyright © 2011. Published by Elsevier Ltd.

  19. Dissemination and Exploitation Strategy

    DEFF Research Database (Denmark)

    Badger, Merete; Monaco, Lucio; Fransson, Torsten

    The research infrastructure project Virtual Campus Hub (VCH) runs from October 1, 2011 to September 30, 2013. Four technical universities in Europe, who are all active in the field of sustainable energy, form the project consortium: the Technical University of Denmark, The Royal Institute...... of Technology in Sweden, Politecnico di Torino in Italy, and Eindhoven University of Technology in the Netherlands. The project is partially funded by the European Commission under the 7th Framework Programme (project no. RI-283746). This report describes the final dissemination and exploitation strategy...... for project Virtual Campus Hub. A preliminary dissemination and exploitation plan was setup early in the project as described in the deliverable D6.1 Dissemination strategy paper - preliminary version. The plan has been revised on a monthly basis during the project’s lifecycle in connection with the virtual...

  20. Hacking the art of exploitation

    CERN Document Server

    Erickson, Jon


    A comprehensive introduction to the techniques of exploitation and creative problem-solving methods commonly referred to as "hacking," Hacking: The Art of Exploitation is for both technical and non-technical people who are interested in computer security. It shows how hackers exploit programs and write exploits, instead of just how to run other people's exploits. Unlike many so-called hacking books, this book explains the technical aspects of hacking, including stack based overflows, heap based overflows, string exploits, return-into-libc, shellcode, and cryptographic attacks on 802.11b.

  1. Exploitation of eukaryotic subcellular targeting mechanisms by bacterial effectors. (United States)

    Hicks, Stuart W; Galán, Jorge E


    Several bacterial species have evolved specialized secretion systems to deliver bacterial effector proteins into eukaryotic cells. These effectors have the capacity to modulate host cell pathways in order to promote bacterial survival and replication. The spatial and temporal context in which the effectors exert their biochemical activities is crucial for their function. To fully understand effector function in the context of infection, we need to understand the mechanisms that lead to the precise subcellular localization of effectors following their delivery into host cells. Recent studies have shown that bacterial effectors exploit host cell machinery to accurately target their biochemical activities within the host cell.

  2. The Geohazards Exploitation Platform (United States)

    Laur, Henri; Casu, Francesco; Bally, Philippe; Caumont, Hervé; Pinto, Salvatore


    The Geohazards Exploitation Platform, or Geohazards TEP (GEP), is an ESA originated R&D activity of the EO ground segment to demonstrate the benefit of new technologies for large scale processing of EO data. This encompasses on-demand processing for specific user needs, systematic processing to address common information needs of the geohazards community, and integration of newly developed processors for scientists and other expert users. The platform supports the geohazards community's objectives as defined in the context of the International Forum on Satellite EO and Geohazards organised by ESA and GEO in Santorini in 2012. The GEP is a follow on to the Supersites Exploitation Platform (SSEP) an ESA initiative to support the Geohazards Supersites & Natural Laboratories initiative (GSNL). Today the GEP allows to exploit 70+ Terabyte of ERS and ENVISAT archive and the Copernicus Sentinel-1 data available on line. The platform has already engaged 22 European early adopters in a validation activity initiated in March 2015. Since September, this validation has reached 29 single user projects. Each project is concerned with either integrating an application, running on demand processing or systematically generating a product collection using an application available in the platform. The users primarily include 15 geoscience centres and universities based in Europe: British Geological Survey (UK), University of Leeds (UK), University College London (UK), ETH University of Zurich (CH), INGV (IT), CNR-IREA and CNR-IRPI (IT), University of L'Aquila (IT), NOA (GR), Univ. Blaise Pascal & CNRS (FR), Ecole Normale Supérieure (FR), ISTERRE / University of Grenoble-Alpes (FR). In addition, there are users from Africa and North America with the University of Rabat (MA) and the University of Miami (US). Furthermore two space agencies and four private companies are involved: the German Space Research Centre DLR (DE), the European Space Agency (ESA), Altamira Information (ES

  3. Exploitative Learning by Exporting

    DEFF Research Database (Denmark)

    Golovko, Elena; Lopes Bento, Cindy; Sofka, Wolfgang

    Decisions on entering foreign markets are among the most challenging but also potentially rewarding strategy choices managers can make. In this study, we examine the effect of export entry on the firm investment decisions in two activities associated with learning about new technologies...... and learning about new markets ? R&D investments and marketing investments, in search of novel insights into the content and process underlying learning by exporting. We draw from organizational learning theory for predicting changes in both R&D and marketing investment patterns that accompany firm entry......, it is predominantly the marketing-related investment decisions associated with starting to export that lead to increases in firm productivity. We conclude that learning-by-exporting might be more properly characterized as ?learning about and exploiting new markets? rather than ?learning about new technologies...

  4. Butyrate-Loaded Chitosan/Hyaluronan Nanoparticles: A Suitable Tool for Sustained Inhibition of ROS Release by Activated Neutrophils

    DEFF Research Database (Denmark)

    Sacco, Pasquale; Decleva, Eva; Tentor, Fabio


    of neutrophil ROS production by free butyrate declines over time, that of butyrate-loaded chitosan/hyaluronan nanoparticles (B-NPs) is sustained. Additional valuable features of these nanoparticles are inherent ROS scavenger activity, resistance to cell internalization, and mucoadhesiveness. B-NPs appear...... that butyrate inhibits neutrophil ROS release in a dose and time-dependent fashion. Given the short half-life of butyrate, chitosan/hyaluronan nanoparticles are next designed and developed as controlled release carriers able to provide cells with a long-lasting supply of this SCFA. Notably, while the inhibition...

  5. Image exploitation for MISAR (United States)

    Heinze, N.; Edrich, M.; Saur, G.; Krüger, W.


    The miniature SAR-system MiSAR has been developed by EADS Germany for lightweight UAVs like the LUNASystem. MiSAR adds to these tactical UAV-systems the all-weather reconnaissance capability, which is missing until now. Unlike other SAR sensors, that produce large strip maps at update rates of several seconds, MiSAR generates sequences of SAR images with approximately 1 Hz frame rate. photo interpreters (PI) of tactical drones, now mainly experienced with visual interpretation, are not used to SARimages, especially not with SAR-image sequence characteristics. So they should be supported to improve their ability to carry out their task with a new, demanding sensor system. We have therefore analyzed and discussed with military PIs in which task MiSAR can be used and how the PIs can be supported by special algorithms. We developed image processing- and exploitation-algorithms for such SAR-image sequences. A main component is the generation of image sequence mosaics to get more oversight. This mosaicing has the advantage that also non straight /linear flight-paths and varying squint angles can be processed. Another component is a screening-component for manmade objects to mark regions of interest in the image sequences. We use a classification based approach, which can be easily adapted to new sensors and scenes. These algorithms are integrated into an image exploitation system to improve the image interpreters ability to get a better oversight, better orientation and helping them to detect relevant objects, especially considering long endurance reconnaissance missions.

  6. Learning Metasploit exploitation and development

    CERN Document Server

    Balapure, Aditya


    A practical, hands-on tutorial with step-by-step instructions. The book will follow a smooth and easy-to-follow tutorial approach, covering the essentials and then showing the readers how to write more sophisticated exploits.This book targets exploit developers, vulnerability analysts and researchers, network administrators, and ethical hackers looking to gain advanced knowledge in exploitation development and identifying vulnerabilities. The primary goal is to take readers wishing to get into more advanced exploitation discovery and reaching the next level.Prior experience exploiting basic st

  7. IgG-loaded hyaluronan-based dissolving microneedles for intradermal protein delivery. (United States)

    Mönkäre, Juha; Reza Nejadnik, M; Baccouche, Khalil; Romeijn, Stefan; Jiskoot, Wim; Bouwstra, Joke A


    Dissolving microneedles are an attractive approach for non-invasive delivery of drugs via the skin, particularly when the doses are in the microgram or low-milligram range. The aim of the study was to develop hyaluronan-based, monoclonal IgG-loaded microneedles for intradermal delivery enabling efficient penetration and rapid dissolution in the skin while preserving protein stability. Microscopic analysis showed successful preparation of sharp microneedles with the tip length of ~280 μm and with up to 10% (w/w) of IgG content. The water content of the microneedles was ~12% and was not affected by the protein content. The protein distribution was uniform within microneedle tips and individual arrays but some array-to-array variation of IgG level within a single preparation batch was detected. After dissolution of microneedle arrays in PBS, N80% of protein was recovered and no conformational changes were detected by fluorescence spectroscopy. At submicron level, only weak and reversible interaction between HA and IgG was found by asymmetric flow field flow fractionation analysis after the dissolution of prepared microneedles. Although, the formation of insoluble micron-size particles was detected by flow imaging microscopy the IgG amount incorporated into these particles was negligible (b5%). Finally, microneedles were able to penetrate into the epidermis of ex vivo human skin followed by the rapid dissolution of the microneedle tips in the skin. After 10 min of application, the majority of the original tip length was dissolved and IgG and hyaluronan were co-deposited until a depth of 150-200 μm in the skin. In conclusion, developed hyaluronan-based dissolving microneedles allow rapid noninvasive intradermal protein delivery.

  8. Role of hyaluronan synthase 2 to promote CD44-dependent oral cavity squamous cell carcinoma progression. (United States)

    Wang, Steven J; Earle, Christine; Wong, Gabriel; Bourguignon, Lilly Y W


    CD44 is a transmembrane receptor found on many different benign and malignant cells. Hyaluronan (HA), a major component of the extracellular matrix, is the primary ligand for CD44 receptors. In cancer cells, HA interaction with CD44 promotes multiple signaling pathways that influence tumor cell progression behaviors in a variety of solid tumors. Increasing evidence indicates that HA and CD44 signaling play an important role in oral cavity squamous cell carcinoma progression. HA is primarily synthesized by hyaluronan synthases, and the current study investigated the role of hyaluronan synthase 2 (HAS 2) in oral cavity carcinoma progression behaviors. Analysis of HAS 2 mRNA and protein expression, HA production, and HAS 2-mediated tumor cell proliferation and migration behaviors with and without HAS 2 suppression were carried out on 2 established oral cavity cancer cell lines. Immunohistochemical analysis of HAS 2 and CD44 expression in oral cavity carcinoma tumor specimens was performed. HAS 2 was expressed in the 2 oral cancer cell lines, HSC-3 and SCC-4. Suppression of HAS 2 expression resulted in CD44-dependent decreased tumor cell migration, decreased tumor cell growth, and increased cisplatin sensitivity, suggesting the importance of tumor cell HA production to promote in vitro tumor progression behaviors in oral cancer cells. Increased HAS 2 expression in oral cavity carcinoma clinical specimens was associated with poor clinicopathologic characteristics and worse disease-free survival. HAS 2 may be a potential therapeutic target for the treatment of oral cavity cancer. Copyright © 2012 Wiley Periodicals, Inc.

  9. Shigella hacks host immune responses by reprogramming the host epigenome. (United States)

    Ashida, Hiroshi; Sasakawa, Chihiro


    Bacterial pathogens alter host transcriptional programs to promote infection. Shigella OspF is an essential virulence protein with a unique phosphothreonine lyase activity. A new study in The EMBO Journal (Harouz et al, 2014) reveals a novel function of OspF: targeting of heterochromatin protein 1γ (HP1γ) and downregulation of a subset of immune genes. These results illustrate how bacterial pathogens exploit epigenetic modifications to counteract host immune responses.

  10. Stability of Hyaluronan-Pectic Gel Particles in the Conditions of the Artificial Gastrointestinal Environment

    Directory of Open Access Journals (Sweden)

    Elena A. Mikhailova


    Full Text Available Spherical hyaluronan-pectic gel particles (HPGPs from hyaluronic acid (HA and low-methyl esterified pectins of callus cultures (CC of tansy, duckweed, campion and commercial apple pectin were obtained by the method of ionotropic gelation in the presence of calcium ions. We investigated the morphology, swelling and degradation of the obtained HPGPs in the conditions of a simulated gastrointestinal environment and established that the greatest stability in the artificial environment of the digestive tract is achieved with HPGPs obtained from the pectin of tansy CC. HPGPs can be used as potential carriers for drug delivery systems in parts of the small and large intestine.

  11. Hypochlorite-mediated fragmentation of hyaluronan, chondroitin sulfates, and related N-acetyl glycosamines

    DEFF Research Database (Denmark)

    Rees, Martin D; Hawkins, Clare Louise; Davies, Michael Jonathan


    Myeloperoxidase released from activated phagocytes reacts with H(2)O(2) in the presence of chloride ions to give hypochlorous acid. This oxidant has been implicated in the fragmentation of glycosaminoglycans, such as hyaluronan and chondroitin sulfates. In this study it is shown that reaction......) and at C-4 on the neighboring uronic acid residues (via 1,5-hydrogen atom shifts). The C-4 carbon-centered radicals, and analogous species derived from model glycosides, undergo pH-independent beta-scission reactions that result in glycosidic bond cleavage. With N-acetyl glucosamine C-1 alkyl glycosides...

  12. Targeting gallbladder cancer: hyaluronan sensitizes cancer cells to chemo-therapeutics. (United States)

    Ma, Mingzhe; Weng, Mingzhe; Zhang, Mingdi; Qin, Yiyu; Gong, Wei; Quan, Zhiwei


    Gallbladder cancer is the most common biliary tract malignancy and the fifth most common gastrointestinal malignancy. Chemo-resistance is the most remarkable characteristic of gallbladder cancer. The relatively dense extracellular space in tumor is the main barrier to nanotherapeutics' anticancer efficacy. Hyaluronan (HA) was shown in our previous study to significantly improve the myxoma virus distribution via promoting the MMP-9 production, which degrades collagen IV. We demonstrated that HA increased the chemo-sensitivity of gallbladder cancer cells both in vitro and in vivo. The in vivo chemo-sensitization effect of HA could partially be due to the penetration-promoting effect of HA via degrading collagen IV.

  13. Aphid Heritable Symbiont Exploits Defensive Mutualism. (United States)

    Doremus, Matthew R; Oliver, Kerry M


    Insects and other animals commonly form symbioses with heritable bacteria, which can exert large influences on host biology and ecology. The pea aphid, Acyrthosiphon pisum , is a model for studying effects of infection with heritable facultative symbionts (HFS), and each of its seven common HFS species has been reported to provide resistance to biotic or abiotic stresses. However, one common HFS, called X-type, rarely occurs as a single infection in field populations and instead typically superinfects individual aphids with Hamiltonella defensa , another HFS that protects aphids against attack by parasitic wasps. Using experimental aphid lines comprised of all possible infection combinations in a uniform aphid genotype, we investigated whether the most common strain of X-type provides any of the established benefits associated with aphid HFS as a single infection or superinfection with H. defensa We found that X-type does not confer protection to any tested threats, including parasitoid wasps, fungal pathogens, or thermal stress. Instead, component fitness assays identified large costs associated with X-type infection, costs which were ameliorated in superinfected aphids. Together these findings suggest that X-type exploits the aphid/ H. defensa mutualism and is maintained primarily as a superinfection by "hitchhiking" via the mutualistic benefits provided by another HFS. Exploitative symbionts potentially restrict the functions and distributions of mutualistic symbioses with effects that extend to other community members. IMPORTANCE Maternally transmitted bacterial symbionts are widespread and can have major impacts on the biology of arthropods, including insects of medical and agricultural importance. Given that host fitness and symbiont fitness are tightly linked, inherited symbionts can spread within host populations by providing beneficial services. Many insects, however, are frequently infected with multiple heritable symbiont species, providing potential

  14. Hyaluronan-binding by CD44 reduces the memory potential of activated murine CD8 T cells. (United States)

    Lee-Sayer, Sally S M; Maeshima, Nina; Dougan, Meghan N; Dahiya, Anita; Arif, Arif A; Dosanjh, Manisha; Maxwell, Christopher A; Johnson, Pauline


    Expansion and death of effector CD8 T cells are regulated to limit immunopathology and cells that escape contraction go on to generate immunological memory. CD44, a receptor for the extracellular matrix component hyaluronan, is a marker of activated and memory T cells. Here, we show with a murine model that the increase in CD44 expression and hyaluronan binding induced upon CD8 T cell activation was proportional to the strength of TCR engagement, thereby identifying the most strongly activated T cells. When CD44-/- and CD44+/+ OT-I CD8 T cells were adoptively transferred into mice challenged with Listeria-OVA, there was a slight increase in the percentage of CD44+/+ cells at the effector site. However, CD44+/+ cells were out-competed by CD44-/- cells after the contraction phase in the lymphoid tissues, and the CD44-/- cells preferentially formed more memory cells. The hyaluronan-binding CD44+/+ CD8 effector T cells showed increased pAkt expression, higher glucose uptake, and were more susceptible to cell death during the contraction phase compared to non-binding CD44+/+ and CD44-/- OT-I CD8 T cells, suggesting that CD44 and its engagement with hyaluronan skews CD8 T cells toward a terminal effector differentiation state that reduces their ability to form memory cells. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Inhibition of Ovarian Cancer Chemoresistance and Metastasis with Antagonists of Hyaluronan-CD44-CD147 Interactions (United States)


    measured after sacrifice. P values: Control siRNA vs. Combo = 0.0068; Control siRNA + Cisplatin vs. Combo = 0.0047; Control siRNA vs. CD147 siRNA...2006. Acylation of CD44 and its association with lipid rafts are required for receptor and hyaluronan endocytosis . J Biol Chem. 281:34601-34609. Toole

  16. Calcium oxalate crystal adherence to hyaluronan-, osteopontin-, and CD44-expressing injured/regenerating tubular epithelial cells in rat kidneys

    NARCIS (Netherlands)

    M. Asselman (Marino); A. Verhulst; M.E. de Broe; C.F. Verkoelen


    textabstractRetention of crystals in the kidney is an essential early step in renal stone formation. Studies with renal tubular cells in culture indicate that hyaluronan (HA) and osteopontin (OPN) and their mutual cell surface receptor CD44 play an important role in calcium oxalate

  17. Can Plasma Hyaluronan and Hyaluronidase Be Used As Markers of the Endothelial Glycocalyx State in Patients with Kidney Disease?

    NARCIS (Netherlands)

    Vlahu, Carmen A.; Krediet, Raymond T.


    Hyaluronan (HA) is widely spread in the body and is an important component of the extracellular matrix, including the endothelial glycocalyx (EG). Essential for its vasculoprotective function, HA is involved in vascular permeability and many other processes. In patients with kidney disease, plasma

  18. The effect of hyaluronan combined with KI3 complex (Hyiodine wound dressing) on keratinocytes and immune cells

    Czech Academy of Sciences Publication Activity Database

    Franková, J.; Kubala, Lukáš; Velebný, V.; Číž, Milan; Lojek, Antonín


    Roč. 17, č. 10 (2006), s. 891-898 ISSN 0957-4530 R&D Projects: GA ČR(CZ) GA524/02/0395 Institutional research plan: CEZ:AV0Z50040507 Keywords : chemiluminescence * hyaluronan * polymorphonuclear leukocytes Subject RIV: BO - Biophysics Impact factor: 1.562, year: 2006

  19. Survival of cord blood haematopoietic stem cells in a hyaluronan hydrogel for ex vivo biomimicry. (United States)

    Demange, Elise; Kassim, Yusra; Petit, Cyrille; Buquet, Catherine; Dulong, Virginie; Cerf, Didier Le; Buchonnet, Gérard; Vannier, Jean-Pierre


    Haematopoietic stem cells (HSCs) and haematopoietic progenitor cells (HPCs) grow in a specified niche in close association with the microenvironment, the so-called 'haematopoietic niche'. Scaffolds have been introduced to overcome the liquid culture limitations, mimicking the presence of the extracellular matrix (ECM). In the present study the hyaluronic acid scaffold, already developed in the laboratory, has been used for the first time to maintain long-term cultures of CD34⁺ haematopoietic cells obtained from human cord blood. One parameter investigated was the impact on ex vivo survival of CD34⁺ cord blood cells (CBCs) on the hyaluronic acid surface, immobilized with peptides containing the RGD motif. This peptide was conjugated by coating the hyaluronan hydrogel and cultured in serum-free liquid phase complemented with stem cell factor (SCF), a commonly indispensable cytokine for haematopoiesis. Our work demonstrated that these hyaluronan hydrogels were superior to traditional liquid cultures by maintaining and expanding the HPCs without the need for additional cytokines, and a colonization of 280-fold increment in the hydrogel compared with liquid culture after 28 days of ex vivo expansion. Copyright © 2012 John Wiley & Sons, Ltd.

  20. Hyaluronan functionalizing QDs as turn-on fluorescent probe for targeted recognition CD44 receptor (United States)

    Zhou, Shang; Huo, Danqun; Hou, Changjun; Yang, Mei; Fa, Huanbao


    The recognition of tumor markers in living cancer cells has attracted increasing interest. In the present study, the turn-on fluorescence probe was designed based on the fluorescence of thiolated chitosan-coated CdTe QDs (CdTe/TCS QDs) quenched by hyaluronan, which could provide the low background signal for sensitive cellular imaging. This system is expected to offer specific recognition of CD44 receptor over other substances owing to the specific affinity of hyaluronan and CD44 receptor ( 8-9 kcal/mol). The probe is stable in aqueous and has little toxicity to living cells; thus, it can be utilized for targeted cancer cell imaging. The living lung cancer cell imaging experiments further demonstrate its value in recognizing cell-surface CD44 receptor with turn-on mode. In addition, the probe can be used to recognize and differentiate the subtypes of lung cancer cells based on the difference of CD44 expression on the surface of lung cancer cells. And, the western blot test further confirmed that the expression level of the CD44 receptor in lung cancer cells is different. Therefore, this probe may be potentially applied in recognizing lung cancer cells with higher contrast and sensitivity and provide new tools for cancer prognosis and therapy. [Figure not available: see fulltext.

  1. Intra-articular hyaluronans: the treatment of knee pain in osteoarthritis

    Directory of Open Access Journals (Sweden)

    Victor M Goldberg


    Full Text Available Victor M Goldberg1, Laura Goldberg21Department of Orthopaedics, Case Medical Center, Cleveland, Ohio, USA; 2Cleveland Clinic, Cleveland, Ohio, USAAbstract: The etiology of pain in osteoarthritis is multifactoral, and includes mechanical and inflammatory processes. Intra-articular injections of hyaluronans (HAs are indicated when non-pharmacological and simple analgesics have failed to relieve symptoms. The HAs appear to reduce pain by restoring both mechanical and biomechanical homeostasis in the joint. There are five FDA-approved injectable preparations of HAs: Hyalgan®, Synvisc®, Supartz®, Orthovisc® and Euflexxa®. They all appear to relieve pain from 4 to 14 weeks after injection and may have disease-modification properties. Although several randomized controlled trials have established the efficacy of this treatment modality, additional high quality randomized control studies with appropriate comparison are still required to clearly define the role of intra-articular HA injections in the treatment of osteoarthritis.Keywords: hyaluronans, knee, pain, osteoarthritis

  2. Wound dressing based on chitosan/hyaluronan/nonwoven fabrics: Preparation, characterization and medical applications. (United States)

    Abdel-Rahman, Rasha M; Abdel-Mohsen, A M; Hrdina, R; Burgert, L; Fohlerova, Z; Pavliňák, D; Sayed, O N; Jancar, J


    Thin layers of chitosan (positively charged)/sodium hyaluronate (negatively charged)/nonwoven fabrics were constructed by polyelectrolyte multilayer pad-dry-cure technique. Pure chitosan (CS) was isolated from shrimp shell and immobilized onto nonwoven fabrics (NWFs) using citric acid (CTA) as cross linker and solvent agents through a pad-dry-cure method. The prepared thin layer of chitosan citrate/nonwoven fabrics (CSCTA/NWFs) were consequently impregnated with hyaluronan (CSCTA/HA/NWFs) in the second path through a pad-dry-cure method. Chitosan/hyaluronan/nonwoven fabrics wound dressing was characterized by different techniques such as FTIR-ATR, TGA and SEM. The antibacterial activity and the cytotoxicity of the dressing sheets were evaluated against Escherichia coli (E. coli) and Streptococcus aureus (S. aureus), mouse fibroblast (NIH-3T3) and keratinocytes (HaCaT) cell lines, respectively. The cell-fabrics interaction was also investigated using fluorescence microscope, based on live/dead staining assay of 3T3 cells. The healing properties of the new wound dressing were evaluated and compared with the control sample. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Can hyaluronan injections augment deficient papillae at implant-supported crowns in the anterior maxilla?

    DEFF Research Database (Denmark)

    Bertl, Kristina; Gotfredsen, Klaus; Jensen, Simon S


    OBJECTIVES: The present randomized controlled trial aimed to assess the effect of hyaluronan (HY) injections to augment deficient interproximal papillae at implant-supported crowns in the anterior maxilla. METHODS: Twenty-two patients with a deficient papilla in the anterior maxilla next to an im......OBJECTIVES: The present randomized controlled trial aimed to assess the effect of hyaluronan (HY) injections to augment deficient interproximal papillae at implant-supported crowns in the anterior maxilla. METHODS: Twenty-two patients with a deficient papilla in the anterior maxilla next...... to an implant-supported crown were randomly assigned to receive twice either HY (test) or saline solution (control) injection. The following parameters were recorded prior to injection (baseline) and 3 and 6 months after injection: distance between the papilla tip and contact point (PT-CP), modified papilla...... index score (MPIS), and standard clinical periodontal parameters. Pain level after injection was recorded on a visual analogue scale (VAS). The deficient area was evaluated on clinical photographs, and the esthetic appearance was recorded on a VAS. Differences in mucosal volume were assessed after 3...

  4. Self-reinforcement and protein sustained delivery of hyaluronan hydrogel by tailoring a dually cross-linked network

    Energy Technology Data Exchange (ETDEWEB)

    Luo, Chunhong; Xu, Guoguang; Wang, Xinghui [Department of Materials Science and Engineering, College of Science and Engineering, Jinan University, Guangzhou 510632 (China); Tu, Mei; Zeng, Rong; Rong, Jianhua [Department of Materials Science and Engineering, College of Science and Engineering, Jinan University, Guangzhou 510632 (China); Engineering Research Center of Artificial Organs and Materials, Ministry of Education, Guangzhou 510632 (China); Zhao, Jianhao, E-mail: [Department of Materials Science and Engineering, College of Science and Engineering, Jinan University, Guangzhou 510632 (China); Engineering Research Center of Artificial Organs and Materials, Ministry of Education, Guangzhou 510632 (China)


    A series of self-reinforcing hyaluronan hydrogels were developed to improve mechanical properties and protein sustained delivery thanks to a dually cross-linked network. Hyaluronan gel particles (HGPs, 1–5 μm in diameter) with different cross-linking densities, i.e. HGPs-1.5, HGPs-3 and HGPs-15, were prepared in an inverse emulsion system and used as the reinforcing phase after glycidyl methacrylation, while glycidyl methacrylated hyaluronan with a substitution degree of 45.2% was synthesized as the matrix phase. These two phases were cross-linked under ultraviolet irradiation to form self-reinforcing hyaluronan hydrogels (srHAs) that showed typical cross-linked structure of HGPs connecting the matrix phase by cross-section observation. In comparison to hyaluronan bulk gels and their blends with HGPs, srHAs distinctly enhanced the mechanical properties and BSA long-term sustained delivery, especially srHA-1.5 showed the highest compressive modulus of 220 ± 15 kPa and the slowest BSA delivery (67% release at 14 d). The 3T3 fibroblast cell culture showed that all the srHAs had no cytotoxicity. - Highlights: • New self-reinforcing HA hydrogels with a dually cross-linked network were developed. • Self-reinforcing HA hydrogels greatly enhanced the mechanical properties. • Self-reinforcing HA hydrogels prolonged the sustained delivery of BSA. • The self-reinforcing mechanism and BSA diffusion mechanism were discussed. • Self-reinforcing HA hydrogels had no cytotoxicity to 3T3 fibroblast cells.

  5. Effect of molecular weight and concentration of hyaluronan on cell proliferation and osteogenic differentiation in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Ningbo, E-mail:; Wang, Xin, E-mail:; Qin, Lei, E-mail:; Guo, Zhengze, E-mail:; Li, Dehua, E-mail:


    Hyaluronan (HA), the simplest glycosaminoglycan and a major component of the extracellular matrix, exists in various tissues. It is involved in some critical biological procedures, including cellular signaling, cell adhesion and proliferation, and cell differentiation. The effect of molecular weight (MW) and concentration of HA on cell proliferation and differentiation was controversial. In this study, we investigated the effect of MW and concentration of HA on the proliferation and osteogenic differentiation of rabbit bone marrow-derived stem cells in vitro. Results showed that high MW HA decreased the cell adhesion rate in a concentration-dependant manner. The cell adhesion rate was decreased by increasing MW of HA. Cell proliferation was significantly enhanced by low MW HA (P < 0.05). The factorial analysis indicated that MW and concentration had an interactive effect on the cell adhesion rate and cell proliferation (P < 0.05). High MW HA increased the mRNA expressions of ALP, RUNX-2 and OCN. The higher the MW was, the higher the mRNA expressions were. The factorial analysis indicated that MW and concentration had an interactive effect on ALP mRNA expression (P < 0.05). HA of higher MW and higher concentration promoted bone formation. These findings provide some useful information in understanding the mechanism underlying the effect of MW and concentration of HA on cell proliferation and differentiation. - Highlights: • Effect of hyaluronan on cell proliferation and differentiation is evaluated in vitro. • Hyaluronan of low molecular weight increases cell proliferation. • Hyaluronan of high molecular weight promotes cell osteogenic differentiation. • Molecular weight and concentration of hyaluronan show interactive effect.

  6. The effect of different doses of hyaluronan on sperm morphology, motility, vitality and fertilization capability in mouse

    Directory of Open Access Journals (Sweden)

    S. Sayadi


    Full Text Available Background: Hyaluronan has an important role on the permeability and motility of sperm and the interaction of gametes and these can play a considerable role on the fertility rate. Therefore, in this study, we assessed the effect of different doses of hyaluronan on the morphology, motility, vitality and fertility rate of mice. Methods: We used 40 mice (6-8 week in this study which twenty of them were male and the rest were female. The sperm of each male mouse were divided into four groups. The group 1 (control: They were maintained in RPMI media without any hyaluronan supplementation for 2 hour. Hyaluronan with the doses of 750, 1000 and 1250 µg/ml were added into RPMI media in groups 2, 3 and 4, respectively. After 2 hour. incubation, the numbers of sperms were assessed, using haemocytometer. Also, their morphology with papanicolaeu staining and their vitality with Eosin B dye were assessed. As well as sperms motility measured under inverted microscope by observation and fertility rate evaluated after routine IVF by counting two-cell stage embryos. Results: Our results demonstrated that, the dose of 750 µ g/ml has the greatest effect on the motility, vitality and fertility rate of sperms. The effect of dose of 1000 µ g/ml also was positive on them. On the other hand, none of these doses had any effect on sperm morphology. Conclusion: Hyaluronan may have an influence on motility, vitality and fertility rate of sperms and the dose of 750µ g/ml had a significant effect on these factors.

  7. Desiring TESOL and International Education: Market Abuse and Exploitation (United States)

    Chowdhury, Raqib; Ha, Phan Le


    This book addresses how Western universities have constructed themselves as global providers of education, and are driven to be globally competitive. It examines how the term "international" has been exploited by the market in the form of government educational policies and agencies, host institutions, academia and the mass media. The…

  8. Enhancing hyaluronan pseudoplasticity via 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride-mediated conjugation with short alkyl moieties

    NARCIS (Netherlands)

    Petta, Dalila; Eglin, D.; Grijpma, Dirk W.; D'Este, M.


    Hyaluronan (HA) is widely used in the clinical practice and in biomedical research. Through chemical modification, HA shear-thinning properties, essential for injectability and additive manufacturing, can be optimized. In this study, we employed

  9. Exploitation Strategies in Social Parasites of Fungus Growing Ants

    DEFF Research Database (Denmark)

    Clement, Janni Dolby

    One of the most remarkable and complex parasitic interactions is social parasitism, where a parasite exploits a complete society, rather than an individual organism. By integrating into a society the parasite gains protection against predators and diseases, and can redirect resources from the host...... to increase its own fitness. The host will use a sophisticated recognition system in order to accept nestmates and expel intruders from their societies. However this defence barrier can be overcome by parasites. Among the most specialized social parasites are the inquilines that exploit social insect colonies...... to this are Acromyrmex insinuator and Acromyrmex ameliae, parasites of fungus-growing ants. By still producing a worker caste both species offers a rare opportunity to study adaptive features in parasite worker behaviour. Furthermore can closely related inquiline-host combinations give us an insight in the trade...

  10. Thermo-and pH-sensitive hydrogel membranes composed of poly(N-isopropylacrylamide)-hyaluronan for biomedical applications: Influence of hyaluronan incorporation on the membrane properties. (United States)

    Kamoun, Elbadawy A; Fahmy, Alaa; Taha, Tarek H; El-Fakharany, Esmail M; Makram, Mohamed; Soliman, Hesham M A; Shehata, Hassan


    Interpenetrating hydrogel membranes consisting of pH-sensitive hyaluronan (HA) and thermo-sensitive poly(N-isopropylacrylamide) (PNIPAAM) were synthesized using redox polymerization, followed by N,N-methylenebisacrylamide (BIS) and epichlorohydrin (EPI) were added as chemical crosslinkers. The interaction between membrane compositions has been characterized by FTIR spectroscopy and discussed intensively. The result indicates that HA incorporation in membranes increase the gel fraction, swelling uptake, and the flexibility/elasticity of crosslinked membranes, however it reduced oppositely the mechanical elongation of membranes. PNIPAAm-HA hydrogels responded to both temperature and pH changes and the stimuli-responsiveness was reversible. However, in vitro bioevaluation results revealed that the released ampicillin during the burst release time was sharply influenced and increased with increasing HA contents in membranes; afterwards it became sustainable. Whereas, high HA contents in hydrogels unexpectedly impacted negatively on the cells viability, owing to the viscosity of cell culture media changed. A big resistance was observed against microbial growth of Staphylococcus aureus, Salmonella typhi, and Candida albicans in case of pure PNIPAAm hydrogel membranes without HA or ampicillin. However, HA incorporation or the loaded ampicillin in membranes showed unexpected easily microbial growth. The fast release performance with dual pH-thermo-sensitive hydrogels were suggested as promising materials for quick drug carrier in the biomedical field. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Hyaluronan and Hyaluronan-Binding Proteins Accumulate in Both Human Type 1 Diabetic Islets and Lymphoid Tissues and Associate With Inflammatory Cells in Insulitis (United States)

    Bogdani, Marika; Johnson, Pamela Y.; Potter-Perigo, Susan; Nagy, Nadine; Day, Anthony J.; Bollyky, Paul L.


    Hyaluronan (HA) is an extracellular matrix glycosaminoglycan that is present in pancreatic islets, but little is known about its involvement in the development of human type 1 diabetes (T1D). We have evaluated whether pancreatic islets and lymphoid tissues of T1D and nondiabetic organ donors differ in the amount and distribution of HA and HA-binding proteins (hyaladherins), such as inter-α-inhibitor (IαI), versican, and tumor necrosis factor–stimulated gene-6 (TSG-6). HA was dramatically increased both within the islet and outside the islet endocrine cells, juxtaposed to islet microvessels in T1D. In addition, HA was prominent surrounding immune cells in areas of insulitis. IαI and versican were present in HA-rich areas of islets, and both molecules accumulated in diabetic islets and regions exhibiting insulitis. TSG-6 was observed within the islet endocrine cells and in inflammatory infiltrates. These patterns were only observed in tissues from younger donors with disease duration of cell areas in lymph nodes and spleens in T1D patients compared with control subjects. Our observations highlight potential roles for HA and hyaladherins in the pathogenesis of diabetes. PMID:24677718

  12. Nanofilms of hyaluronan/chitosan assembled layer-by-layer: An antibacterial surface for Xylella fastidiosa. (United States)

    Hernández-Montelongo, Jacobo; Nascimento, Vicente F; Murillo, Duber; Taketa, Thiago B; Sahoo, Prasana; de Souza, Alessandra A; Beppu, Marisa M; Cotta, Monica A


    In this work, nanofilms of hyaluronan/chitosan (HA/CHI) assembled layer by layer were synthesized; their application as a potential antimicrobial material was demonstrated for the phytopathogen Xylella fastidiosa, a gram-negative bacterium, here used as a model. For the synthesis, the influence of pH and ionic strength of these natural polymer stem-solutions on final characteristics of the HA/CHI nanofilms was studied in detail. The antibacterial effect was evaluated using widefield fluorescence microscopy. These results were correlated with the chemical properties of the nanofilms, studied by FTIR and Raman spectroscopy, as well as with their morphology and surface properties characterized using SEM and AFM. The present findings can be extended to design and optimize HA/CHI nanofilms with enhanced antimicrobial behavior for other type of phytopathogenic gram-negative bacteria species, such as Xanthomonas citri, Xanthomas campestri and Ralstonia solanacearum. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Anti-inflammatory effects of hyaluronan in arthritis therapy: Not just for viscosity

    Directory of Open Access Journals (Sweden)

    Kayo Masuko


    Full Text Available Kayo Masuko1, Minako Murata2, Kazuo Yudoh2, Tomohiro Kato1, Hiroshi Nakamura31Department of Biochemistry; 2Institute of Medical Science, St. Marianna University School of Medicine, Kawasaki-shi, Kanagawa, Japan; 3Department of Joint Disease and Rheumatism, Nippon Medical School, Bunkyo-ku, Tokyo, JapanAbstract: Hyaluronic acid (HA has been widely used for viscosupplementation of diseased or aged articular joints. However, recent investigations have revealed the active anti-inflammatory or chondroprotective effect of HA, suggesting its potential role in attenuation of joint damage. In particular, interactions between HA and other inflammatory mediators are attracting interest. This review summarizes several aspects of recent investigations of the anti-inflammatory effects of HA in arthritis.Keywords: hyaluronan, inflammation, chondroprotection

  14. Adverse reaction after hyaluronan injection for minimally invasive papilla volume augmentation

    DEFF Research Database (Denmark)

    Bertl, Kristina; Gotfredsen, Klaus; Jensen, Simon S


    tenderness with a burning sensation on the lip next to the injection area, after the second injection session. In one of the cases, a net-like skin discoloration (livedo reticularis) was also noted. The symptoms lasted for up to 7 days, and in both cases, symptoms resolved without any signs of skin......OBJECTIVES: To report two cases of adverse reaction after mucosal hyaluronan (HY) injection around implant-supported crowns, with the aim to augment the missing interdental papilla. MATERIAL AND METHODS: Two patients with single, non-neighbouring, implants in the anterior maxilla, who were treated...... within the frames of a randomized controlled clinical trial testing the effectiveness of HY gel injection to reconstruct missing papilla volume at single implants, presented an adverse reaction. Injection of HY was performed bilaterally using a 3-step technique: (i) creation of a reservoir in the mucosa...

  15. Growth promoting effect of hyaluronan synthesis promoting substances on Japanese eel leptocephali.

    Directory of Open Access Journals (Sweden)

    Yutaka Kawakami

    Full Text Available Hyaluronans (HAs are glycosaminoglycans produced in the bodies of Anguilliform and Elopiform leptocephali, and play a role in metabolic energy. In mammals, HA synthesis-promoting substances (HASPS up-regulate the expression of HA synthase (HAS and increase the amount of HA in the body. In this study, Japanese eel leptocephali were fed a HASPS containing diet. We analyzed HAS1s and HAS2 expression, HA content, and their influence on growth. HASPS extracted from Grifola frondosa promoted HAS1s and HAS2 mRNA and HA content. Other than mammals, these results are first reported in vertebrate. Moreover, HASPS extracted from G. frondosa promoted leptocephalus growth. The relationship between growth and HA in the leptocephali is not yet clear. However, based on our results we hypothesize that HA is involved in the storage of energy, which is metabolized to sugars when needed for metabolic energy.

  16. Growth Promoting Effect of Hyaluronan Synthesis Promoting Substances on Japanese Eel Leptocephali (United States)

    Kawakami, Yutaka; Nomura, Kazuharu; Tanaka, Hideki


    Hyaluronans (HAs) are glycosaminoglycans produced in the bodies of Anguilliform and Elopiform leptocephali, and play a role in metabolic energy. In mammals, HA synthesis-promoting substances (HASPS) up-regulate the expression of HA synthase (HAS) and increase the amount of HA in the body. In this study, Japanese eel leptocephali were fed a HASPS containing diet. We analyzed HAS1s and HAS2 expression, HA content, and their influence on growth. HASPS extracted from Grifola frondosa promoted HAS1s and HAS2 mRNA and HA content. Other than mammals, these results are first reported in vertebrate. Moreover, HASPS extracted from G. frondosa promoted leptocephalus growth. The relationship between growth and HA in the leptocephali is not yet clear. However, based on our results we hypothesize that HA is involved in the storage of energy, which is metabolized to sugars when needed for metabolic energy. PMID:24896609

  17. Hyaluronan and RHAMM in Wound Repair and the “Cancerization” of Stromal Tissues

    Directory of Open Access Journals (Sweden)

    Cornelia Tolg


    Full Text Available Tumors and wounds share many similarities including loss of tissue architecture, cell polarity and cell differentiation, aberrant extracellular matrix (ECM remodeling (Ballard et al., 2006 increased inflammation, angiogenesis, and elevated cell migration and proliferation. Whereas these changes are transient in repairing wounds, tumors do not regain tissue architecture but rather their continued progression is fueled in part by loss of normal tissue structure. As a result tumors are often described as wounds that do not heal. The ECM component hyaluronan (HA and its receptor RHAMM have both been implicated in wound repair and tumor progression. This review highlights the similarities and differences in their roles during these processes and proposes that RHAMM-regulated wound repair functions may contribute to “cancerization” of the tumor microenvironment.

  18. Commercial sexual exploitation of children

    National Research Council Canada - National Science Library

    Mauricio Rojas Betancur; Raquel Mendez Villamizar; Diana Lucía Moreno


      We study the sexual exploitation of children contributing to the understanding of risk and situations favouring the entry and permanence of children and adolescents from the reconstruction of the...

  19. Hyaluronan Production by Renomedullary Interstitial Cells: Influence of Endothelin, Angiotensin II and Vasopressin

    Directory of Open Access Journals (Sweden)

    Sara Stridh


    Full Text Available The content of hyaluronan (HA in the interstitium of the renal medulla changes in relation to body hydration status. We investigated if hormones of central importance for body fluid homeostasis affect HA production by renomedullary interstitial cells in culture (RMICs. Simultaneous treatment with vasopressin and angiotensin II (Ang II reduced HA by 69%. No change occurred in the mRNA expressions of hyaluronan synthase 2 (HAS2 or hyaluronidases (Hyals, while Hyal activity in the supernatant increased by 67% and CD44 expression reduced by 42%. The autocoid endothelin (ET-1 at low concentrations (10−10 and 10−8 M increased HA 3-fold. On the contrary, at a high concentration (10−6 M ET-1 reduced HA by 47%. The ET-A receptor antagonist BQ123 not only reversed the reducing effect of high ET-1 on HA, but elevated it to the same level as low concentration ET-1, suggesting separate regulating roles for ET-A and ET-B receptors. This was corroborated by the addition of ET-B receptor antagonist BQ788 to low concentration ET-1, which abolished the HA increase. HAS2 and Hyal2 mRNA did not alter, while Hyal1 mRNA was increased at all ET-1 concentrations tested. Hyal activity was elevated the most by high ET-1 concentration, and blockade of ET-A receptors by BQ123 prevented about 30% of this response. The present study demonstrates an important regulatory influence of hormones involved in body fluid balance on HA handling by RMICs, thereby supporting the concept of a dynamic involvement of interstitial HA in renal fluid handling.

  20. Hyaluronan Rich Microenvironment in the Limbal Stem Cell Niche Regulates Limbal Stem Cell Differentiation. (United States)

    Gesteira, Tarsis F; Sun, Mingxia; Coulson-Thomas, Yvette M; Yamaguchi, Yu; Yeh, Lung-Kun; Hascall, Vincent; Coulson-Thomas, Vivien J


    Limbal epithelial stem cells (LSCs), located in the basal layer of the corneal epithelium in the corneal limbus, are vital for maintaining the corneal epithelium. LSCs have a high capacity of self-renewal with increased potential for error-free proliferation and poor differentiation. To date, limited research has focused on unveiling the composition of the limbal stem cell niche, and, more important, on the role the specific stem cell niche may have in LSC differentiation and function. Our work investigates the composition of the extracellular matrix in the LSC niche and how it regulates LSC differentiation and function. Hyaluronan (HA) is naturally synthesized by hyaluronan synthases (HASs), and vertebrates have the following three types: HAS1, HAS2, and HAS3. Wild-type and HAS and TSG-6 knockout mice-HAS1-/-;HAS3-/-, HAS2Δ/ΔCorEpi, TSG-6-/--were used to determine the importance of the HA niche in LSC differentiation and specification. Our data demonstrate that the LSC niche is composed of a HA rich extracellular matrix. HAS1-/-;HAS3-/-, HAS2Δ/ΔCorEpi, and TSG-6-/- mice have delayed wound healing and increased inflammation after injury. Interestingly, upon insult the HAS knock-out mice up-regulate HA throughout the cornea through a compensatory mechanism, and in turn this alters LSC and epithelial cell specification. The LSC niche is composed of a specialized HA matrix that differs from that present in the rest of the corneal epithelium, and the disruption of this specific HA matrix within the LSC niche leads to compromised corneal epithelial regeneration. Finally, our findings suggest that HA has a major role in maintaining the LSC phenotype.

  1. Increased concentration of hyaluronan in tears after soaking contact lenses in Biotrue multipurpose solution

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    Scheuer CA


    Full Text Available Catherine A Scheuer, Marjorie J Rah, William T Reindel Vision Care, Bausch & Lomb Incorporated, Rochester, NY, USA Purpose: This study was conducted to determine 1 the concentration of hyaluronan (HA in the tear films of contact lens (CL wearers versus non-CL wearers and 2 whether HA sorbed from Biotrue, an HA-containing multipurpose solution (MPS, onto senofilcon A lenses affects the concentration of HA in tears after 2 hours of wear.Patients and methods: Tears of habitual CL wearers and non-CL wearers were collected on Schirmer strips at baseline and after 2 hours of wear of senofilcon A CLs that had first been either rinsed with Sensitive Eyes Saline or soaked in Biotrue MPS for 14 hours. HA concentrations were measured by enzyme-linked immunosorbent assay (ELISA and adjusted for sample volumes.Results: No difference in baseline concentrations of HA in tears was found between CL wearers and non-CL wearers (P=0.07, nor between males and females (P=0.06. However, age was significantly negatively associated with HA concentration (P<0.01, and mostly, CL wear contributed to a significant association (P<0.01. Among saline-rinsed CL wearers, no change in HA concentration in tears was observed after 2 hours of wear (P=0.38. By contrast, a significant increase in HA concentration was observed in the tears from eyes that had worn CLs soaked in Biotrue MPS when compared to baseline (P=0.01 or to saline-rinsed control (P=0.03.Conclusion: 1 In this study population, no difference in baseline concentration of HA was observed between CL wearers and non-CL wearers, and 2 after 2 hours of wear of senofilcon A lenses that were soaked in Biotrue MPS, HA concentrations in the tear films of CL wearers increased. Keywords: contact lens, dry eye, hyaluronan, MPS

  2. Sulfated hyaluronan improves bone regeneration of diabetic rats by binding sclerostin and enhancing osteoblast function. (United States)

    Picke, Ann-Kristin; Salbach-Hirsch, Juliane; Hintze, Vera; Rother, Sandra; Rauner, Martina; Kascholke, Christian; Möller, Stephanie; Bernhardt, Ricardo; Rammelt, Stefan; Pisabarro, M Teresa; Ruiz-Gómez, Gloria; Schnabelrauch, Matthias; Schulz-Siegmund, Michaela; Hacker, Michael C; Scharnweber, Dieter; Hofbauer, Christine; Hofbauer, Lorenz C


    Bone fractures in patients with diabetes mellitus heal poorly and require innovative therapies to support bone regeneration. Here, we assessed whether sulfated hyaluronan included in collagen-based scaffold coatings can improve fracture healing in diabetic rats. Macroporous thermopolymerized lactide-based scaffolds were coated with collagen including non-sulfated or sulfated hyaluronan (HA/sHA3) and inserted into 3 mm femoral defects of non-diabetic and diabetic ZDF rats. After 12 weeks, scaffolds coated with collagen/HA or collagen/sHA3 accelerated bone defect regeneration in diabetic, but not in non-diabetic rats as compared to their non-coated controls. At the tissue level, collagen/sHA3 promoted bone mineralization and decreased the amount of non-mineralized bone matrix. Moreover, collagen/sHA3-coated scaffolds from diabetic rats bound more sclerostin in vivo than the respective controls. Binding assays confirmed a high binding affinity of sHA3 to sclerostin. In vitro, sHA3 induced BMP-2 and lowered the RANKL/OPG expression ratio, regardless of the glucose concentration in osteoblastic cells. Both sHA3 and high glucose concentrations decreased the differentiation of osteoclastic cells. In summary, scaffolds coated with collagen/sHA3 represent a potentially suitable biomaterial to improve bone defect regeneration in diabetic conditions. The underlying mechanism involves improved osteoblast function and binding sclerostin, a potent inhibitor of Wnt signaling and osteoblast function. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Cryo-survival and development of bovine blastocysts are enhanced by culture with recombinant albumin and hyaluronan. (United States)

    Lane, Michelle; Maybach, Jeffrey M; Hooper, Kathy; Hasler, John F; Gardner, David K


    Recombinant albumin can be used to supplement culture medium for the maturation and fertilization of bovine oocytes and subsequent embryo development to the blastocyst stage. Recombinant albumin was able to support blastocyst development at rates equivalent to that of bovine serum albumin (BSA) supplemented media. Supplementation of media containing recombinant albumin and citrate stimulated blastocyst expansion. Culture with recombinant albumin and citrate significantly increased the ability of the resultant blastocysts to re-expand and hatch following cryopreservation. The further addition of the glycosaminoglycan hyaluronan to the culture medium containing either BSA or recombinant albumin also increased the ability of blastocysts to survive cryopreservation. Inclusion of recombinant albumin and hyaluronan in culture media facilitates the development of physiological defined culture conditions. For bovine embryos this has implications for both research and commercial applications where defined reproducible conditions are desirable. Copyright 2003 Wiley-Liss, Inc.

  4. A role for the endothelial glycosaminoglycan hyaluronan in neutrophil recruitment by endothelial cells cultured for prolonged periods


    Butler, Lynn M.; Rainger, G.Ed; Nash, Gerard B


    Glycosaminoglycans (GAGs) presented on the surface of endothelial cells (ECs) are believed to influence leukocyte recruitment during inflammation, but their roles remain uncertain. Here we report an in vitro model of prolonged culture of human EC in which the contributions of heparan sulphate (HS) and hyaluronan (HA) to the process of neutrophil recruitment could be studied. Previously, we reported that increasing EC culture duration (up to 20?days) enhanced neutrophil recruitment in response...

  5. Effect of addition of hyaluronan to embryo culture medium on survival of bovine embryos in vitro following vitrification and establishment of pregnancy after transfer to recipients. (United States)

    Block, J; Bonilla, L; Hansen, P J


    Two experiments were conducted to determine whether addition of hyaluronan to culture medium could improve survival of bovine embryos after vitrification or following embryo transfer. In Experiment 1, embryos were produced in vitro and cultured for 7 days in modified synthetic oviductal fluid (SOF) containing one of four concentrations of hyaluronan (0, 0.1, 0.5, or 1mg/mL), with or without 4 mg/mL of bovine serum albumin (BSA). On Day 7 after insemination, blastocysts and expanded blastocysts were vitrified using open-pulled straws. At a concentration of 1mg/mL, hyaluronan increased (Pembryo hatching rate at 24 and 72 h. Treatment with BSA caused a slight reduction in cleavage rate (Pembryos were produced in vitro and cultured in modified SOF containing 4 mg/mL BSA, with or without 1mg/mL hyaluronan. At 159-162 h after insemination, grade 1 morula, blastocysts and expanded blastocysts were harvested for embryo transfer. Harvested embryos were transferred individually to lactating Holstein recipients with a palpable corpus luteum on Day 7 after presumptive ovulation. There was an interaction (Pembryo stage on pregnancy rate. Recipients that received morula and blastocyst stage embryos treated with hyaluronan had a higher pregnancy rate than recipients that received control embryos of the same stage. There was no effect of hyaluronan on pregnancy rates of recipients that received expanded blastocysts. In conclusion, addition of hyaluronan to embryo culture enhanced blastocyst yield, improved survival following vitrification, and enhanced the post-transfer survival of fresh morula and blastocyst stage embryos.

  6. Exploitation et obligation de travailler

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    Pierre-Étienne Vandamme


    Full Text Available Cet article défend une définition de l’exploitation, restreinte aux relations de travail, en tentant d’une part d’expliciter une certaine compréhension de sens commun du concept (rémunération inéquitable en fonction du travail presté, et d’autre part d’échapper aux difficultés qui ont affecté la définition marxiste traditionnelle de l’exploitation comme extorsion de la plus-value (dans ses diverses variantes. Il explore ainsi le lien entre l’exploitation et l’obligation matérielle de travailler pour subvenir à ses besoins fondamentaux. Après avoir mis en garde contre les politiques d’activation des chômeurs, il conclut que l’exploitation est un phénomène contre lequel on peut lutter à l’aide de mécanismes relativement simples, même dans les sociétés capitalistes. Il rappelle toutefois que cela ne suffit pas à réaliser la justice sociale, resituant l’exploitation parmi d’autres enjeux fondamentaux pour une philosophie politique égalitariste

  7. Hyaluronan-Based Nanohydrogels as Effective Carriers for Transdermal Delivery of Lipophilic Agents: Towards Transdermal Drug Administration in Neurological Disorders

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    Seong Uk Son


    Full Text Available We suggest a convenient nanoemulsion fabrication method to create hyaluronan (HA-based nanohydrogels for effective transdermal delivery. First, hyaluronan-conjugated dodecylamine (HA–Do HA-based polymers to load the lipophilic agents were synthesized with hyaluronan (HA and dodecylamine (Do by varying the substitution ratio of Do to HA. The synthetic yield of HA–Do was more than 80% (HA–Do (A: 82.7 ± 4.7%, HA–Do (B: 87.1 ± 3.9% and HA–Do (C: 81.4 ± 4.5%. Subsequently, nanohydrogels were fabricated using the nanoemulsion method. Indocyanine green (ICG simultaneously self-assembled with HA–Do, and the size depended on the substitution ratio of Do in HA–Do (nanohydrogel (A: 118.0 ± 2.2 nm, nanohydrogel (B: 121.9 ± 11.4 nm, and nanohydrogel (C: 142.2 ± 3.8 nm. The nanohydrogels were delivered into cells, and had excellent biocompatibility. Especially, nanohydrogel (A could deliver and permeate ICG into the deep skin layer, the dermis. This suggests that nanohydrogels can be potent transdermal delivery systems.

  8. Green synthesis, characterization, and anticancer activity of hyaluronan/zinc oxide nanocomposites

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    Namvar F


    Full Text Available Farideh Namvar,1,2 Susan Azizi,3 Heshu Sulaiman Rahman,4–6 Rosfarizan Mohamad,1,3 Abdullah Rasedee,4 Mozhgan Soltani,2 Raha Abdul Rahim71Institute of Tropical Forestry and Forest Products (INTROP, Universiti Putra Malaysia, UPM Serdang, Selangor, Malaysia; 2Research Center for Animal Development Applied Biology, Mashhad Branch, Islamic Azad University, Mashhad, Iran; 3Department of Bioprocess Technology, Faculty of Biotechnology and Biomolecular Sciences, 4Department of Veterinary Laboratory Diagnosis, Faculty of Veterinary Medicine, Universiti Putra Malaysia, UPM Serdang, Selangor, Malaysia; 5Department of Clinic and Internal Medicine, College of Veterinary Medicine, University of Sulaimani, 6Department of Laboratory Medical Sciences, Komar University of Science and Technology, Sulaimani City, Kurdistan Region, Northern Iraq; 7Department of Cell and Molecular Biology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, UPM Serdang, Selangor, Malaysia Abstract: The study describes an in situ green biosynthesis of zinc oxide nanocomposite using the seaweed Sargassum muticum water extract and hyaluronan biopolymer. The morphology and optical properties of the hyaluronan/zinc oxide (HA/ZnO nanocomposite were determined by Fourier transform infrared spectroscopy, X-ray diffraction, field emission scanning electron microscopy, transmission electron microscopy, and ultraviolet–vis analysis. Electron microscopy and X-ray diffraction analysis showed that the zinc oxide nanoparticles were polydispersed with a mean size of 10.2±1.5 nm. The nanoparticles were mostly hexagonal in crystalline form. The HA/ZnO nanocomposite showed the absorption properties in the ultraviolet zone that is ascribed to the band gap of zinc oxide nanocomposite. In the cytotoxicity study, cancer cells, pancreatic adenocarcinoma (PANC-1, ovarian adenocarcinoma (CaOV-3, colonic adenocarcinoma (COLO205, and acute promyelocytic leukemia (HL-60 cells

  9. Tumor targeting profiling of hyaluronan-coated lipid based-nanoparticles (United States)

    Mizrahy, Shoshy; Goldsmith, Meir; Leviatan-Ben-Arye, Shani; Kisin-Finfer, Einat; Redy, Orit; Srinivasan, Srimeenakshi; Shabat, Doron; Godin, Biana; Peer, Dan


    Hyaluronan (HA), a naturally occurring high Mw (HMw) glycosaminoglycan, has been shown to play crucial roles in cell growth, embryonic development, healing processes, inflammation, and tumor development and progression. Low Mw (LMw, melanoma cells. LMw HA-tsNPs exhibited weak binding, while binding of tsNPs coated with HMw HA was characterized by high binding. Both types of tsNPs had no measured effect on cytokine induction in vivo following intravenous administration to healthy C57BL/6 mice suggesting no immune activation. HMw HA-tsNPs showed enhanced circulation time and tumor targeting specificity, mainly by accumulating in the tumor and its vicinity compared with LMw HA-tsNPs. Finally, we show that methotrexate (MTX), a drug commonly used in cancer chemotherapy, entrapped in HMw HA-tsNPs slowly diffused from the particles with a half-life of 13.75 days, and improved the therapeutic outcome in a murine B16F10 melanoma model compared with NPs suggesting an active cellular targeting beyond the Enhanced Permeability and Retention (EPR) effect. Taken together, these findings have major implications for the use of high molecular weight HA in nanomedicine as a selective and safe active cellular targeting moiety.Hyaluronan (HA), a naturally occurring high Mw (HMw) glycosaminoglycan, has been shown to play crucial roles in cell growth, embryonic development, healing processes, inflammation, and tumor development and progression. Low Mw (LMw, melanoma cells. LMw HA-tsNPs exhibited weak binding, while binding of tsNPs coated with HMw HA was characterized by high binding. Both types of tsNPs had no measured effect on cytokine induction in vivo following intravenous administration to healthy C57BL/6 mice suggesting no immune activation. HMw HA-tsNPs showed enhanced circulation time and tumor targeting specificity, mainly by accumulating in the tumor and its vicinity compared with LMw HA-tsNPs. Finally, we show that methotrexate (MTX), a drug commonly used in cancer

  10. Hosting a Katrina Evacuee. (United States)

    Hoagland, David


    No individual or institution anticipated the impact on the academic research community of hurricane Katrina. When Tulane physicist Wayne Reed asked me to host his research group just a day or two after the disaster, with no authorization or understanding of the commitment, I agreed immediately and then pondered implications. Fortunately, colleagues helped in making the commitment real, only the bureaucracy of my public university posing small hindrances. Industry was remarkably generous in providing Reed with significant ``loaner'' equipment, and amazingly, a suite of custom Reed experiments was running within weeks. At the end, the most productive collaborations for Reed seemed not to have been with my group, with its similar research, but to other groups at my institution, particularly the synthetic chemists, who gained access to methods previously unique to Tulane while offering samples previously unique to UMass. Quickly designed projects exploiting this match turned out remarkably productive. Although begun with trepidation, hosting of Reed had huge positive benefits to me and UMass, and I believe, also to Reed and Tulane. Some key lessons for the future: (i) industry has capacity and willingness to help academic research during disruption (ii) commitment of a host institution must be immediate, without a wait for formal approvals or arrangement of special funding -- delay leads only to discouragement, (iii) continuing academic progress of displaced students must come first, and (iv) intellectual synergy rather than overlap should be the basis for seeking a host. Lastly, NSF or other funding agency should consider a program directly addressing the research needs of unexpectedly disrupted academic scientists, and most particularly, graduate students who face greatly extended studies.

  11. Masquerading microbial pathogens: Capsular polysaccharides mimic host-tissue molecules (United States)

    Cress, Brady F.; Englaender, Jacob A.; He, Wenqin; Kasper, Dennis; Linhardt, Robert J.; Koffas, Mattheos A. G.


    Summary Bacterial pathogens bearing capsular polysaccharides identical to mammalian glycans benefit from an additional level of protection from host immune response. The increasing prevalence of antibiotic resistant bacteria portends an impending post-antibiotic age, characterized by diminishing efficacy of common antibiotics and routine application of multifaceted, complementary therapeutic approaches to treat bacterial infections, particularly multidrug-resistant organisms. The first line of defense for most bacterial pathogens consists of a physical and immunological barrier known as the capsule, commonly composed of a viscous layer of carbohydrates that are covalently bound to the cell wall in Gram-positive bacteria or often to lipids of the outer membrane in many Gram-negative bacteria. Bacterial capsular polysaccharides are a diverse class of high molecular weight polysaccharides contributing to virulence of many human pathogens in the gut, respiratory tree, urinary tract, and other host tissues, by hiding cell-surface components that might otherwise elicit host immune response. This review highlights capsular polysaccharides that are structurally identical or similar to polysaccharides found in mammalian tissues, including polysialic acid and glycosaminoglycan capsules hyaluronan, heparosan, and chondroitin. Such non-immunogenic coatings render pathogens insensitive to certain immune responses, effectively increasing residence time in host tissues and enabling pathologically relevant population densities to be reached. Biosynthetic pathways and capsular involvement in immune system evasion are described providing a basis for potential therapies aimed at supplementing or replacing antibiotic treatment. PMID:24372337

  12. Hyaluronan-Phosphatidylethanolamine Polymers Form Pericellular Coats on Keratinocytes and Promote Basal Keratinocyte Proliferation (United States)

    Symonette, Caitlin J.; Tan, Xiao Cherie; Tolg, Cornelia; Ma, Jenny; Perera, Francisco; Turley, Eva A.


    Aged keratinocytes have diminished proliferative capacity and hyaluronan (HA) cell coats, which are losses that contribute to atrophic skin characterized by reduced barrier and repair functions. We formulated HA-phospholipid (phosphatidylethanolamine, HA-PE) polymers that form pericellular coats around cultured dermal fibroblasts independently of CD44 or RHAMM display. We investigated the ability of these HA-PE polymers to penetrate into aged mouse skin and restore epidermal function in vivo. Topically applied Alexa647-HA-PE penetrated into the epidermis and dermis, where it associated with both keratinocytes and fibroblasts. In contrast, Alexa647-HA was largely retained in the outer cornified layer of the epidermis and quantification of fluorescence confirmed that significantly more Alexa647-HA-PE penetrated into and was retained within the epidermis than Alexa647-HA. Multiple topical applications of HA-PE to shaved mouse skin significantly stimulated basal keratinocyte proliferation and epidermal thickness compared to HA or vehicle cream alone. HA-PE had no detectable effect on keratinocyte differentiation and did not promote local or systemic inflammation. These effects of HA-PE polymers are similar to those reported for endogenous epidermal HA in youthful skin and show that topical application of HA-PE polymers can restore some of the impaired functions of aged epidermis. PMID:25276814

  13. Hyaluronan reduces surfactant inhibition and improves rat lung function after meconium injury. (United States)

    Lu, Karen W; Goerke, Jon; Clements, John A; Taeusch, H William


    Hyaluronan (HA), an ionic polymer, is normally present in the alveolar subphase and is known to decrease lung surfactant inactivation caused by serum in vitro. In this study, we examined whether HA can ameliorate the inactivating effects of meconium in vitro and in vivo. Surface activities of various mixtures of Survanta, HA, and meconium were measured using a modified pulsating bubble surfactometer. With meconium, almost all surface activity measures were improved by the addition of HA of several molecular weights at a concentration of 0.25%. Anesthetized, paralyzed rats were maintained on positive-pressure ventilation. After lung injury by instillation of meconium, they were treated with Survanta, Survanta with HA, or control mixtures. Serial measures of blood gases and peak inspiratory pressure were recorded for the duration of the experiment. When the Survanta plus HA group was compared with the Survanta alone group, arterial oxygen tension averaged 117% higher, peak inspiratory pressure was 27% lower at the end of the experiment, and lung compliance also showed significant improvement. These results indicate that HA added to Survanta decreases inactivation caused by meconium in vitro and improves gas exchange and pulmonary mechanics of animals with meconium-induced acute lung injury.

  14. Hydrogels of collagen/chondroitin sulfate/hyaluronan interpenetrating polymer network for cartilage tissue engineering. (United States)

    Guo, Yan; Yuan, Tun; Xiao, Zhanwen; Tang, Pingping; Xiao, Yumei; Fan, Yujiang; Zhang, Xingdong


    The network structure of a three-dimensional hydrogel scaffold dominates its performance such as mechanical strength, mass transport capacity, degradation rate and subsequent cellular behavior. The hydrogels scaffolds with interpenetrating polymeric network (IPN) structure have an advantage over the individual component gels and could simulate partly the structure of native extracellular matrix of cartilage tissue. In this study, to develop perfect cartilage tissue engineering scaffolds, IPN hydrogels of collagen/chondroitin sulfate/hyaluronan were prepared via two simultaneous processes of collagen self-assembly and cross linking polymerization of chondroitin sulfate-methacrylate (CSMA) and hyaluronic acid-methacrylate. The degradation rate, swelling performance and compressive modulus of IPN hydrogels could be adjusted by varying the degree of methacrylation of CSMA. The results of proliferation and fluorescence staining of rabbit articular chondrocytes in vitro culture demonstrated that the IPN hydrogels possessed good cytocompatibility. Furthermore, the IPN hydrogels could upregulate cartilage-specific gene expression and promote the chondrocytes secreting glycosaminoglycan and collagen II. These results suggested that IPN hydrogels might serve as promising hydrogel scaffolds for cartilage tissue engineering.

  15. Relationship between serum undercarboxylated osteocalcin and hyaluronan levels in patients with bilateral knee osteoarthritis. (United States)

    Naito, Kiyohito; Watari, Taiji; Obayashi, Osamu; Katsube, Sadanobu; Nagaoka, Isao; Kaneko, Kazuo


    Serum undercarboxylated osteocalcin (s-ucOC) is a marker for vitamin K metabolism (deficiency). The aim of this study was to investigate the serum levels of ucOC in patients with bilateral knee osteoarthritis (K-OA), and the correlation between ucOC and other biomarkers for K-OA. A total of 25 patients (22 women, 3 men, mean age 76.0±7.8, range 54-88 years, mean BMI 24.9±4.7) with a Kellgren-Lawrence grade of 3 or 4 for bilateral knee were enrolled in this study. The levels of s-ucOC and other biomarkers were measured. The levels of s-ucOC (5.66±4.70 ng/ml) as well as other cartilage metabolism markers, were elevated in the patients; however, bone metabolism markers were within the normal ranges. Of interest, there was a significant correlation between s-ucOC and serum hyaluronan (a marker for synovitis) (Pvitamin K metabolism may be associated with synovitis in patients with K-OA, and s-ucOC could be a biomarker for K-OA.

  16. Anticancer Effects of Sinulariolide-Conjugated Hyaluronan Nanoparticles on Lung Adenocarcinoma Cells

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    Kuan Yin Hsiao


    Full Text Available Lung cancer is one of the most clinically challenging malignant diseases worldwide. Sinulariolide (SNL, extracted from the farmed coral species Sinularia flexibilis, has been used for suppressing malignant cells. For developing anticancer therapeutic agents, we aimed to find an alternative for non-small cell lung cancer treatment by using SNL as the target drug. We investigated the SNL bioactivity on A549 lung cancer cells by conjugating SNL with hyaluronan nanoparticles to form HA/SNL aggregates by using a high-voltage electrostatic field system. SNL was toxic on A549 cells with an IC50 of 75 µg/mL. The anticancer effects of HA/SNL aggregates were assessed through cell viability assay, apoptosis assays, cell cycle analyses, and western blotting. The size of HA/SNL aggregates was approximately 33–77 nm in diameter with a thin continuous layer after aggregating numerous HA nanoparticles. Flow cytometric analysis revealed that the HA/SNL aggregate-induced apoptosis was more effective at a lower SNL dose of 25 µg/mL than pure SNL. Western blotting indicated that caspases-3, -8, and -9 and Bcl-xL and Bax played crucial roles in the apoptotic signal transduction pathway. In summary, HA/SNL aggregates exerted stronger anticancer effects on A549 cells than did pure SNL via mitochondria-related pathways.

  17. Evaluation of serum chondroitin sulfate and hyaluronan: biomarkers for osteoarthritis in canine hip dysplasia. (United States)

    Nganvongpanit, Korakot; Itthiarbha, Akanit; Ong-Chai, Siriwan; Kongtawelert, Prachya


    Hip dysplasia (HD) is one of the most important bone and joint diseases in dogs. Making the radiographic diagnosis is sometime possible when the disease has markedly progressed. Chondroitin sulfate (CS) and hyaluronan (HA) are the most important cartilage biomolecules that are elevated in the serum taken from dogs with osteoarthritis. The serum CS and HA can be detected by an ELISA technique, with using monoclonal antibodies against CS epitope 3B3 and WF6 and the HA chain as the primary antibodies. The aim of this study was to compare the levels of serum CS (both epitopes) and HA in non-HD and HD dogs. All 123 dogs were categorized into 2 groups. The non-HD group was composed of 98 healthy dogs, while the HD group was comprised of 25 HD dogs. Blood samples were collected for analyzing the serum CS and HA levels with using the ELISA technique. The results showed that the average serum level of the CS epitope WF6 in the HD group (2,594 +/- 3,036.10 ng/ml) was significantly higher than that in the non-HD group (465 +/- 208.97 ng/ml) (p dogs.

  18. Microvasculature of the Mouse Cerebral Cortex Exhibits Increased Accumulation and Synthesis of Hyaluronan With Aging. (United States)

    Reed, May J; Vernon, Robert B; Damodarasamy, Mamatha; Chan, Christina K; Wight, Thomas N; Bentov, Itay; Banks, William A


    The microvasculature of the aged brain is less dense and more vulnerable to dysfunction than that of the young brain. Brain microvasculature is supported by its surrounding extracellular matrix, which is comprised largely of hyaluronan (HA). HA is continually degraded into lower molecular weight forms that induce neuroinflammation. We examined HA associated with microvessels (MV) of the cerebral cortex of young (4 months), middle-aged (14 months), and aged (24-26 months) mice. We confirmed that the density of cortical MV decreased with age. Perivascular HA levels increased with age, but there was no age-associated change in HA molecular weight profile. MV isolated from aged cortex had more HA than MV from young cortex. Examination of mechanisms that might account for elevated HA levels with aging showed increased HA synthase 2 (HAS2) mRNA and protein in aged MV relative to young MV. In contrast, mRNAs for HA-degrading hyaluronidases or hyaladherins that mitigate HA degradation showed no changes with age. Corresponding to increased HAS2, aged MV synthesized significantly more HA (of all molecular weight classes) in vitro than young MV. We propose that increased HA synthesis and accumulation in brain MV contributes to neuroinflammation and reduced MV density and function in aging. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail:

  19. Distribution of versican and hyaluronan in the mouse uterus during decidualization

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    San Martin S.


    Full Text Available Preparation for embryo implantation requires extensive adaptation of the uterine microenvironment. This process consists of cell proliferation and cell differentiation resulting in the transformation of endometrial fibroblasts into a new type of cell called decidual cell. In the present study, we followed the space-time distribution of versican and hyaluronan (HA in different tissues of the uterus before and after embryo implantation. Fragments of mouse uteri obtained on the fourth, fifth, sixth and seventh days of pregnancy were fixed in Methacarn, embedded in Paraplast and cut into 5-µm thick sections. HA was detected using a biotinylated fragment of the proteoglycan aggrecan, which binds to this glycosaminoglycan with high affinity and specificity. Versican was detected by a polyclonal antibody. Both reactions were developed by peroxidase methods. Before embryo implantation, both HA and versican were present in the endometrial stroma. However, after embryo implantation, HA disappeared from the decidual region immediately surrounding the implantation chamber, whereas versican accumulated in the same region. The differences observed in the expression of HA and versican suggest that both molecules may participate in the process of endometrial decidualization and/or embryo implantation.

  20. Elasticity, biodegradability and cell adhesive properties of chitosan/hyaluronan multilayer films

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    Schneider, Aurore; Richert, Ludovic; Francius, Gregory; Voegel, Jean-Claude; Picart, Catherine [Present address: Universite de Montpellier II, CNRS-UMR 5539, cc107, Place Eugene Bataillon, 34 095 Montpellier Cedex 5 (France)


    In the bioengineering field, a recent and promising approach to modifying biomaterial surfaces is the layer-by-layer (LbL) technique used to build thin polyelectrolyte multilayer films. In this work, we focused on polyelectrolyte multilayer films made of two polysaccharides, chitosan (CHI) and hyaluronan (HA), and on the control of their physico-chemical and cell adhesive properties by chemical cross-linking. CHI/HA films were cross-linked using a water soluble carbodiimide and observed by confocal laser scanning microscopy (CLSM) with a fluorescently labeled CHI. Film thicknesses were similar for native and cross-linked films. The film nanometer roughness was measured by atomic force microscopy and was found to be higher for cross-linked films. Cross-linking the films also leads to a drastic change in film stiffness. The elastic modulus of the films (Young's modulus) as measured by AFM nano-indentation was about tenfold increased for cross-linked films as compared to native ones. From a biological point of view, cross-liked films are more resistant to enzymatic degradation by hyaluronidase. Furthermore, the increase in film stiffness has a favorable effect on the adhesion and spreading of chondrosarcoma cells. Thus, the CHI/HA cross-linked films could be used for various applications due to their adhesive properties and to their mechanical properties (including stability in enzymatic media)

  1. Oleyl-hyaluronan micelles loaded with upconverting nanoparticles for bio-imaging

    Energy Technology Data Exchange (ETDEWEB)

    Pospisilova, Martina, E-mail:; Mrazek, Jiri; Matuska, Vit; Kettou, Sofiane; Dusikova, Monika; Svozil, Vit; Nesporova, Kristina; Huerta-Angeles, Gloria; Vagnerova, Hana; Velebny, Vladimir [Contipro Biotech (Czech Republic)


    Hyaluronan (HA) represents an interesting polymer for nanoparticle coating due to its biocompatibility and enhanced cell interaction via CD44 receptor. Here, we describe incorporation of oleate-capped β–NaYF{sub 4}:Yb{sup 3+}, Er{sup 3+} nanoparticles (UCNP-OA) into amphiphilic HA by microemulsion method. Resulting structures have a spherical, micelle-like appearance with a hydrodynamic diameter of 180 nm. UCNP-OA-loaded HA micelles show a good stability in PBS buffer and cell culture media. The intensity of green emission of UCNP-OA-loaded HA micelles in water is about five times higher than that of ligand-free UCNP, indicating that amphiphilic HA effectively protects UCNP luminescence from quenching by water molecules. We found that UCNP-OA-loaded HA micelles in concentrations up to 50 μg mL{sup −1} increase cell viability of normal human dermal fibroblasts (NHDF), while viability of human breast adenocarcinoma cells MDA–MB–231 is reduced at these concentrations. The utility of UCNP-OA-loaded HA micelles as a bio-imaging probe was demonstrated in vitro by successful labelling of NHDF and MDA–MB–231 cells overexpressing the CD44 receptor.

  2. Evaluation of radius of gyration and intrinsic viscosity molar mass dependence and stiffness of hyaluronan. (United States)

    Mendichi, Raniero; Soltés, Ladislav; Giacometti Schieroni, Alberto


    Nine hyaluronan (HA) samples were fractionated by size-exclusion chromatography, and molar mass (M), radius of gyration (Rg), and intrinsic viscosity ([eta]) were measured in 0.15 M NaCl at 37 degrees C by on-line multiangle light scattering and viscometer detectors. Using such method, we investigated the Rg and [eta] molar mass dependence for HA over a very wide range of molar masses: M ranging from 4 x 10(4) to 5.5 x 10(6) g/mol. The Rg and the [eta] molar mass dependence found for HA showed a meaningful difference. The Rg = f(M) power law was substantially linear in the whole range of molar masses explored with a constant slope of 0.6. In contrast, the [eta] = f(M) power law (Mark-Houwink-Sakurada plot) showed a marked curve shape, and a linear regression over the whole range of molar masses does not make sense. Also the persistence length (stiffness) for HA was estimated. The persistence length derived by using both the Odijk's model (7.5 nm from Rg vs M data) and the Bohdanecky's plot (6.8 nm from [eta] vs M data) were quite similar. These persistence length values are congruent with a semistiff conformation of HA macromolecules.

  3. Study on mutual interactions and electronic structures of hyaluronan with Lysine, 6-Aminocaproic acid and Arginine. (United States)

    Chytil, Martin; Trojan, Martin; Kovalenko, Alexander


    Interactions between polyelectrolytes and oppositely charged surfactants have been in a great interest for several decades, yet the conventional surfactants may cause a problem in medical applications. Interactivity between polysaccharide hyaluronan (HA) and amino acids Lysine, 6-Aminocaproic acid (6-AcA), and Arginine as an alternative system is reported. The interactions were investigated by means of rheology and electric conductance and the electronic structures were explored by the density functional theory (DFT). Lysine exhibits the strongest interaction of all, which was manifested, e.g. by nearly 6-time drop of the initial viscosity comparing with only 1.3-time lower value in the case of 6-AcA. Arginine interaction with HA was surprisingly weaker in terms of viscosity than that of Lysine due to a lower and delocalized charge density on its guanidine group. According to the DFT calculations, the binding of Lysine to HA was found to be more flexible, while Arginine creates more rigid structure with HA. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. BMP-2 induces versican and hyaluronan that contribute to post-EMT AV cushion cell migration.

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    Kei Inai

    Full Text Available Distal outgrowth and maturation of mesenchymalized endocardial cushions are critical morphogenetic events during post-EMT atrioventricular (AV valvuloseptal morphogenesis. We explored the role of BMP-2 in the regulation of valvulogenic extracellular matrix (ECM components, versican and hyaluronan (HA, and cell migration during post-EMT AV cushion distal outgrowth/expansion. We observed intense staining of versican and HA in AV cushion mesenchyme from the early cushion expansion stage, Hamburger and Hamilton (HH stage-17 to the cushion maturation stage, HH stage-29 in the chick. Based on this expression pattern we examined the role of BMP-2 in regulating versican and HA using 3D AV cushion mesenchymal cell (CMC aggregate cultures on hydrated collagen gels. BMP-2 induced versican expression and HA deposition as well as mRNA expression of versican and Has2 by CMCs in a dose dependent manner. Noggin, an antagonist of BMP, abolished BMP-2-induced versican and HA as well as mRNA expression of versican and Has2. We further examined whether BMP-2-promoted cell migration was associated with expression of versican and HA. BMP-2- promoted cell migration was significantly impaired by treatments with versican siRNA and HA oligomer. In conclusion, we provide evidence that BMP-2 induces expression of versican and HA by AV CMCs and that these ECM components contribute to BMP-2-induced CMC migration, indicating critical roles for BMP-2 in distal outgrowth/expansion of mesenchymalized AV cushions.

  5. Teotihuacan, tepeapulco, and obsidian exploitation. (United States)

    Charlton, T H


    Current cultural ecological models of the development of civilization in central Mexico emphasize the role of subsistence production techniques and organization. The recent use of established and productive archeological surface survey techniques along natural corridors of communication between favorable niches for cultural development within the Central Mexican symbiotic region resulted in the location of sites that indicate an early development of a decentralized resource exploitation, manufacturing, and exchange network. The association of the development of this system with Teotihuacán indicates the importance such nonsubsistence production and exchange had in the evolution of this first central Mexican civilization. The later expansion of Teotihuacán into more distant areas of Mesoamerica was based on this resource exploitation model. Later civilizations centered at Tula and Tenochtitlán also used such a model in their expansion.

  6. Dark matters: exploitation as cooperation. (United States)

    Dasgupta, Partha


    The empirical literature on human cooperation contains studies of communitarian institutions that govern the provision of public goods and management of common property resources in poor countries. Scholars studying those institutions have frequently used the Prisoners' Dilemma game as their theoretical tool-kit. But neither the provision of local public goods nor the management of local common property resources involves the Prisoners' Dilemma. That has implications for our reading of communitarian institutions. By applying a fundamental result in the theory of repeated games to a model of local common property resources, it is shown that communitarian institutions can harbour exploitation of fellow members, something that would not be possible in societies where cooperation amounts to overcoming the Prisoners' Dilemma. The conclusion we should draw is that exploitation can masquerade as cooperation. Copyright © 2011 Elsevier Ltd. All rights reserved.

  7. Network exploitation using WAMI tracks (United States)

    Rimey, Ray; Record, Jim; Keefe, Dan; Kennedy, Levi; Cramer, Chris


    Creating and exploiting network models from wide area motion imagery (WAMI) is an important task for intelligence analysis. Tracks of entities observed moving in the WAMI sensor data are extracted, then large numbers of tracks are studied over long time intervals to determine specific locations that are visited (e.g., buildings in an urban environment), what locations are related to other locations, and the function of each location. This paper describes several parts of the network detection/exploitation problem, and summarizes a solution technique for each: (a) Detecting nodes; (b) Detecting links between known nodes; (c) Node attributes to characterize a node; (d) Link attributes to characterize each link; (e) Link structure inferred from node attributes and vice versa; and (f) Decomposing a detected network into smaller networks. Experimental results are presented for each solution technique, and those are used to discuss issues for each problem part and its solution technique.

  8. Free-radical degradation of high-molar-mass hyaluronan induced by ascorbate plus cupric ions: evaluation of antioxidative effect of cysteine-derived compounds. (United States)

    Hrabárová, Eva; Valachová, Katarína; Juránek, Ivo; Soltés, Ladislav


    Based on our previous findings, the present study has focused on free-radical-mediated degradation of the synovial biopolymer hyaluronan. The degradation was induced in vitro by the Weissberger's system comprising ascorbate plus cupric ions in the presence of oxygen, representing a model of the early phase of acute synovial joint inflammation. The study presents a novel strategy for hyaluronan protection against oxidative degradation with the use of cysteine-derived compounds. In particular, the work objectives were to evaluate potential protective effects of reduced form of L-glutathione, L-cysteine, N-acetyl-L-cysteine, and cysteamine, against free-oxygen-radical-mediated degradation of high-molar-mass hyaluronan in vitro. The hyaluronan degradation was influenced by variable activity of the tested thiol compounds, also in dependence of their concentration applied. It was found that L-glutathione exhibited the most significant protective and chain-breaking antioxidative effect against the hyaluronan degradation. Thiol antioxidative activity, in general, can be influenced by many factors such as various molecule geometry, type of functional groups, radical attack accessibility, redox potential, thiol concentration and pK(a), pH, ionic strength of solution, as well as different ability to interact with transition metals. Antioxidative activity was found to decrease in the following order: L-glutathione, cysteamine, N-acetyl-L-cysteine, and L-cysteine. These findings might be beneficial in future development of potential drugs in the treatment of synovial hyaluronan depletion-derived diseases. Copyright © 2012 Verlag Helvetica Chimica Acta AG, Zürich.

  9. Physico-chemical properties and degradability of non-woven hyaluronan benzylic esters as tissue engineering scaffolds. (United States)

    Milella, E; Brescia, E; Massaro, C; Ramires, P A; Miglietta, M R; Fiori, V; Aversa, P


    The development of biocompatible materials which can be processed into three-dimensional scaffolds and the design of appropriate configurations in order to enable the cellular infiltration and proliferation is a major issue in the tissue engineering. The hyaluronan total benzyl ester (Hyaff 11) has been found to be suitable substrate to grow a variety of cell types. Since structural, physical, chemical and biological data can help for tailoring appropriate scaffold for tissue engineering, information on chemicophysical properties on degradability of hyaluronan total benzyl ester non-woven has been obtained. The thermal analysis, the evaluation of the surface chemical composition, the morphology, the mechanical behaviour and the swelling tests were carried out on these materials. The hyaluronan total benzyl ester non-woven showed a thermal stability up to 220 degrees C and the surface composition differed from that of the bulk for C-O and C-C contribution. No contaminant were detected. The non-woven swelled in culture medium. Moreover the mechanical tests showed that when submitted to a press treatment, the samples have best mechanical properties. The pressed Hyaff 11 non-woven undergoes degradation when exposed to DMEM. The frying and breaking of the fibres, a decrease of the mechanical properties and a molecular weight loss have been observed. First, the ester bond of the Hyaff 11 non-woven is hydrolysed and the benzylic alcohol is released and the low molecular weight values indicate that a cleavage of the polymer is promoted by the components of the culture medium. After 11 days, some fragments, constituted by hyaluronic acid with a molecular weight of 23,000 Da became soluble in the medium. No oligomer was detected.

  10. Host specificity in phylogenetic and geographic space. (United States)

    Poulin, Robert; Krasnov, Boris R; Mouillot, David


    The measurement of host specificity goes well beyond counting how many host species can successfully be used by a parasite. In particular, specificity can be assessed with respect to how closely related the host species are, or whether a parasite exploits the same or different hosts across its entire geographic range. Recent developments in the measurement of biodiversity offer a new set of analytical tools that can be used to quantify the many aspects of host specificity. We describe here the multifaceted nature of host specificity, summarize the indices available to measure its different facets one at a time or in combination, and discuss their implications for parasite evolution and disease epidemiology. Copyright © 2011 Elsevier Ltd. All rights reserved.

  11. Hyaluronan (Erectus(R in der Behandlung der Osteoarthritis (OA des Kniegelenks - Ergebnisse einer offenen Anwendungsbeobachtung

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    Leeb BF


    Full Text Available Ziel der Untersuchung war es, praxisrelevante Daten hinsichtlich der Wirksamkeit, Verträglichkeit und Auswirkung auf die Lebensqualität einer in Österreich neu zugelassenen Hyaluronan-Präparation (Erectus(R; MW 1.100 KD zu erhalten. Patienten und Methodik: Zu diesem Zweck wurden 204 Patienten mit OA des Kniegelenkes, Kellgren-Lawrence (KL I–III (mean 61,1 a [31 a–100 a]; mean BMI 26,9; 57,2% weiblich, 42,8 % männlich von Oktober 2005 bis April 2006 in diese offene multizentrische Anwendungsbeobachtung eingeschlossen. Die Patienten erhielten fünf Injektionen Erectus(Rintraartikulär im Abstand von einer Woche. Primärer Endpunkt war die Verbesserung des Ruheschmerzes zu Visite 5 (Woche 5. Sekundäre Endpunkte waren Verbesserung des Ruheschmerzes bei Visite 6 (Woche 13 sowie des Bewegungsschmerzes, der Beweglichkeit und der Zufriedenheit mit der Lebenssituation. Alle Parameter wurden von den Patienten anhand einer Likert-Skala (0–10 beurteilt. Darüber hinaus erfolgte die Beurteilung von Gesamtwirksamkeit, Verträglichkeit und Gesamtzufriedenheit durch Prüfarzt und PatientIn. Die statistische Auswertung erfolgte mittels T-Test und Chi-Quadrat-Test. Fehlende Werte wurden gemäß LOCF ersetzt. Ergebnisse: Der Ruheschmerz wurde von den Patienten zu Beginn mit im Mittel 4,68 angegeben und verbesserte sich auf 2,04 bei Visite 5 bzw. auf 1,8 bei Visite 6 (p 0,01. Die Verbesserung war bei Patienten mit KL Grad I am stärksten und bei KL III am geringsten ausgeprägt. Die subjektive Beurteilung der Beweglichkeit sowie die Zufriedenheit, mit dem aktuellen Krankheitszustand längerfristig leben zu müssen, verbesserte sich ebenfalls signifikant (p 0,01, wobei dabei interessanterweise die stärksten Veränderungen bei Patienten mit KL III festzustellen waren. Patienten und Behandler beurteilten die globale Wirksamkeit parallel positiv, wie auch die Verträglichkeit. Die Beurteilung der Gesamtzufriedenheit nach einem Schulnotensystem (1–5 ergab

  12. Characterization of hyaluronan-binding proteins on guinea pig polymorphonuclear leukocytes: possible involvement of complement receptor type 3 (CR3, CD11b/CD18) in the hyaluronan-leukocyte interaction. (United States)

    Nochi, Hiromi; Shinomiya, Takahisa; Tamoto, Koichi


    Hyaluronan (HA), a high-molecular-weight glycosaminoglycan ubiquitously present in the extracellular matrices (ECMs) of animals, plays important roles in ECM organization and cell behavior through binding to hyaluronan-binding proteins (HABPs). We previously reported that HA has anti-inflammatory effects on guinea pig phagocytes, although the nature of guinea pig HABPs was unknown. In this study, we characterized guinea pig HABPs on peritoneal polymorphonuclear leukocytes (PMNs) and blood neutrophils by flow cytometry and affinity chromatography. It was found that PMNs express diverse HABPs with different molecular weights. These HABPs maximally bound with HA over a wide pH range (6-8), and recognized HAs as small as the pentadisaccharide units of d-glucuronic acid and N-acetyl-d-glucosamine. Furthermore, they could be divided into Mg(2+)-dependent and Ca(2+)/Mg(2+)-independent groups. Interestingly, two proteins in the Mg(2+)-dependent group were found to be the two subunits of complement receptor type 3 (CR3, CD11b/CD18). Unlike PMNs, blood neutrophils expressed several functionally inactive HABPs. Among these inactive HABPs, Mg(2+)-dependent proteins including CR3 but not Ca(2+)/Mg(2+)-independent proteins were activated on phorbol ester-stimulation. These results show the existence of diverse HABPs on guinea pig neutrophils and the cell activation-dependent activation of HABPs. It is also suggested that the CR3-HA interaction is possibly involved in the regulation of neutrophil function.

  13. Full-Length Recombinant Human Proteoglycan 4 Interacts with Hyaluronan to Provide Cartilage Boundary Lubrication. (United States)

    Abubacker, Saleem; Dorosz, Samuel G; Ponjevic, Dragana; Jay, Gregory D; Matyas, John R; Schmidt, Tannin A


    Proteoglycan 4 (PRG4) is a mucin-like glycoprotein present in synovial fluid and at the surface of articular cartilage. The objectives of this study were to (1) assess the articular cartilage surface adsorption and in vitro cartilage boundary lubricating ability of full-length recombinant human PRG4 (rhPRG4), and (2) cartilage boundary lubricating ability of purified rhPRG4, both alone and in combination with hyaluronan (HA). rhPRG4 adsorption onto articular cartilage explants was assessed by immunohistochemistry and dot blot. An in vitro cartilage-cartilage friction test was used to assess rhPRG4's cartilage boundary lubricating ability compared to bovine PRG4, and that of purified rhPRG4 both alone and in combination with HA. rhPRG4 was able to adsorb to the articular surface, as well as the cut surface, of cartilage explants. The kinetic coefficient of friction of rhPRG4 was similar to that of PRG4 (p = 0.16) and lower than phosphate-buffered saline (p < 0.05), while that of purified rhPRG4 + HA was significantly lower than rhPRG4 alone (p < 0.05). This study demonstrates that rhPRG4 can adsorb to an intact articular cartilage surface and functions as an effective boundary lubricant, both alone and with HA, and provides the foundation for in vivo evaluation of this clinically relevant full-length rhPRG4 for treatment of osteoarthritis.

  14. Sulfation of the bikunin chondroitin sulfate chain determines heavy chain·hyaluronan complex formation. (United States)

    Lord, Megan S; Day, Anthony J; Youssef, Peter; Zhuo, Lisheng; Watanabe, Hideto; Caterson, Bruce; Whitelock, John M


    Inter-α-trypsin inhibitor (IαI) is a complex comprising two heavy chains (HCs) that are covalently bound by an ester bond to chondroitin sulfate (CS), which itself is attached to Ser-10 of bikunin. IαI is essential for the trans-esterification of HCs onto hyaluronan (HA). This process is important for the stabilization of HA-rich matrices during ovulation and some inflammatory processes. Bikunin has been isolated previously by anion exchange chromatography with a salt gradient up to 0.5 M NaCl and found to contain unsulfated and 4-sulfated CS disaccharides. In this study, bikunin-containing fractions in plasma and urine were separated by anion exchange chromatography with a salt gradient of 0.1-1.0 M NaCl, and fractions were analyzed for their reactivity with the 4-sulfated CS linkage region antibody (2B6). The fractions that reacted with the 2B6 antibody (0.5-0.8 M NaCl) were found to predominantly contain sulfated CS disaccharides, including disulfated disaccharides, whereas the fractions that did not react with this antibody (0.1-0.5 M NaCl) contained unsulfated and 4-sulfated CS disaccharides. IαI in the 0.5-0.8 M NaCl plasma fraction was able to promote the trans-esterification of HCs to HA in the presence of TSG-6, whereas the 0.1-0.5 M NaCl fraction had a much reduced ability to transfer HC proteins to HA, suggesting that the CS containing 4-sulfated linkage region structures and disulfated disaccharides are involved in the HC transfer. Furthermore, these data highlight that the structure of the CS attached to bikunin is important for the transfer of HC onto HA and emphasize a specific role of CS chain sulfation.

  15. Visible light crosslinking of methacrylated hyaluronan hydrogels for injectable tissue repair. (United States)

    Fenn, Spencer L; Oldinski, Rachael A


    Tissue engineering hydrogels are primarily cured in situ using ultraviolet (UV) radiation which limits the use of hydrogels as drug or cell carriers. Visible green light activated crosslinking systems are presented as a safe alternative to UV photocrosslinked hydrogels, without compromising material properties such as viscosity and stiffness. The objective of this study was to fabricate and characterize photocrosslinked hydrogels with well-regulated gelation kinetics and mechanical properties for the repair or replacement of soft tissue. An anhydrous methacrylation of hyaluronan (HA) was performed to control the degree of modification (DOM) of HA, verified by (1) H-NMR spectroscopy. UV-activated crosslinking was compared to visible green light activated crosslinking. While the different photocrosslinking techniques resulted in varied crosslinking times, comparable mechanical properties of UV and green light activated crosslinked hydrogels were achieved using each photocrosslinking method by adjusting time of light exposure. Methacrylated HA (HA-MA) hydrogels of varying molecular weight, DOM, and concentration exhibited compressive moduli ranging from 1 kPa to 116 kPa, for UV crosslinking, and 3 kPa to 146 kPa, for green light crosslinking. HA-MA molecular weight and concentration were found to significantly influence moduli values. HA-MA hydrogels did not exhibit any significant cytotoxic effects toward human mesenchymal stem cells. Green light activated crosslinking systems are presented as a viable method to form natural-based hydrogels in situ. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1229-1236, 2016. © 2015 Wiley Periodicals, Inc.

  16. Specific sizes of hyaluronan oligosaccharides stimulate fibroblast migration and excisional wound repair.

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    Cornelia Tolg

    Full Text Available The extracellular matrix polysaccharide hyaluronan (HA plays a key role in both fibrotic and regenerative tissue repair. Accumulation of high molecular weight HA is typical of regenerative repair, which is associated with minimal inflammation and fibrosis, while fragmentation of HA is typical of postnatal wounds, which heal in the presence of inflammation and transient fibrosis. It is generally considered that HA oligosaccharides and fragments of a wide size range support these processes of adult, fibrotic wound repair yet the consequences of sized HA fragments/oligosaccharides to each repair stage is not well characterized. Here, we compared the effects of native HA, HA oligosaccharide mixtures and individual sizes (4-10 mer oligosaccharides, 5 and, 40 kDa of HA oligosaccharides and fragments, on fibroblast migration in scratch wound assays and on excisional skin wound repair in vivo. We confirm that 4-10 mer mixtures significantly stimulated scratch wound repair and further report that only the 6 and 8 mer oligosaccharides in this mixture are responsible for this effect. The HA 6 mer promoted wound closure, accumulation of wound M1 and M2 macrophages and the M2 cytokine TGFβ1, but did not increase myofibroblast differentiation. The effect of 6 mer HA on wound closure required both RHAMM and CD44 expression. In contrast, The 40 kDa HA fragment inhibited wound closure, increased the number of wound macrophages but had no effect on TGFβ1 accumulation or subsequent fibrosis. These results show that specific sizes of HA polymer have unique effects on postnatal wound repair. The ability of 6 mer HA to promote wound closure and inflammation resolution without increased myofibroblast differentiation suggests that this HA oligosaccharide could be useful for treatment of delayed or inefficient wound repair where minimal fibrosis is advantageous.

  17. Proteoglycan 4 and hyaluronan as boundary lubricants for model contact lens hydrogels. (United States)

    Samsom, Michael; Iwabuchi, Yuno; Sheardown, Heather; Schmidt, Tannin A


    Clinical data show that in vitro contact lens friction is related to in vivo comfort. Solutions of biological lubricants hyaluronan (HA) and proteoglycan 4 (PRG4, also known as lubricin) reduce friction at a cornea-polydimethylsiloxane (PDMS) interface. The purpose of this study was to (1) determine if PRG4 can sorb to and lubricate model contact lens materials and (2) assess the boundary lubricating ability of PRG4 and HA compared to saline on model contact lens materials. PRG4 was obtained from bovine cartilage culture and suspended in saline at 300 µg/mL. N,N-Dimethylacrylamidetris (trimethylsiloxy) silane, (DMAA/TRIS) and methacryloxypropyltris (trimethylsiloxy) silane (pHEMA/TRIS) silicone hydrogels were prepared. A previously described in vitro eyelid-hydrogel and cornea-hydrogel biomechanical friction test was used to determine boundary lubricant effect. PRG4 sorption to the hydrogels was assessed using a soak-rinse protocol and western blotting. PRG4 effectively lubricated both silicone hydrogel materials and HA effectively lubricated pHEMA/TRIS, as indicated by a statistically significant reduction in friction compared to the saline control lubricant. An HA and PRG4 combination showed a synergistic effect for pHEMA/TRIS and effectively lubricated DMAA/TRIS. Biological boundary lubricants HA and PRG4 were shown to effectively lubricate silicone hydrogels when in solution. Additionally, HA and PRG4 showed synergistic lubrication for pHEMA/TRIS. The purpose of this study was not to replicate the friction coefficients of contact lenses, but rather to investigate lubricant-surface interactions for common contact lens constituents. These findings contribute to the potential development of biomolecule based lubricant drops for contact lens wearers. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2017. © 2017 Wiley Periodicals, Inc.

  18. Hyperglycaemia and aberrated insulin signalling stimulate tumour progression via induction of the extracellular matrix component hyaluronan. (United States)

    Twarock, Sören; Reichert, Christina; Peters, Ulrike; Gorski, Daniel J; Röck, Katharina; Fischer, Jens W


    Epidemiological studies have detected a higher incidence of various tumour entities in diabetic patients. However, the underlying mechanisms remain insufficiently understood. Glucose-derived pericellular and extracellular hyaluronan (HA) promotes tumour progression and development. In our study, we tested the hypothesis that a diabetic metabolic state, characterised by hyperglycaemia and concomitant aberrant insulin signalling, stimulates tumour progression via the induction of HA synthesis. In a streptozotocin-induced diabetic nude mouse tumour xenograft model, hyperglycaemia and lack of insulin caused an increased formation of tumour-associated HA-matrix, which in turn accelerated tumour progression and neoangiogenesis. This process was effectively attenuated by treatment with 4-methylumbelliferone, a pharmacological inhibitor of HA-synthesis. To define the mechanisms behind these in vivo observations, we investigated the impact of hyperglycaemia and insulin on the glucose metabolism in oesophageal squamous cell cancer cells (ESCC). Hyperglycaemia induced HA synthesis while insulin diminished HA production by directing glucose metabolites to glycolysis. Vice versa, inhibition of glycolysis, either by knockdown of the glycolytic key enzyme phosphofructokinase or by an experimental abrogation of insulin signalling (knockdown of the insulin receptor and long-term treatment with insulin) augmented HA synthesis. Consequently, these processes induced invasion, anchorage-independent growth and adhesion of ESCC to endothelial cells in vitro. Thus, the cellular shift in glucose usage from catabolism of glucose to anabolism of HA driven by hyperglycaemia and insulin resistance may represent an important link between diabetes and cancer progression. Hence, therapeutical inhibition of HA synthesis may represent a promising approach for tumour treatment in diabetic patients. © 2017 UICC.

  19. Growth factor PDGF-BB stimulates cultured cardiomyocytes to synthesize the extracellular matrix component hyaluronan.

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    Urban Hellman

    Full Text Available BACKGROUND: Hyaluronan (HA is a glycosaminoglycan located in the interstitial space which is essential for both structural and cell regulatory functions in connective tissue. We have previously shown that HA synthesis is up-regulated in a rat model of experimental cardiac hypertrophy and that cardiac tissue utilizes two different HA synthases in the hypertrophic process. Cardiomyocytes and fibroblasts are two major cell types in heart tissue. The fibroblasts are known to produce HA, but it has been unclear if cardiomyocytes share the same feature, and whether or not the different HA synthases are activated in the different cell types. METHODOLOGY/PRINCIPAL FINDINGS: This study shows, for the first time that cardiomyocytes can produce HA. Cardiomyocytes (HL-1 and fibroblasts (NIH 3T3 were cultivated in absence or presence of the growth factors FGF2, PDGF-BB and TGFB2. HA concentration was quantified by ELISA, and the size of HA was estimated using dynamic light scattering. Cardiomyocytes synthesized HA but only when stimulated by PDGF-BB, whereas fibroblasts synthesized HA without addition of growth factors as well as when stimulated by any of the three growth factors. When fibroblasts were stimulated by the growth factors, reverse dose dependence was observed, where the highest dose induced the least amount of HA. With the exception of TGFB2, a trend of reverse dose dependence of HA size was also observed. CONCLUSIONS/SIGNIFICANCE: Co-cultivation of cardiomyocytes and fibroblasts (80%/20% increased HA concentration far more that can be explained by HA synthesis by the two cell types separately, revealing a crosstalk between cardiomyocytes and fibroblasts that induces HA synthesis. We conclude that dynamic changes of the myocardium, such as in cardiac hypertrophy, do not depend on the cardiomyocyte alone, but are achieved when both cardiomyocytes and fibroblasts are present.

  20. Viscoelastic Properties of Hyaluronan in Physiological Conditions [version 1; referees: 2 approved

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    Mary K. Cowman


    Full Text Available Hyaluronan (HA is a high molecular weight glycosaminoglycan of the extracellular matrix (ECM, which is particularly abundant in soft connective tissues. Solutions of HA can be highly viscous with non-Newtonian flow properties. These properties affect the movement of HA-containing fluid layers within and underlying the deep fascia. Changes in the concentration, molecular weight, or even covalent modification of HA in inflammatory conditions, as well as changes in binding interactions with other macromolecules, can have dramatic effects on the sliding movement of fascia. The high molecular weight and the semi-flexible chain of HA are key factors leading to the high viscosity of dilute solutions, and real HA solutions show additional nonideality and greatly increased viscosity due to mutual macromolecular crowding. The shear rate dependence of the viscosity, and the viscoelasticity of HA solutions, depend on the relaxation time of the molecule, which in turn depends on the HA concentration and molecular weight. Temperature can also have an effect on these properties. High viscosity can additionally affect the lubricating function of HA solutions. Immobility can increase the concentration of HA, increase the viscosity, and reduce lubrication and gliding of the layers of connective tissue and muscle. Over time, these changes can alter both muscle structure and function. Inflammation can further increase the viscosity of HA-containing fluids if the HA is modified via covalent attachment of heavy chains derived from Inter-α-Inhibitor. Hyaluronidase hydrolyzes HA, thus reducing its molecular weight, lowering the viscosity of the extracellular matrix fluid and making outflow easier. It can also disrupt any aggregates or gel-like structures that result from HA being modified. Hyaluronidase is used medically primarily as a dispersion agent, but may also be useful in conditions where altered viscosity of the fascia is desired, such as in the treatment of

  1. Inhibition of hyaluronan synthesis reduces versican and fibronectin levels in trabecular meshwork cells.

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    Kate E Keller

    Full Text Available Hyaluronan (HA is a major component of the extracellular matrix (ECM and is synthesized by three HA synthases (HAS. Similarities between the HAS2 knockout mouse and the hdf mutant mouse, which has a mutation in the versican gene, suggest that HA and versican expression may be linked. In this study, the relationship between HA synthesis and levels of versican, fibronectin and several other ECM components in trabecular meshwork cells from the anterior segment of the eye was investigated. HA synthesis was inhibited using 4-methylumbelliferone (4MU, or reduced by RNAi silencing of each individual HAS gene. Quantitative RT-PCR and immunoblotting demonstrated a reduction in mRNA and protein levels of versican and fibronectin. Hyaluronidase treatment also reduced versican and fibronectin levels. These effects could not be reversed by addition of excess glucose or glucosamine or exogenous HA to the culture medium. CD44, tenascin C and fibrillin-1 mRNA levels were reduced by 4MU treatment, but SPARC and CSPG6 mRNA levels were unaffected. Immunostaining of trabecular meshwork tissue after exposure to 4MU showed an altered localization pattern of HA-binding protein, versican and fibronectin. Reduction of versican by RNAi silencing did not affect HA concentration as assessed by ELISA. Together, these data imply that HA concentration affects synthesis of certain ECM components. Since precise regulation of the trabecular meshwork ECM composition and organization is required to maintain the aqueous humor outflow resistance and intraocular pressure homeostasis in the eye, coordinated coupling of HA levels and several of its ECM binding partners should facilitate this process.

  2. Peritoneal Adhesion and Angiogenesis in Ovarian Carcinoma Are Inversely Regulated by Hyaluronan: The Role of Gonadotropins

    Directory of Open Access Journals (Sweden)

    Yael Chagit Tzuman


    Full Text Available Ovarian carcinoma is the leading cause of death among gynecologic cancers. Although transformation of the outer ovarian epithelium was linked with ovulation, the disease is significantly more prevalent and severe in postmenopausal women. We postulated that menopause could augment ovarian cancer progression through the effects of gonadotropins on multifocal seeding to the mesothelial layer lining the peritoneum. This seeding is mediated by integrins as well as by CD44 interaction with hyaluronan (HA. Here, we report the effect of gonadotropins on HA synthesis and degradation and on peritoneal adhesion. A significant concentration- and time-dependent induction in expression levels of HA synthases (HASs and hyaluronidases (Hyals was observed in vitro on stimulation of human epithelial ovarian carcinoma cells by gonadotropins. Hormonal regulation of HA-mediated adhesion was manifested in vivo as well, by fluorescence microscopy of stained MLS multicellular tumor spheroids. The number of spheroids adhered to the mesothelium of ovariectomized CD-1 nude mice 9.5 hours after intraperitoneal insertion was significantly higher than in nonovariectomized mice. Inhibition of HA synthesis by 6-diazo-5-oxo-1-norleucine (DON both in spheroids and ovariectomized mice significantly reduced the number of adhered spheroids. Thus, the change in the hormonal environment during menopause assists in HA-dependent adherence of ovarian cancer spheroids onto the peritoneum. However, HA is antiangiogenic and it can significantly suppress tumor progression. Accordingly, angiogenesis of the adhered spheroids was significantly elevated in DON-treated tumors. These results can explain the selective pressure that can lead to simultaneously increased tumor expression of both HASs and Hyals.

  3. Three-year clinical outcome after chondrocyte transplantation using a hyaluronan matrix for cartilage repair

    Energy Technology Data Exchange (ETDEWEB)

    Nehrer, S. [Department of Orthopedics, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria)]. E-mail:; Domayer, S. [Department of Orthopedics, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria); Dorotka, R. [Department of Orthopedics, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria); Schatz, K. [Department of Orthopedics, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria); Bindreiter, U. [Department of Orthopedics, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria); Kotz, R. [Department of Orthopedics, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria)


    Repair of articular cartilage represents a significant clinical problem and although various new techniques - including the use of autologous chondrocytes - have been developed within the last century the clinical efficacy of these procedures is still discussed controversially. Although autologous chondrocyte transplantation (ACT) has been widely used with success, it has several inherent limitations, including its invasive nature and problems related to the use of the periosteal flap. To overcome these problems autologous chondrocytes transplantation combined with the use of biodegradable scaffolds has received wide attention. Among these, a hyaluronan-based scaffold has been found useful for inducing hyaline cartilage regeneration. In the present study, we have investigated the mid-term efficacy and safety of Hyalograft[reg] C grafts in a group of 36 patients undergoing surgery for chronic cartilage lesions of the knee. Clinical Outcome was assessed prospectively before and at 12, 24, and 36 months after surgery. No major adverse events have been reported during the 3-year follow-up. Significant improvements of the evaluated scores were observed (P < 0.02) at 1 year and a continued increase of clinical performance was evident at 2 and 3 years follow-up. Patients under 30 years of age with single lesions showed statistically significant improvements at all follow-up visits compared to those over 30 with multiple defects (P < 0.01). Hyalograft[reg] C compares favorably with classic ACT and is particularly indicated in younger patients with single lesions. The graft can be implanted through a miniarthrotomy and needs no additional fixation with sutures except optional fibrin gluing at the defect borders. These results suggest that Hyalograft[reg] C is a valid alternative to ACT.

  4. Mechanisms involved in extracellular matrix remodeling and arterial stiffness induced by hyaluronan accumulation. (United States)

    Lorentzen, Karen Axelgaard; Chai, Song; Chen, Hui; Danielsen, Carl Christian; Simonsen, Ulf; Wogensen, Lise


    Hyperglycemia induces hyaluronan (HA) accumulation in the vasculature. Excessive accumulation of HA around the vascular smooth muscle cells (VSMC) results in increased aortic stiffness and strength and accelerated atherosclerosis in ApoE(-)/(-) mice. We hypothesized that HA accumulation primes the vasculature for atherosclerosis by crosslinking and reorganizing the extracellular matrix (ECM) and by pushing VSMC differentiation towards a less mature phenotype. Aortas from HAS-2 transgenic (Tg) mice and wild type mice were used for all experiments. Biomechanics and cross-sectional area measurements were performed before and after HA digestion. The vessel and ECM composition was examined by immunoblotting and electron microscopy. Primary VSMC cultures were examined by qPCR and thymidine incorporation. Tg mice aorta cross-sectional area was increased before (14%, p = 0.0148), but not after HA digestion (p = 0.3437). The increase in vessel stiffness (32%, p = 0.0217) and strength (31%, p = 0.0043) in the Tg aorta persisted after HA digestion. Crosslinking of HA by heavy chains from Inter-α-Inhibitor was increased (175%, p = 0.0006). The Tg VSMCs have the appearance of a synthetic phenotype supported by a 40% decrease in α-smooth muscle actin isoform X1 (p = 0.0296) and an increase in proliferation (63%, p = 0.0048) and osteoprotegerin production (133%, p = 0.0010) in cultured Tg VSMCs. Our results show that induced HA accumulation is followed by increased HA crosslinking and create a shift in VSMC phenotype and proliferation. These findings may provide a mechanism for how hyperglycemia through HA accumulation prime the vascular wall for cholesterol and leucocyte accumulation and development of atherosclerosis. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.


    African Journals Online (AJOL)


    The sexual exploitation of children by peacekeepers is particularly insidious. Educational interventions and training initiatives to bring about behaviour change to address sexual exploitation and abuse .... its own peacekeeping personnel are engaging in acts of sexual exploitation and abuse, including such crimes as rape.

  6. The exploitation argument against commercial surrogacy. (United States)

    Wilkinson, Stephen


    This paper discusses the exploitation argument against commercial surrogacy: the claim that commercial surrogacy is morally objectionable because it is exploitative. The following questions are addressed. First, what exactly does the exploitation argument amount to? Second, is commercial surrogacy in fact exploitative? Third, if it were exploitative, would this provide a sufficient reason to prohibit (or otherwise legislatively discourage) it? The focus throughout is on the exploitation of paid surrogates, although it is noted that other parties (e.g. 'commissioning parents') may also be the victims of exploitation. It is argued that there are good reasons for believing that commercial surrogacy is often exploitative. However, even if we accept this, the exploitation argument for prohibiting (or otherwise legislatively discouraging) commercial surrogacy remains quite weak. One reason for this is that prohibition may well 'backfire' and lead to potential surrogates having to do other things that are more exploitative and/or more harmful than paid surrogacy. It is concluded therefore that those who oppose exploitation should (rather than attempting to stop particular practices like commercial surrogacy) concentrate on: (a) improving the conditions under which paid surrogates 'work'; and (b) changing the background conditions (in particular, the unequal distribution of power and wealth) which generate exploitative relationships.

  7. The survival of fetal and bone marrow monocyte-derived alveolar macrophages is promoted by CD44 and its interaction with hyaluronan. (United States)

    Dong, Y; Poon, G F T; Arif, A A; Lee-Sayer, S S M; Dosanjh, M; Johnson, P


    Alveolar macrophages maintain lung homeostasis by performing important roles in immunosurveillance and lung surfactant catabolism. They express high levels of CD44 and are one of the few macrophage populations that constitutively bind hyaluronan, a ligand for CD44 and component of pericellular and extracellular matrices. Using adoptive transfer experiments and a mouse model of inflammation, we found that alveolar macrophages are initially depleted after an inflammatory insult then rapidly self-renew and return to original numbers after the resolution phase. Monocytes recruited to an inflamed lung differentiate and contribute to the alveolar macrophage pool, but this occurs over a much slower time frame than alveolar macrophage self-renewal. CD44 expression on both fetal and bone marrow-derived alveolar macrophages promoted their survival and provided a competitive advantage over CD44-deficient alveolar macrophages at homeostasis and after inflammation. CD44-mediated hyaluronan binding was induced by the alveolar environment, and this interaction promoted alveolar macrophage survival both ex vivo and in vivo. Without CD44, alveolar macrophages lacked a hyaluronan coat, were more susceptible to death, and were present at lower numbers in the alveolar space. This demonstrates a new role for CD44 and hyaluronan in promoting alveolar macrophage survival.Mucosal Immunology advance online publication 25 October 2017. doi:10.1038/mi.2017.83.

  8. Clinical and biomaterial evaluation of hyaluronan-based heparin-bonded extracorporeal circuits with reduced versus full systemic anticoagulation in reoperation for coronary revascularization. (United States)

    Gunaydin, Serdar; Farsak, Bora; McCusker, Kevin; Vijay, Venkataramana; Sari, Tamer; Onur, M Ali; Gurpinar, Aylin; Zorlutuna, Yaman


    This prospective randomized study compares full and reduced heparinization on novel hyaluronan-based heparin-bonded circuits vs. uncoated controls under challenging clinical setting including biomaterial evaluation. 100 patients undergoing reoperation for coronary artery bypass grafting were allocated into two equal groups (n = 50): Group one was treated with hyaluronan-based heparin bonded preconnected circuits (Vision HFOGBS, Gish, California, USA) and Group two with identical uncoated controls (Vision HFO, Gish, USA). In the study group, half of the patients (n = 25) received low-systemic heparin (125 IU/kg, ACT >250 s) or full dose like control group. Blood samples were collected after induction of anesthesia (T1) and heparin administration before cardiopulmonary bypass (CPB) (T2), 15 min after initiation of CPB (T3), before cessation of CPB (T4), 15 min after reversal with protamine (T5), and the first postoperative day at 08: 00 h (T6). Platelet counts were preserved significantly better at T5, T6 in hyaluronan groups (P full and low-dose heparin groups at any time point. Amount of desorbed protein was 1.41 +/- 0.01 in full and 1.43 +/- 0.01 in low dose vs. 1.78 +/- 0.01 mg/dl in control (P better clinical outcome and less inflammatory response compared with uncoated surfaces. Reduced systemic heparinization combined with hyaluronan-based heparin-bonded circuits is feasible and clinically well tolerated.

  9. Intra-articular hyaluronan is without clinical effect in knee osteoarthritis: a multicentre, randomised, placebo-controlled, double-blind study of 337 patients followed for 1 year

    DEFF Research Database (Denmark)

    Jørgensen, Anette; Stengaard-Pedersen, Kristian; Simonsen, Lars Ole


    osteoarthritis (clinical and laboratory) and with a Lequesne algofunctional index score (LFI) of 10 or greater. Patients received a hyaluronan product (sodium hyaluronate; Hyalgan) (n= 167) or saline (n= 170) intra-articularly weekly for 5 weeks and were followed up to 1 year. Time to recurrence was the primary...

  10. Local delivery of hyaluronan as an adjunct to scaling and root planing in the treatment of chronic periodontitis. (United States)

    Johannsen, Annsofi; Tellefsen, Monica; Wikesjö, Ulf; Johannsen, Gunnar


    The aim of the present study was to evaluate the adjunctive effect of the local application of a hyaluronan gel to scaling and root planing in the treatment of chronic periodontitis. Twelve patients with chronic periodontitis were recruited to participate in a study with a split-mouth design and provided informed consent. Plaque formation and bleeding on probing were evaluated pretreatment (baseline) and at 1, 4, and 12 weeks post-treatment. Probing depths and attachment levels were evaluated at baseline and at 12 weeks. The patients received full-mouth scaling and root planing. A hyaluronan gel was administered subgingivally in the test sites at baseline and after 1 week. Significant differences between test and control were evaluated using the paired t test, repeated-measures analysis of variance (Wilks lambda), and a non-parametric Wilcoxon signed-rank test. A significant reduction in bleeding on probing scores and probing depths was observed in both groups at 12 weeks (P scaling and root planing may have a beneficial effect on periodontal health in patients with chronic periodontitis.

  11. Use of novel silver nanoparticles with Hyaluronan as potential biological labels for determining the quality of embryos development (United States)

    Syrvatka, Vasyl J.; Slyvchuk, Yurij I.; Rozgoni, Ivan I.; Hevkan, Ivan I.; Bilyi, Oleksandr I.; Osypchuk, Oleksandr S.; Zyuzyun, Aza B.


    In reproductive medicine it is important to determine the quality of embryo development without interference in their function and viability. The surface plasmon resonance of silver nanoparticles makes them promising candidates for optical sensing, molecular labeling and imaging applications. Furthermore unique optical properties of silver nanoparticles provide an opportunity to use them as real time analytic tools in living state especially for observation of dynamic processes in gametes and embryos. The main aim of the study was to investigate the physicochemical properties and biological activities of novel silver nanoparticles with prospect of their use for the determining the quality of embryo development. For this purpose, we investigated the optical properties of new silver nanoparticles in biological mediums during cultivation and their influence on rabbit's embryos development in vitro. The physicochemical and biological properties of novel silver nanoparticles were compared with silver nanoparticles identical in size and shapes but with different chemical surfaces modifications by polyvinylpyrrolidone and bovine serum albumin. The results suggest that silver nanoparticles with hyaluronic acid were disintegrated with the formation of new complexes with proteins in biological mediums. This property with strong optical surface plasmon resonance of novel silver nanoparticles with hyaluronan makes them promising candidates in diagnostic area and gives reasons to explore them as biomarkers of target molecules. Nevertheless novel silver nanoparticles with hyaluronan at the concentrations of 0.1-1 μg/ml have no toxic effect on rabbit's embryos development and can be successfully applied in reproductive medicine.

  12. A case of cervical cancer expressed three mRNA variant of Hyaluronan-mediated motility receptor (United States)

    Villegas-Ruíz, Vanessa; Salcedo, Mauricio; Zentella-Dehesa, Alejandro; de Oca, Edén V Montes; Román-Basaure, Edgar; Mantilla-Morales, Alejandra; Dávila-Borja, Víctor M; Juárez-Méndez, Sergio


    Cervical cancer is the second malignancy in Mexico, little is known about the prognostic factors associated with this disease. Several cellular components are important in their transformation and progression. Alternative mRNA splice is an important mechanism for generating protein diversity, nevertheless, in cancer unknown mRNA diversity is expressed. Hyaluronan-mediated motility receptor (HMMR, RHAMM, CD168) is a family member of proteins, hyaluronan acid dependent, and has been associated with different malignant processes such as: angiogenesis, cell invasiveness, proliferation, metastasis and poor outcome in some tumors. In the present study we identified expression of HMMR in cervical cancer by means of RT-PCR and sequencing. Our results indicate co-expression of two HMMR variants in all samples, and one case expressed three alternative HMMR splice transcripts. These results showed the heterogeneity of mRNA transcripts of HMMR that could express in cancer and the expression of HMMR could be marker of malignancy in CC. PMID:24966934

  13. The Exploitation of Evolving Resources

    CERN Document Server

    McGlade, Jacqueline; Law, Richard


    The impact of man on the biosphere is profound. Quite apart from our capacity to destroy natural ecosystems and to drive species to extinction, we mould the evolution of the survivors by the selection pressures we apply to them. This has implications for the continued health of our natural biological resources and for the way in which we seek to optimise yield from those resources. Of these biological resources, fish stocks are particularly important to mankind as a source of protein. On a global basis, fish stocks provide the major source of protein for human consumption from natural ecosystems, amounting to some seventy million tonnes in 1970. Although fisheries management has been extensively developed over the last century, it has not hitherto considered the evolutionary consequences of fishing activity. While this omission may not have been serious in the past, the ever increasing intensity of exploitation and the deteriorating health of fish stocks has generated an urgent need for a better understanding...

  14. Hyaluronan microgel as a potential carrier for protein sustained delivery by tailoring the crosslink network. (United States)

    Luo, Chunhong; Zhao, Jianhao; Tu, Mei; Zeng, Rong; Rong, Jianhua


    Hyaluronan (HA) microgels with different crosslink network, i.e. HGPs-1, HGPs-1.5, HGPs-3, HGPs-6 and HGPs-15, were synthesized using divinyl sulfone (DVS) as the crosslinker in an inverse microemulsion system for controlling the sustained delivery of bovine serum albumin (BSA). With increasing the crosslinker content, the average particle size slightly increased from 1.9 ± 0.3 μm to 3.6 ± 0.5 μm by dynamic laser scattering analysis. However, the crosslinker content had no significant effect on the morphology of HA microgels by scanning and transmission electron microscopes. Fourier transform infrared spectroscopy and elemental analysis proved more sulfur participated in the crosslink reaction when raising the crosslinker amount. The water swelling test confirmed the increasing crosslink density with the crosslinker content by calculating the average molecular weight between two crosslink points to be 8.25 ± 2.51 × 10(5), 1.26 ± 0.43 × 10(5), 0.96 ± 0.09 × 10(5), 0.64 ± 0.03 × 10(5), and 0.11 ± 0.01 × 10(5) respectively. The degradation of HA microgels by hyaluronidase slowed down by enhancing the crosslink density, only about 5% of HGPs-15 was degraded as opposed to over 90% for HGPs-1. BSA loading had no obvious influence on the surface morphology of HA microgels but seemed to induce their aggregation. The increase of crosslink density decreased the BSA loading capacity but facilitated its long-term sustained delivery. When the molar ratio of DVS to repeating unit of HA reached 3 or higher, similar delivery profiles were obtained. Among all these HA microgels, HGPs-3 was the optimal carrier for BSA sustained delivery in this system because it possessed both high BSA loading capacity and long-term delivery profile simultaneously. Copyright © 2013 Elsevier B.V. All rights reserved.

  15. Hyaluronan microgel as a potential carrier for protein sustained delivery by tailoring the crosslink network

    Energy Technology Data Exchange (ETDEWEB)

    Luo, Chunhong [Department of Materials Science and Engineering, College of Science and Engineering, Jinan University, Guangzhou 510632 (China); Zhao, Jianhao, E-mail: [Department of Materials Science and Engineering, College of Science and Engineering, Jinan University, Guangzhou 510632 (China); Engineering Research Center of Artificial Organs and Materials, Ministry of Education, Guangzhou 510632 (China); Tu, Mei; Zeng, Rong; Rong, Jianhua [Department of Materials Science and Engineering, College of Science and Engineering, Jinan University, Guangzhou 510632 (China); Engineering Research Center of Artificial Organs and Materials, Ministry of Education, Guangzhou 510632 (China)


    Hyaluronan (HA) microgels with different crosslink network, i.e. HGPs-1, HGPs-1.5, HGPs-3, HGPs-6 and HGPs-15, were synthesized using divinyl sulfone (DVS) as the crosslinker in an inverse microemulsion system for controlling the sustained delivery of bovine serum albumin (BSA). With increasing the crosslinker content, the average particle size slightly increased from 1.9 ± 0.3 μm to 3.6 ± 0.5 μm by dynamic laser scattering analysis. However, the crosslinker content had no significant effect on the morphology of HA microgels by scanning and transmission electron microscopes. Fourier transform infrared spectroscopy and elemental analysis proved more sulfur participated in the crosslink reaction when raising the crosslinker amount. The water swelling test confirmed the increasing crosslink density with the crosslinker content by calculating the average molecular weight between two crosslink points to be 8.25 ± 2.51 × 10{sup 5}, 1.26 ± 0.43 × 10{sup 5}, 0.96 ± 0.09 × 10{sup 5}, 0.64 ± 0.03 × 10{sup 5}, and 0.11 ± 0.01 × 10{sup 5} respectively. The degradation of HA microgels by hyaluronidase slowed down by enhancing the crosslink density, only about 5% of HGPs-15 was degraded as opposed to over 90% for HGPs-1. BSA loading had no obvious influence on the surface morphology of HA microgels but seemed to induce their aggregation. The increase of crosslink density decreased the BSA loading capacity but facilitated its long-term sustained delivery. When the molar ratio of DVS to repeating unit of HA reached 3 or higher, similar delivery profiles were obtained. Among all these HA microgels, HGPs-3 was the optimal carrier for BSA sustained delivery in this system because it possessed both high BSA loading capacity and long-term delivery profile simultaneously. - Highlights: • HA microgels with different crosslink densities were prepared. • The crosslinker content had little effect on the morphology and size of HA microgels. • The crosslink density

  16. The Gaia scientific exploitation networks (United States)

    Figueras, F.; Jordi, C.


    On July 2014 the Gaia satellite, placed at L2 since January 2014, finished their commissioning phase and started collecting high accurate scientific data. New and more realistic estimations of the astrometric, photometric and spectroscopic accuracy expected after five years mission operation (2014-2019) have been recently published in the Gaia Science Performance Web page. Here we present the coordination efforts and the activities being conducted through the two GREAT (Gaia Research for European Astronomy Training) European Networks, the GREAT-ESF, a programme supported by the European Science Foundation (2010-2015), and the GREAT-ITN network, from the European Union's Seventh Framework Programme (2011-2015). The main research theme of these networks is to unravel the origin and history of our home galaxy. Emphasis is placed on the research projects being conducted by the Spanish Researchers through these networks, well coordinated by the Red Española de Explotación Científica de Gaia (REG network, with more than 140 participants). Members of the REG play an important role on the collection of complementary spectroscopic data from ground based telescopes, on the development of new tools for an optimal scientific exploitation of Gaia data and on the preparation task to create the Gaia archive.

  17. Influence of host profitability and microenvironmental conditions on parasite specialization on a main and an alternative hosts. (United States)

    Lemoine, M; Doligez, B; Passerault, M; Richner, H


    Parasite success depends on both host profitability and the microenvironment provided by the host, which together define host-parasite compatibility and can differ between hosts. We experimentally disentangled the effects of host profitability and microenvironmental conditions provided by nest material on the reproduction of a nest-based ectoparasite when exploiting its main and an alternative avian host species. Parasite reproductive performance was similar on both hosts when breeding in nests of their own species, suggesting no difference in host-parasite compatibility between hosts. The apparent parasite specialization could therefore result from differences in host-parasite encounter processes. However, when hosts were successful, the main host produced more young in infested nests, whereas the alternative host produced less; furthermore, host reproductive performance was higher in nests of the main host species, suggesting that this nest material alleviates parasitism cost. Therefore, our results suggest different evolutionary responses to parasites of the main and alternative hosts, with either higher tolerance or higher resistance, modulated by nest material. © 2011 The Authors. Journal of Evolutionary Biology © 2011 European Society For Evolutionary Biology.

  18. A Hyaluronan-Based Injectable Hydrogel Improves the Survival and Integration of Stem Cell Progeny following Transplantation

    Directory of Open Access Journals (Sweden)

    Brian G. Ballios


    Full Text Available The utility of stem cells and their progeny in adult transplantation models has been limited by poor survival and integration. We designed an injectable and bioresorbable hydrogel blend of hyaluronan and methylcellulose (HAMC and tested it with two cell types in two animal models, thereby gaining an understanding of its general applicability for enhanced cell distribution, survival, integration, and functional repair relative to conventional cell delivery in saline. HAMC improves cell survival and integration of retinal stem cell (RSC-derived rods in the retina. The pro-survival mechanism of HAMC is ascribed to the interaction of the CD44 receptor with HA. Transient disruption of the retinal outer limiting membrane, combined with HAMC delivery, results in significantly improved rod survival and visual function. HAMC also improves the distribution, viability, and functional repair of neural stem and progenitor cells (NSCs. The HAMC delivery system improves cell transplantation efficacy in two CNS models, suggesting broad applicability.

  19. An in situ hybridization study of Hyaluronan synthase (Has) mRNA in developing mouse molar and incisor tooth germs. (United States)

    Morita, Tsuyoshi; Fujikawa, Kaoru; Baba, Otto; Shibata, Shunichi


    Hyaluronan (HA) is a major constituent molecule in most extracellular matrices and is synthesized by Hyaluronan synthase (Has). In the present study, we examined expression patterns of Has1, -2, -3 mRNA in developing mouse molar and incisor tooth germs from embryonic day (E) 11.5 to postnatal day (P) 7, focusing on Hertwig's epithelial root sheath (HERS) and the apical bud in particular. Has1 mRNA expression was not detected in all tooth germs examined. Has2 mRNA was expressed in the surrounding mesenchyme from E12.0 to 18.0 in both molar and incisor tooth germs, but disappeared after birth. Meanwhile, Has3 mRNA was exclusively expressed within the enamel organ, especially in the inner enamel epithelium (IEE), stellate reticulum (SR), and stratum intermedium (SI) until the early bell stage at E16.0. Has3 mRNA disappeared as IEE differentiated into differentiating ameloblasts (dABs), but remained in SI until the root developmental stage of the molar tooth germ at P7. Has3 mRNA was also expressed in HERS until P7. In incisors, Has3 mRNA was expressed in the apical bud, especially in the transit-amplifying (TA) cell region from E16.0 to P7, and in the papillary layer (PL) adjacent to the mature enamel. These gene expression patterns suggested that Has3 is the main control factor for prenatal and postnatal HA synthesis of the tooth germ, and may in part regulate crown and root formation of the tooth germ, maintenance of stem cell niches in the apical bud as well as mineral transport in PL. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Increased Hyaluronan Acid Binding Ability of Spermatozoa Indicating a Better Maturity, Morphology, and Higher DNA Integrity After Micronutrient Supplementation

    Directory of Open Access Journals (Sweden)

    Markus Lipovac


    Full Text Available Measuring the hyaluronan-binding ability of spermatozoa is useful in predicting the ability of spermatozoa to fertilise oocytes during in vitro fertilisation (IVF. Recent publications discuss an influence of micronutrients on sperm quality. The objective of this paper was to evaluate the effect of a non-prescription nutraceutical containing eight micronutrients on sperm-hyaluronan binding assay (SHBA values among males with idiopathic sub-/infertility, using an open comparative pilot study. The study took place at the Outpatient Fertility Centre IMI, Vienna, Austria, and involved 67 sub-/infertile males. Sub-/infertile males were invited to participate and take two daily capsules of the active compound for a 3-month period between the first and the follow-up semen analysis. Each capsule contained L-carnitine, L-arginine, zinc, vitamin E, glutathione, selenium, coenzyme Q10 (CoQ10, and folic acid (Profertil®. 40 sub-/infertile men receiving no active treatment served as controls; this was measured by change in SHBA after 3 months. It was found that SHBA values significantly increased after 3 months of treatment with the active compound, from a median baseline value of 56.0% to 74% (p<0.05. This represented a 19.7% increase compared to baseline, which was significantly higher than the 2.1% decrease observed in the control group. The rate of subjects displaying an increase in SHBA values after 3 months was significantly higher in the active group (74.6% versus 30.0%, p=0.0001, which showed that sub-/infertile men treated with the active micronutrient compound displayed increased SHBA ability. However, more research is necessary to get detailed information on this specific subject.

  1. Revealing the mechanisms of protein disorder and N-glycosylation in CD44-hyaluronan binding using molecular simulation

    Directory of Open Access Journals (Sweden)

    Olgun eGuvench


    Full Text Available The extracellular N-terminal hyaluronan binding domain (HABD of CD44 is a small globular domain that confers hyaluronan (HA binding functionality to this large transmembrane glycoprotein. When recombinantly expressed by itself, HABD exists as a globular water-soluble protein that retains the capacity to bind HA. This has enabled atomic-resolution structural biology experiments that have revealed the structure of HABD and its binding mode with oligomeric HA. Such experiments have also pointed to an order-to-disorder transition in HABD that is associated with HA binding. However, it had remained unclear how this structural transition was involved in binding since it occurs in a region of HABD distant from the HA-binding site. Furthermore, HABD is known to be N-glycosylated, and such glycosylation can diminish HA binding when the associated N-glycans are capped with sialic acid residues. The intrinsic flexibility of disordered proteins and of N-glycans makes it difficult to apply experimental structural biology approaches to probe the molecular mechanisms of how the order-to-disorder transition and N-glycosylation can modulate HA binding by HABD. We review recent results from molecular dynamics simulations that provide atomic-resolution mechanistic understanding of such modulation to help bridge gaps between existing experimental binding and structural biology data. Findings from these simulations include: Tyr42 may function as a molecular switch that converts the HA binding site from a low affinity to a high affinity state; in the partially-disordered form of HABD, basic amino acids in the C-terminal region can gain sufficient mobility to form direct contacts with bound HA to further stabilize binding; and terminal sialic acids on covalently-attached N-glycans can form charge-paired hydrogen bonding interactions with basic amino acids that could otherwise bind to HA, thereby blocking HA binding to glycosylated CD44 HABD.

  2. Mandatory Access Control applications to web hosting (United States)

    Prandini, Marco; Faldella, Eugenio; Laschi, Roberto

    "Hosting" represents a commonplace solution for the low-cost implementation of web sites through the efficient sharing of the resources of a single server. The arising security problems, however, are not always easily dealt with under the Discretionary Access Control model implemented by traditional operating systems. More robust separation between the hosted sites, as well as more robust protection of the host system, can be attained by exploiting the features typical of Mandatory Access Control systems. Recently, these systems have recently been made available to the vast Linux community through projects like SELinux and grsecurity. This paper describes the architecture of a secure hosting server, integrating SELinux functionalities into the Apache/PHP platform, designed with the goal of increasing security without adding administrative burdens or impacting performance.

  3. Packaging of Sin Goods - Commitment or Exploitation?

    DEFF Research Database (Denmark)

    Nafziger, Julia

    to such self-control problems, and possibly exploit them, by offering different package sizes. In a competitive market, either one or three (small, medium and large) packages are offered. In contrast to common intuition, the large, and not the small package is a commitment device. The latter serves to exploit...

  4. Exploration, Exploitation, and Organizational Coordination Mechanisms

    Directory of Open Access Journals (Sweden)

    Silvio Popadiuk


    Full Text Available This paper presents an empirical relationship among exploration, exploitation, and organizational coordination mechanisms, classified as the centralization of decision-making, formalization, and connectedness. In order to analyze the findings of this survey, we used two techniques: Principal Component Analysis (PCA and Partial Least Squares Path Modeling (PLS-PM. Our analysis was supported by 249 answers from managers of companies located in Brazil (convenience sampling. Contrary to expectations, centralization and exploitation were negatively associated. Our data supports the research hypothesis that formalization is positively associated with exploitation. Although the relationship between formalization and exploration were significant, the result is contrary to the research hypothesis that we made. The relationships among connectedness and exploitation, and connectedness and exploration were both positive and significant. This relationship means that the more connectedness increases, the higher the likelihood of exploitation and exploration.

  5. Proba-V Mission Exploitation Platform (United States)

    Goor, Erwin; Dries, Jeroen


    VITO and partners developed the Proba-V Mission Exploitation Platform (MEP) as an end-to-end solution to drastically improve the exploitation of the Proba-V (a Copernicus contributing mission) EO-data archive (, the past mission SPOT-VEGETATION and derived vegetation parameters by researchers, service providers and end-users. The analysis of time series of data (+1PB) is addressed, as well as the large scale on-demand processing of near real-time data on a powerful and scalable processing environment. Furthermore data from the Copernicus Global Land Service is in scope of the platform. From November 2015 an operational Proba-V MEP environment, as an ESA operation service, is gradually deployed at the VITO data center with direct access to the complete data archive. Since autumn 2016 the platform is operational and yet several applications are released to the users, e.g. - A time series viewer, showing the evolution of Proba-V bands and derived vegetation parameters from the Copernicus Global Land Service for any area of interest. - Full-resolution viewing services for the complete data archive. - On-demand processing chains on a powerfull Hadoop/Spark backend e.g. for the calculation of N-daily composites. - Virtual Machines can be provided with access to the data archive and tools to work with this data, e.g. various toolboxes (GDAL, QGIS, GrassGIS, SNAP toolbox, …) and support for R and Python. This allows users to immediately work with the data without having to install tools or download data, but as well to design, debug and test applications on the platform. - A prototype of jupyter Notebooks is available with some examples worked out to show the potential of the data. Today the platform is used by several third party projects to perform R&D activities on the data, and to develop/host data analysis toolboxes. In parallel the platform is further improved and extended. From the MEP PROBA-V, access to Sentinel-2 and landsat data will

  6. Relative fitness of a generalist parasite on two alternative hosts: a cross-infestation experiment to test host specialization of the hen flea Ceratophyllus gallinae (Schrank)


    Appelgren A.; McCoy K.D.; Richner H.; Doligez B.


    Host range is a key element of a parasite's ecology and evolution and can vary greatly depending on spatial scale. Generalist parasites frequently show local population structure in relation to alternative sympatric hosts (i.e. host races) and may thus be specialists at local scales. Here we investigated local population specialization of a common avian nest based parasite the hen flea Ceratophyllus gallinae (Schrank) exploiting two abundant host species that share the same breeding sites the...

  7. Efficacy of auto-crosslinked hyaluronan gel for adhesion prevention in laparoscopy and hysteroscopy: a systematic review and meta-analysis of randomized controlled trials. (United States)

    Mais, Valerio; Cirronis, Maria G; Peiretti, Michele; Ferrucci, Giuliano; Cossu, Ester; Melis, Gian B


    Prevention of postoperative adhesions is a clinical need. We undertook a systematic review to explore the available clinical evidence of the efficacy of auto-crosslinked hyaluronan gel for postoperative adhesion prevention following endoscopic gynecological surgery. An electronic database search of MEDLINE, Cochrane Database of Systematic Reviews and EMBASE, and a comprehensive hand-search of reference lists of published and review articles were performed. No language restrictions were applied. Randomized controlled trials (RCTs) on the use of auto-crosslinked hyaluronan gel for the prevention of postoperative adhesions in gynecological surgery were included in the meta-analysis if they reported outcomes as evaluated at a blind second-look assessment. Three authors independently selected studies and extracted data on study characteristics, quality and accuracy. The Jadad scoring system was used for validity assessment. Meta-analysis was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The outcome was the incidence of postoperative adhesions based on a binary response (present or not present). Only five RCTs were eligible for inclusion in the meta-analysis. The incidence of postoperative adhesions in patients who received auto-crosslinked hyaluronan gel was significantly lower than in patients who underwent standard surgery only. The gel prevented both intraperitoneal adhesions after laparoscopic myomectomy (OR 0.248, 95% CI 0.098, 0.628) and intrauterine adhesions after hysteroscopic surgery (OR 0.408, 95% CI 0.217, 0.766). Further RCTs are needed to assess the efficacy of auto-crosslinked hyaluronan gel in women undergoing different laparoscopic intra-abdominal surgical procedures. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  8. Genetic Association and Gene-gene interaction of HAS2, HABP1 and HYAL3 Implicate Hyaluronan Metabolic Genes in Glaucomatous Neurodegeneration

    Directory of Open Access Journals (Sweden)

    Kaustuv Basu


    Full Text Available Hyaluronan (HA plays a significant role in maintaining aqueous humor outflow in trabecular meshwork, the primary ocular tissue involved in glaucoma. We examined potential association of the single nucleotide polymorphisms (SNPs of the HA synthesizing gene – hyaluronan synthase 2 (HAS2, hyaluronan binding protein 1 (HABP1 and HA catabolic gene hyaluronidase 3 (HYAL3 in the primary open angle glaucoma (POAG patients in the Indian population. Thirteen tagged SNPs (6 for HAS2, 3 for HABP1 and 4 for HYAL3 were genotyped in 116 high tension (HTG, 321 non-high tension glaucoma (NHTG samples and 96 unrelated, age-matched, glaucoma-negative, control samples. Allelic and genotypic association were analyzed by PLINK v1.04; haplotypes were identified using PHASE v2.1 and gene-gene interaction was analyzed using multifactor dimensionality reduction (MDR v2.0. An allelic association (rs6651224; p = 0.03; OR: 0.49; 95% CI: 0.25–0.94 was observed at the second intron (C>G of HAS2 both for NHTG and HTG. rs1057308 revealed a genotypic association (p = 0.03 at the 5’ UTR of HAS2 with only HTG. TCT haplotype (rs1805429 – rs2472614 – rs8072363 in HABP1 and TTAG and TTGA (rs2285044 – rs3774753 – rs1310073 – rs1076872 in HYAL3 were found to be significantly high (p < 0.05 both for HTG and NHTG compared to controls. Gene-gene interaction revealed HABP1 predominantly interacts with HAS2 in HTG while it associates with both HYAL3 and HAS2 in NHTG. This is the first genetic evidence, albeit from a smaller study, that the natural polymorphisms in the genes involved in hyaluronan metabolism are potentially involved in glaucomatous neurodegeneration.

  9. Artificial extracellular matrices composed of collagen I and high-sulfated hyaluronan promote phenotypic and functional modulation of human pro-inflammatory M1 macrophages. (United States)

    Franz, Sandra; Allenstein, Francie; Kajahn, Jennifer; Forstreuter, Inka; Hintze, Vera; Möller, Stephanie; Simon, Jan C


    The sequential phases of biomaterial integration and wound healing require different macrophage functions mediated by distinct macrophage subsets. During the initial phase of healing, pro-inflammatory M1 macrophages (MΦ1) are required to clear the wound from microbes and debris; however, their unopposed, persistent activation often leads to disturbed integration of biomaterials and perturbed wound healing. Here we investigated whether pro-inflammatory macrophage functions are affected by immunomodulatory biomaterials based on artificial extracellular matrices (aECM). To address this issue, we tested the capacity of two-dimensional aECM consisting of collagen I and hyaluronan or sulfated derivatives of hyaluronan to affect functions of in vitro polarized human pro-inflammatory MΦ1. The aECM containing high-sulfated hyaluronan substantially decreased inflammatory macrophage functions, including pathogen uptake and release of the pro-inflammatory cytokines tumor necrosis factor alpha and interleukin-12 due to impaired activation of nuclear factor "kappa-light-chain-enhancer" of activated B-cells. Moreover, these macrophages secreted immunregulatory IL-10 and showed reduced activity of the transcription factors signal transducer and activator of transcription 1 and interferon-regulating factor 5, both controlling macrophage polarization to MΦ1 subsets. Our data reveal that the collagen I matrix containing high-sulfated hyaluronan possesses immunomodulating properties and dampens inflammatory macrophage activities by impeding signaling pathways crucial for polarization of pro-inflammatory MΦ1. We therefore suggest this aECM as a promising coating for biomaterials to modulate inflammatory macrophage functions during the healing response and recommend its further testing as a three-dimensional construct and in in vivo models. Copyright © 2012 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  10. Global Climate Responses to Anthropogenic Groundwater Exploitation (United States)

    Zeng, Y.; Xie, Z.


    In this study, a groundwater exploitation scheme is incorporated into the earth system model, Community Earth System Model 1.2.0 (CESM1.2.0), which is called CESM1.2_GW, and the climatic responses to anthropogenic groundwater withdrawal are then investigated on global scale. The scheme models anthropogenic groundwater exploitation and consumption, which are then divided into agricultural irrigation, industrial use and domestic use. A group of 41-year ensemble groundwater exploitation simulations with six different initial conditions, and a group of ensemble control simulations without exploitation are conducted using the developed model CESM1.2_GW with water supplies and demands estimated. The results reveal that the groundwater exploitation and water consumption cause drying effects on soil moisture in deep layers and wetting effects in upper layers, along with a rapidly declining groundwater table in Central US, Haihe River Basin in China and Northern India and Pakistan where groundwater extraction are most severe in the world. The atmosphere also responds to anthropogenic groundwater exploitation. Cooling effects on lower troposphere appear in large areas of North China Plain and of Northern India and Pakistan. Increased precipitation occurs in Haihe River Basin due to increased evapotranspiration from irrigation. Decreased precipitation occurs in Northern India because water vapor here is taken away by monsoon anomalies induced by anthropogenic alteration of groundwater. The local reducing effects of anthropogenic groundwater exploitation on total terrestrial water storage evinces that water resource is unsustainable with the current high exploitation rate. Therefore, a balance between slow groundwater withdrawal and rapid human economic development must be achieved to maintain a sustainable water resource, especially in over-exploitation regions such as Central US, Northern China, India and Pakistan.

  11. Reasoning About Programs by Exploiting the Environment (United States)


    1i TITLE ( lude Security Ca .fcation) Reasoning about Programs by Exploiting the Environment rt 12. PERSONAL AUTHOR(S) w]ba1oa A Limor Fix axd...editions are obsolete. Reasoning About Programs by Exploiting the Environment * Limor Fix Fred B. Schneider TR 94-1409 February 1994 Department of Computer...agencies. Limor Fix is also supported, in part, by a Fullbright post-doctoral award. Reasoning about Programs by Exploiting the Environment ---- NITIS GRA&I

  12. Exploiting Bisphosphonate-Bioactive-Glass Interactions for the Development of Self-Healing and Bioactive Composite Hydrogels. (United States)

    Diba, Mani; An, Jie; Schmidt, Stephan; Hembury, Mathew; Ossipov, Dmitri; Boccaccini, Aldo R; Leeuwenburgh, Sander C G


    Hydrogels are widely recognized as promising candidates for various biomedical applications, such as tissue engineering. Recently, extensive research efforts have been devoted to the improvement of the biological and mechanical performance of hydrogel systems by incorporation of functional groups and/or inorganic particles in their composition. Bisphosphonates are a class of drugs, commonly used for treatment of osteoporosis, which exhibit a strong binding affinity for hydroxyapatite. In this study, the binding affinity of a bisphosphonate-functionalized polymer, hyaluronan, toward a bioactive glass (i.e., 45S5 Bioglass) is evaluated using force-distance measurements with atomic force microscopy. The strong interaction between bisphosphonate and bioactive glass is then exploited to develop organic-inorganic composite hydrogels and the viscoelastic and self-healing ability of these materials are investigated. Finally, the stability and mineralization behavior of these hydrogels are evaluated in simulated body fluid. Following this approach, injectable, bioactive and self-healing organic-inorganic composite hydrogels are produced, which mineralize abundantly and rapidly in simulated body fluid. These properties render these composite gels suitable for applications in bone-tissue engineering. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Exploitative and Deceptive Resource Acquisition Strategies

    Directory of Open Access Journals (Sweden)

    Joshua J. Reynolds


    Full Text Available Life history strategy (LHS and life history contingencies (LHCs should theoretically influence the use of exploitative and deceptive resource acquisition strategies. However, little research has been done in this area. The purpose of the present work was to create measures of exploitative strategies and test the predictions of life history theory. Pilot studies developed and validated a behavioral measure of cheating called the Dot Game. The role of individual LHS and LHCs (manipulated via validated story primes on cheating was investigated in Study 1. Studies 2a through 2c were conducted to develop and validate a self-report measure called the Exploitative and Deceptive Resource Acquisition Strategy Scale (EDRASS. Finally, Study 3 investigated life history and EDRASS. Results indicated that while LHS influences exploitative strategies, life history contingences had little effect. Implications of these findings are discussed.

  14. Life History Theory and Exploitative Strategies

    Directory of Open Access Journals (Sweden)

    Joshua J. Reynolds


    Full Text Available Exploitative strategies involve depriving others of resources while enhancing one’s own. Life history theory suggests that there are individual differences (life history strategy and environmental characteristics (life history contingencies [LHCs] that influence the use of exploitative strategies. However, past work manipulating LHCs has found mixed evidence for the influence of this information on exploitative behavior. We present three studies that help clarify the effects of this type of information. Results indicated that younger individuals are most sensitive to LHC information. We also found, contrary to predictions, that communicating slow LHC information (i.e., high population density, intraspecific competition, and resource scarcity increased rather than decreased the temptation to engage in exploitative behavior. Limitations and future directions are discussed.

  15. Liposomal cancer therapy: exploiting tumor characteristics

    DEFF Research Database (Denmark)

    Kaasgaard, Thomas; Andresen, Thomas Lars


    the reader will gain: The review focuses on strategies that exploit characteristic features of solid tumors, such as abnormal vasculature, overexpression of receptors and enzymes, as well as acidic and thiolytic characteristics of the tumor microenvironment. Take home message: It is concluded that the design...... of new liposomal drug delivery systems that better exploit tumor characteristic features is likely to result in more efficacious cancer treatments....

  16. Molecular weight specific impact of soluble and immobilized hyaluronan on CD44 expressing melanoma cells in 3D collagen matrices. (United States)

    Sapudom, Jiranuwat; Ullm, Franziska; Martin, Steve; Kalbitzer, Liv; Naab, Johanna; Möller, Stephanie; Schnabelrauch, Matthias; Anderegg, Ulf; Schmidt, Stephan; Pompe, Tilo


    Hyaluronan (HA) and its principal receptor CD44 are known to be involved in regulating tumor cell dissemination and metastasis. The direct correlation of CD44-HA interaction on proliferation and invasion of tumor cells in dependence on the molecular weight and the presentation form of HA is not fully understood because of lack of appropriate matrix models. To address this issue, we reconstituted 3D collagen (Coll I) matrices and functionalized them with HA of molecular weight of 30-50kDa (low molecular weight; LMW-HA) and 500-750kDa (high molecular weight; HMW-HA). A post-modification strategy was applied to covalently immobilize HA to reconstituted fibrillar Coll I matrices, resulting in a non-altered Coll I network microstructure and stable immobilization over days. Functionalized Coll I matrices were characterized regarding topological and mechanical characteristics as well as HA amount using confocal laser scanning microscopy, colloidal probe force spectroscopy and quantitative Alcian blue assay, respectively. To elucidate HA dependent tumor cell behavior, BRO melanoma cell lines with and without CD44 receptor expression were used for in vitro cell experiments. We demonstrated that only soluble LMW-HA promoted cell proliferation in a CD44 dependent manner, while HMW-HA and immobilized LMW-HA did not. Furthermore, an enhanced cell invasion was found only for immobilized LMW-HA. Both findings correlated with a very strong and specific adhesive interaction of LMW-HA and CD44+ cells quantified in single cell adhesion measurements using soft colloidal force spectroscopy. Overall, our results introduce an in vitro biomaterials model allowing to test presentation mode and molecular weight specificity of HA in a 3D fibrillar matrix thus mimicking important in vivo features of tumor microenvironments. Molecular weight and presentation form (bound vs. soluble) of hyaluronan (HA) are intensively discussed as key regulators in tumor progression and inflammation. We

  17. Mesenchymal stem cell interaction with a non-woven hyaluronan-based scaffold suitable for tissue repair. (United States)

    Pasquinelli, G; Orrico, C; Foroni, L; Bonafè, F; Carboni, M; Guarnieri, C; Raimondo, S; Penna, C; Geuna, S; Pagliaro, P; Freyrie, A; Stella, A; Caldarera, C M; Muscari, C


    The fabrication of biodegradable 3-D scaffolds enriched with multipotent stem cells seems to be a promising strategy for the repair of irreversibly injured tissues. The fine mechanisms of the interaction of rat mesenchymal stem cells (rMSCs) with a hyaluronan-based scaffold, i.e. HYAFF(R)11, were investigated to evaluate the potential clinical application of this kind of engineered construct. rMSCs were seeded (2 x 10(6) cells cm(-2)) on the scaffold, cultured up to 21 days and analysed using appropriate techniques. Light (LM), scanning (SEM) and transmission (TEM) electron microscopy of untreated scaffold samples showed that scaffolds have a highly porous structure and are composed of 15-microm-thick microfibres having a rough surface. As detected by trypan blue stain, cell adhesion was high at day 1. rMSCs were viable up to 14 days as shown by CFDA assay and proliferated steadily on the scaffold as revealed by MTT assay. LM showed rMSCs in the innermost portions of the scaffold at day 3. SEM revealed a subconfluent cell monolayer covering 40 +/- 10% of the scaffold surface at day 21. TEM of early culture showed rMSCs wrapping individual fibres with regularly spaced focal contacts, whereas confocal microscopy showed polarized expression of CD44 hyaluronan receptor; TEM of 14-day cultures evidenced fibronexus formation. Immunohistochemistry of 21-day cultures showed that fibronectin was the main matrix protein secreted in the extracellular space; decorin and versican were seen in the cell cytoplasm only and type IV collagen was minimally expressed. The expression of CD90, a marker of mesenchymal stemness, was found unaffected at the end of cell culture. Our results show that HYAFF(R)11 scaffolds support the adhesion, migration and proliferation of rMSCs, as well as the synthesis and delivery of extracellular matrix components under static culture conditions without any chemical induction. The high retention rate and viability of the seeded cells as well as their

  18. Sevoflurane mitigates shedding of hyaluronan from the coronary endothelium, also during ischemia/reperfusion: an ex vivo animal study

    Directory of Open Access Journals (Sweden)

    Chen C


    Full Text Available Congcong Chen,1,3 Daniel Chappell,2,3 Thorsten Annecke,2,3 Peter Conzen,2 Matthias Jacob,2,3 Ulrich Welsch,4 Bernhard Zwissler,2 Bernhard F Becker3 1Department of Anesthesiology, Second Affiliated Hospital of Zhejiang University, Hangzhou, People's Republic of China; 2Clinic of Anesthesiology, Ludwig-Maximilians-University, Munich, Germany; 3Walter-Brendel-Centre of Experimental Medicine, Ludwig-Maximilians-University, Munich, Germany; 4Institute of Anatomy, Ludwig-Maximilians-University, Munich, Germany Abstract: Glycosaminoglycan hyaluronan (HA, a major constituent of the endothelial glycocalyx, helps to maintain vascular integrity. Preconditioning the heart with volatile anesthetic agents protects against ischemia/reperfusion injury. We investigated a possible protective effect of sevoflurane on the glycocalyx, especially on HA. The effect of pre-ischemic treatment with sevoflurane (15 minutes at 2% vol/vol gas on shedding of HA was evaluated in 28 isolated, beating guinea pig hearts, subjected to warm ischemia (20 minutes at 37°C followed by reperfusion (40 minutes, half with and half without preconditioning by sevoflurane. HA concentration was measured in the coronary effluent. Over the last 20 minutes of reperfusion hydroxyethyl starch (1 g% was continuously infused and the epicardial transudate collected over the last 5 minutes for measuring the colloid extravasation. Additional hearts were fixed by perfusion after the end of reperfusion for immunohistology and electron microscopy. Sevoflurane did not significantly affect post-ischemic oxidative stress, but strongly inhibited shedding of HA during the whole period, surprisingly even prior to ischemia. Immunohistology demonstrated that heparan sulfates and SDC1 of the glycocalyx were also preserved by sevoflurane. Electron microscopy revealed shedding of glycocalyx caused by ischemia and a mostly intact glycocalyx in hearts exposed to sevoflurane. Coronary vascular permeability of the

  19. Schistosoma mansoni cercariae exploit an elastohydrodynamic coupling to swim efficiently

    CERN Document Server

    Krishnamurthy, Deepak; Bhargava, Arjun; Prakash, Manu


    The motility of many parasites is critical for the infection process of their host, as exemplified by the transmission cycle of the blood fluke Schistosoma mansoni. In their human infectious stage, immature, submillimetre-scale forms of the parasite known as cercariae swim in freshwater and infect humans by penetrating through the skin. This infection causes Schistosomiasis, a parasitic disease that is comparable to malaria in its global socio-economic impact. Given that cercariae do not feed and hence have a finite lifetime of around 12 hours, efficient motility is crucial for the parasite's survival and transmission of Schistosomiasis. However, a first-principles understanding of how cercariae swim is lacking. Via a combined experimental, theoretical and robotics based approach, we demonstrate that cercariae propel themselves against gravity by exploiting a unique elastohydrodynamic coupling. We show that cercariae beat their tail in a periodic fashion while maintaining a fixed flexibility near their poster...

  20. Exploiting GPUs in Virtual Machine for BioCloud

    Directory of Open Access Journals (Sweden)

    Heeseung Jo


    Full Text Available Recently, biological applications start to be reimplemented into the applications which exploit many cores of GPUs for better computation performance. Therefore, by providing virtualized GPUs to VMs in cloud computing environment, many biological applications will willingly move into cloud environment to enhance their computation performance and utilize infinite cloud computing resource while reducing expenses for computations. In this paper, we propose a BioCloud system architecture that enables VMs to use GPUs in cloud environment. Because much of the previous research has focused on the sharing mechanism of GPUs among VMs, they cannot achieve enough performance for biological applications of which computation throughput is more crucial rather than sharing. The proposed system exploits the pass-through mode of PCI express (PCI-E channel. By making each VM be able to access underlying GPUs directly, applications can show almost the same performance as when those are in native environment. In addition, our scheme multiplexes GPUs by using hot plug-in/out device features of PCI-E channel. By adding or removing GPUs in each VM in on-demand manner, VMs in the same physical host can time-share their GPUs. We implemented the proposed system using the Xen VMM and NVIDIA GPUs and showed that our prototype is highly effective for biological GPU applications in cloud environment.

  1. Exploiting GPUs in Virtual Machine for BioCloud (United States)

    Jo, Heeseung; Jeong, Jinkyu; Lee, Myoungho; Choi, Dong Hoon


    Recently, biological applications start to be reimplemented into the applications which exploit many cores of GPUs for better computation performance. Therefore, by providing virtualized GPUs to VMs in cloud computing environment, many biological applications will willingly move into cloud environment to enhance their computation performance and utilize infinite cloud computing resource while reducing expenses for computations. In this paper, we propose a BioCloud system architecture that enables VMs to use GPUs in cloud environment. Because much of the previous research has focused on the sharing mechanism of GPUs among VMs, they cannot achieve enough performance for biological applications of which computation throughput is more crucial rather than sharing. The proposed system exploits the pass-through mode of PCI express (PCI-E) channel. By making each VM be able to access underlying GPUs directly, applications can show almost the same performance as when those are in native environment. In addition, our scheme multiplexes GPUs by using hot plug-in/out device features of PCI-E channel. By adding or removing GPUs in each VM in on-demand manner, VMs in the same physical host can time-share their GPUs. We implemented the proposed system using the Xen VMM and NVIDIA GPUs and showed that our prototype is highly effective for biological GPU applications in cloud environment. PMID:23710465

  2. Sumoylation at the Host-Pathogen Interface

    Directory of Open Access Journals (Sweden)

    Van G. Wilson


    Full Text Available Many viral proteins have been shown to be sumoylated with corresponding regulatory effects on their protein function, indicating that this host cell modification process is widely exploited by viral pathogens to control viral activity. In addition to using sumoylation to regulate their own proteins, several viral pathogens have been shown to modulate overall host sumoylation levels. Given the large number of cellular targets for SUMO addition and the breadth of critical cellular processes that are regulated via sumoylation, viral modulation of overall sumoylation presumably alters the cellular environment to ensure that it is favorable for viral reproduction and/or persistence. Like some viruses, certain bacterial plant pathogens also target the sumoylation system, usually decreasing sumoylation to disrupt host anti-pathogen responses. The recent demonstration that Listeria monocytogenes also disrupts host sumoylation, and that this is required for efficient infection, extends the plant pathogen observations to a human pathogen and suggests that pathogen modulation of host sumoylation may be more widespread than previously appreciated. This review will focus on recent aspects of how pathogens modulate the host sumoylation system and how this benefits the pathogen.

  3. Exploitation in International Paid Surrogacy Arrangements. (United States)

    Wilkinson, Stephen


    Many critics have suggested that international paid surrogacy is exploitative. Taking such concerns as its starting point, this article asks: (1) how defensible is the claim that international paid surrogacy is exploitative and what could be done to make it less exploitative? (2) In the light of the answer to (1), how strong is the case for prohibiting it? Exploitation could in principle be dealt with by improving surrogates' pay and conditions. However, doing so may exacerbate problems with consent. Foremost amongst these is the argument that surrogates from economically disadvantaged countries cannot validly consent because their background circumstances are coercive. Several versions of this argument are examined and I conclude that at least one has some merit. The article's overall conclusion is that while ethically there is something to be concerned about, paid surrogacy is in no worse a position than many other exploitative commercial transactions which take place against a backdrop of global inequality and constrained options, such as poorly-paid and dangerous construction work. Hence, there is little reason to single surrogacy out for special condemnation. On a policy level, the case for prohibiting international commercial surrogacy is weak, despite legitimate concerns about consent and background poverty.


    DEFF Research Database (Denmark)

    Ding, Ming

    .5 months of age) were randomly divided into 5 groups studied in a short-term and a long-term experimental period. All HA groups received intra-articular injection of HA 0.4 mg/kg/week for 5 weeks in both knee joints. HA-II received injection for additional 5 weeks; HA-III received no more injection......)-related cartilage degradation. In the short-term study, compared with the control group, HA-injection resulted in a significantly decreased subchondral plate volume fraction and plate thickness. HA-treated cancellous bone had significantly lower bone volume fraction, and typical rod-like structure. In the long-term......Introduction: It is not known whether hyaluronan (HA) has any effect on the underlying subchondral bone tissues. This study was to investigate the effects of high molecular weight HA (1.5x106 Daltons) intra-articular injection on subchondral bone tissues. Methods: Fifty-six male guinea pigs (6...

  5. Tissue hyaluronan expression, as reflected in the sputum of lung cancer patients, is an indicator of malignancy

    Energy Technology Data Exchange (ETDEWEB)

    Rangel, M.P.; Sá, V.K. de; Martins, V. [Departamento de Patologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Martins, J.R.M. [Disciplina de Biologia Molecular, Departamento de Bioquímica, Faculdade de Medicina, Universidade Federal de São Paulo, São Paulo, SP (Brazil); Disciplina de Endocrinologia e Metabolismo, Laboratório de Endocrinologia Molecular e Translacional-LEMT, Departamento de Medicina, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP (Brazil); Parra, E.R. [Departamento de Patologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Mendes, A. [Disciplina de Biologia Molecular, Departamento de Bioquímica, Faculdade de Medicina, Universidade Federal de São Paulo, São Paulo, SP (Brazil); Andrade, P.C. [Departamento de Patologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Reis, R.M. [Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga (Portugal); ICVS/3B' s - PT Government Associate Laboratory, Guimarães (Portugal); Centro de Pesquisa em Oncologia Molecular, Hospital de Câncer de Barretos, Fundação Pio XII, Barretos, SP (Brazil); Longatto-Filho, A. [Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga (Portugal); ICVS/3B' s - PT Government Associate Laboratory, Guimarães (Portugal); Laboratório de Investigação Médica (LIM 14), Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Centro de Pesquisa em Oncologia Molecular, Hospital de Câncer de Barretos, Fundação Pio XII, Barretos, SP (Brazil); Oliveira, C.Z. [Centro de Pesquisa em Oncologia Molecular, Hospital de Câncer de Barretos, Fundação Pio XII, Barretos, SP (Brazil); Takagaki, T. [Divisão de Pneumologia, Instituto do Coração, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Carraro, D.M. [Centro Internacional de Pesquisa/CIPE, AC Camargo Cancer Center, São Paulo, SP (Brazil); Nader, H.B. [Disciplina de Biologia Molecular, Departamento de Bioquímica, Faculdade de Medicina, Universidade Federal de São Paulo, São Paulo, SP (Brazil); Capelozzi, V.L. [Departamento de Patologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil)


    Hyaluronan (HA) shows promise for detecting cancerous change in pleural effusion and urine. However, there is uncertainty about the localization of HA in tumor tissue and its relationship with different histological types and other components of the extracellular matrix, such as angiogenesis. We evaluated the association between HA and degree of malignancy through expression in lung tumor tissue and sputum. Tumoral tissue had significantly increased HA compared to normal tissue. Strong HA staining intensity associated with cancer cells was significant in squamous cell carcinoma compared to adenocarcinoma and large cell carcinoma. A significant direct association was found between tumors with a high percentage of HA and MVD (microvessel density) in tumoral stroma. Similarly significant was the direct association between N1 tumors and high levels of HA in cancer cells. Cox multivariate analysis showed significant association between better survival and low HA. HA increased in sputum from lung cancer patients compared to cancer-free and healthy volunteers and a significant correlation was found between HA in sputum and HA in cancer tissue. Localization of HA in tumor tissue was related to malignancy and reflected in sputum, making this an emerging factor for an important diagnostic procedure in patients suspected to have lung cancer. Further study in additional patients in a randomized prospective trial is required to finalize these results and to validate our quantitative assessment of HA, as well as to couple it to gold standard sputum cytology.

  6. Synthesis of photo-crosslinkable hyaluronan with tailored degree of substitution suitable for production of water resistant nanofibers. (United States)

    Huerta-Angeles, Gloria; Brandejsová, Martina; Knotková, Kateřina; Hermannová, Martina; Moravcová, Martina; Šmejkalová, Daniela; Velebný, Vladimír


    In this work, hyaluronan (HA) was grafted by a novel and an efficient mixed anhydrides methodology with (hetero)-aryl and aliphatic acrylic moieties suitable for cross-linking. A precise control of stoichiometry was achieved. Derivatives with degree of substitution (DS) below 20% did not show self-crosslinking. Due to mild reaction conditions, a negligible degradation of the polysaccharide was obtained. The influence of the feed components on the reaction efficiency and DS were studied up to 200 g/batch. The structure of the modified HA was characterized by Infrared Spectroscopy, Nuclear Magnetic Resonance, SEC-MALS and chromatographic analyses. Enzymatic degradation of derivatives was performed and isolated dimers demonstrated to be non-cytotoxic. The feasibility of the grafted HA for electrospinning with subsequent photo-crosslinking to avoid nanofibers water dissolution was demonstrated. The biocompatibility of the material, its degradation products, and the formation of honeycomb porous structures also proved the potential of the material for future in vivo applications. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. The production of injectable hydrazone crosslinked gellan gum-hyaluronan-hydrogels with tunable mechanical and physical properties. (United States)

    Karvinen, Jennika; Koivisto, Janne T; Jönkkäri, Ilari; Kellomäki, Minna


    Gellan gum (GG) has been proposed for use in tissue engineering (TE) due to its structural and functional similarities with alginate. The most traditional crosslinking methods of GG, ionical and photocrosslinking, have downsides such as loss of stability or phototoxicity, which can limit their use in certain applications. In this study, an alternative hydrazone crosslinking method is introduced. Hydrazone crosslinking is a simple method that produces no toxic reagents or side-products. The method enables the fabrication of injectable hydrogels. GG was combined with hyaluronan (HA) to improve some properties such as cell attachment. The mechanical and physical properties of GG-HA hydrogels were controlled by changing the molecular weight, the degree of modification, and the ratio of polymer components. GG-HA hydrogels showed ionic nature of deswelling in the presence of cations enabling the control of physical properties in different solution environments. Due to the non-linear elastic behavior of hydrogels and tissues, the stiffness as a function of strain was represented instead of solely giving the second-order elastic constants. The stiffness of GG-HA hydrogels was similar to that of soft tissues at small strains. Copyright © 2017. Published by Elsevier Ltd.

  8. Cross-Linking Chemistry of Tyramine-Modified Hyaluronan Hydrogels Alters Mesenchymal Stem Cell Early Attachment and Behavior. (United States)

    Loebel, Claudia; Szczesny, Spencer E; Cosgrove, Brian D; Alini, Mauro; Zenobi-Wong, Marcy; Mauck, Robert L; Eglin, David


    Given the significance of hydrogels as cell-instructive materials, it is important to understand how differences in their chemical and physical properties are able to direct cell fate. For example, it remains unclear how different hydrogel cross-linking chemistries and gelation mechanisms influence cell behavior. Here, we report on hyaluronan-tyramine (HA-Tyr) hydrogels prepared either with enzymatic cross-linking using horseradish peroxidase and H2O2 or with visible light (500 nm) triggered gelation. We demonstrate that when hydrogels are polymerized to equivalent Young's moduli, the specific cross-linking chemistry of HA-Tyr hydrogels can have a substantial impact on mesenchymal stem cell (MSC) behavior. MSCs cultured on HA-Tyr hydrogels exhibit increased cell spread areas on enzymatically formed substrates relative to photo-cross-linked matrices. While enzymatically formed hydrogels led to MSCs exhibiting greater cell focal adhesion length, MSCs cultured on the photo-cross-linked matrices exhibited smaller cell spread area and shorter focal adhesion length but generated increased traction stress. These findings highlight the importance of understanding hydrogel cross-linking chemistries when the role of biophysical cues in regulating stem cell fate is investigated.

  9. Improvement of the Digestibility of Sulfated Hyaluronans by Bovine Testicular Hyaluronidase: A UV Spectroscopic and Mass Spectrometric Study

    Directory of Open Access Journals (Sweden)

    Katharina Lemmnitzer


    Full Text Available Glycosaminoglycans (GAGs such as hyaluronan (HA and chondroitin sulfate (CS are important, natural polysaccharides which occur in biological (connective tissues and have various biotechnological and medical applications. Additionally, there is increasing evidence that chemically (oversulfated GAGs possess promising properties and are useful as implant coatings. Unfortunately, a detailed characterization of these GAGs is challenging: although mass spectrometry (MS is one of the most powerful tools to elucidate the structures of (polysaccharides, MS is not applicable to high mass polysaccharides, but characteristic oligosaccharides are needed. These oligosaccharides are normally generated by enzymatic digestion. However, chemically modified (particularly sulfated GAGs are extremely refractive to enzymatic digestion. This study focuses on the investigation of the digestibility of GAGs with different degrees of sulfation by bovine testicular hyaluronidase (BTH. It will be shown by using an adapted spectrophotometric assay that all investigated GAGs can be basically digested if the reaction conditions are carefully adjusted. However, the oligosaccharide yield correlates reciprocally with the number of sulfate residues per polymer repeating unit. Finally, matrix-laser desorption and ionization (MALDI MS will be used to study the released oligosaccharides and their sulfation patterns.

  10. Force spectroscopy of hyaluronan by atomic force microscopy: from hydrogen-bonded networks toward single-chain behavior. (United States)

    Giannotti, Marina I; Rinaudo, Marguerite; Vancso, G Julius


    The conformational behavior of hyaluronan (HA) polysaccharide chains in aqueous NaCl solution was characterized directly at the single-molecule level. This communication reports on one of the first single-chain atomic force microscopy (AFM) experiments performed at variable temperatures, investigating the influence of the temperature on the stability of the HA single-chain conformation. Through AFM single-molecule force spectroscopy, the temperature destabilization of a local structure was proven. This structure involved a hydrogen-bonded network along the polymeric chain, with hydrogen bonds between the polar groups of HA and possibly water, and a change from a nonrandom coil to a random coil behavior was observed when increasing the temperature from 29 +/- 1 to 46 +/- 1 degrees C. As a result of the applied force, this superstructure was found to break progressively at room temperature. The use of a hydrogen-bonding breaker solvent demonstrated the hydrogen-bonded water-bridged nature of the network structure of HA single chains in aqueous NaCl solution.

  11. Alterations in the Secretome of Clinically Relevant Preparations of Adipose-Derived Mesenchymal Stem Cells Cocultured with Hyaluronan

    Directory of Open Access Journals (Sweden)

    Peter Succar


    Full Text Available Osteoarthritis (OA can be a debilitating degenerative disease and is the most common form of arthritic disease. There is a general consensus that current nonsurgical therapies are insufficient for younger OA sufferers who are not candidates for knee arthroplasties. Adipose-derived mesenchymal stem cells (MSCs therapy for the treatment of OA can slow disease progression and lead to neocartilage formation. The mechanism of action is secretion driven. Current clinical preparations from adipose tissue for the treatment of OA include autologous stromal vascular fraction (SVF, SVF plus mature adipocytes, and culture-purified MSCs. Herein we have combined these human adipose-derived preparations with Hyaluronan (Hylan G-F 20: Synvisc in vitro and measured alterations in cytokine profile. SVF plus mature adipocytes showed the greatest decreased in the proinflammatory cytokines IL-1β, IFN-γ, and VEGF. MCP-1 and MIP-1α decreased substantially in the SVF preparations but not the purified MSCs. The purified MSC preparation was the only one to show increase in MIF. Overall the SVF plus mature adipocytes preparation may be most suited of all the preparations for combination with HA for the treatment of OA, based on the alterations of heavily implicated cytokines in OA disease progression. This will require further validation using in vivo models.

  12. Hyaluronan-CD44 interaction promotes growth of decidual stromal cells in human first-trimester pregnancy.

    Directory of Open Access Journals (Sweden)

    Rui Zhu

    Full Text Available Hyaluronan (HA and its receptor CD44 are expressed at the maternal-fetal interface, but its role in early pregnancy remains unclear. Here, we found that primary decidual stromal cells (DSCs continuously secreted HA and expressed its receptor CD44. Pregnancy-associated hormones up-regulated HA synthetase (HAS 2 transcription and HA release from DSCs. High molecular weight-HA (HMW-HA, but not medium molecular weight (MMW-HA or low molecular weight (LMW-HA, promoted proliferation and inhibited apoptosis of DSCs in a CD44-dependent manner. The in-cell Western analysis revealed HMW-HA activated PI3K/AKT and mitogen-activated protein kinase (MAPK/ERK1/2 signaling pathways time-dependently. Blocking these pathways by specific inhibitor LY294002 or U0126 abrogated HMW-HA-regulated DSc proliferation and apoptosis. Finally, we have found that HA content, HA molecular weight, HAS2 mRNA level, and CD44 expression were significantly decreased in DSCs from unexplained miscarriage compared with the normal pregnancy. Collectively, our results indicate that higher level and greater molecular mass of HA at maternal-fetal interface contributes to DSc growth and maintenance of DSCs in human early pregnancy.

  13. Formation and remodeling of the brain extracellular matrix in neural plasticity: Roles of chondroitin sulfate and hyaluronan. (United States)

    Miyata, Shinji; Kitagawa, Hiroshi


    The extracellular matrix (ECM) of the brain is rich in glycosaminoglycans such as chondroitin sulfate (CS) and hyaluronan. These glycosaminoglycans are organized into either diffuse or condensed ECM. Diffuse ECM is distributed throughout the brain and fills perisynaptic spaces, whereas condensed ECM selectively surrounds parvalbumin-expressing inhibitory neurons (PV cells) in mesh-like structures called perineuronal nets (PNNs). The brain ECM acts as a non-specific physical barrier that modulates neural plasticity and axon regeneration. Here, we review recent progress in understanding of the molecular basis of organization and remodeling of the brain ECM, and the involvement of several types of experience-dependent neural plasticity, with a particular focus on the mechanism that regulates PV cell function through specific interactions between CS chains and their binding partners. We also discuss how the barrier function of the brain ECM restricts dendritic spine dynamics and limits axon regeneration after injury. The brain ECM not only forms physical barriers that modulate neural plasticity and axon regeneration, but also forms molecular brakes that actively controls maturation of PV cells and synapse plasticity in which sulfation patterns of CS chains play a key role. Structural remodeling of the brain ECM modulates neural function during development and pathogenesis. Genetic or enzymatic manipulation of the brain ECM may restore neural plasticity and enhance recovery from nerve injury. This article is part of a Special Issue entitled Neuro-glycoscience, edited by Kenji Kadomatsu and Hiroshi Kitagawa. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Expression of the hyaluronan-mediated motility receptor RHAMM in tumor budding cells identifies aggressive colorectal cancers. (United States)

    Koelzer, Viktor Hendrik; Huber, Bettina; Mele, Valentina; Iezzi, Giandomenica; Trippel, Mafalda; Karamitopoulou, Eva; Zlobec, Inti; Lugli, Alessandro


    Expression of the hyaluronan-mediated motility receptor (RHAMM, CD168) predicts adverse clinicopathological features and decreased survival for colorectal cancer (CRC) patients. Using full tissue sections, we investigated the expression of RHAMM in tumor budding cells of 103 primary CRCs to characterize the biological processes driving single-cell invasion and early metastatic dissemination. RHAMM expression in tumor buds was analyzed with clinicopathological data, molecular features and survival. Tumor budding cells at the invasive front of CRC expressed RHAMM in 68% of cases. Detection of RHAMM-positive tumor budding cells was significantly associated with poor survival outcome (P = .0312), independent of TNM stage and adjuvant therapy in multivariate analysis (P = .0201). RHAMM-positive tumor buds were associated with frequent lymphatic invasion (P = .0007), higher tumor grade (P = .0296), and nodal metastasis (P = .0364). Importantly, the prognostic impact of RHAMM expression in tumor buds was maintained independently of the number of tumor buds found in an individual case (P = .0246). No impact of KRAS/BRAF mutation, mismatch repair deficiency and CpG island methylation was observed. RHAMM expression identifies an aggressive subpopulation of tumor budding cells and is an independent adverse prognostic factor for CRC patients. These data support ongoing efforts to develop RHAMM as a target for precision therapy. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Effect of Hyaluronan on Developmental Competence and Quality of Oocytes and Obtained Blastocysts from In Vitro Maturation of Bovine Oocytes

    Directory of Open Access Journals (Sweden)

    Jolanta Opiela


    Full Text Available The objective of the present study was to evaluate the effect of hyaluronan (HA during IVM on meiotic maturation, embryonic development, and the quality of oocytes, granulosa cells (GC, and obtained blastocysts. COCs were matured in vitro in control medium and medium with additional 0.035% or 0.07% of exogenous HA. The meiotic maturity did not differ between the analysed groups. The best rate and the highest quality of obtained blastocysts were observed when 0.07% HA was used. A highly significant difference (P<0.001 was noted in the mean number of apoptotic nuclei per blastocyst and in the DCI between the 0.07% HA and the control blastocysts (P<0.01. Our results suggest that addition of 0.035% HA and 0.07% HA to oocyte maturation media does not affect oocyte nuclear maturation and DNA fragmentation. However, the addition of 0.07% HA during IVM decreases the level of blastocysts DNA fragmentation. Finally, our results suggest that it may be risky to increase the HA concentration during IVM above 0.07% as we found significantly higher Bax mRNA expression levels in GC cultured with 0.07% HA. The final concentration of HA being supplemented to oocyte maturation media is critical for the success of the IVP procedure.

  16. Chitin-Hyaluronan Nanoparticles: A Multifunctional Carrier to Deliver Anti-Aging Active Ingredients through the Skin

    Directory of Open Access Journals (Sweden)

    Pierfrancesco Morganti


    Full Text Available The paper describes the process to produce Chitin Nanofibril-Hyaluronan nanoparticles (CN-HA, showing their ability to easily load active ingredients, facilitate penetration through the skin layers, and increase their effectiveness and safety as an anti-aging agent. Size and characterization of CN-HA nanoparticles were determined by Scanning Electron Microscopy (SEM and Zetasizer, while encapsulation efficiency and loading capacity of the entrapped ingredients were controlled by chromatographic and spectrophotometric methods. Safeness was evidenced on fibroblasts and keratinocytes culture viability by the MTT (Methylthiazol assay; anti-aging activity was evaluated in vitro measuring antioxidant capacity, anti-collagenase activity, and metalloproteinase and pro-inflammatory release; efficacy was shown in vivo by a double-blind vehicle-controlled study for 60 days on 60 women affected by photo-aging. In addition, the CN-HA nanoparticles have shown interesting possibility to be used as active ingredients, for designing and making advanced medication by the electrospinning technology, as well as to produce transparent films for food packaging, by the casting method, and can be used also in their dry form as tissues or films without adding preservatives. These unusual CN-HA nanoparticles obtained from the use of raw materials of waste origin may offer an unprecedented occasion for making innovative products, ameliorating the quality of life, reducing pollution and safeguarding the environment’s integrity.

  17. A sustained release formulation of novel quininib-hyaluronan microneedles inhibits angiogenesis and retinal vascular permeability in vivo. (United States)

    Galvin, Orla; Srivastava, Akshay; Carroll, Oliver; Kulkarni, Rajiv; Dykes, Steve; Vickers, Steven; Dickinson, Keith; Reynolds, Alison L; Kilty, Claire; Redmond, Gareth; Jones, Rob; Cheetham, Sharon; Pandit, Abhay; Kennedy, Breandán N


    Pathologic neovascularisation and ocular permeability are hallmarks of proliferative diabetic retinopathy and age-related macular degeneration. Current pharmacologic interventions targeting VEGF are effective in only 30-60% of patients and require multiple intraocular injections associated with iatrogenic infection. Thus, our goal is to develop novel small molecule drugs that are VEGF-independent are amenable to sustained ocular-release, and which reduce retinal angiogenesis and retinal vascular permeability. Here, the anti-angiogenic drug quininib was formulated into hyaluronan (HA) microneedles whose safety and efficacy was evaluated in vivo. Quininib-HA microneedles were formulated via desolvation from quininib-HA solution and subsequent cross-linking with 4-arm-PEG-amine prior to freeze-drying. Scanning electron microscopy revealed hollow needle-shaped particle ultrastructure, with a zeta potential of -35.5mV determined by electrophoretic light scattering. The incorporation efficiency and pharmacokinetic profile of quininib released in vitro from the microneedles was quantified by HPLC. Quininib incorporation into these microneedles was 90%. In vitro, 20% quininib was released over 4months; or in the presence of increasing concentrations of hyaluronidase, 60% incorporated quininib was released over 4months. Zebrafish hyaloid vasculature assays demonstrated quininib released from these microneedles significantly (pmicroneedles allow for sustained release of quininib; are safe in vivo and quininib released from these microneedles effectively inhibits angiogenesis and RVP in vivo. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. A complete hyaluronan hydrodynamic characterization using a size exclusion chromatography-triple detector array system during in vitro enzymatic degradation. (United States)

    La Gatta, Annalisa; De Rosa, Mario; Marzaioli, Iolanda; Busico, Teresa; Schiraldi, Chiara


    Size exclusion chromatography coupled with triple detection (online laser light scattering, refractometry, and viscosimetry) (SEC-TDA) was applied for the study of hyaluronan (HA) fragments produced during hydrolysis catalyzed by bovine testicular hyaluronidase (BTH). The main advantage this approach provides is the complete hydrodynamic characterization without requiring further experiments. HA was hydrolyzed using several BTH amounts and for increasing incubation times. Fragments were characterized in terms of weight and number average molecular weights (M(w) and M(n), respectively), polydispersity index (M(w)/M(n)), hydrodynamic radius (R(h)), and intrinsic viscosity ([eta]). The Mark-Houwink-Sakurada (MHS) curves (log[eta] versus logM(w)) were then derived directly. Fragments covering a whole range of M(w) (10-900kDa) and size (R(h)=4-81nm) and presenting a rather narrow distribution of molar masses (M(w)/M(n)=1.6-1.7) were produced. From the MHS curves, HA conformation resulted in a change from a random coil toward a rigid rod structure while decreasing the M(w). HA enzymatic hydrolysis in the presence of a BTH inhibitor was also monitored, revealing that inhibition profiles are affected by ionic strength. Finally, a comparison of the kinetic data derived from SEC-TDA with the data from rheological measurements suggested different strengths of the two methods in the determination of the depolymerization rate depending on the hydrolysis conditions. 2010 Elsevier Inc. All rights reserved.

  19. Rethinking exploitation: a process-centered account. (United States)

    Jansen, Lynn A; Wall, Steven


    Exploitation has become an important topic in recent discussions of biomedical and research ethics. This is due in no small measure to the influence of Alan Wertheimer's path-breaking work on the subject. This paper presents some objections to Wertheimer's account of the concept. The objections attempt to show that his account places too much emphasis on outcome-based considerations and too little on process-based considerations. Building on these objections, the paper develops an alternative process-centered account of the concept. This alternative account of exploitation takes as its point of departure the broadly Kantian notion that it is wrong to use another as an instrument for the advancement of one's own ends. It sharpens this slippery notion and adds a number of refinements to it. The paper concludes by arguing that process-centered accounts of exploitation better illuminate the ethical challenges posed by research on human subjects than outcome-centered accounts.

  20. Exploitation of complement regulatory proteins by Borrelia and Francisella. (United States)

    Madar, Marian; Bencurova, Elena; Mlynarcik, Patrik; Almeida, André M; Soares, Renata; Bhide, Katarina; Pulzova, Lucia; Kovac, Andrej; Coelho, Ana V; Bhide, Mangesh


    Pathogens have developed sophisticated mechanisms of complement evasion such as binding to the host complement regulatory proteins (CRPs) on their surface or expression of CRP mimicking molecules. The ability of pathogens to evade the complement system has been correlated with pathogenesis and host selectivity. Hitherto, little work has been undertaken to determine whether Borrelia and Francisella exploit various CRPs to block complement attack. Seventeen Borrelia (twelve species) and six Francisella (three subspecies) strains were used to assess their ability to bind human, sheep and cattle CRPs or mimic membrane associated complement regulators. A series of experiments including affinity ligand binding experiments, pull-down assays and mass spectrometry based protein identification, revealed an array of CRP binding proteins of Borrelia and Francisella. Unlike Francisella, Borrelia strains were able to bind multiple human CRPs. Three strains of Borrelia (SKT-4, SKT-2 and HO14) showed the presence of a human CD46-homologous motif, indicating their ability to possess putative human CD46 mimicking molecules. Similarly, five strains of Borrelia and two strains of Francisella may have surface proteins with human CD59-homologous motifs. Among ovine and bovine CRPs, the only CRP bound by Francisella (LVS, Tul4 strain) was vitronectin, while ovine C4BP, ovine factor H and bovine factor H were bound to Borrelia strains SKT-2, DN127 and Co53. This study presents an array of proteins of Borrelia and Francisella that bind CRPs or may mimic membrane-CRPs, thus enabling multiphasic complement evasion strategies of these pathogens.

  1. Bacterial communities associated with host-adapted populations of pea aphids revealed by deep sequencing of 16S ribosomal DNA.


    Jean-Pierre Gauthier; Yannick Outreman; Lucie Mieuzet; Jean-Christophe Simon


    International audience; Associations between microbes and animals are ubiquitous and hosts may benefit from harbouring microbial communities through improved resource exploitation or resistance to environmental stress. The pea aphid, Acyrthosiphon pisum, is the host of heritable bacterial symbionts, including the obligate endosymbiont Buchnera aphidicola and several facultative symbionts. While obligate symbionts supply aphids with key nutrients, facultative symbionts influence their hosts in...

  2. Fluorescent molecularly imprinted polymers as plastic antibodies for selective labeling and imaging of hyaluronan and sialic acid on fixed and living cells. (United States)

    Panagiotopoulou, Maria; Kunath, Stephanie; Medina-Rangel, Paulina Ximena; Haupt, Karsten; Tse Sum Bui, Bernadette


    Altered glycosylation levels or distribution of sialic acids (SA) or hyaluronan in animal cells are indicators of pathological conditions like infection or malignancy. We applied fluorescently-labeled molecularly imprinted polymer (MIP) particles for bioimaging of fixed and living human keratinocytes, to localize hyaluronan and sialylation sites. MIPs were prepared with the templates D-glucuronic acid (GlcA), a substructure of hyaluronan, and N-acetylneuraminic acid (NANA), the most common member of SA. Both MIPs were found to be highly selective towards their target monosaccharides, as no cross-reactivity was observed with other sugars like N-acetyl-D-glucosamine, N-acetyl-D-galactosamine, D-glucose and D-galactose, present on the cell surface. The dye rhodamine and two InP/ZnS quantum dots (QDs) emitting in the green and in the red regions were used as fluorescent probes. Rhodamine-MIPGlcA and rhodamine-MIPNANA were synthesized as monodispersed 400nm sized particles and were found to bind selectively their targets located in the extracellular region, as imaged by epifluorescence and confocal microscopy. In contrast, when MIP-GlcA and MIP-NANA particles with a smaller size (125nm) were used, the MIPs being synthesized as thin shells around green and red emitting QDs respectively, it was possible to stain the intracellular and pericellular regions as well. In addition, simultaneous dual-color imaging with the two different colored QDs-MIPs was demonstrated. Importantly, the MIPs were not cytotoxic and did not affect cell viability; neither was the cells morphology affected as demonstrated by live cell imaging. These synthetic receptors could offer a new and promising imaging tool to monitor disease progression. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Growth, Mortality and Exploitation Rates of Sarotherodon ...

    African Journals Online (AJOL)


    ABSTRACT. Sarotherodon melanotheron population of Dominli Lagoon in the Western Region of Ghana was studied for its growth and mortality parameters as well as exploitation rate. The study generally aimed at providing basic information necessary for the assessment and management of the fish stock in the lagoon.

  4. Biodegradation of hydrocarbons exploiting spent substrate from ...

    African Journals Online (AJOL)



    Aug 13, 2014 ... Biodegradation of hydrocarbons exploiting spent substrate from Pleurotus ostreatus in agricultural soils. A. Mauricio-Gutiérrez1, T. Jiménez-Salgado2, A. Tapia-Hernández2, J. Cavazos-Arroyo1 and. B. Pérez-Armendáriz1*. 1Interdisciplinary Research and Consulting, Autonomus Popular University of State ...

  5. Exploiting a natural auxotrophy for genetic selection. (United States)

    Ramage, Elizabeth; Gallagher, Larry; Manoil, Colin


    We exploited the natural histidine auxotrophy of Francisella species to develop hisD (encodes histidinol dehydrogenase) as a positive selection marker. A shuttle plasmid (pBR103) carrying Escherichia coli hisD and designed for cloning of PCR fragments replicated in both attenuated and highly virulent Francisella strains. During this work, we formulated a simplified defined growth medium for Francisella novicida.

  6. Courseware Design: Exploiting the Colour Micro. (United States)

    Kidd, Marilyn E.; Holmes, Glyn


    Discusses the impact of the presentation of data on the educational effectiveness of computer assisted learning systems, describes some of the existing systems for controlling the display of instructional data on CRTs, and outlines a project undertaken at the University of Western Ontario to exploit the capabilities of microcomputer color…

  7. Child Exploitation: Some Pieces of the Puzzle. (United States)

    Rohlader, Dorothy

    The report addresses the status in North Carolina and in the nation of child exploitation. Legislative and judicial backgrounds of child pornography and child prostitution are reviewed, and difficulties in obtaining statistical data are noted. Law enforcement issues in pornography are cited, and suggestions for further legislation regarding child…

  8. On the dynamics of exploited fish populations

    National Research Council Canada - National Science Library

    Beverton, R. J. H; Holt, Sidney J


    ...-brooding cichlids, and viviparity in many sharks and toothcarps. Moreover, fish are of considerable importance to the survival of the human species in the form of nutritious, delicious and diverse food. Rational exploitation and management of our global stocks of fishes must rely upon a detailed and precise insight of their biology. The...

  9. Exploiting indigenous knowledge in the environmental conservation ...

    African Journals Online (AJOL)

    ... of agriculture and reared livestock (especially goats). Over several years, they developed sustainable and effective exploitation mechanisms of the existing biodiversity resources to satisfy their individual needs and those of their societies in general. Journal of Language, Technology and Entrepreneurship in Africa Vol.

  10. Groundwater exploitation in the Abakaliki metropolis (southeastern ...

    African Journals Online (AJOL)


    Full Length Research Paper. Groundwater exploitation in the Abakaliki metropolis. (southeastern Nigeria): Issues and challenges. O. P. Aghamelu*, H. N. Ezeh and A. I. Obasi. Department of Geology and Exploration Geophysics, Ebonyi State University, P.M.B., 053,. Abakaliki, Ebonyi State, Nigeria. Accepted 24 September ...

  11. The Illegal Exploitation of Natural Resources

    NARCIS (Netherlands)

    Boekhout van Solinge, T.|info:eu-repo/dai/nl/156696207


    This essay discusses the involvement of organized crime in natural resource exploitation and trade. This is accomplished by examining case studies from different tropical regions in the world: Africa (Liberia, Sierra Leone, and DR Congo), Southeast Asia (Indonesia), and Latin America (Brazilian

  12. National Center for Missing and Exploited Children (United States)

    ... Have you experienced the tragedy of a missing child? We're here to help. Learn More >> × KidSmartz New Parent Tips to Help Kids Set Physical Boundaries! Download Resources >> × Subscribe EN SP Blog Media About Us Contact Us Legal T&C Careers Copyright © National Center for Missing & Exploited Children. All ...

  13. Finding All Elementary Circuits Exploiting Transconductance

    NARCIS (Netherlands)

    Klumperink, Eric A.M.; Bruccoleri, F.; Nauta, Bram

    Commonly used elementary circuits like single transistor amplifier stages, the differential pair and current mirror basically exploit the transconductance of transistors. This paper aims at finding ALL elementary transconductance based circuits. For this purpose, all graphs of two-port circuits with

  14. Finding all elementary circuits exploiting transconductance

    NARCIS (Netherlands)

    Klumperink, Eric A.M.; Bruccoleri, F.; Nauta, Bram


    Commonly used elementary circuits like single-transistor amplifier stages, the differential pair, and current mirrors basically exploit the transconductance property of transistors. This paper aims at finding all elementary transconductance-based circuits. For this purpose, all graphs of two-port

  15. In vitro synthesis of hyaluronan by a single protein derived from mouse HAS1 gene and characterization of amino acid residues essential for the activity. (United States)

    Yoshida, M; Itano, N; Yamada, Y; Kimata, K


    HAS1 was expressed as a FLAG-tagged HAS1 fusion protein in COS-1 cells. This recombinant protein was extracted with CHAPS (3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonic acid) from the membrane fraction and purified by anti-FLAG affinity chromatography and subsequent SDS-polyacrylamide gel electrophoresis. A protein solubilized from the one single band on the gel was able to synthesize hyaluronan when incubated with UDP-GlcNAc and UDP-GlcA as donor substrates without any further additions. The detergent-solubilized and purified HAS1 protein, however, exhibited quite different kinetic properties from the membrane-bound protein. When assayed under the reconstitutive conditions where the reaction mixture was layered onto the buffer containing high concentration of CHAPS, the activity was enhanced and the kinetic properties became similar to those of the membrane-bound protein. In addition, a HAS1 gene product by an in vitro transcription/translation system also showed HAS1 activity under the reconstitutive conditions. To our surprise, when incubated with UDP-GlcNAc alone, the protein was found to synthesize chito-oligosaccharide. Taking advantage of these enzyme reaction properties, active sites on the protein involved in for hyaluronan and chito-oligosaccharide synthesis were characterized. Site-directed mutagenesis induced in the cytoplasmic central loop domain of the protein revealed that several amino acid residues conserved among those domains of various proteins of a HAS family were essential for both hyaluronan and chito-oligosaccharide syntheses but one of them was not for chito-oligosaccharide synthesis. The substitutions that caused partial or severe loss of the activity gave no significant changes of the K(m) values of the mutated proteins, suggesting that no conformational or other indirect changes were involved in the effect. Taken together, the results suggest that the HAS1 protein alone is able to synthesize hyaluronan and different amino acid

  16. Dissemination and Exploitation: Project Goals beyond Science (United States)

    Hamann, Kristin; Reitz, Anja


    Dissemination and Exploitation are essential parts of public funded projects. In Horizon 2020 a plan for the exploitation and dissemination of results (PEDR) is a requirement. The plan should contain a clear vision on the objectives of the project in relation to actions for dissemination and potential exploitation of the project results. The actions follow the basic idea to spread the knowledge and results gathered within the project and face the challenge of how to bring the results into potentially relevant policy circle and how they impact the market. The plan follows the purpose to assess the impact of the project and to address various target groups who are interested in the project results. Simply put, dissemination concentrates on the transfer of knowledge and exploitation on the commercialization of the project. Beyond the question of the measurability of project`s impact, strategies within science marketing can serve purposes beyond internal and external communication. Accordingly, project managers are facing the challenge to implement a dissemination and exploitation strategy that ideally supports the identification of all partners with the project and matches the current discourse of the project`s content within the society, politics and economy. A consolidated plan might unite all projects partners under a central idea and supports the identification with the project beyond the individual research questions. Which applications, strategies and methods can be used to bring forward a PEDR that accompanies a project successfully and allows a comprehensive assessment of the project afterwards? Which hurdles might project managers experience in the dissemination process and which tasks should be fulfilled by the project manager?

  17. Trolling may intensify exploitation in crappie fisheries (United States)

    Meals, K. O.; Dunn, A. W.; Miranda, Leandro E.


    In some parts of the USA, anglers targeting crappies Pomoxis spp. are transitioning from mostly stationary angling with a single pole around submerged structures to using multiple poles while drifting with the wind or under power. This shift in fishing methods could result in a change in catch efficiency, possibly increasing exploitation rates to levels that would be of concern to managers. We studied the catch statistics of anglers fishing while trolling with multiple poles (trollers) and those fishing with single poles (polers) in Mississippi reservoirs. Specifically, we tested whether (1) various catch statistics differed between trollers and polers, (2) catch rates of trollers were related to the number of poles fished, and (3) trollers could raise exploitation rates to potentially unsustainable levels. Results showed that participation in the crappie fisheries was about equally split between polers and trollers. In spring, 90% of crappie anglers were polers; in summer, 85% of crappie anglers were trollers. The size of harvested crappies was similar for the two angler groups, but the catch per hour was almost three times higher for trollers than for polers. Catch rates by trollers were directly correlated to the number of poles fished, although the relationship flattened as the number of poles increased. The average harvest rate for one troller fishing with three poles was similar to the harvest rate obtained by one poler. Simulations predicted that at the existing mix of about 50% polers and 50% trollers and with no restrictions on the number of poles used by trollers, exploitation of crappies is about 1.3 times higher than that in a polers-only fishery; under a scenario in which 100% of crappie anglers were trollers, exploitation was forecasted to increase to about 1.7 times the polers-only rate. The efficiency of trolling for crappies should be of concern to fishery managers because crappie fisheries are mostly consumptive and may increase exploitation

  18. Radiosensitizing and Hyperthermic Properties of Hyaluronan Conjugated, Dextran-Coated Ferric Oxide Nanoparticles: Implications for Cancer Stem Cell Therapy

    Directory of Open Access Journals (Sweden)

    Ranjeeta Thapa


    Full Text Available Cytotoxicity, radiosensitivity, and hyperthermia sensitivity of hyaluronan-mediated dextran-coated super paramagnetic iron oxide nanoparticles (HA-DESPIONs were assessed in CD44-expressing head and neck squamous cell carcinoma (HNSCC cell lines at clinically relevant radiation dose and temperatures. Low-passage HNSCC cells were exposed to HA-DESPIONs and cytotoxicity was assessed using MTT assay. Radiosensitizing properties of graded doses of HA-DESPIONs were assessed in both unsorted and CD44-sorted cells using clonogenic assay in combination with 2 Gy exposure to X-rays. Hyperthermia-induced toxicity was measured at 40°C, 41°C, and 42°C using clonogenic assay. Cell death was assessed 24 hours after treatment using a flow cytometry-based apoptosis analysis. Results showed that HA-DESPIONs were nontoxic at moderate concentrations and did not directly radiosensitize the cell lines. Further, there was no significant difference in the radiosensitivity of CD44high and CD44low cells. However, HA-DESPIONs enhanced the effect of hyperthermia which resulted in reduced cell survival that appeared to be mediated through apoptosis. We demonstrated that HA-DESPIONs are nontoxic and although they do not enhance radiation sensitivity, they did increase the effect of local hyperthermia. These results support further development of drug-attached HA-DESPIONs in combination with radiation for targeting cancer stem cells (CSCs and the development of an alternating magnetic field approach to activate the HA-DESPIONs attached to CSCs.

  19. The clinical outcomes of using a new cross-linked hyaluronan gel in endoscopic frontal sinus surgery. (United States)

    Dal, Teoman; Bahar, Seçil


    In endoscopic sinus surgery (ESS) synechiae formation and ostial stenosis are frequently encountered. This is not uncommon after frontal recess and ostium interventions due to the narrow recess and difficult anatomy of the region. The goal of this study is to evaluate the efficacy of the new cross-linked hyaluronan gel-PureRegen® Gel Sinus-on wound healing and synechiae prevention in endoscopic frontal sinus surgery. The study consists of two groups of patients who underwent ESS, including frontal sinus surgery. In the study group of 37 patients, PureRegen® Gel Sinus was applied to both the frontal recess and ostium at the end of the procedure. The control group consisted of 28 patients. In this group, nasal dressing material was not applied at the end of surgery-neither to the frontal recess nor to the ostium. Postoperatively, epithelization was found to be significantly better at 2 and 4 weeks in the study group when compared with the findings in patients where no postoperative dressing was applied. In the eighth week, there was no significant difference found between the two groups in terms of epithelization. Synechiae formation was significantly lower in the PureRegen® Gel Sinus group than the control group at all 2, 4 and 8 weeks postoperative evaluations. The effects of PureRegen® Gel Sinus on wound healing, especially in reepithelization, have shown to occur earlier in the postoperative period. Rapid reepithelization and control of infection related granulation tissue formation with antibiotics in the early postoperative period may explain the low stenosis rate in frontal sinus ostia in PureRegen® Gel Sinus applied patients.

  20. A role for the endothelial glycosaminoglycan hyaluronan in neutrophil recruitment by endothelial cells cultured for prolonged periods. (United States)

    Butler, Lynn M; Rainger, G Ed; Nash, Gerard B


    Glycosaminoglycans (GAGs) presented on the surface of endothelial cells (ECs) are believed to influence leukocyte recruitment during inflammation, but their roles remain uncertain. Here we report an in vitro model of prolonged culture of human EC in which the contributions of heparan sulphate (HS) and hyaluronan (HA) to the process of neutrophil recruitment could be studied. Previously, we reported that increasing EC culture duration (up to 20 days) enhanced neutrophil recruitment in response to low dose (1 U/ml) but not high dose (100 U/ml) of tumour necrosis factor-alpha (TNF). Here we found that HS and HA were present at much higher levels on the surface of day 20 cultures than day 3 cultures. Neutrophil recruitment on both day 3 and day 20 ECs was mediated through CXCR chemokine receptors and interleukin-8 (IL-8). In addition, mRNA levels for TNF receptors, signalling pathway constituents, adhesion receptors, and chemokines involved in neutrophil recruitment were similar for day 3 and day 20 ECs. To test whether the enhanced neutrophil recruitment on day 20 EC was mediated by GAGs, they were removed enzymatically. Removal of HA (but not HS) inhibited neutrophil recruitment, as did antibody blockade of CD44, a counter-receptor for HA on neutrophils. Supernatants from hyaluronidase-treated day 20 ECs were more potent in activating neutrophils than supernatants from untreated EC. Thus, HA has a role in neutrophil recruitment that is revealed in long-term cultures where it increases potency of response to sub-optimal levels of TNF. This effect appears to occur through a dual mechanism involving chemokine presentation and interaction with CD44.

  1. Hyaluronan esters drive Smad gene expression and signaling enhancing cardiogenesis in mouse embryonic and human mesenchymal stem cells.

    Directory of Open Access Journals (Sweden)

    Margherita Maioli

    Full Text Available BACKGROUND: Development of molecules chemically modifying the expression of crucial orchestrator(s of stem cell commitment may have significant biomedical impact. We have recently developed hyaluronan mixed esters of butyric and retinoic acids (HBR, turning cardiovascular stem cell fate into a high-yield process. The HBR mechanism(s remain still largely undefined. METHODOLOGY/PRINCIPAL FINDINGS: We show that in both mouse embryonic stem (ES cells and human mesenchymal stem cells from fetal membranes of term placenta (FMhMSCs, HBR differentially affected the patterning of Smad proteins, one of the major conductors of stem cell cardiogenesis. Real-time RT-PCR and Western blot analyses revealed that in both cell types HBR enhanced gene and protein expression of Smad1,3, and 4, while down-regulating Smad7. HBR acted at the transcriptional level, as shown by nuclear run-off experiments in isolated nuclei. Immunofluorescence analysis indicated that HBR increased the fluorescent staining for Smad1,3, and 4, confirming that the transcriptional action of HBR encompassed the upregulation of the encoded Smad proteins. Chromatin immune precipitation and transcriptional analyses showed that HBR increased the transcription of the cardiogenic gene Nkx-2.5 through Smad4 binding to its own consensus Smad site. Treatment of mouse ES cells and FMhMSCs with HBR led to the concomitant overexpression of both Smad4 and α-sarcomeric actinin. Smad4 silencing by the aid of lentiviral-mediated Smad4 shRNA confirmed a dominant role of Smad4 in HBR-induced cardiogenesis. CONCLUSIONS/SIGNIFICANCE: The use of HBR may pave the way to novel combinatorial strategies of molecular and stem cell therapy based on fine tuning of targeted Smad transciption and signaling leading to a high-throughput of cardiogenesis without the needs of gene transfer technologies.

  2. CRISPR/Cas9 knockout of HAS2 in rat chondrosarcoma chondrocytes demonstrates the requirement of hyaluronan for aggrecan retention. (United States)

    Huang, Yi; Askew, Emily B; Knudson, Cheryl B; Knudson, Warren


    Hyaluronan (HA) plays an essential role in cartilage where it functions to retain aggrecan. Previous studies have suggested that aggrecan is anchored indirectly to the plasma membrane of chondrocytes via its binding to cell-associated HA. However, reagents used to test these observations such as hyaluronidase and HA oligosaccharides are short term and may have side activities that complicate interpretation. Using the CRISPR/Cas9 gene editing approach, a model system was developed by generating HA-deficient chondrocyte cell lines. HA synthase-2 (Has2)-specific single guide RNA was introduced into two different variant lines of rat chondrosarcoma chondrocytes; knockout clones were isolated and characterized. Two other members of the HA synthase gene family were expressed at very low relative copy number but showed no compensatory response in the Has2 knockouts. Wild type chondrocytes of both variants exhibited large pericellular matrices or coats extending from the plasma membrane. Addition of purified aggrecan monomer expanded the size of these coats as the proteoglycan became retained within the pericellular matrix. Has2 knockout chondrocytes lost all capacity to assemble a particle-excluding pericellular matrix and more importantly, no matrices formed around the knockout cells following the addition of purified aggrecan. When grown as pellet cultures so as to generate a bioengineered neocartilage tissue, the Has2 knockout chondrocytes assumed a tightly-compacted morphology as compared to the wild type cells. When knockout chondrocytes were transduced with Adeno-ZsGreen1-mycHas2, the cell-associated pericellular matrices were restored including the capacity to bind and incorporate additional exogenous aggrecan into the matrix. These results suggest that HA is essential for aggrecan retention and maintaining cell separation during tissue formation. Copyright © 2016 International Society of Matrix Biology. Published by Elsevier B.V. All rights reserved.

  3. Thrombin Cleavage of Inter-α-inhibitor Heavy Chain 1 Regulates Leukocyte Binding to an Inflammatory Hyaluronan Matrix. (United States)

    Petrey, Aaron C; de la Motte, Carol A


    Dynamic alterations of the extracellular matrix in response to injury directly modulate inflammation and consequently the promotion and resolution of disease. During inflammation, hyaluronan (HA) is increased at sites of inflammation where it may be covalently modified with the heavy chains (HC) of inter-α-trypsin inhibitor. Deposition of this unique, pathological form of HA (HC-HA) leads to the formation of cable-like structures that promote adhesion of leukocytes. Naive mononuclear leukocytes bind specifically to inflammation-associated HA matrices but do not adhere to HA constitutively expressed under homeostatic conditions. In this study, we have directly investigated a role for the blood-coagulation protease thrombin in regulating the adhesion of monocytic cells to smooth muscle cells producing an inflammatory matrix. Our data demonstrate that the proteolytic activity of thrombin negatively regulates the adhesion of monocytes to an inflammatory HC-HA complex. This effect is independent of protease-activated receptor activation but requires proteolytic activity toward a novel substrate. Components of HC-HA complexes were predicted to contain conserved thrombin-susceptible cleavage sites based on sequence analysis, and heavy chain 1 (HC1) was confirmed to be a substrate of thrombin. Thrombin treatment is sufficient to cleave HC1 associated with either cell-surface HA or serum inter-α-trypsin inhibitor. Furthermore, thrombin treatment of the inflammatory matrix leads to dissolution of HC-HA cable structures and abolishes leukocyte adhesion. These data establish a novel mechanism whereby thrombin cleavage of HC1 regulates the adhesive properties of an inflammatory HA matrix. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  4. Sericin accelerates the production of hyaluronan and decreases the incidence of polyspermy fertilization in bovine oocytes during in vitro maturation. (United States)

    Hosoe, Misa; Yoshida, Nao; Hashiyada, Yutaka; Teramoto, Hidetoshi; Takahashi, Toru; Niimura, Sueo


    Fetal bovine serum (FBS) has been widely used as a supplement in the maturation medium of bovine oocytes in vitro. However, serum contains many undefined factors and is potentially infectious to humans and animals. As a serum replacement, we evaluated the feasibility of using the silk protein, sericin, derived from the cocoons of silkworm. To examine the rates of oocyte maturation and fertilization, cumulus-oocyte complexes were cultured in TCM-199 supplemented with 0.01%, 0.05%, 0.1% or 0.15% sericin or 5% FBS. The sizes of the perivitelline space that might relate to polyspermy, the expressions of Has2 and CD44 mRNA, the amount of hyaluronan (hyaluronic acid: HA) contained in the oocytes and the rates of blastocyst formation following insemination were then compared between the oocytes cultured with 0.05% sericin and 5% FBS, because the polyspermy rates in oocytes cultured with 0.05% sericin were significantly lower than in those cultured with 5% FBS. After in vitro maturation (IVM), the mean size of the perivitelline space was significantly greater in oocytes cultured with sericin than in those cultured with FBS, although the rates of nuclear maturation, fertilization and blastocyst formation of oocytes under both IVM conditions were not significantly different. The expression of HAS2 and CD44 mRNA and the amount of HA in the denuded oocytes cultured with 0.05% sericin were significantly greater than in those cultured with FBS. These results indicate the feasibility of sericin as an alternative protein supplement for IVM in bovine oocytes.

  5. Hyaluronan Mixed Esters of Butyric and Retinoic Acid Affording Myocardial Survival and Repair without Stem Cell Transplantation* (United States)

    Lionetti, Vincenzo; Cantoni, Silvia; Cavallini, Claudia; Bianchi, Francesca; Valente, Sabrina; Frascari, Irene; Olivi, Elena; Aquaro, Giovanni D.; Bonavita, Francesca; Scarlata, Ignazio; Maioli, Margherita; Vaccari, Valentina; Tassinari, Riccardo; Bartoli, Antonietta; Recchia, Fabio A.; Pasquinelli, Gianandrea; Ventura, Carlo


    Possible cardiac repair by adult stem cell transplantation is currently hampered by poor cell viability and delivery efficiency, uncertain differentiating fate in vivo, the needs of ex vivo cell expansion, and consequent delay in transplantation after the onset of heart attack. By the aid of magnetic resonance imaging, positron emission tomography, and immunohistochemistry, we show that injection of a hyaluronan mixed ester of butyric and retinoic acid (HBR) into infarcted rat hearts afforded substantial cardiovascular repair and recovery of myocardial performance. HBR restored cardiac [18F]fluorodeoxyglucose uptake and increased capillary density and led to the recruitment of endogenous Stro-1-positive stem cells. A terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling assay demonstrated that HBR-treated hearts exhibited a decrease in the number of apoptotic cardiomyocytes. In isolated rat cardiomyocytes and Stro-1 stem cells, HBR enhanced the transcription of vascular endothelial growth factor, hepatocyte growth factor, kdr, akt, and pim-1. HBR also increased the secretion of vascular endothelial growth factor and hepatocyte growth factor, suggesting that the mixed ester may have recruited both myocardial and Stro-1 cells also. An increase in capillarogenesis was induced in vitro with medium obtained from HBR-exposed cells. In the infarcted myocardium, HBR injection increased histone H4 acetylation significantly. Acetyl-H4 immunoreactivity increased in rat cardiomyocytes and Stro-1 cells exposed to HBR, compared with untreated cells. In conclusion, efficient cardiac regenerative therapy can be afforded by HBR without the need of stem cell transplantation or vector-mediated gene delivery. PMID:20097747

  6. Key roles of hyaluronan and its CD44 receptor in the stemness and survival of cancer stem cells

    Directory of Open Access Journals (Sweden)

    Theerawut eChanmee


    Full Text Available Cancer stem cells (CSCs represent a unique subpopulation of self-renewing oncogenic cells that drive cancer initiation and progression. CSCs often acquire multidrug and oxidative stress resistance and are thereby thought to be responsible for tumor recurrence following treatment and remission. Although the mechanisms responsible for CSC generation, maintenance, and expansion have become a major focus in cancer research, the molecular characteristics of CSCs remain poorly understood. The stemness and subsequent expansion of CSCs are believed to be highly influenced by changes in microenvironmental signals as well as genetic and epigenetic alterations. Hyaluronan (HA, a major component of the extracellular matrix, has recently been demonstrated to provide a favorable microenvironment for the self-renewal and maintenance of stem cells. HA directly and indirectly affects CSC self-renewal by influencing the behaviour of both cancer and stromal cells. For instance, HA in the tumor microenvironment modulates the function of tumor-associated macrophages to support CSC self-renewal, and excessive HA production promotes the acquisition of CSC signatures through epithelial-to-mesenchymal transition. The importance of HA in mediating CSC self-renewal has been strengthened by the finding that interactions between HA and its receptor, CD44, propagate the stemness of CSCs. HA-CD44 interactions evoke a wide range of signals required for CSC self-renewal and maintenance. CD44 also plays a critical role in the preservation and multidrug resistance of CSCs by transmitting survival and anti-apoptotic signals. Thus, a better understanding of the molecular mechanisms involved in HA and CD44 control of CSC stemness may help in the design of more effective therapies for cancer patients. In this review, we address the key roles of HA and CD44 in CSC self-renewal and maintenance. We also discuss the involvement of CD44 in the oxidative stress and multidrug resistance of

  7. Hyaluronan mixed esters of butyric and retinoic acid affording myocardial survival and repair without stem cell transplantation. (United States)

    Lionetti, Vincenzo; Cantoni, Silvia; Cavallini, Claudia; Bianchi, Francesca; Valente, Sabrina; Frascari, Irene; Olivi, Elena; Aquaro, Giovanni D; Bonavita, Francesca; Scarlata, Ignazio; Maioli, Margherita; Vaccari, Valentina; Tassinari, Riccardo; Bartoli, Antonietta; Recchia, Fabio A; Pasquinelli, Gianandrea; Ventura, Carlo


    Possible cardiac repair by adult stem cell transplantation is currently hampered by poor cell viability and delivery efficiency, uncertain differentiating fate in vivo, the needs of ex vivo cell expansion, and consequent delay in transplantation after the onset of heart attack. By the aid of magnetic resonance imaging, positron emission tomography, and immunohistochemistry, we show that injection of a hyaluronan mixed ester of butyric and retinoic acid (HBR) into infarcted rat hearts afforded substantial cardiovascular repair and recovery of myocardial performance. HBR restored cardiac [(18)F]fluorodeoxyglucose uptake and increased capillary density and led to the recruitment of endogenous Stro-1-positive stem cells. A terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling assay demonstrated that HBR-treated hearts exhibited a decrease in the number of apoptotic cardiomyocytes. In isolated rat cardiomyocytes and Stro-1 stem cells, HBR enhanced the transcription of vascular endothelial growth factor, hepatocyte growth factor, kdr, akt, and pim-1. HBR also increased the secretion of vascular endothelial growth factor and hepatocyte growth factor, suggesting that the mixed ester may have recruited both myocardial and Stro-1 cells also. An increase in capillarogenesis was induced in vitro with medium obtained from HBR-exposed cells. In the infarcted myocardium, HBR injection increased histone H4 acetylation significantly. Acetyl-H4 immunoreactivity increased in rat cardiomyocytes and Stro-1 cells exposed to HBR, compared with untreated cells. In conclusion, efficient cardiac regenerative therapy can be afforded by HBR without the need of stem cell transplantation or vector-mediated gene delivery.

  8. Organizational Factors for Exploration and Exploitation

    Directory of Open Access Journals (Sweden)

    Sharadindu Pandey


    Full Text Available The Purpose of the paper is to develop a conceptual framework which suggests a relationship between organisational factors and exploratory and exploitative innovation types. We searched major databases like ABI/INFORM global, EBSCO, Elsevier’s science direct, Springer link and Emerald full text. Most of studies were included from published sources. We explored the literature of organisational culture, motivational bases of the rewards system and leadership values which are responsible for increasing creative and productive output. Our study has attempted to identify common patterns and themes in the literature regarding the drivers that increase both sides of the organisational creativity. The paper discusses the role of culture, system and styles in the initiation and implementation phases of the innovation called herein exploitative and exploratory innovation.

  9. Tribal children are most exploited - UNICEF. (United States)

    A workshop sponsored by the UN Children's Fund in the Philippines examined the status of the children of indigenous people and found that exploitation of the assets of indigenous people in the name of development has resulted in social inequalities that have damaged the indigenous children. As examples of the disregard for the human rights of the children, participants cited projects in Davao, Boracay, and Benguet that have displaced native children. These include mining schemes that have "raped" ancestral lands, large-scale agricultural enterprises, promotion of tourism, and creation of hydroelectric dams. The children rarely benefit at all from any of these projects as their families are moved from a position of isolated independence to one of exploited dependence. Social changes accompanying development ruin traditional culture without providing a better or even similar basis of existence.

  10. Sustainable exploitation and management of aquatic resources

    DEFF Research Database (Denmark)

    Neuenfeldt, Stefan; Köster, Fritz


    DTU Aqua conducts research, provides advice,educates at university level and contributes toinnovation in sustainable exploitation andmanagement of aquatic resources. The vision of DTUAqua is to enable ecologically and economicallysustainable exploitation of aquatic resourcesapplying an integrated...... ecosystem approach whichutilizes synergies in natural and technical sciencedisciplines. DTU Aqua advises the Danish Ministry ofFood, Agriculture and Fisheries and other publicauthorities, the commercial fisheries, theaquaculture industry and international commissions.DTU Aqua deals with all types ofaquatic...... in the ocean and how these factors impact the living conditions formarine organisms. Population genetics aims at gaining knowledge on how to preserve and managebiodiversity sustainably. Individual biology deals with the biology of aquatic organisms and theirinteraction with other organisms...

  11. Automatic exploitation system for photographic dosemeters; Systeme d`exploitation automatique des dosimetres photographiques

    Energy Technology Data Exchange (ETDEWEB)

    Magri, Y.; Devillard, D.; Godefroit, J.L.; Barillet, C.


    The Laboratory of Dosimetry Exploitation (LED) has realized an equipment allowing to exploit automatically photographic film dosemeters. This system uses an identification of the films by code-bars and gives the doses measurement with a completely automatic reader. The principle consists in putting in ribbon the emulsions to be exploited and to develop them in a circulation machine. The measurement of the blackening film is realized on a reading plate having fourteen points of reading, in which are circulating the emulsions in ribbon. The exploitation is made with the usual dose calculation method, with special computers codes. A comparison on 2000 dosemeters has shown that the results are the same in manual and automatical methods. This system has been operating since July 1995 by the LED. (N.C.).

  12. The intermediate host immune response in cystic echinococcosis. (United States)

    Tamarozzi, F; Mariconti, M; Neumayr, A; Brunetti, E


    Cystic echinococcosis (CE) is a chronic, complex and neglected zoonotic infection. In most cases, CE cysts and the intermediate host co-habit for a long time in the absence of symptoms and elicit very little inflammation. However, the immune interplay between the parasite and the host is complex, encompassing effective parasite-killing immune mechanisms implemented by the host, which in turn are modulated by the parasite. The immune response to the parasite has been exploited for the diagnosis of the disease and for the development of an effective vaccine to use in the natural intermediate host, but the mechanisms of parasite killing and immunomodulation are still unknown. Here, we reviewed the immune effector mechanisms and the strategies of immune evasion in the intermediate host. © 2015 John Wiley & Sons Ltd.

  13. Host manipulation by cancer cells: Expectations, facts, and therapeutic implications. (United States)

    Tissot, Tazzio; Arnal, Audrey; Jacqueline, Camille; Poulin, Robert; Lefèvre, Thierry; Mery, Frédéric; Renaud, François; Roche, Benjamin; Massol, François; Salzet, Michel; Ewald, Paul; Tasiemski, Aurélie; Ujvari, Beata; Thomas, Frédéric


    Similar to parasites, cancer cells depend on their hosts for sustenance, proliferation and reproduction, exploiting the hosts for energy and resources, and thereby impairing their health and fitness. Because of this lifestyle similarity, it is predicted that cancer cells could, like numerous parasitic organisms, evolve the capacity to manipulate the phenotype of their hosts to increase their own fitness. We claim that the extent of this phenomenon and its therapeutic implications are, however, underappreciated. Here, we review and discuss what can be regarded as cases of host manipulation in the context of cancer development and progression. We elaborate on how acknowledging the applicability of these principles can offer novel therapeutic and preventive strategies. The manipulation of host phenotype by cancer cells is one more reason to adopt a Darwinian approach in cancer research. © 2016 WILEY Periodicals, Inc.

  14. Macropinocytosis Exploitation by Cancers and Cancer Therapeutics

    Directory of Open Access Journals (Sweden)

    Kevin D Ha


    Full Text Available Macropinocytosis has long been known as a primary method for cellular intake of fluid-phase and membrane-bound bulk cargo. This review seeks to re-examine the latest studies to emphasize how cancers exploit macropinocytosis to further their tumorigenesis, including details in how macropinocytosis can be adapted to serve diverse functions. Furthermore, this review will also cover the latest endeavors in targeting macropinocytosis as an avenue for novel therapeutics.

  15. Macropinocytosis Exploitation by Cancers and Cancer Therapeutics. (United States)

    Ha, Kevin D; Bidlingmaier, Scott M; Liu, Bin


    Macropinocytosis has long been known as a primary method for cellular intake of fluid-phase and membrane-bound bulk cargo. This review seeks to re-examine the latest studies to emphasize how cancers exploit macropinocytosis to further their tumorigenesis, including details in how macropinocytosis can be adapted to serve diverse functions. Furthermore, this review will also cover the latest endeavors in targeting macropinocytosis as an avenue for novel therapeutics.

  16. Macropinocytosis Exploitation by Cancers and Cancer Therapeutics


    Ha, Kevin D.; Bidlingmaier, Scott M.; Liu, Bin


    Macropinocytosis has long been known as a primary method for cellular intake of fluid-phase and membrane-bound bulk cargo. This review seeks to re-examine the latest studies to emphasize how cancers exploit macropinocytosis to further their tumorigenesis, including details in how macropinocytosis can be adapted to serve diverse functions. Furthermore, this review will also cover the latest endeavors in targeting macropinocytosis as an avenue for novel therapeutics.

  17. Flare Systems Exploitation and Impact on Permafrost (United States)

    Filimonov, M. Yu; Vaganova, N. A.


    Mathematical models and numerical algorithms of horizontal and vertical flare systems exploitation in northern oil and gas fields located in permafrost zone are developed. Computations of long-term forecasts of permafrost degradation around such constructions have been carried out for various types of operation, including emergency situations, which cause a short-term increase in the heat flow near the ground surface, which leads to an additional soil temperature increasing.

  18. The effect of salivary gland extract of Lucilia sericata maggots on human dermal fibroblast proliferation within collagen/hyaluronan membrane in vitro: transmission electron microscopy study. (United States)

    Polakovičova, Simona; Polák, Štefan; Kuniaková, Marcela; Čambal, Marek; Čaplovičová, Mária; Kozánek, Milan; Danišovič, L'uboš; Kopáni, Martin


    Lucilia sericata maggots are applied to chronic wounds to aid healing when conventional treatments have failed. After their application into a necrotic wound, they potentially influence wound healing with a combination of specific proteinases that are involved in the remodeling of extracellular matrix. These proteases cause changes in fibroblast adhesion and spread upon extracellular matrix protein surfaces, affecting integrity of the protein surfaces-especially fibronectin-while maintaining cell viability. This study focused on in vitro monitoring of the effect of homogenate substances prepared from maggot salivary gland of L sericata on the ultrastructure of human neonatal fibroblasts. Collagen/hyaluronan membrane was used as the synthetic substitute of extracellular matrix. The cultured human neonatal fibroblasts B-HNF-1 were seeded on the surface of the collagen/hyaluronan membrane and cultured with maggot salivary gland extract (SGE) at a concentration of 2.4 glands/1 mL. The authors observed increased cell metabolism and protein production (euchromatic nucleus, voluminous nuclear membrane, large reticular nuclei, distended and filled cisterns of rough endoplasmic reticulum, Golgi apparatus with saccules, and vesicles packed with fine fibrillar material) after incubating the cells in culture medium with SGE. The authors believe that increased cell metabolism and protein production corresponded with formation of microfibrillar net used for migration of fibroblasts in culture, but mainly for proper production of extracellular matrix. The authors suggest that their results may help explain the effect of SGE on wound healing and support implementation of maggot therapy into human medicine.

  19. Host age modulates within-host parasite competition


    Izhar, Rony; Routtu, Jarkko; Ben-Ami, Frida


    In many host populations, one of the most striking differences among hosts is their age. While parasite prevalence differences in relation to host age are well known, little is known on how host age impacts ecological and evolutionary dynamics of diseases. Using two clones of the water flea Daphnia magna and two clones of its bacterial parasite Pasteuria ramosa, we examined how host age at exposure influences within-host parasite competition and virulence. We found that multiply-exposed hosts...

  20. Use of Host-like Peptide Motifs in Viral Proteins Is a Prevalent Strategy in Host-Virus Interactions

    Directory of Open Access Journals (Sweden)

    Tzachi Hagai


    Full Text Available Viruses interact extensively with host proteins, but the mechanisms controlling these interactions are not well understood. We present a comprehensive analysis of eukaryotic linear motifs (ELMs in 2,208 viral genomes and reveal that viruses exploit molecular mimicry of host-like ELMs to possibly assist in host-virus interactions. Using a statistical genomics approach, we identify a large number of potentially functional ELMs and observe that the occurrence of ELMs is often evolutionarily conserved but not uniform across virus families. Some viral proteins contain multiple types of ELMs, in striking similarity to complex regulatory modules in host proteins, suggesting that ELMs may act combinatorially to assist viral replication. Furthermore, a simple evolutionary model suggests that the inherent structural simplicity of ELMs often enables them to tolerate mutations and evolve quickly. Our findings suggest that ELMs may allow fast rewiring of host-virus interactions, which likely assists rapid viral evolution and adaptation to diverse environments.

  1. Larval size in acanthocephalan parasites: Influence of intraspecific competition and effects on intermediate host behavioural changes

    Directory of Open Access Journals (Sweden)

    Dianne Lucile


    Full Text Available Abstract Background Parasites often face a trade-off between exploitation of host resources and transmission probabilities to the next host. In helminths, larval growth, a major component of adult parasite fitness, is linked to exploitation of intermediate host resources and is influenced by the presence of co-infecting conspecifics. In manipulative parasites, larval growth strategy could also interact with their ability to alter intermediate host phenotype and influence parasite transmission. Methods We used experimental infections of Gammarus pulex by Pomphorhynchus laevis (Acanthocephala, to investigate larval size effects on host behavioural manipulation among different parasite sibships and various degrees of intra-host competition. Results Intra-host competition reduced mean P. laevis cystacanth size, but the largest cystacanth within a host always reached the same size. Therefore, all co-infecting parasites did not equally suffer from intraspecific competition. Under no intra-host competition (1 parasite per host, larval size was positively correlated with host phototaxis. At higher infection intensities, this relationship disappeared, possibly because of strong competition for host resources, and thus larval growth, and limited manipulative abilities of co-infecting larval acanthocephalans. Conclusions Our study indicates that behavioural manipulation is a condition-dependant phenomenon that needs the integration of parasite-related variables to be fully understood.

  2. Host plant use drives genetic differentiation in syntopic populations of Maculinea alcon

    DEFF Research Database (Denmark)

    Tartally, András; Kelager, Andreas; Fürst, Matthias Alois


    The rare socially parasitic butterfly Maculinea alcon occurs in two forms, which are characteristic of hygric or xeric habitats and which exploit different host plants and host ants. The status of these two forms has been the subject of considerable controversy. Populations of the two forms...... on different host plants, each with a distinct flowering phenology, providing a temporal rather than spatial barrier to gene flow....

  3. Exploitation of subsea gas hydrate reservoirs (United States)

    Janicki, Georg; Schlüter, Stefan; Hennig, Torsten; Deerberg, Görge


    Natural gas hydrates are considered to be a potential energy resource in the future. They occur in permafrost areas as well as in subsea sediments and are stable at high pressure and low temperature conditions. According to estimations the amount of carbon bonded in natural gas hydrates worldwide is two times larger than in all known conventional fossil fuels. Besides technical challenges that have to be overcome climate and safety issues have to be considered before a commercial exploitation of such unconventional reservoirs. The potential of producing natural gas from subsea gas hydrate deposits by various means (e.g. depressurization and/or injection of carbon dioxide) is numerically studied in the frame of the German research project »SUGAR«. The basic mechanisms of gas hydrate formation/dissociation and heat and mass transport in porous media are considered and implemented into a numerical model. The physics of the process leads to strong non-linear couplings between hydraulic fluid flow, hydrate dissociation and formation, hydraulic properties of the sediment, partial pressures and seawater solution of components and the thermal budget of the system described by the heat equation. This paper is intended to provide an overview of the recent development regarding the production of natural gas from subsea gas hydrate reservoirs. It aims at giving a broad insight into natural gas hydrates and covering relevant aspects of the exploitation process. It is focused on the thermodynamic principles and technological approaches for the exploitation. The effects occurring during natural gas production within hydrate filled sediment layers are identified and discussed by means of numerical simulation results. The behaviour of relevant process parameters such as pressure, temperature and phase saturations is described and compared for different strategies. The simulations are complemented by calculations for different safety relevant problems.

  4. Predictors of host specificity among behavior-manipulating parasites. (United States)

    Fredensborg, B L


    A trade-off between resource-specialization and the breadth of the ecological niche is one of the most fundamental biological characteristics. A true generalist (Jack-of-all-trades) displays a broad ecological niche with little resource specialization while the opposite is true for a resource-specialist that has a restricted ecological niche that it masters. Parasites that manipulate hosts' behavior are often thought to represent resource-specialists based on a few spectacular examples of manipulation of the host's behavior. However, the determinants of which, and how many, hosts a manipulating parasite can exploit (i.e., niche breadth) are basically unknown. Here, I present an analysis based on published records of the use of hosts by 67 species from 38 genera of helminths inducing parasite increased trophic transmission, a widespread strategy of parasites that has been reported from many taxa of parasites and hosts. Using individual and multivariate analyses, I examined the effect of the host's and parasite's taxonomy, location of the parasite in the host, type of behavioral change, and the effect of debilitation on host-specificity, measured as the mean taxonomic relatedness of hosts that a parasite can manipulate. Host-specificity varied substantially across taxa suggesting great variation in the level of resource-specialization among manipulating parasites. Location of the parasite, level of debilitation, and type of host were all significant predictors of host-specificity. More specifically, hosts' behavioral modification that involves interaction with the central nervous system presumably restricts parasites to more closely related hosts than does manipulation of the host's behavior via debilitation of the host's physiology. The results of the analysis suggest that phylogenetic relatedness of hosts is a useful measure of host-specificity in comparative studies of the complexity of interactions taking place between manipulating parasites and their hosts.

  5. Exploiting Redundancy in an OFDM SDR Receiver

    Directory of Open Access Journals (Sweden)

    Tomas Palenik


    Full Text Available Common OFDM system contains redundancy necessary to mitigate interblock interference and allows computationally effective single-tap frequency domain equalization in receiver. Assuming the system implements an outer error correcting code and channel state information is available in the receiver, we show that it is possible to understand the cyclic prefix insertion as a weak inner ECC encoding and exploit the introduced redundancy to slightly improve error performance of such a system. In this paper, an easy way to implement modification to an existing SDR OFDM receiver is presented. This modification enables the utilization of prefix redundancy, while preserving full compatibility with existing OFDM-based communication standards.

  6. Art Therapy Exhibitions: Exploitation or Advocacy? (United States)

    Davis, Terri


    Promoting awareness of human trafficking by sharing trauma survivors' art and summaries of their life stories suggests ethical complexities that have been typically neglected by bioethicists. Although these survivors voluntarily share the objects they created during art therapy sessions, they are still at risk of harm, including further exploitation, due to their vulnerability, high rates of victim sensitivity, and the mental health consequences of their traumatic experiences. While some argue that the benefits of sublimation and art therapy for human trafficking survivors make sharing their art worth the risk, anti-trafficking organizations and supporters of such art exhibitions have responsibilities to be trauma informed. © 2017 American Medical Association. All Rights Reserved.

  7. Geothermal resources: exploration and exploitation. A bibliography

    Energy Technology Data Exchange (ETDEWEB)


    This comprehensive bibliography contains 5476 citations of foreign and domestic research reports, journal articles, patents, conference proceedings, and books concerned with the exploration and exploitation of geothermal resources. The coverage dates back as far as useful references could be obtained and extends through June 1976. References are arranged in broad subject categories and are made up of complete bibliographic citations. These are followed by a listing of subject descriptors used to describe the subject content of each reference. Four indexes are included: Corporate, Personal Author, Subject, and Report Number. Also included is a list of journals from which articles were selected. (LBS)

  8. Competing Discourses about Youth Sexual Exploitation in Canadian News Media. (United States)

    Saewyc, Elizabeth M; Miller, Bonnie B; Rivers, Robert; Matthews, Jennifer; Hilario, Carla; Hirakata, Pam


    Media holds the power to create, maintain, or break down stigmatizing attitudes, which affect policies, funding, and services. To understand how Canadian news media depicts the commercial sexual exploitation of children and youth, we examined 835 Canadian newspaper articles from 1989-2008 using a mixed methods critical discourse analysis approach, comparing representations to existing research about sexually exploited youth. Despite research evidence that equal rates of boys and girls experience exploitation, Canadian news media depicted exploited youth predominantly as heterosexual girls, and described them alternately as victims or workers in a trade, often both in the same story. News media mentioned exploiters far less often than victims, and portrayed them almost exclusively as male, most often called 'customers' or 'consumers,' and occasionally 'predators'; in contrast, research has documented the majority of sexually exploited boys report female exploiters. Few news stories over the past two decades portrayed the diversity of victims, perpetrators, and venues of exploitation reported in research. The focus on victims but not exploiters helps perpetuate stereotypes of sexual exploitation as business or a 'victimless crime,' maintains the status quo, and blurs responsibility for protecting youth under the UN Convention on the Rights of the Child. Health care providers and researchers can be advocates for accuracy in media coverage about sexual exploitation; news reporters and editors should focus on exploiters more than victims, draw on existing research evidence to avoid perpetuating stereotypes, and use accurate terms, such as commercial sexual exploitation, rather than terms related to business or trade.

  9. Augmented reality enabling intelligence exploitation at the edge (United States)

    Kase, Sue E.; Roy, Heather; Bowman, Elizabeth K.; Patton, Debra


    Today's Warfighters need to make quick decisions while interacting in densely populated environments comprised of friendly, hostile, and neutral host nation locals. However, there is a gap in the real-time processing of big data streams for edge intelligence. We introduce a big data processing pipeline called ARTEA that ingests, monitors, and performs a variety of analytics including noise reduction, pattern identification, and trend and event detection in the context of an area of operations (AOR). Results of the analytics are presented to the Soldier via an augmented reality (AR) device Google Glass (Glass). Non-intrusive AR devices such as Glass can visually communicate contextually relevant alerts to the Soldier based on the current mission objectives, time, location, and observed or sensed activities. This real-time processing and AR presentation approach to knowledge discovery flattens the intelligence hierarchy enabling the edge Soldier to act as a vital and active participant in the analysis process. We report preliminary observations testing ARTEA and Glass in a document exploitation and person of interest scenario simulating edge Soldier participation in the intelligence process in disconnected deployment conditions.

  10. Host Plant Use by Competing Acacia-Ants: Mutualists Monopolize While Parasites Share Hosts (United States)

    Kautz, Stefanie; Ballhorn, Daniel J.; Kroiss, Johannes; Pauls, Steffen U.; Moreau, Corrie S.; Eilmus, Sascha; Strohm, Erhard; Heil, Martin


    Protective ant-plant mutualisms that are exploited by non-defending parasitic ants represent prominent model systems for ecology and evolutionary biology. The mutualist Pseudomyrmex ferrugineus is an obligate plant-ant and fully depends on acacias for nesting space and food. The parasite Pseudomyrmex gracilis facultatively nests on acacias and uses host-derived food rewards but also external food sources. Integrative analyses of genetic microsatellite data, cuticular hydrocarbons and behavioral assays showed that an individual acacia might be inhabited by the workers of several P. gracilis queens, whereas one P. ferrugineus colony monopolizes one or more host trees. Despite these differences in social organization, neither of the species exhibited aggressive behavior among conspecific workers sharing a tree regardless of their relatedness. This lack of aggression corresponds to the high similarity of cuticular hydrocarbon profiles among ants living on the same tree. Host sharing by unrelated colonies, or the presence of several queens in a single colony are discussed as strategies by which parasite colonies could achieve the observed social organization. We argue that in ecological terms, the non-aggressive behavior of non-sibling P. gracilis workers — regardless of the route to achieve this social structure — enables this species to efficiently occupy and exploit a host plant. By contrast, single large and long-lived colonies of the mutualist P. ferrugineus monopolize individual host plants and defend them aggressively against invaders from other trees. Our findings highlight the necessity for using several methods in combination to fully understand how differing life history strategies affect social organization in ants. PMID:22662191

  11. Ultrasonic Flaw Imaging via Multipath Exploitation

    Directory of Open Access Journals (Sweden)

    Yimin D. Zhang


    Full Text Available We consider ultrasonic imaging for the visualization of flaws in a material. Ultrasonic imaging is a powerful nondestructive testing (NDT tool which assesses material conditions via the detection, localization, and classification of flaws inside a structure. We utilize reflections of ultrasonic signals which occur when encountering different media and interior boundaries. These reflections can be cast as direct paths to the target corresponding to the virtual sensors appearing on the top and bottom side of the target. Some of these virtual sensors constitute a virtual aperture, whereas in others, the aperture changes with the transmitter position. Exploitations of multipath extended virtual array apertures provide enhanced imaging capability beyond the limitation of traditional multisensor approaches. The waveforms observed at the physical as well as the virtual sensors yield additional measurements corresponding to different aspect angles, thus allowing proper multiview imaging of flaws. We derive the wideband point spread functions for dominant multipaths and show that fusion of physical and virtual sensor data improves the flaw perimeter detection and localization performance. The effectiveness of the proposed multipath exploitation approach is demonstrated using real data.

  12. Compressed sensing MRI exploiting complementary dual decomposition. (United States)

    Park, Suhyung; Park, Jaeseok


    Compressed sensing (CS) MRI exploits the sparsity of an image in a transform domain to reconstruct the image from incoherently under-sampled k-space data. However, it has been shown that CS suffers particularly from loss of low-contrast image features with increasing reduction factors. To retain image details in such degraded experimental conditions, in this work we introduce a novel CS reconstruction method exploiting feature-based complementary dual decomposition with joint estimation of local scale mixture (LSM) model and images. Images are decomposed into dual block sparse components: total variation for piecewise smooth parts and wavelets for residuals. The LSM model parameters of residuals in the wavelet domain are estimated and then employed as a regional constraint in spatially adaptive reconstruction of high frequency subbands to restore image details missing in piecewise smooth parts. Alternating minimization of the dual image components subject to data consistency is performed to extract image details from residuals and add them back to their complementary counterparts while the LSM model parameters and images are jointly estimated in a sequential fashion. Simulations and experiments demonstrate the superior performance of the proposed method in preserving low-contrast image features even at high reduction factors. Copyright © 2014 Elsevier B.V. All rights reserved.


    Directory of Open Access Journals (Sweden)



    Full Text Available The link between socioeconomics and conservation and the role of legislation in conservation work was discussed in the group with participants from nine European countries. Interest and knowledge among the general public, stakeholders and managers is the key to successful conservation of native crayfish species. Exploitation and conservation do not necessarily exclude each other. A controlled fishery, where it can be sustained, may be an essential tool for conservation by increasing the general awareness and involving more people in the task of protecting the native crayfish species. This strategy is mainly possible for the noble crayfish in the northern part of its distribution, where strong traditions connected to crayfish also exist. A balance between utilisation and overexploitation has to be found and local guidelines for sustainable exploitation produced. Media, the Internet and educational material aimed at schools and stakeholders are excellent ways of reaching a wide audience with information. Universal objectives, rules and regulations at the European level are desirable and the noble crayfish and the stone crayfish should be included in Annex II of the Habitat Directive. Based on this framework detailed regulations are best worked out at the national level, considering the specific crayfish situation in the country. Information about the legislation, the purpose of the legislation and the consequences when not obeying it should be distributed. Stricter regulation of the trade with live alien crayfish is vital because of the associated risk of introducing new diseases and species.

  14. Exploiting time in electronic health record correlations. (United States)

    Hripcsak, George; Albers, David J; Perotte, Adler


    To demonstrate that a large, heterogeneous clinical database can reveal fine temporal patterns in clinical associations; to illustrate several types of associations; and to ascertain the value of exploiting time. Lagged linear correlation was calculated between seven clinical laboratory values and 30 clinical concepts extracted from resident signout notes from a 22-year, 3-million-patient database of electronic health records. Time points were interpolated, and patients were normalized to reduce inter-patient effects. The method revealed several types of associations with detailed temporal patterns. Definitional associations included low blood potassium preceding 'hypokalemia.' Low potassium preceding the drug spironolactone with high potassium following spironolactone exemplified intentional and physiologic associations, respectively. Counterintuitive results such as the fact that diseases appeared to follow their effects may be due to the workflow of healthcare, in which clinical findings precede the clinician's diagnosis of a disease even though the disease actually preceded the findings. Fully exploiting time by interpolating time points produced less noisy results. Electronic health records are not direct reflections of the patient state, but rather reflections of the healthcare process and the recording process. With proper techniques and understanding, and with proper incorporation of time, interpretable associations can be derived from a large clinical database. A large, heterogeneous clinical database can reveal clinical associations, time is an important feature, and care must be taken to interpret the results.

  15. PROBA-V Mission Exploitation Platform

    Directory of Open Access Journals (Sweden)

    Erwin Goor


    Full Text Available As an extension of the PROBA-Vegetation (PROBA-V user segment, the European Space Agency (ESA, de Vlaamse Instelling voor Technologisch Onderzoek (VITO, and partners TRASYS and Spacebel developed an operational Mission Exploitation Platform (MEP to drastically improve the exploitation of the PROBA-V Earth Observation (EO data archive, the archive from the historical SPOT-VEGETATION mission, and derived products by researchers, service providers, and thematic users. The analysis of the time series of data (petabyte range is addressed, as well as the large scale on-demand processing of the complete archive, including near real-time data. The platform consists of a private cloud environment, a Hadoop-based processing environment and a data manager. Several applications are released to the users, e.g., a full resolution viewing service, a time series viewer, pre-defined on-demand processing chains, and virtual machines with powerful tools and access to the data. After an initial release in January 2016 a research platform was deployed gradually, allowing users to design, debug, and test applications on the platform. From the PROBA-V MEP, access to, e.g., Sentinel-2 and Sentinel-3 data will be addressed as well.

  16. Foraging behavior of egg parasitoids exploiting chemical information

    NARCIS (Netherlands)

    Fatouros, N.E.; Dicke, M.; Mumm, R.; Meiners, T.; Hilker, M.


    Female parasitic wasps seek hosts for their offspring often in a dynamic environment. Foraging egg parasitoids rely on a variety of chemical cues originating from the adult host, host products, or the host plant rather than from the attacked host stage¿the insect egg itself. Besides pupae, insect

  17. Hijacking host cell highways: manipulation of the host actin cytoskeleton by obligate intracellular bacterial pathogens

    Directory of Open Access Journals (Sweden)

    Punsiri M Colonne


    Full Text Available Intracellular bacterial pathogens replicate within eukaryotic cells and display unique adaptations that support key infection events including invasion, replication, immune evasion, and dissemination. From invasion to dissemination, all stages of the intracellular bacterial life cycle share the same three-dimensional cytosolic space containing the host cytoskeleton. For successful infection and replication, many pathogens hijack the cytoskeleton using effector proteins introduced into the host cytosol by specialized secretion systems. A subset of effectors contains eukaryotic-like motifs that mimic host proteins to exploit signaling and modify specific cytoskeletal components such as actin and microtubules. Cytoskeletal rearrangement promotes numerous events that are beneficial to the pathogen, including internalization of bacteria, subversion of cell intrinsic immunity, structural support for bacteria-containing vacuoles, altered vesicular trafficking, actin-dependent bacterial movement, and pathogen dissemination. This review highlights a diverse group of obligate intracellular bacterial pathogens that manipulate the host cytoskeleton to thrive within eukaryotic cells and discusses underlying molecular mechanisms that promote these dynamic host-pathogen interactions.

  18. Chitosan-hyaluronan based 3D co-culture platform for studying the crosstalk of lung cancer cells and mesenchymal stem cells. (United States)

    Han, Hao-Wei; Hsu, Shan-Hui


    The controversial roles of mesenchymal stem cells (MSCs) in lung cancer development are not yet resolved because of the lack of an extracellular environment that mimics the tumor microenvironment. Three-dimensional (3D) culture system is an emerging research tool for biomedical applications such as drug screening. In this study, MSCs and human non-small cell lung carcinoma cells (A549) were co-cultured on a thin biomaterial-based substratum (hyaluronan-grafted chitosan, CS-HA; ∼2μm), and they were self-organized into the 3D tumor co-spheroids with core-shell structure. The gene expression levels of tumorigenicity markers in cancer cells associated with cancer stemness, epithelial-mesenchymal transition (EMT) property, and cell mobility were up-regulated for more than twofold in the MSC-tumor co-spheroids, through the promoted expression of certain tumor enhancers and the direct cell-cell interaction. To verify the different extents of tumorigenicity, A549 cells or those co-cultured with MSCs were transplanted into zebrafish embryos for evaluation in vivo. The tumorigenicity obtained from the zebrafish xenotransplantation model was consistent with that observed in vitro. These evidences suggest that the CS-HA substrate-based 3D co-culture platform for cancer cells and MSCs may be a convenient tool for studying the cell-cell interaction in a tumor-like microenvironment and potentially for cancer drug testing. Mesenchymal stem cells (MSCs) have been found in several types of tumor tissues. However, the controversial roles of MSCs in cancer development are still unsolved. Chitosan and hyaluronan are commonly used materials in the biomedical field. In the current study, we co-cultured lung cancer cells and MSCs on the planar hyaluronan-grafted chitosan (CS-HA) hybrid substrates, and discovered that lung cancer cells and MSCs were rapidly self-assembled into 3D tumor spheroids with core-shell structure on the substrates after only two days in culture. Therefore, CS

  19. Seasonal changes in english walnut (Juglans regia L.) (Juglandaceae), fruit properties and host use patterns by Rhagoletis zoqui (Diptera: Tephritidae) (United States)

    Rhagoletis zoqui Bush is a Neosubtropical, univoltine, frugivorous tephritid fly that exploits both native Juglans spp. and the introduced, Palearctic English walnut, Juglans regia. The seasonal development of commercial J. regia fruit and the pattern of host exploitation by R. zoqui were tracked ov...

  20. Virtual Exploitation Environment Demonstration for Atmospheric Missions (United States)

    Natali, Stefano; Mantovani, Simone; Hirtl, Marcus; Santillan, Daniel; Triebnig, Gerhard; Fehr, Thorsten; Lopes, Cristiano


    The scientific and industrial communities are being confronted with a strong increase of Earth Observation (EO) satellite missions and related data. This is in particular the case for the Atmospheric Sciences communities, with the upcoming Copernicus Sentinel-5 Precursor, Sentinel-4, -5 and -3, and ESA's Earth Explorers scientific satellites ADM-Aeolus and EarthCARE. The challenge is not only to manage the large volume of data generated by each mission / sensor, but to process and analyze the data streams. Creating synergies among the different datasets will be key to exploit the full potential of the available information. As a preparation activity supporting scientific data exploitation for Earth Explorer and Sentinel atmospheric missions, ESA funded the "Technology and Atmospheric Mission Platform" (TAMP) [1] [2] project; a scientific and technological forum (STF) has been set-up involving relevant European entities from different scientific and operational fields to define the platforḿs requirements. Data access, visualization, processing and download services have been developed to satisfy useŕs needs; use cases defined with the STF, such as study of the SO2 emissions for the Holuhraun eruption (2014) by means of two numerical models, two satellite platforms and ground measurements, global Aerosol analyses from long time series of satellite data, and local Aerosol analysis using satellite and LIDAR, have been implemented to ensure acceptance of TAMP by the atmospheric sciences community. The platform pursues the "virtual workspace" concept: all resources (data, processing, visualization, collaboration tools) are provided as "remote services", accessible through a standard web browser, to avoid the download of big data volumes and for allowing utilization of provided infrastructure for computation, analysis and sharing of results. Data access and processing are achieved through standardized protocols (WCS, WPS). As evolution toward a pre

  1. Total exploitation of an ornamental granite quarry

    Directory of Open Access Journals (Sweden)

    Taboada, J.


    Full Text Available In this paper we propose a methodology to estimate the recovery percentage for each of the products which can be obtained from the exploitation of an ornamental granite quarry: block, semiblock, masonry-transverse stone, and the smaller materials that can be used to obtain construction aggregates. This methodology ensures that quarry exploitation is exhaustive, thereby minimising the production of spoils and the consequent negative impact on the environment. The analysis is based on a detailed and exhaustive compilation of discontinuity data from the research fronts, which are then interpreted statistically and projected over the three weakness planes that are a particular feature of ornamental granite deposits. Using this information, and bearing in mind the minimum commercially viable sizes for each kind of granite, the corresponding recovery rates are calculated for each material in each plane. The results are then integrated using spatial techniques, and the result is an evaluation of quarry contents with a view to total exploitation. This methodology was applied to a quarry in the opening phase in order to carry out an a priori assessment of the economic feasibility of the quarry.

    En este trabajo se propone una metodología para estimar el porcentaje de recuperación de cada uno de los productos que se pueden obtener en la explotación de una cantera de granito ornamental: bloque, semibloque, manpostería y per piaños, y material restante destinado a la obtención de áridos. De esta manera se logra un aprovechamiento integral de la cantera, evitándose la generación de estériles y el subsiguiente impacto ambiental producido por éstos. La metodología de análisis se basa en la recopilación detallada y exhaustiva de datos de discontinuidades en los frentes de investigación, que se interpretan estadísticamente y se proyectan sobre los tres planos de debilidad propios del granito ornamental. Con esta información, y las

  2. Association and host selectivity in multi-host pathogens.

    Directory of Open Access Journals (Sweden)

    José M Malpica


    Full Text Available The distribution of multi-host pathogens over their host range conditions their population dynamics and structure. Also, host co-infection by different pathogens may have important consequences for the evolution of hosts and pathogens, and host-pathogen co-evolution. Hence it is of interest to know if the distribution of pathogens over their host range is random, or if there are associations between hosts and pathogens, or between pathogens sharing a host. To analyse these issues we propose indices for the observed patterns of host infection by pathogens, and for the observed patterns of co-infection, and tests to analyse if these patterns conform to randomness or reflect associations. Applying these tests to the prevalence of five plant viruses on 21 wild plant species evidenced host-virus associations: most hosts and viruses were selective for viruses and hosts, respectively. Interestingly, the more host-selective viruses were the more prevalent ones, suggesting that host specialisation is a successful strategy for multi-host pathogens. Analyses also showed that viruses tended to associate positively in co-infected hosts. The developed indices and tests provide the tools to analyse how strong and common are these associations among different groups of pathogens, which will help to understand and model the population biology of multi-host pathogens.

  3. Exploiting CRISPR/Cas systems for biotechnology. (United States)

    Sampson, Timothy R; Weiss, David S


    The Cas9 endonuclease is the central component of the Type II CRISPR/Cas system, a prokaryotic adaptive restriction system against invading nucleic acids, such as those originating from bacteriophages and plasmids. Recently, this RNA-directed DNA endonuclease has been harnessed to target DNA sequences of interest. Here, we review the development of Cas9 as an important tool to not only edit the genomes of a number of different prokaryotic and eukaryotic species, but also as an efficient system for site-specific transcriptional repression or activation. Additionally, a specific Cas9 protein has been observed to target an RNA substrate, suggesting that Cas9 may have the ability to be programmed to target RNA as well. Cas proteins from other CRISPR/Cas subtypes may also be exploited in this regard. Thus, CRISPR/Cas systems represent an effective and versatile biotechnological tool, which will have significant impact on future advancements in genome engineering. © 2014 WILEY Periodicals, Inc.

  4. Exploiting HRM in support of lean manufacturing

    DEFF Research Database (Denmark)

    Jørgensen, Frances; Matthiesen, Rikke

    The purpose of this paper is to investigate the ways in HRM practices are-and could potentially be-exploited to support lean manufacturing in practice. First, a review of the pertinent literature regarding HRM, SHRM, and lean manufacturing is presented to provide an understanding of the mechanisms...... by which HRM practices could, theoretically, be used to support a lean implementation. Data presented in the paper are derived from 1) a longitudinal case study on lean implementation and 2) from managers currently involved with lean manufacturing in a second company. The relevant literature and the data......'s contribution to the change process itself and through bundling particular HRM practices that are aligned with the lean strategy. The paper contributes to both theory and practice, by suggesting specific ways in which HRM can be strategically aligned with a major change implementation such as lean manufacturing....

  5. Automatic image exploitation system for small UAVs (United States)

    Heinze, N.; Esswein, M.; Krüger, W.; Saur, G.


    For surveillance and reconnaissance tasks small UAVs are of growing importance. These UAVs have an endurance of several hours, but a small payload of about some kilograms. As a consequence lightweight sensors and cameras have to be used without having a mechanical stabilized high precision sensor-platform, which would exceed the payload and cost limitations. An example of such a system is the German UAV Luna with optical and IR sensors on board. For such platforms we developed image exploitation algorithms. The algorithms comprise mosaiking, stabilization, image enhancement, video based moving target indication, and stereo-image generation. Other products are large geo-coded image mosaics, stereo mosaics, and 3-D-model generation. For test and assessment of these algorithms the experimental system ABUL has been developed, in which the algorithms are integrated. The ABUL system is used for tests and assessment by military PIs.

  6. Protocol to Exploit Waiting Resources for UASNs

    Directory of Open Access Journals (Sweden)

    Li-Ling Hung


    Full Text Available The transmission speed of acoustic waves in water is much slower than that of radio waves in terrestrial wireless sensor networks. Thus, the propagation delay in underwater acoustic sensor networks (UASN is much greater. Longer propagation delay leads to complicated communication and collision problems. To solve collision problems, some studies have proposed waiting mechanisms; however, long waiting mechanisms result in low bandwidth utilization. To improve throughput, this study proposes a slotted medium access control protocol to enhance bandwidth utilization in UASNs. The proposed mechanism increases communication by exploiting temporal and spatial resources that are typically idle in order to protect communication against interference. By reducing wait time, network performance and energy consumption can be improved. A performance evaluation demonstrates that when the data packets are large or sensor deployment is dense, the energy consumption of proposed protocol is less than that of existing protocols as well as the throughput is higher than that of existing protocols.

  7. Exploitation of bioremediation in the environment protection

    Directory of Open Access Journals (Sweden)

    Alena Luptáková


    Full Text Available Soils and waters contaminated with toxic metals pose a major environmental problem that needs an effective and affordable technological solution. Many areas remain contaminated with no remediation in sight because it is too expensive to clean them up with available technologies. Bioremediation may provide an economically viable solution for remediation of some of these sites. The bioremediation is an application of the biological treatment to the cleanup of hazardous chemicals and is an example of the environmental biotechnology. The aim of this paper is to give a theoretical and practical view concerning the possibility of the bioremediation exploitation in the environment protection. This paper includes some results of the bioremediation of the acid mine drainage by sulphate-reducing bacteria.

  8. Intertemporal Choice of Marine Ecosystem Exploitation

    DEFF Research Database (Denmark)

    Ravn-Jonsen, Lars

    Management, however, requires models that can link the ecosystem level to the operation level, so this paper examines an ecosystem production model and shows that it is suitable for applying ground rent theory. This model is the simplest possible that incorporates the principles of size as the main...... at the ecosystem level in the present management. Therefore, economic predictions for an ecosystem managed as a common pool resource must be that  the exploitation probably are conducted at lower sized than optimum. In addition, given its population stock approach, the present management probably overlooks...... the ability of an ecosystem to sustain total volume of harvest. Given the two aspects of intertemporal choice revealed by the model, the conclusion must be that the Fishing Down Marine Food Webs is probably driven by the current management's inability to conduct adequate intertemporal balancing; therefore...


    Directory of Open Access Journals (Sweden)

    Vanja Lež


    Full Text Available The existence of large quantities of hydrocarbons is supposed within the Arctic Circle. Assumed quantities are 25% of the total undiscovered hydrocarbon reserves on Earth, mostly natural gas. Over 500 major and minor gas accumulations within the Arctic Circle were discovered so far, but apart from Snøhvit gas field, there is no commercial exploitation of natural gas from these fields. Arctic gas projects are complicated, technically hard to accomplish, and pose a great threat to the return of investment, safety of people and equipment and for the ecosystem. Russia is a country that is closest to the realization of the Arctic gas projects that are based on the giant gas fields. The most extreme weather conditions in the seas around Greenland are the reason why this Arctic region is the least explored and furthest from the realization of any gas project (the paper is published in Croatian .

  10. Liking and hyperlinking: Community detection in online child sexual exploitation networks. (United States)

    Westlake, Bryce G; Bouchard, Martin


    The online sexual exploitation of children is facilitated by websites that form virtual communities, via hyperlinks, to distribute images, videos, and other material. However, how these communities form, are structured, and evolve over time is unknown. Collected using a custom-designed webcrawler, we begin from known child sexual exploitation (CE) seed websites and follow hyperlinks to connected, related, websites. Using a repeated measure design we analyze 10 networks of 300 + websites each - over 4.8 million unique webpages in total, over a period of 60 weeks. Community detection techniques reveal that CE-related networks were dominated by two large communities hosting varied material -not necessarily matching the seed website. Community stability, over 60 weeks, varied across networks. Reciprocity in hyperlinking between community members was substantially higher than within the full network, however, websites were not more likely to connect to homogeneous-content websites. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Exploiting Unique Structural and Functional Properties of Malarial Glycolytic Enzymes for Antimalarial Drug Development

    Directory of Open Access Journals (Sweden)

    Asrar Alam


    Full Text Available Metabolic enzymes have been known to carry out a variety of functions besides their normal housekeeping roles known as “moonlighting functions.” These functionalities arise from structural changes induced by posttranslational modifications and/or binding of interacting proteins. Glycolysis is the sole source of energy generation for malaria parasite Plasmodium falciparum, hence a potential pathway for therapeutic intervention. Crystal structures of several P. falciparum glycolytic enzymes have been solved, revealing that they exhibit unique structural differences from the respective host enzymes, which could be exploited for their selective targeting. In addition, these enzymes carry out many parasite-specific functions, which could be of potential interest to control parasite development and transmission. This review focuses on the moonlighting functions of P. falciparum glycolytic enzymes and unique structural differences and functional features of the parasite enzymes, which could be exploited for therapeutic and transmission blocking interventions against malaria.

  12. Evaluation of the ability of xanthan gum/gellan gum/hyaluronan hydrogel membranes to prevent the adhesion of postrepaired tendons. (United States)

    Kuo, Shyh Ming; Chang, Shwu Jen; Wang, Hung-Yi; Tang, Shu Ching; Yang, Shan-Wei


    After tendon-repair surgery, adhesion between the surgical tendon and the synovial sheath is often presented resulting in poor functional repair of the tendon. This may be prevented using a commercially available mechanical barrier implant, Seprafilm, which is composed of hyaluronan (HA) and carboxymethyl cellulose hydrogels. In a rat model, prepared membranes of various compositions of gellan gum (GG), xanthan gum (XG) and HA as well as Seprafilm were wrapped around repaired tendons and the adhesion of the tendons was examined grossly and histologically after 3 weeks of healing. Certain formulations of the XG/GG/HA hydrogel membranes reduced tendon adhesion with equal efficacy but without reducing the tendon strength compared to Seprafilm. The designed membranes swelled rapidly and blanketed onto the tendon tissue more readily and closely than Seprafilm. Also they degraded slowly, which allowed the membranes to function as barriers for extended periods. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. In Vitro and In Vivo Suppression of Cellular Activity by Guanidinoethyl Disulfide Released from Hydrogel Microspheres Composed of Partially Oxidized Hyaluronan and Gelatin (United States)

    Weng, Lihui; Ivanova, Natalia D.; Zakhaleva, Julia; Chen, Weiliam


    This paper describes the preparation of oxidized hyaluronan crosslinked gelatin microspheres for drug delivery. Microspheres were prepared by a modified water-in-oil-emulsion crosslinking method, where 3-dimensional crosslinked hydrogel microspheres formed in the absence of any extraneous crosslinker. SEM analyses of the microspheres showed rough surfaces in their dried state with an average diameter of 90 µm. Lyophilization of fully-swollen microspheres revealed a highly porous structure. Guanidinoethyl disulfide (GED) was used as a model drug for incorporation into the microspheres; encapsulation of GED was confirmed by HPLC. There was an inverse correlation between the diameters of the microspheres with their GED loading. Macrophage was used as a model cell to evaluate the in vitro efficacy of GED release from the microspheres. The in vivo efficacy of the microspheres was further validated in a mouse full-thickness transcutaneous dermal wound model through suppression of cell infiltration. PMID:18678403

  14. Parasite host range and the evolution of host resistance

    NARCIS (Netherlands)

    Gorter, F.A.; Hall, A.R.; A., Buckling; P.D., Scanlan


    Parasite host range plays a pivotal role in the evolution and ecology of hosts
    and the emergence of infectious disease. Although the factors that promote
    host range and the epidemiological consequences of variation in host range
    are relatively well characterized, the effect of parasite

  15. Biological warfare: Microorganisms as drivers of host-parasite interactions. (United States)

    Dheilly, Nolwenn M; Poulin, Robert; Thomas, Frédéric


    Understanding parasite strategies for evasion, manipulation or exploitation of hosts is crucial for many fields, from ecology to medical sciences. Generally, research has focused on either the host response to parasitic infection, or the parasite virulence mechanisms. More recently, integrated studies of host-parasite interactions have allowed significant advances in theoretical and applied biology. However, these studies still provide a simplistic view of these as mere two-player interactions. Host and parasite are associated with a myriad of microorganisms that could benefit from the improved fitness of their partner. Illustrations of such complex multi-player interactions have emerged recently from studies performed in various taxa. In this conceptual article, we propose how these associated microorganisms may participate in the phenotypic alterations induced by parasites and hence in host-parasite interactions, from an ecological and evolutionary perspective. Host- and parasite-associated microorganisms may participate in the host-parasite interaction by interacting directly or indirectly with the other partner. As a result, parasites may develop (i) the disruptive strategy in which the parasite alters the host microbiota to its advantage, and (ii) the biological weapon strategy where the parasite-associated microorganism contributes to or modulates the parasite's virulence. Some phenotypic alterations induced by parasite may also arise from conflicts of interests between the host or parasite and its associated microorganism. For each situation, we review the literature and propose new directions for future research. Specifically, investigating the role of host- and parasite-associated microorganisms in host-parasite interactions at the individual, local and regional level will lead to a holistic understanding of how the co-evolution of the different partners influences how the other ones respond, both ecologically and evolutionary. The conceptual framework we

  16. A hyaluronan hydrogel scaffold-based xeno-free culture system for ex vivo expansion of human corneal epithelial stem cells. (United States)

    Chen, D; Qu, Y; Hua, X; Zhang, L; Liu, Z; Pflugfelder, S C; Li, D-Q


    PurposeTo develop a hyaluronan hydrogel scaffold-based xeno-free culture system for ex vivo cultivation of human corneal epithelial stem cells (CESCs).Patients and MethodsCESCs were cultivated from donor limbal explants on the HyStem-C Hydrogel bio-scaffold in 12-well plates for 3 weeks. Group A used the traditional supplemented hormonal epidermal medium (SHEM) and group B used the defined SHEM (without fetal bovine serum and toxin A, adding 20% serum replacement). The growth and morphology of the cultured cells were assessed by phase contrast microscope. The expressions of specific cell markers were assessed by immunofluorescence staining and quantitative real-time PCR (qRT-PCR).ResultsSuccessful cultures of CESCs were obtained in both groups, resulting in multilayered stratified epithelia. Comparing to group A, the cells in group B was grown slightly slower and formed less cellular layers at the end of culture. The corneal specific cytokeratin (K) 12 and differentiation markers, involucrin, and connexin 43, were mainly expressed in the superficial cellular layers in both groups. Interestingly, certain basal cells were immune-positive to proposed stem cell markers such as K19, ABCG2, and integrin β1 in both groups. There was no significant difference between the two groups with regard to the gene expression levels of all these selected corneal markers (all P>0.05).ConclusionsThe hyaluronan hydrogel scaffold-based xeno-free culture system may support the expansion of regenerative CESCs without the risk of xeno component contamination. The regenerated epithelium maintains similar characteristics of native corneal epithelium.

  17. Crohn’s Disease Fibroblasts Overproduce the Novel Protein KIAA1199 to Create Proinflammatory Hyaluronan FragmentsSummary

    Directory of Open Access Journals (Sweden)

    Artin Soroosh


    Full Text Available Background & Aims: Crohn’s Disease (CD is a chronic inflammatory disease of the gastrointestinal tract. Fibrosis, a serious complication of CD, occurs when activated intestinal fibroblasts deposit excessive amounts of extracellular matrix (ECM in affected areas. A major component of the ECM is high-molecular-weight hyaluronan (HA that, when depolymerized to low-molecular-weight fragments, becomes proinflammatory and profibrotic. Mechanisms for HA degradation are incompletely understood, but the novel protein KIAA1199 recently was discovered to degrade HA. We hypothesized that KIAA1199 protein is increased in CD colon fibroblasts and generates HA fragments that foster inflammation and fibrosis. Methods: Fibroblasts were isolated from explants of surgically resected colon tissue from CD and non–inflammatory bowel disease control (ND patients. Protein levels and tissue distribution of KIAA1199 were assessed by immunoblot and immunostaining, and functional HA degradation was measured biochemically. Results: Increased levels of KIAA1199 protein were produced and deposited in the ECM by cultured CD fibroblasts compared with controls. Treatment of fibroblasts with the proinflammatory cytokine interleukin (IL 6 increased deposition of KIAA1199 in the ECM. CD fibroblasts also produce significantly higher levels of IL6 compared with controls, and antibody blockade of IL6 receptors in CD colon fibroblasts decreased the level of KIAA1199 protein in the ECM. Colon fibroblasts degrade HA, however, small interfering RNA silencing of KIAA1199 abrogated that ability. Conclusions: CD fibroblasts produce increased levels of KIAA1199 primarily through an IL6-driven autocrine mechanism. This leads to excessive degradation of HA and the generation of proinflammatory HA fragments, which contributes to maintenance of gut inflammation and fibrosis. Keywords: Crohn’s Disease, Fibrosis, Hyaluronan, KIAA1199

  18. Detecting peripheral-based attacks on the host memory

    CERN Document Server

    Stewin, Patrick


    This work addresses stealthy peripheral-based attacks on host computers and presents a new approach to detecting them. Peripherals can be regarded as separate systems that have a dedicated processor and dedicated runtime memory to handle their tasks. The book addresses the problem that peripherals generally communicate with the host via the host’s main memory, storing cryptographic keys, passwords, opened files and other sensitive data in the process – an aspect attackers are quick to exploit.  Here, stealthy malicious software based on isolated micro-controllers is implemented to conduct an attack analysis, the results of which provide the basis for developing a novel runtime detector. The detector reveals stealthy peripheral-based attacks on the host’s main memory by exploiting certain hardware properties, while a permanent and resource-efficient measurement strategy ensures that the detector is also capable of detecting transient attacks, which can otherwise succeed when the applied strategy only me...

  19. Use of hyaluronan in the selection of sperm for intracytoplasmic sperm injection (ICSI): significant improvement in clinical outcomes--multicenter, double-blinded and randomized controlled trial. (United States)

    Worrilow, K C; Eid, S; Woodhouse, D; Perloe, M; Smith, S; Witmyer, J; Ivani, K; Khoury, C; Ball, G D; Elliot, T; Lieberman, J


    Does the selection of sperm for ICSI based on their ability to bind to hyaluronan improve the clinical pregnancy rates (CPR) (primary end-point), implantation (IR) and pregnancy loss rates (PLR)? In couples where ≤ 65% of sperm bound hyaluronan, the selection of hyaluronan-bound (HB) sperm for ICSI led to a statistically significant reduction in PLR. HB sperm demonstrate enhanced developmental parameters which have been associated with successful fertilization and embryogenesis. Sperm selected for ICSI using a liquid source of hyaluronan achieved an improvement in IR. A pilot study by the primary author demonstrated that the use of HB sperm in ICSI was associated with improved CPR. The current study represents the single largest prospective, multicenter, double-blinded and randomized controlled trial to evaluate the use of hyaluronan in the selection of sperm for ICSI. Using the hyaluronan binding assay, an HB score was determined for the fresh or initial (I-HB) and processed or final semen specimen (F-HB). Patients were classified as >65% or ≤ 65% I-HB and stratified accordingly. Patients with I-HB scores ≤ 65% were randomized into control and HB selection (HYAL) groups whereas patients with I-HB >65% were randomized to non-participatory (NP), control or HYAL groups, in a ratio of 2:1:1. The NP group was included in the >65% study arm to balance the higher prevalence of patients with I-HB scores >65%. In the control group, oocytes received sperm selected via the conventional assessment of motility and morphology. In the HYAL group, HB sperm meeting the same visual criteria were selected for injection. Patient participants and clinical care providers were blinded to group assignment. Eight hundred two couples treated with ICSI in 10 private and hospital-based IVF programs were enrolled in this study. Of the 484 patients stratified to the I-HB > 65% arm, 115 participants were randomized to the control group, 122 participants were randomized to the HYAL group

  20. Exploiting tRNAs to Boost Virulence

    Directory of Open Access Journals (Sweden)

    Suki Albers


    Full Text Available Transfer RNAs (tRNAs are powerful small RNA entities that are used to translate nucleotide language of genes into the amino acid language of proteins. Their near-uniform length and tertiary structure as well as their high nucleotide similarity and post-transcriptional modifications have made it difficult to characterize individual species quantitatively. However, due to the central role of the tRNA pool in protein biosynthesis as well as newly emerging roles played by tRNAs, their quantitative assessment yields important information, particularly relevant for virus research. Viruses which depend on the host protein expression machinery have evolved various strategies to optimize tRNA usage—either by adapting to the host codon usage or encoding their own tRNAs. Additionally, several viruses bear tRNA-like elements (TLE in the 5′- and 3′-UTR of their mRNAs. There are different hypotheses concerning the manner in which such structures boost viral protein expression. Furthermore, retroviruses use special tRNAs for packaging and initiating reverse transcription of their genetic material. Since there is a strong specificity of different viruses towards certain tRNAs, different strategies for recruitment are employed. Interestingly, modifications on tRNAs strongly impact their functionality in viruses. Here, we review those intersection points between virus and tRNA research and describe methods for assessing the tRNA pool in terms of concentration, aminoacylation and modification.

  1. Host specialist clownfishes are environmental niche generalists (United States)

    Litsios, Glenn; Kostikova, Anna; Salamin, Nicolas


    Why generalist and specialist species coexist in nature is a question that has interested evolutionary biologists for a long time. While the coexistence of specialists and generalists exploiting resources on a single ecological dimension has been theoretically and empirically explored, biological systems with multiple resource dimensions (e.g. trophic, ecological) are less well understood. Yet, such systems may provide an alternative to the classical theory of stable evolutionary coexistence of generalist and specialist species on a single resource dimension. We explore such systems and the potential trade-offs between different resource dimensions in clownfishes. All species of this iconic clade are obligate mutualists with sea anemones yet show interspecific variation in anemone host specificity. Moreover, clownfishes developed variable environmental specialization across their distribution. In this study, we test for the existence of a relationship between host-specificity (number of anemones associated with a clownfish species) and environmental-specificity (expressed as the size of the ecological niche breadth across climatic gradients). We find a negative correlation between host range and environmental specificities in temperature, salinity and pH, probably indicating a trade-off between both types of specialization forcing species to specialize only in a single direction. Trade-offs in a multi-dimensional resource space could be a novel way of explaining the coexistence of generalist and specialists. PMID:25274370

  2. Hyaluronan size alters chondrogenesis of adipose-derived stem cells via the CD44/ERK/SOX-9 pathway. (United States)

    Wu, Shun-Cheng; Chen, Chung-Hwan; Wang, Jyun-Ya; Lin, Yi-Shan; Chang, Je-Ken; Ho, Mei-Ling


    Hyaluronan (HA) is a natural linear polymer that is one of the main types of extracellular matrix during the early stage of chondrogenesis. We found that the chondrogenesis of adipose-derived stem cells (ADSCs) can be initiated and promoted by the application of HA to mimic the chondrogenic niche. The aim of this study is to investigate the optimal HA molecular weight (Mw) for chondrogenesis of ADSCs and the detailed mechanism. In this study, we investigated the relationships among HA Mw, CD44 clustering, and the extracellular signal-regulated kinase (ERK)/SOX-9 pathway during chondrogenesis of ADSCs. Human ADSCs (hADSCs) and rabbit ADSCs (rADSCs) were isolated and expanded. Chondrogenesis was induced in rADSCs by culturing cells in HA-coated wells (HA Mw: 80 kDa, 600 kDa and 2000 kDa) and evaluated by examining cell aggregation, chondrogenic gene expression (collagen type II and aggrecan) and sulfated glycosaminoglycan (sGAG) deposition in vitro. Cartilaginous tissue formation in vivo was confirmed by implanting HA/rADSCs into joint cavities. CD44 clustering, ERK phosphorylation, SOX-9 expression and SOX-9 phosphorylation in cultured hADSCs were further evaluated. Isolated and expanded rADSCs showed multilineage potential and anchorage-independent growth properties. Cell aggregation, chondrogenic gene expression, and sGAG deposition increased with increasing HA Mw in rADSCs. The 2000 kDa HA had the most pronounced chondrogenic effect on rADSCs in vitro, and implanted 2000 kDa HA/rADSCs exhibited marked cartilaginous tissue formation in vivo. CD44 clustering and cell aggregation of hADSCs were enhanced by an increase in HA Mw. In addition, higher HA Mws further enhanced CD44 clustering, ERK phosphorylation, and SOX-9 expression and phosphorylation in hADSCs. Inhibiting CD44 clustering in hADSCs reduced HA-induced chondrogenic gene expression. Inhibiting ERK phosphorylation also simultaneously attenuated HA-induced SOX-9 expression and phosphorylation and

  3. Mission Exploitation Platform PROBA-V (United States)

    Goor, Erwin


    VITO and partners developed an end-to-end solution to drastically improve the exploitation of the PROBA-V EO-data archive (, the past mission SPOT-VEGETATION and derived vegetation parameters by researchers, service providers and end-users. The analysis of time series of data (+1PB) is addressed, as well as the large scale on-demand processing of near real-time data. From November 2015 an operational Mission Exploitation Platform (MEP) PROBA-V, as an ESA pathfinder project, will be gradually deployed at the VITO data center with direct access to the complete data archive. Several applications will be released to the users, e.g. - A time series viewer, showing the evolution of PROBA-V bands and derived vegetation parameters for any area of interest. - Full-resolution viewing services for the complete data archive. - On-demand processing chains e.g. for the calculation of N-daily composites. - A Virtual Machine will be provided with access to the data archive and tools to work with this data, e.g. various toolboxes and support for R and Python. After an initial release in January 2016, a research platform will gradually be deployed allowing users to design, debug and test applications on the platform. From the MEP PROBA-V, access to Sentinel-2 and landsat data will be addressed as well, e.g. to support the Cal/Val activities of the users. Users can make use of powerful Web based tools and can self-manage virtual machines to perform their work on the infrastructure at VITO with access to the complete data archive. To realise this, private cloud technology (openStack) is used and a distributed processing environment is built based on Hadoop. The Hadoop ecosystem offers a lot of technologies (Spark, Yarn, Accumulo, etc.) which we integrate with several open-source components. The impact of this MEP on the user community will be high and will completely change the way of working with the data and hence open the large time series to a larger

  4. SARS Pathogenesis: Host Factors

    NARCIS (Netherlands)

    A. de Lang (Anna)


    textabstractWhile it is hypothesized that Sever Acute Respiratory Syndrome (SARS) in humans is caused by a disproportional immune response illustrated by inappropriate induction of inflammatory cytokines, the exact nature of the host response to SARS coronavirus (CoV) infection causing severe

  5. Coevolutionary interactions between farmers and mafia induce host acceptance of avian brood parasites. (United States)

    Abou Chakra, Maria; Hilbe, Christian; Traulsen, Arne


    Brood parasites exploit their host in order to increase their own fitness. Typically, this results in an arms race between parasite trickery and host defence. Thus, it is puzzling to observe hosts that accept parasitism without any resistance. The 'mafia' hypothesis suggests that these hosts accept parasitism to avoid retaliation. Retaliation has been shown to evolve when the hosts condition their response to mafia parasites, who use depredation as a targeted response to rejection. However, it is unclear if acceptance would also emerge when 'farming' parasites are present in the population. Farming parasites use depredation to synchronize the timing with the host, destroying mature clutches to force the host to re-nest. Herein, we develop an evolutionary model to analyse the interaction between depredatory parasites and their hosts. We show that coevolutionary cycles between farmers and mafia can still induce host acceptance of brood parasites. However, this equilibrium is unstable and in the long-run the dynamics of this host-parasite interaction exhibits strong oscillations: when farmers are the majority, accepters conditional to mafia (the host will reject first and only accept after retaliation by the parasite) have a higher fitness than unconditional accepters (the host always accepts parasitism). This leads to an increase in mafia parasites' fitness and in turn induce an optimal environment for accepter hosts.

  6. Tonic dopamine modulates exploitation of reward learning

    Directory of Open Access Journals (Sweden)

    Jeff A Beeler


    Full Text Available The impact of dopamine on adaptive behavior in a naturalistic environment is largely unexamined. Experimental work suggests that phasic dopamine is central to reinforcement learning whereas tonic dopamine may modulate performance without altering learning per se; however, this idea has not been developed formally or integrated with computational models of dopamine function. We quantitatively evaluate the role of tonic dopamine in these functions by studying the behavior of hyperdopaminergic DAT knockdown mice in an instrumental task in a semi-naturalistic homecage environment. In this closed economy paradigm, subjects earn all of their food by pressing either of two levers, but the relative cost for food on each lever shifts frequently. Compared to wild-type mice, hyperdopaminergic mice allocate more lever presses on high-cost levers, thus working harder to earn a given amount of food and maintain their body weight. However, both groups show a similarly quick reaction to shifts in lever cost, suggesting that the hyperdominergic mice are not slower at detecting changes, as with a learning deficit. We fit the lever choice data using reinforcement learning models to assess the distinction between acquisition and expression the models formalize. In these analyses, hyperdopaminergic mice displayed normal learning from recent reward history but diminished capacity to exploit this learning: a reduced coupling between choice and reward history. These data suggest that dopamine modulates the degree to which prior learning biases action selection and consequently alters the expression of learned, motivated behavior.

  7. Efficient Media Exploitation Towards Collective Intelligence (United States)

    Mylonas, Phivos; Solachidis, Vassilios; Geyer-Schulz, Andreas; Hoser, Bettina; Chapman, Sam; Ciravegna, Fabio; Staab, Steffen; Smrz, Pavel; Kompatsiaris, Yiannis; Avrithis, Yannis

    In this work we propose intelligent, automated content analysis techniques for different media to extract knowledge from the multimedia content. Information derived from different sources/modalities will be analyzed and fused, in terms of spatiotemporal, personal and even social contextual information. In order to achieve this goal, semantic analysis will be applied to the content items, taking into account the content itself (e.g., text, images and video), as well as existing personal, social and contextual information (e.g., semantic and machine-processable metadata and tags). The above process exploits the so-called “Media Intelligence” towards the ultimate goal of identifying “Collective Intelligence”, emerging from the collaboration and competition among people, empowering innovative services and user interactions. The utilization of “Media Intelligence” constitutes a departure from traditional methods for information sharing, since semantic multimedia analysis has to fuse information from both the content itself and the social context, while at the same time the social dynamics have to be taken into account. Such intelligence provides added-value to the available multimedia content and renders existing procedures and research efforts more efficient.

  8. Exploitation of parallelism in climate models

    Energy Technology Data Exchange (ETDEWEB)

    Baer, F.; Tribbia, J.J.; Williamson, D.L.


    The US Department of Energy (DOE) through its CHAMMP initiative, hopes to develop the capability to make meaningful regional climate forecasts on time scales exceeding a decade, such capability to be based on numerical prediction type models. We propose research to contribute to each of the specific items enumerated in the CHAMMP announcement (Notice 9103); i.e., to consider theoretical limits to prediction of climate and climate change on appropriate time scales, to develop new mathematical techniques to utilize massively parallel processors (MPP), to actually utilize MPP's as a research tool, and to develop improved representations of some processes essential to climate prediction. To explore these initiatives, we will exploit all available computing technology, and in particular MPP machines. We anticipate that significant improvements in modeling of climate on the decadal and longer time scales for regional space scales will result from our efforts. This report summarizes the activities of our group during a part of the first year's effort to meet the objectives stated in our proposal. We will comment on three research foci, time compression studies, subgrid scale model studies, and distributed climate ensemble studies and additional significant technical matters.

  9. The Spanish network for Gaia Science Exploitation (United States)

    Figueras, F.; Jordi, C.; Luri, X.; Torra, J.; REG Executive Committee Team; Gaia UB Team


    The ''Red Española de Explotación Científica de Gaia'' (REG) continues to intensify its activities facing the imminent publication of the first and second Gaia data releases (14 September, 2016 and Q4-2017, respectively). The network, supported by the MINECO under contract Acciones de dinamizaci ´on, Redes de Excelencia (2016-2017), has as major priority the task to coordinate and support the collective activities developed by its more than 150 members. At present, REG plays a prominent role in the preparation of the Spanish community for the use of the Gaia data archive (a task lead by the Spanish team), in the work to exploit the Gaia-ESO survey collected during the last four years and in supporting the preparation of the science case and survey plan for WEAVE, the new multi-object spectrograph for the WHT at Canary Islands (commissioning, 2018). These activities are described together with the schedule of future national and international science meetings and the outreach activities being organized for the first and second Data Releases

  10. Exploiting Genome Structure in Association Analysis (United States)

    Kim, Seyoung


    Abstract A genome-wide association study involves examining a large number of single-nucleotide polymorphisms (SNPs) to identify SNPs that are significantly associated with the given phenotype, while trying to reduce the false positive rate. Although haplotype-based association methods have been proposed to accommodate correlation information across nearby SNPs that are in linkage disequilibrium, none of these methods directly incorporated the structural information such as recombination events along chromosome. In this paper, we propose a new approach called stochastic block lasso for association mapping that exploits prior knowledge on linkage disequilibrium structure in the genome such as recombination rates and distances between adjacent SNPs in order to increase the power of detecting true associations while reducing false positives. Following a typical linear regression framework with the genotypes as inputs and the phenotype as output, our proposed method employs a sparsity-enforcing Laplacian prior for the regression coefficients, augmented by a first-order Markov process along the sequence of SNPs that incorporates the prior information on the linkage disequilibrium structure. The Markov-chain prior models the structural dependencies between a pair of adjacent SNPs, and allows us to look for association SNPs in a coupled manner, combining strength from multiple nearby SNPs. Our results on HapMap-simulated datasets and mouse datasets show that there is a significant advantage in incorporating the prior knowledge on linkage disequilibrium structure for marker identification under whole-genome association. PMID:21548809

  11. Understanding Online Child Sexual Exploitation Offenses. (United States)

    Ly, Thanh; Murphy, Lisa; Fedoroff, J Paul


    In the past three decades, there has been an exponential increase in the worldwide availability of Internet access and devices that are able to access online materials. This literature review investigated whether increased accessibility of Internet child pornography (CP) increases the risk of in-person child sexual exploitation. The current review found little to no evidence that availability of the Internet has increased the worldwide incidence or prevalence of in-person child sexual abuse. In fact, during the time period in which the Internet has flourished, international crime statistics have shown a steady decrease of in-person child sexual abuse. The only exception to this trend is an increase in Internet child pornography or luring offenses (e.g., Stats Can, 2014), which involves child abuse by definition. This article reviews the impact of the Internet on child sexual abuse. It also reviews the characteristics of online CP offenders. Treatment of these offenders and prevention of such offenses is also discussed.

  12. Exploiting epigenetic vulnerabilities for cancer therapeutics. (United States)

    Mair, Barbara; Kubicek, Stefan; Nijman, Sebastian M B


    Epigenetic deregulation is a hallmark of cancer, and there has been increasing interest in therapeutics that target chromatin-modifying enzymes and other epigenetic regulators. The rationale for applying epigenetic drugs to treat cancer is twofold. First, epigenetic changes are reversible, and drugs could therefore be used to restore the normal (healthy) epigenetic landscape. However, it is unclear whether drugs can faithfully restore the precancerous epigenetic state. Second, chromatin regulators are often mutated in cancer, making them attractive drug targets. However, in most instances it is unknown whether cancer cells are addicted to these mutated chromatin proteins, or whether their mutation merely results in epigenetic instability conducive to the selection of secondary aberrations. An alternative incentive for targeting chromatin regulators is the exploitation of cancer-specific vulnerabilities, including synthetic lethality, caused by epigenetic deregulation. We review evidence for the hypothesis that mechanisms other than oncogene addiction are a basis for the application of epigenetic drugs, and propose future research directions. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. Transnational gestational surrogacy: does it have to be exploitative? (United States)

    Kirby, Jeffrey


    This article explores the controversial practice of transnational gestational surrogacy and poses a provocative question: Does it have to be exploitative? Various existing models of exploitation are considered and a novel exploitation-evaluation heuristic is introduced to assist in the analysis of the potentially exploitative dimensions/elements of complex health-related practices. On the basis of application of the heuristic, I conclude that transnational gestational surrogacy, as currently practiced in low-income country settings (such as rural, western India), is exploitative of surrogate women. Arising out of consideration of the heuristic's exploitation conditions, a set of public education and enabled choice, enhanced protections, and empowerment reforms to transnational gestational surrogacy practice is proposed that, if incorporated into a national regulatory framework and actualized within a low income country, could possibly render such practice nonexploitative.

  14. Postural Hand Synergies during Environmental Constraint Exploitation

    Directory of Open Access Journals (Sweden)

    Cosimo Della Santina


    Full Text Available Humans are able to intuitively exploit the shape of an object and environmental constraints to achieve stable grasps and perform dexterous manipulations. In doing that, a vast range of kinematic strategies can be observed. However, in this work we formulate the hypothesis that such ability can be described in terms of a synergistic behavior in the generation of hand postures, i.e., using a reduced set of commonly used kinematic patterns. This is in analogy with previous studies showing the presence of such behavior in different tasks, such as grasping. We investigated this hypothesis in experiments performed by six subjects, who were asked to grasp objects from a flat surface. We quantitatively characterized hand posture behavior from a kinematic perspective, i.e., the hand joint angles, in both pre-shaping and during the interaction with the environment. To determine the role of tactile feedback, we repeated the same experiments but with subjects wearing a rigid shell on the fingertips to reduce cutaneous afferent inputs. Results show the persistence of at least two postural synergies in all the considered experimental conditions and phases. Tactile impairment does not alter significantly the first two synergies, and contact with the environment generates a change only for higher order Principal Components. A good match also arises between the first synergy found in our analysis and the first synergy of grasping as quantified by previous work. The present study is motivated by the interest of learning from the human example, extracting lessons that can be applied in robot design and control. Thus, we conclude with a discussion on implications for robotics of our findings.

  15. Exploitation of Parallelism in Climate Models

    Energy Technology Data Exchange (ETDEWEB)

    Baer, F.; Tribbia, J.J.; Williamson, D.L.


    The US Department of Energy (DOE), through its CHAMMP initiative, hopes to develop the capability to make meaningful regional climate forecasts on time scales exceeding a decade, such capability to be based on numerical prediction type models. We propose research to contribute to each of the specific items enumerated in the CHAMMP announcement (Notice 91-3); i.e., to consider theoretical limits to prediction of climate and climate change on appropriate time scales, to develop new mathematical techniques to utilize massively parallel processors (MPP), to actually utilize MPPs as a research tool, and to develop improved representations of some processes essential to climate prediction. In particular, our goals are to: (1) Reconfigure the prediction equations such that the time iteration process can be compressed by use of MMP architecture, and to develop appropriate algorithms. (2) Develop local subgrid scale models which can provide time and space dependent parameterization for a state- of-the-art climate model to minimize the scale resolution necessary for a climate model, and to utilize MPP capability to simultaneously integrate those subgrid models and their statistics. (3) Capitalize on the MPP architecture to study the inherent ensemble nature of the climate problem. By careful choice of initial states, many realizations of the climate system can be determined concurrently and more realistic assessments of the climate prediction can be made in a realistic time frame. To explore these initiatives, we will exploit all available computing technology, and in particular MPP machines. We anticipate that significant improvements in modeling of climate on the decadal and longer time scales for regional space scales will result from our efforts.

  16. Beyond Fair Benefits: Reconsidering Exploitation Arguments Against Organ Markets. (United States)

    Koplin, Julian J


    One common objection to establishing regulated live donor organ markets is that such markets would be exploitative. Perhaps surprisingly, exploitation arguments against organ markets have been widely rejected in the philosophical literature on the subject. It is often argued that concerns about exploitation should be addressed by increasing the price paid to organ sellers, not by banning the trade outright. I argue that this analysis rests on a particular conception of exploitation (which I refer to as 'fair benefits' exploitation), and outline two additional ways that the charge of exploitation can be understood (which I discuss in terms of 'fair process' exploitation and complicity in injustice). I argue that while increasing payments to organ sellers may mitigate or eliminate fair benefits exploitation, such measures will not necessarily address fair process exploitation or complicity in injustice. I further argue that each of these three forms of wrongdoing is relevant to the ethics of paid living organ donation, as well as the design of public policy more generally.

  17. A Systematic Review of Financial Exploitation Measures in Prevalence Studies. (United States)

    Jackson, Shelly L


    The financial exploitation of older adults has garnered the attention of society as well as state and federal governments in a way that elder abuse has never been able to achieve. It is frequently asserted that financial exploitation deserves this attention in part because it is the most prevalent form of elder abuse. This article systematically reviews the measurement of financial exploitation in comparison with other forms of elder abuse and concludes that its measurement is considerably more variable than other forms of abuse. Consequently, improvements in the measurement of financial exploitation are warranted.

  18. Characterization of exoplanet hosts

    Directory of Open Access Journals (Sweden)

    Valenti Jeff A.


    Full Text Available Spectroscopic analysis of exoplanet hosts and the stellar sample from which they are drawn provides abundances and other properties that quantitively constrain models of planet formation. The program Spectroscopy Made Easy (SME determines stellar parameters by fitting observed spectra, though line lists must be selected wisely. For giant planets, it is now well established that stars with higher metallicity are more likely to have detected companions. Stellar metallicity does not seem to affect the formation and/or migration of detectable planets less massive than Neptune, especially when considering only the most massive planet in the system. In systems with at least one planet less than 10 times the mass of Earth, the mass of the most massive planet increases dramatically with host star metallicity. This may reflect metallicity dependent timescales for core formation, envelope accretion, and/or migration into the detection zone.

  19. Allergic Host Defenses


    Palm, Noah W.; Rosenstein, Rachel K.; Medzhitov, Ruslan


    Allergies are generally thought to be a detrimental outcome of a mistargeted immune response that evolved to provide immunity to macro-parasites. Here we present arguments to suggest that allergic immunity plays an important role in host defense against noxious environmental substances, including venoms, hematophagous fluids, environmental xenobiotics and irritants. We argue that appropriately targeted allergic reactions are beneficial, although they can become detrimental when excessive. Fur...

  20. Viral Mimicry to Usurp Ubiquitin and SUMO Host Pathways

    Directory of Open Access Journals (Sweden)

    Peter Wimmer


    Full Text Available Posttranslational modifications (PTMs of proteins include enzymatic changes by covalent addition of cellular regulatory determinants such as ubiquitin (Ub and small ubiquitin-like modifier (SUMO moieties. These modifications are widely used by eukaryotic cells to control the functional repertoire of proteins. Over the last decade, it became apparent that the repertoire of ubiquitiylation and SUMOylation regulating various biological functions is not restricted to eukaryotic cells, but is also a feature of human virus families, used to extensively exploit complex host-cell networks and homeostasis. Intriguingly, besides binding to host SUMO/Ub control proteins and interfering with the respective enzymatic cascade, many viral proteins mimic key regulatory factors to usurp this host machinery and promote efficient viral outcomes. Advanced detection methods and functional studies of ubiquitiylation and SUMOylation during virus-host interplay have revealed that human viruses have evolved a large arsenal of strategies to exploit these specific PTM processes. In this review, we highlight the known viral analogs orchestrating ubiquitin and SUMO conjugation events to subvert and utilize basic enzymatic pathways.

  1. Fatty acid-producing hosts (United States)

    Pfleger, Brian F; Lennen, Rebecca M


    Described are hosts for overproducing a fatty acid product such as a fatty acid. The hosts include an exogenous nucleic acid encoding a thioesterase and, optionally, an exogenous nucleic acid encoding an acetyl-CoA carboxylase, wherein an acyl-CoA synthetase in the hosts are functionally delected. The hosts prefereably include the nucleic acid encoding the thioesterase at an intermediate copy number. The hosts are preferably recominantly stable and growth-competent at C. Methods of producing a fatty acid product comprising culturing such hosts at C. are also described.

  2. Exploiting the tumor microenvironment for theranostic imaging. (United States)

    Stasinopoulos, Ioannis; Penet, Marie-France; Chen, Zhihang; Kakkad, Samata; Glunde, Kristine; Bhujwalla, Zaver M


    The integration of chemistry and molecular biology with imaging is providing some of the most exciting opportunities in the treatment of cancer. The field of theranostic imaging, where diagnosis is combined with therapy, is particularly suitable for a disease as complex as cancer, especially now that genomic and proteomic profiling can provide an extensive 'fingerprint' of each tumor. Using this information, theranostic agents can be shaped for personalized treatment to target specific compartments, such as the tumor microenvironment (TME), whilst minimizing damage to normal tissue. These theranostic agents can also be used to target multiple pathways or networks by incorporating multiple small interfering RNAs (siRNAs) within a single agent. A decade ago genetic alterations were the primary focus in cancer research. Now it is apparent that the tumor physiological microenvironment, interactions between cancer cells and stromal cells, such as endothelial cells, fibroblasts and macrophages, the extracellular matrix (ECM), and a host of secreted factors and cytokines, influence progression to metastatic disease, aggressiveness and the response of the disease to treatment. In this review, we outline some of the characteristics of the TME, describe the theranostic agents currently available to target the TME and discuss the unique opportunities the TME provides for the design of novel theranostic agents for cancer therapy. Copyright © 2011 John Wiley & Sons, Ltd.

  3. Sex-specific effects of a parasite evolving in a female-biased host population

    Directory of Open Access Journals (Sweden)

    Duneau David


    Full Text Available Abstract Background Males and females differ in many ways and might present different opportunities and challenges to their parasites. In the same way that parasites adapt to the most common host type, they may adapt to the characteristics of the host sex they encounter most often. To explore this hypothesis, we characterized host sex-specific effects of the parasite Pasteuria ramosa, a bacterium evolving in naturally, strongly, female-biased populations of its host Daphnia magna. Results We show that the parasite proliferates more successfully in female hosts than in male hosts, even though males and females are genetically identical. In addition, when exposure occurred when hosts expressed a sexual dimorphism, females were more infected. In both host sexes, the parasite causes a similar reduction in longevity and leads to some level of castration. However, only in females does parasite-induced castration result in the gigantism that increases the carrying capacity for the proliferating parasite. Conclusions We show that mature male and female Daphnia represent different environments and reveal one parasite-induced symptom (host castration, which leads to increased carrying capacity for parasite proliferation in female but not male hosts. We propose that parasite induced host castration is a property of parasites that evolved as an adaptation to specifically exploit female hosts.

  4. Oil exploitation and its socioeconomic effects on the Niger Delta region of Nigeria. (United States)

    Elum, Z A; Mopipi, K; Henri-Ukoha, A


    The oil exploration and exploitation industry which is majorly centred in the Niger Delta region is without doubt currently the most important earner of foreign exchange to the Nigerian economy. The Niger Delta is home to an extraordinary variety of people; mostly fishers and farmers with a history of rich cultural heritage. However, the region is suffering from devastating oil pollution. Although the effects of oil spill depend on factors such as size or area of spill and geographical location, the socioeconomic and environmental costs of oil production can be extensive; these range from destruction of wildlife, biodiversity loss, air and water pollution, degradation of farmland and damage to aquatic ecosystems. The paper reviews the adverse effects of oil exploitation on the Niger Delta region. It researches the common belief that government and oil multinationals are negatively disposed to the socioeconomic and environmental wellbeing of host communities especially in events of oil spillage. The paper reveals that oil exploitation has increased the rate of environmental degradation and has perpetuated food insecurity as a result of death of fish and crops as well as loss of farm lands and viable rivers for fishing activities leading to loss of livelihood. The paper supports the call for multinationals operating in the region to modernise operating infrastructure and equipment in order to prevent avoidable oil spillages that often lead to community restiveness, and more so, intensification of joint efforts between oil multinationals and government in the capital development of the region is very important.

  5. Simulated population responses of common carp to commercial exploitation

    Energy Technology Data Exchange (ETDEWEB)

    Weber, Michael J.; Hennen, Matthew J.; Brown, Michael L.


    Common carp Cyprinus carpio is a widespread invasive species that can become highly abundant and impose deleterious ecosystem effects. Thus, aquatic resource managers are interested in controlling common carp populations. Control of invasive common carp populations is difficult, due in part to the inherent uncertainty of how populations respond to exploitation. To understand how common carp populations respond to exploitation, we evaluated common carp population dynamics (recruitment, growth, and mortality) in three natural lakes in eastern South Dakota. Common carp exhibited similar population dynamics across these three systems that were characterized by consistent recruitment (ages 3 to 15 years present), fast growth (K = 0.37 to 0.59), and low mortality (A = 1 to 7%). We then modeled the effects of commercial exploitation on size structure, abundance, and egg production to determine its utility as a management tool to control populations. All three populations responded similarly to exploitation simulations with a 575-mm length restriction, representing commercial gear selectivity. Simulated common carp size structure modestly declined (9 to 37%) in all simulations. Abundance of common carp declined dramatically (28 to 56%) at low levels of exploitation (0 to 20%) but exploitation >40% had little additive effect and populations were only reduced by 49 to 79% despite high exploitation (>90%). Maximum lifetime egg production was reduced from 77 to 89% at a moderate level of exploitation (40%), indicating the potential for recruitment overfishing. Exploitation further reduced common carp size structure, abundance, and egg production when simulations were not size selective. Our results provide insights to how common carp populations may respond to exploitation. Although commercial exploitation may be able to partially control populations, an integrated removal approach that removes all sizes of common carp has a greater chance of controlling population abundance

  6. Molecular studies on IAV nucleoprotein: interaction with host factors and its role in virus life cycle


    Batra, Jyoti


    Influenza A viruses (IAV) are obligate intracellular pathogens, causing substantial health and economic impacts worldwide. Like other RNA viruses, IAV greatly rely on the exploitation and subversion of host cellular proteins and pathways to facilitate virus replication. Insight into the molecular biology of these relationships could lead to novel antiviral strategies and has the potential to identify host specific interactions that would act as a barrier to pandemic emergence. IAV genom...

  7. Poverty reduction in a refugee-hosting economy: A natural experiment


    Maystadt, Jean-Francois


    The role of migration in reducing poverty in developing countries has been investigated mainly from the perspective of migrants and their relatives. This paper exploits the time and spatial variations in the way households in the region of Kagera (Tanzania) traced between 1991 and 2004 have been affected by massive refugee inflows to assess how migration may affect poverty in the hosting communities. Large population inflows from Burundi and Rwanda have improved the welfare of the hosting pop...

  8. Entomopathogenic Fungi: New Insights into Host-Pathogen Interactions. (United States)

    Butt, T M; Coates, C J; Dubovskiy, I M; Ratcliffe, N A


    Although many insects successfully live in dangerous environments exposed to diverse communities of microbes, they are often exploited and killed by specialist pathogens. Studies of host-pathogen interactions (HPI) provide valuable insights into the dynamics of the highly aggressive coevolutionary arms race between entomopathogenic fungi (EPF) and their arthropod hosts. The host defenses are designed to exclude the pathogen or mitigate the damage inflicted while the pathogen responds with immune evasion and utilization of host resources. EPF neutralize their immediate surroundings on the insect integument and benefit from the physiochemical properties of the cuticle and its compounds that exclude competing microbes. EPF also exhibit adaptations aimed at minimizing trauma that can be deleterious to both host and pathogen (eg, melanization of hemolymph), form narrow penetration pegs that alleviate host dehydration and produce blastospores that lack immunogenic sugars/enzymes but facilitate rapid assimilation of hemolymph nutrients. In response, insects deploy an extensive armory of hemocytes and macromolecules, such as lectins and phenoloxidase, that repel, immobilize, and kill EPF. New evidence suggests that immune bioactives work synergistically (eg, lysozyme with antimicrobial peptides) to combat infections. Some proteins, including transferrin and apolipophorin III, also demonstrate multifunctional properties, participating in metabolism, homeostasis, and pathogen recognition. This review discusses the molecular intricacies of these HPI, highlighting the interplay between immunity, stress management, and metabolism. Increased knowledge in this area could enhance the efficacy of EPF, ensuring their future in integrated pest management programs. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Host control and nutrient trading in a photosynthetic symbiosis. (United States)

    Dean, Andrew D; Minter, Ewan J A; Sørensen, Megan E S; Lowe, Christopher D; Cameron, Duncan D; Brockhurst, Michael A; Jamie Wood, A


    Photosymbiosis is one of the most important evolutionary trajectories, resulting in the chloroplast and the subsequent development of all complex photosynthetic organisms. The ciliate Paramecium bursaria and the alga Chlorella have a well established and well studied light dependent endosymbiotic relationship. Despite its prominence, there remain many unanswered questions regarding the exact mechanisms of the photosymbiosis. Of particular interest is how a host maintains and manages its symbiont load in response to the allocation of nutrients between itself and its symbionts. Here we construct a detailed mathematical model, parameterised from the literature, that explicitly incorporates nutrient trading within a deterministic model of both partners. The model demonstrates how the symbiotic relationship can manifest as parasitism of the host by the symbionts, mutualism, wherein both partners benefit, or exploitation of the symbionts by the hosts. We show that the precise nature of the photosymbiosis is determined by both environmental conditions (how much light is available for photosynthesis) and the level of control a host has over its symbiont load. Our model provides a framework within which it is possible to pose detailed questions regarding the evolutionary behaviour of this important example of an established light dependent endosymbiosis; we focus on one question in particular, namely the evolution of host control, and show using an adaptive dynamics approach that a moderate level of host control may evolve provided the associated costs are not prohibitive. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  10. Epidemiology in mixed host populations

    National Research Council Canada - National Science Library

    Garrett, K A; Mundt, C C


    ABSTRACT Although plant disease epidemiology has focused on populations in which all host plants have the same genotype, mixtures of host genotypes are more typical of natural populations and offer...

  11. Can host density attenuate parasitism?

    National Research Council Canada - National Science Library

    Magalhães, L; Freitas, R; Dairain, A; De Montaudouin, X

    .... Considering that these parasites infect cockles through filtration activity, our first hypothesis was that high host density will have a dilution effect so that infection intensity decreases with host density...

  12. Exploiting for medical and biological applications (United States)

    Giano, Michael C.

    Biotherapeutics are an emerging class of drug composed of molecules ranging in sizes from peptides to large proteins. Due to their poor stability and mucosal membrane permeability, biotherapeutics are administered by a parenteral method (i.e., syringe, intravenous or intramuscular). Therapeutics delivered systemically often experience short half-lives. While, local administration may involve invasive surgical procedures and suffer from poor retention at the site of application. To compensate, the patient receives frequent doses of highly concentrated therapeutic. Unfortunately, the off-target side effects and discomfort associated with multiple injections results in poor patient compliance. Therefore, new delivery methods which can improve therapeutic retention, reduce the frequency of administration and may aid in decreasing the off-target side effects is a necessity. Hydrogels are a class of biomaterials that are gaining interests for tissue engineering and drug delivery applications. Hydrogel materials are defined as porous, 3-dimensional networks that are primarily composed of water. Generally, they are mechanically rigid, cytocompatible and easily chemically functionalized. Collectively, these properties make hydrogels fantastic candidates to perform as drug delivery depots. Current hydrogel delivery systems physically entrap the target therapeutic which is then subsequently released over time at the site of administration. The swelling and degradation of the material effect the diffusion of the therapy from the hydrogel, and therefore should be controlled. Although these strategies provide some regulation over therapeutic release, full control of the delivery is not achieved. Newer approaches are focused on designing hydrogels that exploit known interactions, covalently attach the therapy or respond to an external stimulus in an effort to gain improved control over the therapy's release. Unfortunately, the biotherapeutic is typically required to be chemically

  13. The Dark Side of Courtship: Violence and Sexual Exploitation. (United States)

    Lloyd, Sally A.


    Reviews literature on physical violence and sexual exploitation between premarital partners. Suggests that two features of dating encourage exploitative behavior: different context of courtship for males versus females encourages male control of relationships and female compliance, and highly romanticized nature of courtship encourages partners to…

  14. A Descriptive Study on Sexually Exploited Children in Residential Treatment (United States)

    Twill, Sarah E.; Green, Denise M.; Traylor, Amy


    Sexual exploitation and prostitution of children and adolescents is a multibillion dollar industry in the United States (Estes and Weiner in "Medical, legal & social science aspects of child sexual exploitation: A comprehensive review of pornography, prostitution, and internet crimes, vol I," G.W. Medical Publishing, Inc, St Louis,…

  15. zero day exploits and national readiness for cyber-warfare

    African Journals Online (AJOL)


    usually vulnerable hosts in a network) to stage an attack against another computer or network. These vulnerable hosts can be discovered through the extensive scanning of networks. Resources such as bandwidth, memory, computing power and.

  16. [Ecotourism exploitation model in Bita Lake Natural Reserve of Yunnan]. (United States)

    Yang, G; Wang, Y; Zhong, L


    Bita lake provincial natural reserve is located in Shangri-La region of North-western Yunnan, and was set as a demonstrating area for ecotourism exploitation in 1998. After a year's exploitation construction and half a year's operation as a branch of the 99' Kunming International Horticulture Exposition to accept tourists, it was proved that the ecotourism demonstrating area attained four integrated functions of ecotourism, i.e., tourism, protection, poverty clearing and environment education. Five exploitation and management models including function zoned exploitation model, featured tourism communication model signs system designing model, local Tibetan family reception model and environmental monitoring model, were also successful, which were demonstrated and spreaded to the whole province. Bita lake provincial natural reserve could be a good sample for the ecotourism exploitation natural reserves of the whole country.

  17. Exploit and ignore the consequences: A mother of planetary issues. (United States)

    Moustafa, Khaled


    Many environmental and planetary issues are due to an exploitation strategy based on exploit, consume and ignore the consequences. As many natural and environmental resources are limited in time and space, such exploitation approach causes important damages on earth, in the sea and maybe soon in the space. To sustain conditions under which humans and other living species can coexist in productive and dynamic harmony with their environments, terrestrial and space exploration programs may need to be based on 'scrutinize the consequences, prepare adequate solutions and then, only then, exploit'. Otherwise, the exploitation of planetary resources may put the environmental stability and sustainability at a higher risk than it is currently predicted. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Legionella pneumophila type IV effectors hijack the transcription and translation machinery of the host cell. (United States)

    Rolando, Monica; Buchrieser, Carmen


    Intracellular bacterial pathogens modulate the host response to persist and replicate inside a eukaryotic cell and cause disease. Legionella pneumophila, the causative agent of Legionnaires' disease, is present in freshwater environments and represents one of these pathogens. During coevolution with protozoan cells, L. pneumophila has acquired highly sophisticated and diverse strategies to hijack host cell processes. It secretes hundreds of effectors into the host cell, and these manipulate host signaling pathways and key cellular processes. Recently it has been shown that L. pneumophila is also able to alter the transcription and translation machinery of the host and to exploit epigenetic mechanisms in the cells it resides in to counteract host responses. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Comparing mechanisms of host manipulation across host and parasite taxa (United States)

    Lafferty, Kevin D.; Shaw, Jenny C.


    Parasites affect host behavior in several ways. They can alter activity, microhabitats or both. For trophically transmitted parasites (the focus of our study), decreased activity might impair the ability of hosts to respond to final-host predators, and increased activity and altered microhabitat choice might increase contact rates between hosts and final-host predators. In an analysis of trophically transmitted parasites, more parasite groups altered activity than altered microhabitat choice. Parasites that infected vertebrates were more likely to impair the host’s reaction to predators, whereas parasites that infected invertebrates were more likely to increase the host’s contact with predators. The site of infection might affect how parasites manipulate their hosts. For instance, parasites in the central nervous system seem particularly suited to manipulating host behavior. Manipulative parasites commonly occupy the body cavity, muscles and central nervous systems of their hosts. Acanthocephalans in the data set differed from other taxa in that they occurred exclusively in the body cavity of invertebrates. In addition, they were more likely to alter microhabitat choice than activity. Parasites in the body cavity (across parasite types) were more likely to be associated with increased host contact with predators. Parasites can manipulate the host through energetic drain, but most parasites use more sophisticated means. For instance, parasites target four physiological systems that shape behavior in both invertebrates and vertebrates: neural, endocrine, neuromodulatory and immunomodulatory. The interconnections between these systems make it difficult to isolate specific mechanisms of host behavioral manipulation.

  20. Host species and developmental stage, but not host social structure, affects bacterial community structure in socially polymorphic bees. (United States)

    McFrederick, Quinn S; Wcislo, William T; Hout, Michael C; Mueller, Ulrich G


    Social transmission and host developmental stage are thought to profoundly affect the structure of bacterial communities associated with honey bees and bumble bees, but these ideas have not been explored in other bee species. The halictid bees Megalopta centralis and M. genalis exhibit intrapopulation social polymorphism, which we exploit to test whether bacterial communities differ by host social structure, developmental stage, or host species. We collected social and solitary Megalopta nests and sampled bees and nest contents from all stages of host development. To survey these bacterial communities, we used 16S rRNA gene 454 pyrosequencing. We found no effect of social structure, but found differences by host species and developmental stage. Wolbachia prevalence differed between the two host species. Bacterial communities associated with different developmental stages appeared to be driven by environmentally acquired bacteria. A Lactobacillus kunkeei clade bacterium that is consistently associated with other bee species was dominant in pollen provisions and larval samples, but less abundant in mature larvae and pupae. Foraging adults appeared to often reacquire L. kunkeei clade bacteria, likely while foraging at flowers. Environmental transmission appears to be more important than social transmission for Megalopta bees at the cusp between social and solitary behavior. © 2014 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

  1. Targeting Host Factors to Treat West Nile and Dengue Viral Infections

    Directory of Open Access Journals (Sweden)

    Manoj N. Krishnan


    Full Text Available West Nile (WNV and Dengue (DENV viruses are major arboviral human pathogens belonging to the genus Flavivirus. At the current time, there are no approved prophylactics (e.g., vaccines or specific therapeutics available to prevent or treat human infections by these pathogens. Due to their minimal genome, these viruses require many host molecules for their replication and this offers a therapeutic avenue wherein host factors can be exploited as treatment targets. Since several host factors appear to be shared by many flaviviruses the strategy may result in pan-flaviviral inhibitors and may also attenuate the rapid emergence of drug resistant mutant viruses. The scope of this strategy is greatly enhanced by the recent en masse identification of host factors impacting on WNV and DENV infection. Excellent proof-of-principle experimental demonstrations for host-targeted control of infection and infection-induced pathogenesis have been reported for both WNV and DENV. These include exploiting not only those host factors supporting infection, but also targeting host processes contributing to pathogenesis and innate immune responses. While these early studies validated the host-targeting approach, extensive future investigations spanning a range of aspects are needed for a successful deployment in humans.

  2. The Drosophila melanogaster host model (United States)

    Igboin, Christina O.; Griffen, Ann L.; Leys, Eugene J.


    The deleterious and sometimes fatal outcomes of bacterial infectious diseases are the net result of the interactions between the pathogen and the host, and the genetically tractable fruit fly, Drosophila melanogaster, has emerged as a valuable tool for modeling the pathogen–host interactions of a wide variety of bacteria. These studies have revealed that there is a remarkable conservation of bacterial pathogenesis and host defence mechanisms between higher host organisms and Drosophila. This review presents an in-depth discussion of the Drosophila immune response, the Drosophila killing model, and the use of the model to examine bacterial–host interactions. The recent introduction of the Drosophila model into the oral microbiology field is discussed, specifically the use of the model to examine Porphyromonas gingivalis–host interactions, and finally the potential uses of this powerful model system to further elucidate oral bacterial-host interactions are addressed. PMID:22368770

  3. Rationalising predictors of child sexual exploitation and sex-trading. (United States)

    Klatt, Thimna; Cavner, Della; Egan, Vincent


    Although there is evidence for specific risk factors leading to child sexual exploitation and prostitution, these influences overlap and have rarely been examined concurrently. The present study examined case files for 175 young persons who attended a voluntary organization in Leicester, United Kingdom, which supports people who are sexually exploited or at risk of sexual exploitation. Based on the case files, the presence or absence of known risk factors for becoming a sex worker was coded. Data were analyzed using t-test, logistic regression, and smallest space analysis. Users of the voluntary organization's services who had been sexually exploited exhibited a significantly greater number of risk factors than service users who had not been victims of sexual exploitation. The logistic regression produced a significant model fit. However, of the 14 potential predictors--many of which were associated with each other--only four variables significantly predicted actual sexual exploitation: running away, poverty, drug and/or alcohol use, and having friends or family members in prostitution. Surprisingly, running away was found to significantly decrease the odds of becoming involved in sexual exploitation. Smallest space analysis of the data revealed 5 clusters of risk factors. Two of the clusters, which reflected a desperation and need construct and immature or out-of-control lifestyles, were significantly associated with sexual exploitation. Our research suggests that some risk factors (e.g. physical and emotional abuse, early delinquency, and homelessness) for becoming involved in sexual exploitation are common but are part of the problematic milieu of the individuals affected and not directly associated with sex trading itself. Our results also indicate that it is important to engage with the families and associates of young persons at risk of becoming (or remaining) a sex worker if one wants to reduce the numbers of persons who engage in this activity. Copyright

  4. High-molar-mass hyaluronan behavior during testing its radical scavenging capacity in organic and aqueous media: effects of the presence of manganese(II) ions. (United States)

    Rapta, Peter; Valachová, Katarína; Gemeiner, Peter; Soltés, Ladislav


    This study compares the radical scavenging capacity of high-molar-mass hyaluronan (HA) using standardized methods applying 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals and 2,2'-azinobis[3-ethylbenzthiazoline sulfonate] (ABTS) radical cations as oxidants. Additionally, spin-trapping technique combined with electron paramagnetic resonance (EPR) was used to evaluate the ability of HA to scavenge reactive radicals. The thermal decomposition of K2S2O8 in pure H2O or in a H2O/dimethyl sulfoxide (DMSO) mixture at 333 K was used as a source of reactive paramagnetic species. We found that HA does not exhibit radical-scavenging activity when DPPH radicals or ABTS(.+) radical cations are used as oxidant, but that HA is an effective radical scavenger at low concentrations, if the oxidation reactions are initiated by the decomposition of K2S2O8. At higher HA concentrations, a more complex behavior and prooxidant HA action was observed. The influence of Mn(II) ions on the reaction mechanisms of radical generation and termination in the K2S2O8/H2O/DMSO system in the presence of HA was studied in detail.

  5. Clinical effects of betamethasone and hyaluronan, and of defocalized carbon dioxide laser treatment on traumatic arthritis in the fetlock joints of horses. (United States)

    Lindholm, A C; Swensson, U; de Mitri, N; Collinder, E


    The clinical effects of intra-articular betamethasone together with hyaluronan (betaM/HA) and treatment with a defocalized carbon dioxide laser on acute traumatic arthritis of the fetlock joint were assessed. The horses in these studies were selected using a thorough lameness examination, including intra-articular anaesthesia abolishing the lameness. This investigation comprised an observer-blind study, including 10 sport horses (10 joints), and a prospective study, including 180 sport horses (333 joints). In both studies, the material was divided into two groups treated with either betaM/HA or a carbon dioxide laser. The treatment doses were 12 mg of betaM, 20 mg of HA or 60 J/cm2 of treated area. Convalescence before training was 21 days for both groups in the observer-blind study. In the prospective study, convalescence in the betaM/HA group was 21 days but was only 7 days for the laser-treated group. In the observer-blind study, three of five treated joints recovered in both cohorts. In the prospective study, the groups had significantly different recovery rates--68% of the betaM/HA-treated joints and 80% of the carbon dioxide laser-treated joints. These results indicate that the defocalized carbon dioxide laser should be an applicable mode of treatment of acute traumatic synovitis in horses. However, the biochemical functions related to carbon dioxide laser treatment require further elucidation.

  6. Hyaluronan viscosupplementation: state of the art and insight into the novel cooperative hybrid complexes based on high and low molecular weight HA of potential interest in osteoarthritis treatment. (United States)

    Schiraldi, Chiara; Stellavato, Antonietta; de Novellis, Francesca; La Gatta, Annalisa; De Rosa, Mario


    Osteoarthritis (OA) represents a group of chronic, painful, disabling conditions affecting synovial joints. It is characterized by degeneration of articular cartilage, alterations of peri-articular and subchondral bone, low-grade synovial inflammation (synovitis). Despite OA is commonly described as a non-inflammatory disease, it is known that its progression and the subsequent increment of symptoms correlate to the production of inflammatory factors that induce the secretion of enzymes responsible for cartilage degradation. In clinical practice, to alleviate pain and stiffness, not only during acute phases but also as maintenance therapy, intra-articular injections of corticosteroids or similar drugs are used, besides it is well diffused the viscosupplementation procedure based on hyaluronan gel. There are many different products containing high molecular weight linear HA or cross-linked derivatives, however the novelty in the field consist in the hybrid cooperative complexes derived from high and low molecular weight HA through a patented processing. This technique permit to double the amount of HA delivered to the injured site without increasing the injected volume, beside in vitro assay on human chondrocytes suggested hybrid complexes as effective in the modulation of several inflammatory cytokines in joints.

  7. Conditional inactivation of Has2 reveals a crucial role for hyaluronan in skeletal growth, patterning, chondrocyte maturation and joint formation in the developing limb. (United States)

    Matsumoto, Kazu; Li, Yingcui; Jakuba, Caroline; Sugiyama, Yoshinori; Sayo, Tetsuya; Okuno, Misako; Dealy, Caroline N; Toole, Bryan P; Takeda, Junji; Yamaguchi, Yu; Kosher, Robert A


    The glycosaminoglycan hyaluronan (HA) is a structural component of extracellular matrices and also interacts with cell surface receptors to directly influence cell behavior. To explore functions of HA in limb skeletal development, we conditionally inactivated the gene for HA synthase 2, Has2, in limb bud mesoderm using mice that harbor a floxed allele of Has2 and mice carrying a limb mesoderm-specific Prx1-Cre transgene. The skeletal elements of Has2-deficient limbs are severely shortened, indicating that HA is essential for normal longitudinal growth of all limb skeletal elements. Proximal phalanges are duplicated in Has2 mutant limbs indicating an involvement of HA in patterning specific portions of the digits. The growth plates of Has2-deficient skeletal elements are severely abnormal and disorganized, with a decrease in the deposition of aggrecan in the matrix and a disruption in normal columnar cellular relationships. Furthermore, there is a striking reduction in the number of hypertrophic chondrocytes and in the expression domains of markers of hypertrophic differentiation in the mutant growth plates, indicating that HA is necessary for the normal progression of chondrocyte maturation. In addition, secondary ossification centers do not form in the central regions of Has2 mutant growth plates owing to a failure of hypertrophic differentiation. In addition to skeletal defects, the formation of synovial joint cavities is defective in Has2-deficient limbs. Taken together, our results demonstrate that HA has a crucial role in skeletal growth, patterning, chondrocyte maturation and synovial joint formation in the developing limb.

  8. Free-radical degradation of high-molecular-weight hyaluronan induced by ascorbate plus cupric ions. Testing of bucillamine and its SA981-metabolite as antioxidants. (United States)

    Valachová, Katarína; Hrabárová, Eva; Priesolová, Elena; Nagy, Milan; Baňasová, Mária; Juránek, Ivo; Soltés, Ladislav


    High-molecular-weight hyaluronan (HA) samples were exposed to free-radical chain-degradation reactions induced by ascorbate in the presence of Cu(II) ions - the so-called Weissberger's oxidative system. The concentrations of both reactants [ascorbate, Cu(II)] were comparable to those that may occur during an early stage of the acute phase of joint inflammation. The time-dependent changes of the viscosity of the HA solution in the absence of the substance tested were monitored by rotational viscometry. However, when the anti- or pro-oxidative effects of the antioxidants/drugs were investigated, their dose-dependency was also examined. Additionally, the anti-oxidative activities of these substances were screened by the well-established ABTS and DPPH decolorization assays. The actions of the disease-modifying anti-rheumatic drugs, namely bucillamine and D-penicillamine, were compared to those of L-cysteine and of SA981, the oxidized metabolite of bucillamine. The results indicated that bucillamine was the most efficient scavenger of hydroxyl- and/or peroxyl-type radicals, even at the lowest drug concentration. In contrast, SA981 demonstrated no scavenging activity against the aforementioned free radicals. D-Penicillamine and L-cysteine showed a dual effect, i.e. a pronounced anti-oxidative effect was, after a given time period, followed by a significant pro-oxidative effect. Copyright © 2011 Elsevier B.V. All rights reserved.

  9. Biomechanical and histologic evaluation of tissue engineered ligaments using chitosan and hyaluronan hybrid polymer fibers: a rabbit medial collateral ligament reconstruction model. (United States)

    Irie, Toru; Majima, Tokifumi; Sawaguchi, Naohiro; Funakoshi, Tadanao; Nishimura, Shin-Ichiro; Minami, Akio


    In this study, we used a rabbit medial collateral ligament reconstruction model to evaluate a novel chitosan-based hyaluronan hybrid polymer fiber scaffold for ligament tissue engineering and to examine whether mechanical forces exerted in an in vivo model increased extracellular matrix production by seeded fibroblasts. Scaffolds were used 2 weeks after incubation with fibroblasts obtained from the same rabbit in a cell-seeded scaffold (CSS) group and without cells in a noncell-seeded scaffold (NCSS) group. At 3, 6, and 12 weeks after surgery, the failure loads of the engineered ligaments in the CSS groups were significantly greater than those in the NCSS groups. At 6 weeks after surgery, the reconstructed tissue of the CSS group was positive for type I collagen, whereas that in the NCSS group was negative for type I collagen. At 12 weeks after surgery, the reconstructed tissue stained positive for type I collagen in the CSS group, but negative in the NCSS group. Our results indicate that the scaffold material enhanced the production of type I collagen and led to improved mechanical strength in the engineered ligament in vivo. Copyright © 2011 Wiley Periodicals, Inc.

  10. The extended nutrigenomics - understanding the interplay between the genomes of food, gut microbes, and human host

    NARCIS (Netherlands)

    Kussmann, M.; Bladeren, van P.J.


    Comprehensive investigation of nutritional health effects at the molecular level requires the understanding of the interplay between three genomes, the food, the gut microbial, and the human host genome. Food genomes are researched for discovery and exploitation of macro- and micronutrients as well

  11. Checklist of available generic names for Microsporidia with type species and type host (United States)

    The science of microsporidiology encompasses a diverse assemblage of pathogens from a large and varied group of hosts. Many members of this group have been studied and exploited for their role in the control of insect pests and vectors as well as their detrimental impact on vertebrates including ma...

  12. Pluriactivite et mode de financement des exploitations agricoles


    Stéphane Krebs


    Cet article se propose de mettre en relation les décisions de pluriactivité des familles d’agriculteurs et les choix qu’ils opèrent en matière de financement de leurs exploitations. Les résultats obtenus à partir d’un panel d’exploitations individuelles françaises font ressortir d’importantes spécificités des exploitations pluriactives, tant en matière d’autofinancement que d’endettement. The aim of this article is to study the possible interrelationships between the off-farm work decision...

  13. Host language, integration language

    Directory of Open Access Journals (Sweden)

    Maria José dos Reis Grosso


    Full Text Available With the development of language research within the Council of Europe and in a context of a stronger multilingual and multicultural Europe, we are witnessing the emergence of terms that are imposed by the frequency of their usage or that (recreate and set re-interpreted concepts according to new social and educational situations. Such is the case of the host language, a concept which is object of analysis in this paper. The relevance of the issue is preceded by other issues related to concepts like native language, second language and foreign language, already comprised in Applied Linguistics and the Teaching of Modern Languages. Nowadays, the indispensability of studying these concepts is fundamental to the pedagogic practice as well as to the language syllabus and its planning. This idea is totally supported by the proposal of the "Common European Framework of Reference for Languages: Learning, Teaching Assessment (CEFR", which provides the appropriate guidelines at the discourse level.

  14. Host lipid droplets: An important source of lipids salvaged by the intracellular parasite Toxoplasma gondii. (United States)

    Nolan, Sabrina J; Romano, Julia D; Coppens, Isabelle


    Toxoplasma is an obligate intracellular parasite that replicates in mammalian cells within a parasitophorous vacuole (PV) that does not fuse with any host organelles. One mechanism developed by the parasite for nutrient acquisition is the attraction of host organelles to the PV. Here, we examined the exploitation of host lipid droplets (LD), ubiquitous fat storage organelles, by Toxoplasma. We show that Toxoplasma replication is reduced in host cells that are depleted of LD, or impaired in TAG lipolysis or fatty acid catabolism. In infected cells, the number of host LD and the expression of host LD-associated genes (ADRP, DGAT2), progressively increase until the onset of parasite replication. Throughout infection, the PV are surrounded by host LD. Toxoplasma is capable of accessing lipids stored in host LD and incorporates these lipids into its own membranes and LD. Exogenous addition of oleic acid stimulates LD biogenesis in the host cell and results in the overaccumulation of neutral lipids in very large LD inside the parasite. To access LD-derived lipids, Toxoplasma intercepts and internalizes within the PV host LD, some of which remaining associated with Rab7, which become wrapped by an intravacuolar network of membranes (IVN). Mutant parasites impaired in IVN formation display diminished capacity of lipid uptake from host LD. Moreover, parasites lacking an IVN-localized phospholipase A2 are less proficient in salvaging lipids from host LD in the PV, suggesting a major contribution of the IVN for host LD processing in the PV and, thus lipid content release. Interestingly, gavage of parasites with lipids unveils, for the first time, the presence in Toxoplasma of endocytic-like structures containing lipidic material originating from the PV lumen. This study highlights the reliance of Toxoplasma on host LD for its intracellular development and the parasite's capability in scavenging neutral lipids from host LD.

  15. Competition for Manganese at the Host-Pathogen Interface. (United States)

    Kelliher, J L; Kehl-Fie, T E


    Transition metals such as manganese are essential nutrients for both pathogen and host. Vertebrates exploit this necessity to combat invading microbes by restricting access to these critical nutrients, a defense known as nutritional immunity. During infection, the host uses several mechanisms to impose manganese limitation. These include removal of manganese from the phagolysosome, sequestration of extracellular manganese, and utilization of other metals to prevent bacterial acquisition of manganese. In order to cause disease, pathogens employ a variety of mechanisms that enable them to adapt to and counter nutritional immunity. These adaptations include, but are likely not limited to, manganese-sensing regulators and high-affinity manganese transporters. Even though successful pathogens can overcome host-imposed manganese starvation, this defense inhibits manganese-dependent processes, reducing the ability of these microbes to cause disease. While the full impact of host-imposed manganese starvation on bacteria is unknown, critical bacterial virulence factors such as superoxide dismutases are inhibited. This chapter will review the factors involved in the competition for manganese at the host-pathogen interface and discuss the impact that limiting the availability of this metal has on invading bacteria. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. A Legionella Effector Disrupts Host Cytoskeletal Structure by Cleaving Actin.

    Directory of Open Access Journals (Sweden)

    Yao Liu


    Full Text Available Legionella pneumophila, the etiological agent of Legionnaires' disease, replicates intracellularly in protozoan and human hosts. Successful colonization and replication of this pathogen in host cells requires the Dot/Icm type IVB secretion system, which translocates approximately 300 effector proteins into the host cell to modulate various cellular processes. In this study, we identified RavK as a Dot/Icm substrate that targets the host cytoskeleton and reduces actin filament abundance in mammalian cells upon ectopic expression. RavK harbors an H95EXXH99 motif associated with diverse metalloproteases, which is essential for the inhibition of yeast growth and for the induction of cell rounding in HEK293T cells. We demonstrate that the actin protein itself is the cellular target of RavK and that this effector cleaves actin at a site between residues Thr351 and Phe352. Importantly, RavK-mediated actin cleavage also occurs during L. pneumophila infection. Cleavage by RavK abolishes the ability of actin to form polymers. Furthermore, an F352A mutation renders actin resistant to RavK-mediated cleavage; expression of the mutant in mammalian cells suppresses the cell rounding phenotype caused by RavK, further establishing that actin is the physiological substrate of RavK. Thus, L. pneumophila exploits components of the host cytoskeleton by multiple effectors with distinct mechanisms, highlighting the importance of modulating cellular processes governed by the actin cytoskeleton in the intracellular life cycle of this pathogen.

  17. Host-selective toxins of Pyrenophora tritici-repentis induce common responses associated with host susceptibility.

    Directory of Open Access Journals (Sweden)

    Iovanna Pandelova

    Full Text Available Pyrenophora tritici-repentis (Ptr, a necrotrophic fungus and the causal agent of tan spot of wheat, produces one or a combination of host-selective toxins (HSTs necessary for disease development. The two most studied toxins produced by Ptr, Ptr ToxA (ToxA and Ptr ToxB (ToxB, are proteins that cause necrotic or chlorotic symptoms respectively. Investigation of host responses induced by HSTs provides better insight into the nature of the host susceptibility. Microarray analysis of ToxA has provided evidence that it can elicit responses similar to those associated with defense. In order to evaluate whether there are consistent host responses associated with susceptibility, a similar analysis of ToxB-induced changes in the same sensitive cultivar was conducted. Comparative analysis of ToxA- and ToxB-induced transcriptional changes showed that similar groups of genes encoding WRKY transcription factors, RLKs, PRs, components of the phenylpropanoid and jasmonic acid pathways are activated. ROS accumulation and photosystem dysfunction proved to be common mechanism-of-action for these toxins. Despite similarities in defense responses, transcriptional and biochemical responses as well as symptom development occur more rapidly for ToxA compared to ToxB, which could be explained by differences in perception as well as by differences in activation of a specific process, for example, ethylene biosynthesis in ToxA treatment. Results of this study suggest that perception of HSTs will result in activation of defense responses as part of a susceptible interaction and further supports the hypothesis that necrotrophic fungi exploit defense responses in order to induce cell death.

  18. Conflicts Related to Natural Resources Exploitation: A Case Study of ...

    African Journals Online (AJOL)

    ... Study of Oil Crisis in Nigeria's Niger Delta Region and its Socio-Political and ... with oil exploration and exploitation have had adverse effects on the environment ... the confused atmosphere to unleash reign of terror on innocent citizens.

  19. Autonomous Industrial Mobile Manipulation (AIMM) - maturation, exploitation and implementation

    DEFF Research Database (Denmark)

    Hvilshøj, Mads

    This thesis introduces the Autonomous Industrial Mobile Manipulator ”Little Helper”, a robotic co-worker which extends the potential of industrial robotics by combining locomotion and manipulation capabilities. The thesis presents promising findings for industrial maturation, exploitation...

  20. 77 FR 36491 - Request for Information Regarding Senior Financial Exploitation (United States)


    ... Americans'') seeks information on consumer financial products and services, financial literacy efforts, and... From the Federal Register Online via the Government Publishing Office BUREAU OF CONSUMER FINANCIAL PROTECTION Request for Information Regarding Senior Financial Exploitation AGENCY: Bureau of Consumer...

  1. L'exploitation des cephalopodes: situation et perspectives

    National Research Council Canada - National Science Library

    Mesnil, B


    Sans attendre que soit atteint ce degre de precision, nous avons voulu aborder une etape plus elementaire en reunissant les informations relatives a l'etat actuel de l'exploitation des cephalopodes at...

  2. Matching Terminological Heterogeneous Ontologies by Exploiting Partial Alignments

    NARCIS (Netherlands)

    Schadd, Frederik Christiaan; Roos, Nico


    Matching ontologies which utilize significantly heterogeneous terminologies is a challenging task for existing matching techniques. These techniques typically exploit lexical resources in order to enrich the ontologies with additional terminology such that more terminological matches can be found.

  3. Sustainable Exploitation of Natural Resources and National Security

    National Research Council Canada - National Science Library

    Maria Constantinescu


    ... to a country’s national security and long term development. The aim of this article is to outline the links and interactions between the availability of natural resources, their sustainable exploitation...

  4. A Practical Guide for Exploiting FBCB2 Capabilities

    National Research Council Canada - National Science Library

    Leibrecht, Bruce


    ... Battle Command Brigade and Below (FBCB2). The Leader's Primer for Exploiting FBCB2 describes twenty-two major FBCB2 capabilities, the tactical significance of each capability, the digital operator and user tasks involved in employing each...

  5. Human trafficking and exploitation: A global health concern. (United States)

    Zimmerman, Cathy; Kiss, Ligia


    In this collection review, Cathy Zimmerman and colleague introduce the PLOS Medicine Collection on Human Trafficking, Exploitation and Health, laying out the magnitude of the global trafficking problem and offering a public health policy framework to guide responses to trafficking.

  6. Exploiting Elementary Landscapes for TSP, Vehicle Routing and Scheduling (United States)


    AFRL-AFOSR-VA-TR-2015-0320 EXPLOITING ELEMENTARY LANDSCAPES FOR TSP , VEHICLE ROUTING AND SCHEDULING Darrell Whitley COLORADO STATE UNIVERSITY Final...4. TITLE AND SUBTITLE Exploiting Elementary Landscapes for TSP , Vehicle Routing and Scheduling 5a. CONTRACT NUMBER 5b. GRANT NUMBER FA9550-11-1-0088...Traveling Salesman Problem ( TSP ) and Graph Coloring are elementary. Problems such as MAX-kSAT are a superposition of k elementary landscapes. This

  7. Typologie des exploitations agricoles familiales : cas de la ...

    African Journals Online (AJOL)

    La gestion durable d'une formation forestière nécessite la prise en compte des activités humaines s'exerçant aux alentours en raison de leurs impacts sur la pérennité et la qualité des produits exploités. Cette étude visait ainsi à caractériser les exploitations agricoles familiales adjacentes de la forêt de Baban rafi. Pour y.

  8. Invasion of the body snatchers: the diversity and evolution of manipulative strategies in host-parasite interactions. (United States)

    Lefèvre, Thierry; Adamo, Shelley A; Biron, David G; Missé, Dorothée; Hughes, David; Thomas, Frédéric


    Parasite-induced alteration of host behaviour is a widespread transmission strategy among pathogens. Understanding how it works is an exciting challenge from both a mechanistic and an evolutionary perspective. In this review, we use key examples to examine the proximate mechanisms by which parasites are known to control the behaviour of their hosts. Special attention is given to the recent developments of post-genomic tools, such as proteomics, for determining the genetic basis of parasitic manipulation. We then discuss two novel perspectives on host manipulation (mafia-like strategy and exploitation of host compensatory responses), arguing that parasite-manipulated behaviours could be the result of compromises between host and parasite strategies. Such compromises may occur when collaborating with the parasite is less costly for the host in terms of fitness than is resisting parasite-induced changes. Therefore, even when changes in host behaviour benefit the parasite, the host may still play some role in the switch in host behaviour. In other words, the host does not always become part of the parasite's extended phenotype. For example, parasites that alter host behaviour appear to induce widely disseminated changes in the hosts' central nervous system, as opposed to targeted attacks on specific neural circuits. In some host-parasite systems, the change in host behaviour appears to require the active participation of the host (e.g., via host immune-neural connections). Even when the change in host behaviour results in clear fitness benefits for the parasite, these behavioural changes may sometimes be produced by the host. Changes in host behaviour that decrease the fitness costs of infection could be selected for, even if these changes also benefit the parasite.

  9. Differential Recognition and Hydrolysis of Host Carbohydrate Antigens by Streptococcus pneumoniae Family 98 Glycoside Hydrolases

    Energy Technology Data Exchange (ETDEWEB)

    Higgins, M.; Whitworth, G; El Warry, N; Randriantsoa, M; Samain, E; Burke, R; Vocadlo, D; Boraston, A


    The presence of a fucose utilization operon in the Streptococcus pneumoniae genome and its established importance in virulence indicates a reliance of this bacterium on the harvesting of host fucose-containing glycans. The identities of these glycans, however, and how they are harvested is presently unknown. The biochemical and high resolution x-ray crystallographic analysis of two family 98 glycoside hydrolases (GH98s) from distinctive forms of the fucose utilization operon that originate from different S. pneumoniae strains reveal that one enzyme, the predominant type among pneumococcal isolates, has a unique endo-{beta}-galactosidase activity on the LewisY antigen. Altered active site topography in the other species of GH98 enzyme tune its endo-{beta}-galactosidase activity to the blood group A and B antigens. Despite their different specificities, these enzymes, and by extension all family 98 glycoside hydrolases, use an inverting catalytic mechanism. Many bacterial and viral pathogens exploit host carbohydrate antigens for adherence as a precursor to colonization or infection. However, this is the first evidence of bacterial endoglycosidase enzymes that are known to play a role in virulence and are specific for distinct host carbohydrate antigens. The strain-specific distribution of two distinct types of GH98 enzymes further suggests that S. pneumoniae strains may specialize to exploit host-specific antigens that vary from host to host, a factor that may feature in whether a strain is capable of colonizing a host or establishing an invasive infection.

  10. Mistletoes as parasites: Host specificity and speciation. (United States)

    Norton, D A; Carpenter, M A


    Recent research on parasite evolution has highlighted the importance of host specialization in speciation, either through host-switching or cospeciation. Many parasites show common patterns of host specificity, with higher host specificity where host abundance is high and reliable, phylogenetically conservative host specificity, and formation of races on or in different host species. Recent advances in our understanding of host specificity and speciation patterns in a variety of animal parasites provides valuable insights into the evolutionary biology of mistletoes.

  11. Oral intake of a liquid high-molecular-weight hyaluronan associated with relief of chronic pain and reduced use of pain medication: results of a randomized, placebo-controlled double-blind pilot study. (United States)

    Jensen, Gitte S; Attridge, Victoria L; Lenninger, Miki R; Benson, Kathleen F


    The goal for this study was to evaluate the effects of daily oral intake of a consumable liquid fermentate containing high-molecular-weight hyaluronan, as well as to perform a basic evaluation of safety and tolerability. A randomized, double-blind placebo-controlled study design was used to examine the effects of oral intake of hyaluronan on chronic pain conditions. Safety assessment included a complete blood count with differential, blood chemistry and electrocardiogram. The study duration was 4 weeks, where three tablespoons (45 mL) product or placebo was ingested during the first 2 weeks, and two tablespoons (30 mL) was consumed during the last 2 weeks. Seventy-eight people between the age of 19 and 71 years enrolled, and 72 people completed the study. Statistical analysis was performed using the two-tailed independent t-test for between-group significance and using the paired t-test for within-group significance. A reduction in pain scores was seen after 2 weeks of consumption of both placebo (Ppain scores was seen after 2 weeks of consumption of three tablespoons of active product (Ppain scores was seen in the placebo group. During the reduced intake for the last 2 weeks of study participation, pain scores showed a slight increase. During the last 2 weeks, a significant increase in the quality of sleep (Ppain reduction during the initial 2 weeks was associated with significant reduction in the use of pain medication (Poral liquid formula containing high-molecular-weight hyaluronan was associated with relief of chronic pain.

  12. Multitask learning for host-pathogen protein interactions. (United States)

    Kshirsagar, Meghana; Carbonell, Jaime; Klein-Seetharaman, Judith


    An important aspect of infectious disease research involves understanding the differences and commonalities in the infection mechanisms underlying various diseases. Systems biology-based approaches study infectious diseases by analyzing the interactions between the host species and the pathogen organisms. This work aims to combine the knowledge from experimental studies of host-pathogen interactions in several diseases to build stronger predictive models. Our approach is based on a formalism from machine learning called 'multitask learning', which considers the problem of building models across tasks that are related to each other. A 'task' in our scenario is the set of host-pathogen protein interactions involved in one disease. To integrate interactions from several tasks (i.e. diseases), our method exploits the similarity in the infection process across the diseases. In particular, we use the biological hypothesis that similar pathogens target the same critical biological processes in the host, in defining a common structure across the tasks. Our current work on host-pathogen protein interaction prediction focuses on human as the host, and four bacterial species as pathogens. The multitask learning technique we develop uses a task-based regularization approach. We find that the resulting optimization problem is a difference of convex (DC) functions. To optimize, we implement a Convex-Concave procedure-based algorithm. We compare our integrative approach to baseline methods that build models on a single host-pathogen protein interaction dataset. Our results show that our approach outperforms the baselines on the training data. We further analyze the protein interaction predictions generated by the models, and find some interesting insights. The predictions and code are available at:∼mkshirsa/ismb2013_paper320.html . Supplementary data are available at Bioinformatics online.

  13. Preference and performance of the hyperparasitoid Syrphophagus aphidivorus (Hymenoptera: Encyrtidae): fitness consequences of selecting hosts in live aphids or aphid mummies

    NARCIS (Netherlands)

    Buitenhuis, R.; Boivin, G.; Vet, L.E.M.; Brodeur, J.


    1. Theoretical models predict that ovipositional decisions of parasitoid females should lead to the selection of the most profitable host for parasitoid development. Most parasitoid species have evolved specific adaptations to exploit a single host stage. However, females of the aphid

  14. Parasitoids and dipteran predators exploit volatiles from microbial symbionts to locate bark beetles. (United States)

    Boone, Celia K; Six, Diana L; Zheng, Yanbing; Raffa, Kenneth F


    Host location by parasitoids and dipteran predators of bark beetles is poorly understood. Unlike coleopteran predators that locate prey by orienting to prey pheromones, wasps and flies often attack life stages not present until after pheromone production ceases. Bark beetles have important microbial symbionts, which could provide sources of cues. We tested host trees, trees colonized by beetles and symbionts, and trees colonized by symbionts alone for attractiveness to hymenopteran parasitoids and dipteran predators. Field studies were conducted with Ips pini in Montana. Three pteromalid wasps were predominant. All were associated with the second and third instars of I. pini. Heydenia unica was more attracted to logs colonized by either I. pini or the fungus Ophiostoma ips than logs alone or blank controls (screen with no log). Rhopalicus pulchripennis was more attracted to logs colonized by I. pini than logs alone or blank controls. Dibrachys cavus was attracted to logs but did not distinguish whether or not they were colonized. Two dolichopodid predators were predominant. A Medetera species was more attracted to colonized than uncolonized logs and more attracted to logs than blank controls. It was also more attracted to logs colonized with the yeast Pichia scolyti than uncolonized logs, but attraction was less consistent. An unidentified dolichopodid was more attracted to logs colonized with I. pini, O. ips, and the bacteria Burkholderia sp., than to uncolonized logs. It was also attracted to uncolonized logs. Its responses were less consistent and pronounced than H. unica. These results suggest some parasitoids and dipteran predators exploit microbial symbionts of bark beetles to locate hosts. Overall, specialists showed strong attraction to fungal cues, whereas generalists were more attracted by plant volatiles. These results also show how microbial symbionts can have conflicting effects on host fitness.

  15. [Tuberculosis in compromised hosts]. (United States)


    Recent development of tuberculosis in Japan tends to converge on a specific high risk group. The proportion of tuberculosis developing particularly from the compromised hosts in the high risk group is especially high. At this symposium, therefore, we took up diabetes mellitus, gastrectomy, dialysis, AIDS and the elderly for discussion. Many new findings and useful reports for practical medical treatment are submitted; why these compromised hosts are predisposed to tuberculosis, tuberculosis diagnostic and remedial notes of those compromised hosts etc. It is an important question for the future to study how to prevent tuberculosis from these compromised hosts. 1. Tuberculosis in diabetes mellitus: aggravation and its immunological mechanism: Kazuyoshi KAWAKAMI (Department of Internal Medicine, Division of Infectious Diseases, Graduate School and Faculty of Medicine, University of the Ryukyus). It has been well documented that diabetes mellitus (DM) is a major aggravating factor in tuberculosis. The onset of this disease is more frequent in DM patients than in individuals with any underlying diseases. However, the precise mechanism of this finding remains to be fully understood. Earlier studies reported that the migration, phagocytosis and bactericidal activity of neutrophils are all impaired in DM patients, which is related to their reduced host defense to infection with extracellular bacteria, such as S. aureus and E. colli. Host defense to mycobacterial infection is largely mediated by cellular immunity, and Th1-related cytokines, such as IFN-gamma and IL-12, play a central role in this response. It is reported that serum level of these cytokines and their production by peripheral blood mononuclear cells (PBMC) are reduced in tuberculosis patients with DM, and this is supposed to be involved in the high incidence of tuberculosis in DM. Our study observed similar findings and furthermore indicated that IFN-gamma and IL-12 production by BCG-stimulated PBMC was lower

  16. Exploitation of Full-Waveform LiDAR to Characterize / Exploit Under Canopy Targets - Foliage Penetration (FOPEN) (United States)


    specific targets, and (3) full waveform application in forestry . Exploitation of Full-waveform LiDAR to Characterize/Exploit under Canopy Targets...Foliage Penetration (FOPEN)   9    The review on current waveform processing methods, LiDAR-specific targets and forestry applications clearly indicates...proceedings of IGARSS 2012, Munich, Germany, July 23-27, 2012. Molnar, B., Laky, S., and Toth, Ch. (2011): Using Full Waveform Data in Urban Areas

  17. MATHEMATICS OF SENSING, EXPLOITATION, AND EXECUTION (MSEE) Sensing, Exploitation, and Execution (SEE) on a Foundation for Representation, Inference, and Learning (United States)


    AFRL-RY-WP-TR-2016-0127 MATHEMATICS OF SENSING, EXPLOITATION, AND EXECUTION (MSEE) Sensing, Exploitation, and Execution (SEE) on a Foundation for...MM-YY) 2. REPORT TYPE 3. DATES COVERED (From - To) July 2016 Final 26 September 2011 – 15 March 2015 4. TITLE AND SUBTITLE MATHEMATICS OF SENSING... mathematical foundation for unified representation, inference, and learning for ISR problems. The result of the project is an end-to-end system for scene and

  18. Subcellular targeting of Salmonella virulence proteins by host-mediated S-palmitoylation. (United States)

    Hicks, Stuart W; Charron, Guillaume; Hang, Howard C; Galán, Jorge E


    Several pathogenic bacteria utilize type III secretion systems (TTSS) to deliver into host cells bacterial virulence proteins with the capacity to modulate a variety of cellular pathways. Once delivered into host cells, the accurate targeting of bacterial effectors to specific locations is critical for their proper function. However, little is known about the mechanisms these virulence effectors use to reach their subcellular destination. Here we show that the Salmonella TTSS effector proteins SspH2 and SseI are localized to the plasma membrane of host cells, a process dependent on S-palmitoylation of a conserved cysteine residue within their N-terminal domains. We also show that effector protein lipidation is mediated by a specific subset of host-cell palmitoyltransferases and that lipidation is critical for effector function. This study describes a remarkable mechanism by which a pathogen exploits host-cell machinery to properly target its virulence factors. Copyright © 2011 Elsevier Inc. All rights reserved.

  19. Host Cell Nuclear Localization of Shigella flexneri Effector OspF Is Facilitated by SUMOylation. (United States)

    Jo, Kyungmin; Kim, Eun Jin; Yu, Hyun Jin; Yun, Cheol-Heui; Kim, Dong Wook


    When Shigella infect host cells, various effecter molecules are delivered into the cytoplasm of the host cell through the type III secretion system (TTSS) to facilitate their invasion process and control the host immune responses. Among these effectors, the S. flexneri effector OspF dephosphorylates mitogen-activated protein kinases and translocates itself to the nucleus, thus preventing histone H3 modification to regulate expression of proinflammatory cytokines. Despite the critical role of OspF, the mechanism by which it localizes in the nucleus has remained to be elucidated. In the present study, we identified a potential small ubiquitin-related modifier (SUMO) modification site within OspF and we demonstrated that Shigella TTSS effector OspF is conjugated with SUMO in the host cell and this modification mediates the nuclear translocation of OspF. Our results show a bacterial virulence factor can exploit host post-translational machinery to execute its intracellular trafficking.

  20. Direct exploitation of a top 500 Supercomputer for Analysis of CMS Data (United States)

    Cabrillo, I.; Cabellos, L.; Marco, J.; Fernandez, J.; Gonzalez, I.


    The Altamira Supercomputer hosted at the Instituto de Fisica de Cantatbria (IFCA) entered in operation in summer 2012. Its last generation FDR Infiniband network used (for message passing) in parallel jobs, supports the connection to General Parallel File System (GPFS) servers, enabling an efficient simultaneous processing of multiple data demanding jobs. Sharing a common GPFS system and a single LDAP-based identification with the existing Grid clusters at IFCA allows CMS researchers to exploit the large instantaneous capacity of this supercomputer to execute analysis jobs. The detailed experience describing this opportunistic use for skimming and final analysis of CMS 2012 data for a specific physics channel, resulting in an order of magnitude reduction of the waiting time, is presented.

  1. The ESA scientific exploitation element results and outlook (United States)

    Desnos, Yves-louis; Regner, Peter; Delwart, Steven; Benveniste, Jerome; Engdahl, Marcus; Donlon, Craig; Mathieu, Pierre-Philippe; Fernandez, Diego; Gascon, Ferran; Zehner, Claus; Davidson, Malcolm; Goryl, Philippe; Koetz, Benjamin; Pinnock, Simon


    The Scientific Exploitation of Operational Missions (SEOM) element of ESA's fourth Earth Observation Envelope Programme (EOEP4) prime objective is to federate, support and expand the international research community built up over the last 25 years exploiting ESA's EO missions. SEOM enables the science community to address new scientific research areas that are opened by the free and open access to data from operational EO missions. Based on community-wide recommendations, gathered through a series of international thematic workshops and scientific user consultation meetings, key research studies have been launched over the last years to further exploit data from the Sentinels ( During 2016 several Science users consultation workshops have been organized, new results from scientific studies have been published and open-source multi-mission scientific toolboxes have been distributed (SNAP 80000 users from 190 countries). In addition the first ESA Massive Open Online Courses on Climate from space have been deployed (20000 participants) and the second EO Open Science conference was organized at ESA in September 2016 bringing together young EO scientists and data scientists. The new EOEP5 Exploitation element approved in 2016 and starting in 2017 is taking stock of all precursor activities in EO Open Science and Innovation and in particular a workplan for ESA scientific exploitation activities has been presented to Member States taking full benefit of the latest information and communication technology. The results and highlights from current scientific exploitation activities will be presented and an outlook on the upcoming activities under the new EOEP5 exploitation element will be given.

  2. Cuticular Hydrocarbons of Tribolium confusum Larvae Mediate Trail Following and Host Recognition in the Ectoparasitoid Holepyris sylvanidis. (United States)

    Fürstenau, Benjamin; Hilker, Monika


    Parasitic wasps which attack insects infesting processed stored food need to locate their hosts hidden inside these products. Their host search is well-known to be guided by host kairomones, perceived via olfaction or contact. Among contact kairomones, host cuticular hydrocarbons (CHCs) may provide reliable information for a parasitoid. However, the chemistry of CHC profiles of hosts living in processed stored food products is largely unknown. Here we showed that the ectoparasitoid Holepyris sylvanidis uses CHCs of its host Tribolium confusum, a worldwide stored product pest, as kairomones for host location and recognition at short range. Chemical analysis of T. confusum larval extracts by gas chromatography coupled with mass spectrometry revealed a rich blend of long-chain (C25-C30) hydrocarbons, including n-alkanes, mono-, and dimethylalkanes. We further studied whether host larvae leave sufficient CHCs on a substrate where they walk along, thus allowing parasitoids to perceive a CHC trail and follow it to their host larvae. We detected 18 CHCs on a substrate that had been exposed to host larvae. These compounds were also found in crude extracts of host larvae and made up about a fifth of the CHC amount extracted. Behavioral assays showed that trails of host CHCs were followed by the parasitoids and reduced their searching time until successful host recognition. Host CHC trails deposited on different substrates were persistent for about a day. Hence, the parasitoid H. sylvanidis exploits CHCs of T. confusum larvae for host finding by following host CHC trails and for host recognition by direct contact with host larvae.

  3. Stennis hosts 2010 Special Olympics (United States)


    Sarah Johnson, 28, of Gulfport, carries in the Olympic torch to signal the start of the 2010 Area III Special Olympic games at NASA's John C. Stennis Space Center on March 27. Stennis volunteers hosted special needs athletes from across the area for the event. Stennis is an annual host of the games.

  4. Larval helminths in intermediate hosts

    DEFF Research Database (Denmark)

    Fredensborg, Brian Lund; Poulin, R


    Density-dependent effects on parasite fitness have been documented from adult helminths in their definitive hosts. There have, however, been no studies on the cost of sharing an intermediate host with other parasites in terms of reduced adult parasite fecundity. Even if larval parasites suffer...... a reduction in size, caused by crowding, virtually nothing is known about longer-lasting effects after transmission to the definitive host. This study is the first to use in vitro cultivation with feeding of adult trematodes to investigate how numbers of parasites in the intermediate host affect the size...... and fecundity of adult parasites. For this purpose, we examined two different infracommunities of parasites in crustacean hosts. Firstly, we used experimental infections of Maritrema novaezealandensis in the amphipod, Paracalliope novizealandiae, to investigate potential density-dependent effects in single...

  5. Expression differences in Aphidius ervi (Hymenoptera: Braconidae) females reared on different aphid host species. (United States)

    Ballesteros, Gabriel I; Gadau, Jürgen; Legeai, Fabrice; Gonzalez-Gonzalez, Angelica; Lavandero, Blas; Simon, Jean-Christophe; Figueroa, Christian C


    The molecular mechanisms that allow generalist parasitoids to exploit many, often very distinct hosts are practically unknown. The wasp Aphidius ervi, a generalist koinobiont parasitoid of aphids, was introduced from Europe into Chile in the late 1970s to control agriculturally important aphid species. A recent study showed significant differences in host preference and host acceptance (infectivity) depending on the host A. ervi were reared on. In contrast, no genetic differentiation between A. ervi populations parasitizing different aphid species and aphids of the same species reared on different host plants was found in Chile. Additionally, the same study did not find any fitness effects in A. ervi if offspring were reared on a different host as their mothers. Here, we determined the effect of aphid host species (Sitobion avenae versus Acyrthosiphon pisum reared on two different host plants alfalfa and pea) on the transcriptome of adult A. ervi females. We found a large number of differentially expressed genes (between host species: head: 2,765; body: 1,216; within the same aphid host species reared on different host plants: alfalfa versus pea: head 593; body 222). As expected, the transcriptomes from parasitoids reared on the same host species (pea aphid) but originating from different host plants (pea versus alfalfa) were more similar to each other than the transcriptomes of parasitoids reared on a different aphid host and host plant (head: 648 and 1,524 transcripts; body: 566 and 428 transcripts). We found several differentially expressed odorant binding proteins and olfactory receptor proteins in particular, when we compared parasitoids from different host species. Additionally, we found differentially expressed genes involved in neuronal growth and development as well as signaling pathways. These results point towards a significant rewiring of the transcriptome of A. ervi depending on aphid-plant complex where parasitoids develop, even if different biotypes

  6. Biophysical and biological characterization of a new line of hyaluronan-based dermal fillers: A scientific rationale to specific clinical indications. (United States)

    La Gatta, Annalisa; De Rosa, Mario; Frezza, Maria Assunta; Catalano, Claudia; Meloni, Marisa; Schiraldi, Chiara


    Chemico-physical and biological characterization of hyaluronan-based dermal fillers is of key importance to differentiate between numerous available products and to optimize their use. These studies on fillers are nowadays perceived as a reliable approach to predict their performance in vivo. The object of this paper is a recent line of hyaluronic acid (HA)-based dermal fillers, Aliaxin®, available in different formulations that claim a complete facial restoration. The aim of the study is to provide biophysical and biological data that may support the clinical indications and allow to predict performance possibly with respect to similar available products. Aliaxin® formulations were tested for their content in soluble HA, water uptake capacity, rheological behavior, stability to enzymatic degradation, and for in vitro capacity to stimulate extracellular matrix components production. The formulations were found to contain a low amount of soluble HA and were equivalent to each other regarding insoluble hydrogel concentration. The different crosslinking degree declared by the producer was consistent with the trend in water uptake capacity, rigidity, viscosity. No significant differences in stability to enzymatic hydrolysis were found. In vitro experiments, using a full thickness skin model, showed an increase in collagen production in the dermoepidermal junction. Results support the claims of different clinical indications, the classification of products regarding hydro-, lift-action and the specifically suggested needle gauge for the delivery. The biological outcomes also support products effectiveness in skin structure restoration. These data predicted a better performance regarding hydro-action, tissue integration, clinical management during delivery, and a high durability of the aesthetic effect when compared to data on marketed similar products. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  7. Hyaluronan incorporation into model contact lens hydrogels as a built-in lubricant: Effect of hydrogel composition and proteoglycan 4 as a lubricant in solution. (United States)

    Samsom, Michael; Korogiannaki, Myrto; Subbaraman, Lakshman N; Sheardown, Heather; Schmidt, Tannin A


    Contact lens friction significantly correlates with subjective comfort. Hyaluronan (HA) and proteoglycan 4 (PRG4) are natural boundary lubricants present in the body. The objective of this study was to assess the effect of crosslinked HA into the bulk of model contact lens materials pHEMA, pHEMA/TRIS, and DMAA/TRIS on surface wettability, protein sorption, and boundary lubricating properties at a material-cornea biointerface, both alone and synergistically with PRG4 in solution. Surface wettability was assessed by water contact angle measurement, protein sorption by lysozyme sorption assay, and boundary lubricating properties using an in vitro friction test method. HA incorporation (HAinc ) increased the surface wettability of all materials, and reduced protein sorption for pHEMA and DMAA/TRIS. HAinc increased friction for pHEMA, and DMAA/TRIS, whereas a decrease was observed for pHEMA/TRIS. A combination of HAinc and PRG4sol had a synergistic effect of reducing friction only for pHEMA/TRIS. This combination had similar friction reduction compared with PRG4sol alone for DMAA/TRIS. These results indicate HA incorporation could be an effective internal wetting agent, antiadhesive, and boundary lubricant for pHEMA/TRIS silicone hydrogels. In conclusion, HA incorporation can reduce friction of hydrogels alone and in combination with PRG4 in solution, though in a hydrogel composition-dependent (e.g., TRIS) manner. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2017. © 2017 Wiley Periodicals, Inc.

  8. Chondroitin sulfate and sulfated hyaluronan-containing collagen coatings of titanium implants influence peri-implant bone formation in a minipig model. (United States)

    Korn, P; Schulz, M C; Hintze, V; Range, U; Mai, R; Eckelt, U; Schnabelrauch, M; Möller, S; Becher, J; Scharnweber, D; Stadlinger, B


    An improved osseous integration of dental implants in patients with lower bone quality is of particular interest. The aim of this study was to evaluate the effect of artificial extracellular matrix implant coatings on early bone formation. The coatings contained collagen (coll) in conjunction with either chondroitin sulfate (CS) or sulfated hyaluronan (sHya). Thirty-six screw-type, grit-blasted, and acid-etched titanium implants were inserted in the mandible of 6 minipigs. Three surface states were tested: (1) uncoated control (2) coll/CS (3) coll/sHya. After healing periods of 4 and 8 weeks, bone implant contact (BIC), bone volume density (BVD) as well as osteoid related parameters were measured. After 4 weeks, control implants showed a BIC of 44% which was comparable to coll/CS coated implants (48%) and significantly higher compared to coll/sHya coatings (37%, p = 0.012). This difference leveled out after 8 weeks. No significant differences could be detected for BVD values after 4 weeks and all surfaces showed reduced BVD values after 8 weeks. However, at that time, BVD around both, coll/CS (30%, p = 0.029), and coll/sHya (32%, p = 0.015), coatings was significantly higher compared to controls (22%). The osteoid implant contact (OIC) showed no significant differences after 4 weeks. After 8 weeks OIC for controls was comparable to coll/CS, the latter being significantly higher compared to coll/sHya (0.9% vs. 0.4%, p = 0.012). There were no significant differences in osteoid volume density. In summary, implant surface coatings by the chosen organic components of the extracellular matrix showed a certain potential to influence osseointegration in vivo. © 2013 Wiley Periodicals, Inc.

  9. Regeneration of dentin-pulp complex with cementum and periodontal ligament formation using dental bud cells in gelatin-chondroitin-hyaluronan tri-copolymer scaffold in swine. (United States)

    Kuo, Tzong-Fu; Huang, An-Ting; Chang, Hao-Hueng; Lin, Feng-Huei; Chen, San-Tai; Chen, Rung-Shu; Chou, Cheng-Hung; Lin, Hsin-Chi; Chiang, Han; Chen, Min-Huey


    The purpose of this study is to use a tissue engineering approach for tooth regeneration. The swine dental bud cells (DBCs) were isolated from the developing mandibular teeth, expanded in vitro, and cultured onto cylinder scaffold gelatin-chrondroitin-hyaluronan-tri-copolymer (GCHT). After culturing in vitro, the DBCs/GCHT scaffold was autografted back into the original alveolar socket. Hematoxylin and eosin (H&E) staining combined with immunohistochemical staining were applied for identification of regenerated tooth structure. After 36-week post-transplantation, tooth-like structures, including well-organized dentin-pulp complex, cementum, and periodontal ligament, were evident in situ in two of six experimental animals. The size of the tooth structure (1 x 0.5 x 0.5 cm(3) and 0.5 x 0.5 x 0.5 cm(3) size) appeared to be dictated by the size of the GCHT scaffold (1 x 1 x 1.5 cm(3)). The third swine was demonstrated with irregular dentin-bony like calcified tissue about 1 cm in diameter without organized tooth or periodontal ligament formation. The other three swine in the experimental group showed normal bone formation and no tooth regeneration in the transplantation sites. The successful rate of tooth regeneration from DBCs/GCHT scaffolds' was about 33.3%. In the control group, three swine's molar teeth buds were removed without DBCs/GCHT implantation, the other three swine received GCHT scaffold implants without DBCs. After evaluation, no regenerated tooth was found in the transplantation site of the control group. The current results using DBSs/GCHT scaffold autotransplantation suggest a technical breakthrough for tooth regeneration.

  10. Targeting gallbladder cancer: oncolytic virotherapy with myxoma virus is enhanced by rapamycin in vitro and further improved by hyaluronan in vivo. (United States)

    Weng, Mingzhe; Gong, Wei; Ma, Mingzhe; Chu, Bingfeng; Qin, Yiyu; Zhang, Mingdi; Lun, Xueqing; McFadden, Grant; Forsyth, Peter; Yang, Yong; Quan, Zhiwei


    Gallbladder carcinoma (GBC) is highly lethal, and effective treatment will require synergistic anti-tumor management. The study is aimed at investigating the oncolytic value of myxoma virus (MYXV) infection against GBC and optimizing MYXV oncolytic efficiency. We examined the permissiveness of GBC cell lines to MYXV infection and compared the effects of MYXV on cell viability among GBC and control permissive glioma cells in vitro and in vivo after MYXV + rapamycin (Rap) treatment, which is known to enhance cell permissiveness to MYXV by upregulating p-Akt levels. We also assessed MYXV + hyaluronan (HA) therapy efficiency by examinating Akt activation status, MMP-9 expression, cell viability, and collagen distribution. We further compared hydraulic conductivity, tumor area, and survival of tumor-bearing mice between the MYXV + Rap and MYXV + HA therapeutic regimens. MYXV + Rap treatment could considerably increase the oncolytic ability of MYXV against GBC cell lines in vitro but not against GBC xenografts in vivo. We found higher levels of collagen IV in GBC tumors than in glioma tumors. Diffusion analysis demonstrated that collagen IV could physically hinder MYXV intratumoral distribution. HA-CD44 interplay was found to activate the Akt signaling pathway, which increases oncolytic rates. HA was also found to enhance the MMP-9 secretion, which contributes to collagen IV degradation. Unlike MYXV + Rap, MYXV + HA therapy significantly enhanced the anti-tumor effects of MYXV in vivo and prolonged survival of GBC tumor-bearing mice. HA may optimize the oncolytic effects of MYXV on GBC via the HA-CD44 interaction which can promote viral infection and diffusion.

  11. Exploitation and Utilization of Oilfield Geothermal Resources in China

    Directory of Open Access Journals (Sweden)

    Shejiao Wang


    Full Text Available Geothermal energy is a clean, green renewable resource, which can be utilized for power generation, heating, cooling, and could effectively replace oil, gas, and coal. In recent years, oil companies have put more efforts into exploiting and utilizing geothermal energy with advanced technologies for heat-tracing oil gathering and transportation, central heating, etc., which has not only reduced resource waste, but also improved large-scale and industrial resource utilization levels, and has achieved remarkable economic and social benefits. Based on the analysis of oilfield geothermal energy development status, resource potential, and exploitation and utilization modes, the advantages and disadvantages of harnessing oilfield geothermal resource have been discussed. Oilfield geothermal energy exploitation and utilization have advantages in resources, technical personnel, technology, and a large number of abandoned wells that could be reconstructed and utilized. Due to the high heat demand in oilfields, geothermal energy exploitation and utilization can effectively replace oil, gas, coal, and other fossil fuels, and has bright prospects. The key factors limiting oilfield geothermal energy exploitation and utilization are also pointed out in this paper, including immature technologies, lack of overall planning, lack of standards in resource assessment, and economic assessment, lack of incentive policies, etc.

  12. Covariance in species diversity and facilitation among non-interactive parasite taxa: all against the host. (United States)

    Krasnov, B R; Mouillot, D; Khokhlova, I S; Shenbrot, G I; Poulin, R


    Different parasite taxa exploit different host resources and are often unlikely to interact directly. It is unclear, however, whether the diversity of any given parasite taxon is indirectly influenced by that of other parasite taxa on the same host. Some components of host immune defences may operate simultaneously against all kinds of parasites, whereas investment by the host in specific defences against one type of parasite may come at the expense of defence against other parasites. We investigated the relationships between the species diversity of 4 higher taxa of ectoparasites (fleas, sucking lice, mesostigmatid mites, and ixodid ticks), and between the species richness of ectoparasites and endoparasitic helminths, across different species of rodent hosts. Our analyses used 2 measures of species diversity, species richness and taxonomic distinctness, and controlled for the potentially confounding effects of sampling effort and phylogenetic relationships among host species. We found positive pairwise correlations between the species richness of fleas, mites and ticks; however, there was no association between species richness of any of these 3 groups and that of lice. We also found a strong positive relationship between the taxonomic distinctness of ecto- and endoparasite assemblages across host species. These results suggest the existence of a process of apparent facilitation among unrelated taxa in the organization of parasite communities. We propose explanations based on host immune responses, involving acquired cross-resistance to infection and interspecific variation in immunocompetence among hosts, to account for these patterns.

  13. Experimental Simulation of the Exploitation of Natural Gas Hydrate

    Directory of Open Access Journals (Sweden)

    Chang-Yu Sun


    Full Text Available Natural gas hydrates are cage-like crystalline compounds in which a large amount of methane is trapped within a crystal structure of water, forming solids at low temperature and high pressure. Natural gas hydrates are widely distributed in permafrost regions and offshore. It is estimated that the worldwide amounts of methane bound in gas hydrates are total twice the amount of carbon to be found in all known fossil fuels on earth. A proper understanding of the relevant exploitation technologies is then important for natural gas production applications. In this paper, the recent advances on the experimental simulation of natural gas hydrate exploitation using the major hydrate production technologies are summarized. In addition, the current situation of the industrial exploitation of natural gas hydrate is introduced, which are expected to be useful for establishing more safe and efficient gas production technologies.

  14. The exploitation of swamp plants for dewatering liquid sewage sludge

    Directory of Open Access Journals (Sweden)

    Jiří Šálek


    Full Text Available The operators of little rural wastewater treatment plants have been interested in economic exploitation of sewage sludge in local conditions. The chance is searching simply and natural ways of processing and exploitation stabilized sewage sludge in agriculture. Manure substrate have been obtained by composting waterless sewage sludge including rest plant biomass after closing 6–8 years period of filling liquid sewage sludge to the basin. Main attention was focused on exploitation of swamp plants for dewatering liquid sewage sludge and determination of influence sewage sludge on plants, intensity and course of evapotranspiration and design and setting of drying beds. On the base of determined ability of swamp plants evapotranspiration were edited suggestion solutions of design and operation sludge bed facilities in the conditions of small rural wastewater treatment plant.

  15. Host entry by gamma-herpesviruses--lessons from animal viruses? (United States)

    Gillet, Laurent; Frederico, Bruno; Stevenson, Philip G


    The oncogenicity of gamma-herpesviruses (γHVs) motivates efforts to control them and their persistence makes early events key targets for intervention. Human γHVs are often assumed to enter naive hosts orally and infect B cells directly. However, neither assumption is supported by direct evidence, and vaccination with the Epstein-Barr virus (EBV) gp350, to block virion binding to B cells, failed to reduce infection rates. Thus, there is a need to re-evaluate assumptions about γHV host entry. Given the difficulty of analysing early human infections, potentially much can be learned from animal models. Genomic comparisons argue that γHVs colonized mammals long before humans speciation, and so that human γHVs are unlikely to differ dramatically in behaviour from those of other mammals. Murid Herpesvirus-4 (MuHV-4), which like EBV and the Kaposi's Sarcoma-associated Herpesvirus (KSHV) persists in memory B cells, enters new hosts via olfactory neurons and exploits myeloid cells to spread. Integrating these data with existing knowledge of human and veterinary γHVs suggests a new model of host entry, with potentially important implications for infection control. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Interactions of Candida albicans with host epithelial surfaces

    Directory of Open Access Journals (Sweden)

    David W. Williams


    Full Text Available Candida albicans is an opportunistic, fungal pathogen of humans that frequently causes superficial infections of oral and vaginal mucosal surfaces of debilitated and susceptible individuals. The organism is however, commonly encountered as a commensal in healthy individuals where it is a component of the normal microflora. The key determinant in the type of relationship that Candida has with its host is how it interacts with the epithelial surface it colonises. A delicate balance clearly exists between the potentially damaging effects of Candida virulence factors and the nature of the immune response elicited by the host. Frequently, it is changes in host factors that lead to Candida seemingly changing from a commensal to pathogenic existence. However, given the often reported heterogeneity in morphological and biochemical factors that exist between Candida species and indeed strains of C. albicans, it may also be the fact that colonising strains differ in the way they exploit resources to allow persistence at mucosal surfaces and as a consequence this too may affect the way Candida interacts with epithelial cells. The aim of this review is to provide an overview of some of the possible interactions that may occur between C. albicans and host epithelial surfaces that may in turn dictate whether Candida removal, its commensal persistence or infection follows.

  17. Towards host-to-host meeting scheduling negotiation

    Directory of Open Access Journals (Sweden)

    Rani Megasari


    Full Text Available This paper presents a different scheme of meeting scheduling negotiation among a large number of personnel in a heterogeneous community. This scheme, named Host-to-Host Negotiation, attempts to produce a stable schedule under uncertain personnel preferences. By collecting information from hosts’ inter organizational meeting, this study intends to guarantee personnel availability. As a consequence, personnel’s and meeting’s profile in this scheme are stored in a centralized manner. This study considers personnel preferences by adapting the Clarke Tax Mechanism, which is categorized as a non manipulated mechanism design. Finally, this paper introduces negotiation strategies based on the conflict handling mode. A host-to-host scheme can give notification if any conflict exist and lead to negotiation process with acceptable disclosed information. Nevertheless, a complete negotiation process will be more elaborated in the future works.

  18. Final Report, “Exploiting Global View for Resilience”

    Energy Technology Data Exchange (ETDEWEB)

    Chien, Andrew [Univ. of Chicago, IL (United States)


    Final technical report for the "Exploiting Global View for Resilience" project. The GVR project aims to create a new approach to portable, resilient applications. The GVR approach builds on a global view data model,, adding versioning (multi-version), user control of timing and rate (multi-stream), and flexible cross layer error signalling and recovery. With a versioned array as a portable abstraction, GVR enables application programmers to exploit deep scientific and application code insights to manage resilience (and its overhead) in a flexible, portable fashion.

  19. The human traffickers and exploitation of children and young adults.

    Directory of Open Access Journals (Sweden)

    Sara Scala


    Full Text Available The article focuses on the traffic of children, who are kidnapped, cheated and purchased by their families to be exploited in many ways. These victims have severe mental and physical traumas. Many of them, slaves of their exploiters, remain invisible and live their lifes without fundamental rights and without any kind of support or help. The traffic in human beings is a new kind of slavery, which acts in the dark, is criminal and involves different subjects of different ages, different nationalities and generations. The traffic in human beings is managed by transnational criminal organizations and is a disturbing and growing phenomena around the world.


    Directory of Open Access Journals (Sweden)

    Biljana Kovačević-Zelić


    Full Text Available Underground exploitation of dimension stone is spreading lately for three main reasons; economy, organisation and environment. Moreover, underground openings can be used for many purposes. Underground exploitation is different from surface quarrying only in the first stage, the removal of top slice, descending slices are worked as in conventional quarries. In underground stone quarries, stability problems require adequate studies in order to avoid expensive artificial support measures, The article presents numerical analyses of an underground stone quarry made using of the finite difference code FLAC (the paper is published in Croatian.

  1. The Hegemony Handbook: Exploiting the Space between War and Peace (United States)


    I N S T I T U T E F O R D E F E N S E A N A L Y S E S The Hegemony Handbook: Exploiting the Space between War and Peace Prashant R. Patel...Jun 2013]. The Hegemony Handbook: Exploiting the Space between War and Peace Prashant R. Patel, Project Leader David A. Sparrow I N S T I T U T E F O...making us appear weak and ineffective because we cannot stop these short-of- war actions. The A2AD systems increase the risk to our conventional forces

  2. Exploiting Thread Parallelism for Ocean Modeling on Cray XC Supercomputers

    Energy Technology Data Exchange (ETDEWEB)

    Sarje, Abhinav [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Jacobsen, Douglas W. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Williams, Samuel W. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Ringler, Todd [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Oliker, Leonid [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)


    The incorporation of increasing core counts in modern processors used to build state-of-the-art supercomputers is driving application development towards exploitation of thread parallelism, in addition to distributed memory parallelism, with the goal of delivering efficient high-performance codes. In this work we describe the exploitation of threading and our experiences with it with respect to a real-world ocean modeling application code, MPAS-Ocean. We present detailed performance analysis and comparisons of various approaches and configurations for threading on the Cray XC series supercomputers.

  3. How a retrotransposon exploits the plant's heat stress response for its activation.

    Directory of Open Access Journals (Sweden)

    Vladimir V Cavrak


    Full Text Available Retrotransposons are major components of plant and animal genomes. They amplify by reverse transcription and reintegration into the host genome but their activity is usually epigenetically silenced. In plants, genomic copies of retrotransposons are typically associated with repressive chromatin modifications installed and maintained by RNA-directed DNA methylation. To escape this tight control, retrotransposons employ various strategies to avoid epigenetic silencing. Here we describe the mechanism developed by ONSEN, an LTR-copia type retrotransposon in Arabidopsis thaliana. ONSEN has acquired a heat-responsive element recognized by plant-derived heat stress defense factors, resulting in transcription and production of full length extrachromosomal DNA under elevated temperatures. Further, the ONSEN promoter is free of CG and CHG sites, and the reduction of DNA methylation at the CHH sites is not sufficient to activate the element. Since dividing cells have a more pronounced heat response, the extrachromosomal ONSEN DNA, capable of reintegrating into the genome, accumulates preferentially in the meristematic tissue of the shoot. The recruitment of a major plant heat shock transcription factor in periods of heat stress exploits the plant's heat stress response to achieve the transposon's activation, making it impossible for the host to respond appropriately to stress without losing control over the invader.

  4. How a retrotransposon exploits the plant's heat stress response for its activation. (United States)

    Cavrak, Vladimir V; Lettner, Nicole; Jamge, Suraj; Kosarewicz, Agata; Bayer, Laura Maria; Mittelsten Scheid, Ortrun


    Retrotransposons are major components of plant and animal genomes. They amplify by reverse transcription and reintegration into the host genome but their activity is usually epigenetically silenced. In plants, genomic copies of retrotransposons are typically associated with repressive chromatin modifications installed and maintained by RNA-directed DNA methylation. To escape this tight control, retrotransposons employ various strategies to avoid epigenetic silencing. Here we describe the mechanism developed by ONSEN, an LTR-copia type retrotransposon in Arabidopsis thaliana. ONSEN has acquired a heat-responsive element recognized by plant-derived heat stress defense factors, resulting in transcription and production of full length extrachromosomal DNA under elevated temperatures. Further, the ONSEN promoter is free of CG and CHG sites, and the reduction of DNA methylation at the CHH sites is not sufficient to activate the element. Since dividing cells have a more pronounced heat response, the extrachromosomal ONSEN DNA, capable of reintegrating into the genome, accumulates preferentially in the meristematic tissue of the shoot. The recruitment of a major plant heat shock transcription factor in periods of heat stress exploits the plant's heat stress response to achieve the transposon's activation, making it impossible for the host to respond appropriately to stress without losing control over the invader.

  5. Efficacy of intra-articular hyaluronan (Synvisc® for the treatment of osteoarthritis affecting the first metatarsophalangeal joint of the foot (hallux limitus: study protocol for a randomised placebo controlled trial

    Directory of Open Access Journals (Sweden)

    Landorf Karl B


    Full Text Available Abstract Background Osteoarthritis of the first metatarsophalangeal joint (MPJ of the foot, termed hallux limitus, is common and painful. Numerous non-surgical interventions have been proposed for this disorder, however there is limited evidence for their efficacy. Intra-articular injections of hyaluronan have shown beneficial effects in case-series and clinical trials for the treatment of osteoarthritis of the first metatarsophalangeal joint. However, no study has evaluated the efficacy of this form of treatment using a randomised placebo controlled trial. This article describes the design of a randomised placebo controlled trial to evaluate the efficacy of intra-articular hyaluronan (Synvisc® to reduce pain and improve function in people with hallux limitus. Methods One hundred and fifty community-dwelling men and women aged 18 years and over with hallux limitus (who satisfy inclusion and exclusion criteria will be recruited. Participants will be randomised, using a computer-generated random number sequence, to receive a single intra-articular injection of up to 1 ml hyaluronan (Synvisc® or sterile saline (placebo into the first MPJ. The injections will be performed by an interventional radiologist using fluoroscopy to ensure accurate deposition of the hyaluronan in the joint. Participants will be given the option of a second and final intra-articular injection (of Synvisc® or sterile saline according to the treatment group they are in either 1 or 3 months post-treatment if there is no improvement in pain and the participant has not experienced severe adverse effects after the first injection. The primary outcome measures will be the pain and function subscales of the Foot Health Status Questionnaire. The secondary outcome measures will be pain at the first MPJ (during walking and at rest, stiffness at the first MPJ, passive non-weightbearing dorsiflexion of the first MPJ, plantar flexion strength of the toe-flexors of the hallux, global

  6. From Exploitation to Industry: Definitions, Risks, and Consequences of Domestic Sexual Exploitation and Sex Work Among Women and Girls (United States)

    Gerassi, Lara


    In the last 15 years, terms such as prostitution, sex trafficking, sexual exploitation, modern-day slavery, and sex work have elicited much confusion and debate as to their definitions. Consequently several challenges have emerged for both law enforcement in the prosecution of criminals and practitioners in service provision. This article reviews the state of the literature with regard to domestic, sexual exploitation among women and girls in the United States and seeks to (1) provide definitions and describe the complexity of all terms relating to domestic sexual exploitation of women and girls in the United States, (2) explore available national prevalence data according to the definitions provided, and (3) review the evidence of mental health, social, and structural risk factors at the micro-, mezzo-, and macrolevels. PMID:26726289

  7. Mistletoe ecophysiology: Host-parasite interactions (United States)

    G. Glatzel; B. W. Geils


    Mistletoes are highly specialized perennial flowering plants adapted to parasitic life on aerial parts of their hosts. In our discussion on the physiological interactions between parasite and host, we focus on water relations, mineral nutrition, and the effect of host vigour. When host photosynthesis is greatest, the xylem water potential of the host is most negative....

  8. Impact of host nutritional status on infection dynamics and parasite virulence in a bird-malaria system. (United States)

    Cornet, Stéphane; Bichet, Coraline; Larcombe, Stephen; Faivre, Bruno; Sorci, Gabriele


    Host resources can drive the optimal parasite exploitation strategy by offering a good or a poor environment to pathogens. Hosts living in resource-rich habitats might offer a favourable environment to developing parasites because they provide a wealth of resources. However, hosts living in resource-rich habitats might afford a higher investment into costly immune defences providing an effective barrier against infection. Understanding how parasites can adapt to hosts living in habitats of different quality is a major challenge in the light of the current human-driven environmental changes. We studied the role of nutritional resources as a source of phenotypic variation in host exploitation by the avian malaria parasite Plasmodium relictum. We investigated how the nutritional status of birds altered parasite within-host dynamics and virulence, and how the interaction between past and current environments experienced by the parasite accounts for the variation in the infection dynamics. Experimentally infected canaries were allocated to control or supplemented diets. Plasmodium parasites experiencing the two different environments were subsequently transmitted in a full-factorial design to new hosts reared under similar control or supplemented diets. Food supplementation was effective since supplemented hosts gained body mass during a 15-day period that preceded the infection. Host nutrition had strong effects on infection dynamics and parasite virulence. Overall, parasites were more successful in control nonsupplemented birds, reaching larger population sizes and producing more sexual (transmissible) stages. However, supplemented hosts paid a higher cost of infection, and when keeping parasitaemia constant, they had lower haematocrit than control hosts. Parasites grown on control hosts were better able to exploit the subsequent hosts since they reached higher parasitaemia than parasites originating from supplemented hosts. They were also more virulent since they

  9. Environmental impact assessment of bitumen exploitation on animal ...

    African Journals Online (AJOL)

    This study was carried out to assess the environmental impact of Bitumen exploitation on wildlife resources in Ode-Irele forest area of Ondo-State, Nigeria. The result of the study showed that there are 9 orders and 40 species of mammals in the study area. Primates recorded the highest specie number (13,) and rodentia as ...

  10. Assisting children born of sexual exploitation and abuse

    Directory of Open Access Journals (Sweden)

    Lauren Rumble


    Full Text Available The UN Secretary-General has issued a strategy tosupport victims of sexual exploitation and abuse by UNstaff. It includes a controversial proposal to introduceDNA sampling for all UN staff. Unless this suggestionis adopted, an important opportunity to implementa truly survivor-centred approach may be lost.

  11. Exporting DNA – striking a balance between preventing exploitation ...

    African Journals Online (AJOL)

    Three important points that complement the above need to be considered: (i) the details in the MTA must reflect what is stipulated in the informed consent ... they not only contain information that may be of importance from ... And how can we achieve a balance between preventing exploitation and promoting innovation?

  12. Exploitation of Bush Mango ( Irvingia wombolu and Irvingia ...

    African Journals Online (AJOL)

    The study was undertaken to assess the exploitation of Bush Mango Irvingia gabonensis and Irvingia wombolu (ogbono) among rural households in Enugu State, Nigeria. Interview schedule was used to collect data from 91 respondents and data were analyzed by use of descriptive statistics and factor analysis. The mean ...

  13. Fishery benefits from exploiting spawning aggregations not solely ...

    African Journals Online (AJOL)

    The vulnerability of spawning aggregations to exploitation varies among fisheries as a result of differences in the population-density changes associated with this behaviour. However, vulnerability to fishing is also influenced by technology, environmental factors, and fish and fisher behaviours. Focusing on a fishery for the ...

  14. Exploiting wild relatives of S. lycopersicum for quality traits

    NARCIS (Netherlands)

    Víquez Zamora, A.M.


    Exploiting wild relatives of S. lycopersicum for quality traits Ana Marcela Víquez Zamora Tomatoes are consumed worldwide and became a model for crop plant research. A part of the research aims at expanding genetic diversity in tomato; this can be done by incorporating

  15. Six scenarios of exploiting an ontology based, mobilized learning environment

    NARCIS (Netherlands)

    Kismihók, G.; Szabó, I.; Vas, R.


    In this article, six different exploitation possibilities of an educational ontology based, mobilized learning management system are presented. The focal point of this system is the educational ontology model. The first version of this educational ontology model serves as a foundation for curriculum

  16. Exploiting network redundancy for low-cost neural network realizations.

    NARCIS (Netherlands)

    Keegstra, H; Jansen, WJ; Nijhuis, JAG; Spaanenburg, L; Stevens, H; Udding, JT


    A method is presented to optimize a trained neural network for physical realization styles. Target architectures are embedded microcontrollers or standard cell based ASIC designs. The approach exploits the redundancy in the network, required for successful training, to replace the synaptic weighting

  17. Software defined radio receivers exploiting noise cancelling: A tutorial review

    NARCIS (Netherlands)

    Klumperink, Eric A.M.; Nauta, Bram


    Traditional radio receivers were narrowband and dedicated to a single frequency band exploiting LC tanks, whereas software defined radios target a flexibly programmable frequency. The broadband noise cancelling circuit technique has proven useful to achieve this target, as it breaks the traditional

  18. Spatial dynamics of fuel wood exploitation in Delta State, Nigeria ...

    African Journals Online (AJOL)

    This study examined the spatial and temporal changes in fuel wood exploitation as a result of environmental degradation, between 2008 and 2013 in Delta State, Nigeria. It utilised data from both primary and secondary sources. Primary data were obtained from a survey of selected settlements using a questionnaire.

  19. Exploiting Policies in an Open Infrastructure for Lifelong Learning

    NARCIS (Netherlands)

    De Coi, Juri L.; Koesling, Arne; Kärger, Philipp; Olmedilla, Daniel


    De Coi, J. L., Kösling, A., Kärger, P., Olmedilla, D., (2007) Exploiting Policies in an Open Infrastructure for Lifelong Learning. In Duval, E., Klamma, R. and Wolpers, M. (Eds.), Second European Conference on Technology Enhanced Learning, Lecture Notes in Computer Science, 4753, pp.26-40.

  20. Traditional exploitation of edible freshwater oyster Etheria elliptica ...

    African Journals Online (AJOL)

    Finally, oyster`s shell, a main substrate for larval settlement and bed restoration, were left on riverbanks after exploitation, reducing stocks reconstitution potential. Appropriate measures were suggested to Reserve staff for sustainable management. Keywords: Freshwater mollusk, harvesting activities, human pressure, ...

  1. Key points in biotechnological patents to be exploited. (United States)

    García, Alfredo Mateos; López-Moya, José Rafael; Ramos, Patricia


    Patents in some biotechnological fields are controversial. Despite this fact, the number of patent applications increases every year. Total revenues in the global biotechnology market are expected to increase in the middle term. Nowadays, the bioeconomy is an important socio-economic area, which is reflected in the number of firms dedicated to or using biotechnology. The exploitation of biotechnological patents is an essential task in the management of intellectual capital. This paper explains the multiplicity of factors that influence the exploitation of biotechnological patents; specifically, the internal and external key points of patents exploitation. The external determining factors for patents are: (i) the market need for biotechnological products and services, (ii) the importance of the freedom to operate analysis before entering the market, and (iii) efficiency in prosecution by Patent Offices. This paper primarily focuses on the internal determining factors, more particularly, the characteristics that the patent's owner must take into consideration in order to have a strong, broad subject-matter in the granted patent. The experimentation needed to obtain an adequate scope of the subject- matter in the claims is a critical issue in the exploitation of a patent or patent application.

  2. Evaluating Maximum Wind Energy Exploitation in Active Distribution Networks

    DEFF Research Database (Denmark)

    Siano, Pierluigi; Chen, Peiyuan; Chen, Zhe


    The increased spreading of distributed and renewable generation requires moving towards active management of distribution networks. In this paper, in order to evaluate maximum wind energy exploitation in active distribution networks, a method based on a multi-period optimal power flow (OPF...

  3. Confirmatory Factor Analysis of Perceived Exploitation of College Athletes Questionnaire (United States)

    Van Rheenen, Derek; Atwood, Jason R.


    The exploitation of college athletes has been a topic of controversy within American higher education for over half of a century. Especially in the revenue-generating sports of men's basketball and football, critics have highlighted the surplus gains expropriated by colleges and universities on the backs of these young men, who are…

  4. Exploring, exploiting and evolving diversity of aquatic ecosystem models

    NARCIS (Netherlands)

    Janssen, A.B.G.; Arhonditsis, G.B.; Beusen, Arthur; Bolding, Karsten; Bruce, Louise; Bruggeman, Jorn; Couture, Raoul Marie; Downing, Andrea S.; Alex Elliott, J.; Frassl, M.A.; Gal, Gideon; Gerla, Daan J.; Hipsey, M.R.; Hu, Fenjuan; Ives, S.C.; Janse, J.H.; Jeppesen, Erik; Jöhnk, K.D.; Kneis, David; Kong, Xiangzhen; Kuiper, J.J.; Lehmann, M.K.; Lemmen, Carsten; Özkundakci, Deniz; Petzoldt, Thomas; Rinke, Karsten; Robson, B.J.; Sachse, René; Schep, S.A.; Schmid, Martin; Scholten, Huub; Teurlincx, Sven; Trolle, Dennis; Troost, T.A.; Dam, Van A.A.; Gerven, Van L.P.A.; Weijerman, Mariska; Wells, S.A.; Mooij, W.M.


    Here, we present a community perspective on how to explore, exploit and evolve the diversity in aquatic ecosystem models. These models play an important role in understanding the functioning of aquatic ecosystems, filling in observation gaps and developing effective strategies for water quality

  5. Efficient Depth Map Compression Exploiting Segmented Color Data

    DEFF Research Database (Denmark)

    Milani, Simone; Zanuttigh, Pietro; Zamarin, Marco


    performances is still an open research issue. This paper presents a novel compression scheme that exploits a segmentation of the color data to predict the shape of the different surfaces in the depth map. Then each segment is approximated with a parameterized plane. In case the approximation is sufficiently...

  6. Rural Fuelwood Exploitation in Mbo Local Government Area – A ...

    African Journals Online (AJOL)

    Rural Fuelwood Exploitation in Mbo Local Government Area – A Nigerian Coastal Settlement. ... Ethiopian Journal of Environmental Studies and Management ... Result show that 90% of the total local energy requirement is from fuelwood, the average per capita production rate of fuelwood in the local area is 0.38m3 and the ...

  7. Sexual exploitation and abuse by UN peacekeepers: the ...

    African Journals Online (AJOL)

    United Nations peacekeepers have been subject to allegations of serious sexual misconduct for many years. Such incidents of sexual assault perpetrated by peacekeepers have been documented over the years in a number of countries. The violation of codes of conduct, particularly regarding sexual exploitation and abuse, ...

  8. Risk assessment by dynamic representation of vulnerability, exploitation, and impact (United States)

    Cam, Hasan


    Assessing and quantifying cyber risk accurately in real-time is essential to providing security and mission assurance in any system and network. This paper presents a modeling and dynamic analysis approach to assessing cyber risk of a network in real-time by representing dynamically its vulnerabilities, exploitations, and impact using integrated Bayesian network and Markov models. Given the set of vulnerabilities detected by a vulnerability scanner in a network, this paper addresses how its risk can be assessed by estimating in real-time the exploit likelihood and impact of vulnerability exploitation on the network, based on real-time observations and measurements over the network. The dynamic representation of the network in terms of its vulnerabilities, sensor measurements, and observations is constructed dynamically using the integrated Bayesian network and Markov models. The transition rates of outgoing and incoming links of states in hidden Markov models are used in determining exploit likelihood and impact of attacks, whereas emission rates help quantify the attack states of vulnerabilities. Simulation results show the quantification and evolving risk scores over time for individual and aggregated vulnerabilities of a network.

  9. Wideband Low Noise Amplifiers Exploiting Thermal Noise Cancellation

    NARCIS (Netherlands)

    Bruccoleri, F.; Klumperink, Eric A.M.; Nauta, Bram


    Low Noise Amplifiers (LNAs) are commonly used to amplify signals that are too weak for direct processing for example in radio or cable receivers. Traditionally, low noise amplifiers are implemented via tuned amplifiers, exploiting inductors and capacitors in resonating LC-circuits. This can render

  10. Human trafficking and exploitation: A global health concern.

    Directory of Open Access Journals (Sweden)

    Cathy Zimmerman


    Full Text Available In this collection review, Cathy Zimmerman and colleague introduce the PLOS Medicine Collection on Human Trafficking, Exploitation and Health, laying out the magnitude of the global trafficking problem and offering a public health policy framework to guide responses to trafficking.

  11. Conflicts Related to Natural Resources Exploitation: A Case Study of ...

    African Journals Online (AJOL)

    Conflicts Related to Natural Resources Exploitation: A Case Study of Oil Crisis in Nigeria's Niger Delta Region and its Socio-Political and Economic Implications. ... This has tremendously disrupted the primary sources of livelihood of the people namely fishing and farming which has left them in abject poverty. It is this ...

  12. Exploitation Rates and Management Implications for the Fisheries of ...

    African Journals Online (AJOL)

    The exploitation rates of eight major component fishery species, Auchenoglanis occidentalis, Brycinus nurse, Clarias gariepinus, Hemichromis fasciatus, Marcusenius senegalensis, Oreochromis niloticus, Sarotherodon galilaeus and Tilapia zillii, of gill net fishery of Bontanga reservoir, were studied from March 2004 to ...

  13. Chlamydia pneumoniae exploits adipocyte lipid chaperone FABP4 to facilitate fat mobilization and intracellular growth in murine adipocytes. (United States)

    Walenna, Nirwana Fitriani; Kurihara, Yusuke; Chou, Bin; Ishii, Kazunari; Soejima, Toshinori; Itoh, Ryota; Shimizu, Akinori; Ichinohe, Takeshi; Hiromatsu, Kenji


    Fatty acid-binding protein 4 (FABP4), a cytosolic lipid chaperone predominantly expressed in adipocytes and macrophages, modulates lipid fluxes, trafficking, signaling, and metabolism. Recent studies have demonstrated that FABP4 regulates metabolic and inflammatory pathways, and in mouse models its inhibition can improve type 2 diabetes mellitus and atherosclerosis. However, the role of FABP4 in bacterial infection, metabolic crosstalk between host and pathogen, and bacterial pathogenesis have not been studied. As an obligate intracellular pathogen, Chlamydia pneumoniae needs to obtain nutrients such as ATP and lipids from host cells. Here, we show that C. pneumoniae successfully infects and proliferates in murine adipocytes by inducing hormone sensitive lipase (HSL)-mediated lipolysis. Chemical inhibition or genetic manipulation of HSL significantly abrogated the intracellular growth of C. pneumoniae in adipocytes. Liberated free fatty acids were utilized to generate ATP via β-oxidation, which C. pneumoniae usurped for its replication. Strikingly, chemical inhibition or genetic silencing of FABP4 significantly abrogated C. pneumoniae infection-induced lipolysis and mobilization of liberated FFAs, resulting in reduced bacterial growth in adipocytes. Collectively, these results demonstrate that C. pneumoniae exploits host FABP4 to facilitate fat mobilization and intracellular replication in adipocytes. This work uncovers a novel strategy used by intracellular pathogens for acquiring energy via hijacking of the host lipid metabolism pathway. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Relative fitness of a generalist parasite on two alternative hosts: a cross-infestation experiment to test host specialization of the hen flea Ceratophyllus gallinae (Schrank). (United States)

    Appelgren, A; McCoy, K D; Richner, H; Doligez, B


    Host range is a key element of a parasite's ecology and evolution and can vary greatly depending on spatial scale. Generalist parasites frequently show local population structure in relation to alternative sympatric hosts (i.e. host races) and may thus be specialists at local scales. Here, we investigated local population specialization of a common avian nest-based parasite, the hen flea Ceratophyllus gallinae (Schrank), exploiting two abundant host species that share the same breeding sites, the great tit Parus major (Linnaeus) and the collared flycatcher Ficedula albicollis (Temminck). We performed a cross-infestation experiment of fleas between the two host species in two distinct study areas during a single breeding season and recorded the reproductive success of both hosts and parasites. In the following year, hosts were monitored again to assess the long-term impact of cross-infestation. Our results partly support the local specialization hypothesis: in great tit nests, tit fleas caused higher damage to their hosts than flycatcher fleas, and in collared flycatcher nests, flycatcher fleas had a faster larval development rates than tit fleas. However, these results were significant in only one of the two studied areas, suggesting that the location and history of the host population can modulate the specialization process. Caution is therefore called for when interpreting single location studies. More generally, our results emphasize the need to explicitly account for host diversity in order to understand the population ecology and evolutionary trajectory of generalist parasites. © 2016 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2016 European Society For Evolutionary Biology.

  15. Studying host cell protein interactions with monoclonal antibodies using high throughput protein A chromatography. (United States)

    Sisodiya, Vikram N; Lequieu, Joshua; Rodriguez, Maricel; McDonald, Paul; Lazzareschi, Kathlyn P


    Protein A chromatography is typically used as the initial capture step in the purification of monoclonal antibodies produced in Chinese hamster ovary (CHO) cells. Although exploiting an affinity interaction for purification, the level of host cell proteins in the protein A eluent varies significantly with different feedstocks. Using a batch binding chromatography method, we performed a controlled study to assess host cell protein clearance across both MabSelect Sure and Prosep vA resins. We individually spiked 21 purified antibodies into null cell culture fluid generated with a non-producing cell line, creating mock cell culture fluids for each antibody with an identical composition of host cell proteins and antibody concentration. We demonstrated that antibody-host cell protein interactions are primarily responsible for the variable levels of host cell proteins in the protein A eluent for both resins when antibody is present. Using the additives guanidine HCl and sodium chloride, we demonstrated that antibody-host cell protein interactions may be disrupted, reducing the level of host cell proteins present after purification on both resins. The reduction in the level of host cell proteins differed between antibodies suggesting that the interaction likely varies between individual antibodies but encompasses both an electrostatic and hydrophobic component. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Interplay between Human Cytomegalovirus and Intrinsic/Innate Host Responses: A Complex Bidirectional Relationship (United States)

    Rossini, Giada; Cerboni, Cristina; Santoni, Angela; Landini, Maria Paola; Landolfo, Santo; Gatti, Deborah; Gribaudo, Giorgio; Varani, Stefania


    The interaction between human cytomegalovirus (HCMV) and its host is a complex process that begins with viral attachment and entry into host cells, culminating in the development of a specific adaptive response that clears the acute infection but fails to eradicate HCMV. We review the viral and cellular partners that mediate early host responses to HCMV with regard to the interaction between structural components of virions (viral glycoproteins) and cellular receptors (attachment/entry receptors, toll-like receptors, and other nucleic acid sensors) or intrinsic factors (PML, hDaxx, Sp100, viperin, interferon inducible protein 16), the reactions of innate immune cells (antigen presenting cells and natural killer cells), the numerous mechanisms of viral immunoevasion, and the potential exploitation of events that are associated with early phases of virus-host interplay as a therapeutic strategy. PMID:22701276

  17. Cellular host responses to gliomas.

    Directory of Open Access Journals (Sweden)

    Joseph Najbauer

    Full Text Available BACKGROUND: Glioblastoma multiforme (GBM is the most aggressive type of malignant primary brain tumors in adults. Molecular and genetic analysis has advanced our understanding of glioma biology, however mapping the cellular composition of the tumor microenvironment is crucial for understanding the pathology of this dreaded brain cancer. In this study we identified major cell populations attracted by glioma using orthotopic rodent models of human glioma xenografts. Marker-specific, anatomical and morphological analyses revealed a robust influx of host cells into the main tumor bed and tumor satellites. METHODOLOGY/PRINCIPAL FINDINGS: Human glioma cell lines and glioma spheroid orthotopic implants were used in rodents. In both models, the xenografts recruited large numbers of host nestin-expressing cells, which formed a 'network' with glioma. The host nestin-expressing cells appeared to originate in the subventricular zone ipsilateral to the tumor, and were clearly distinguishable from pericytes that expressed smooth muscle actin. These distinct cell populations established close physical contact in a 'pair-wise' manner and migrated together to the deeper layers of tumor satellites and gave rise to tumor vasculature. The GBM biopsy xenografts displayed two different phenotypes: (a low-generation tumors (first in vivo passage in rats were highly invasive and non-angiogenic, and host nestin-positive cells that infiltrated into these tumors displayed astrocytic or elongated bipolar morphology; (b high-generation xenografts (fifth passage had pronounced cellularity, were angiogenic with 'glomerulus-like' microvascular proliferations that contained host nestin-positive cells. Stromal cell-derived factor-1 and its receptor CXCR4 were highly expressed in and around glioma xenografts, suggesting their role in glioma progression and invasion. CONCLUSIONS/SIGNIFICANCE: Our data demonstrate a robust migration of nestin-expressing host cells to glioma, which

  18. An in vitro model of renal inflammation after ischemic oxidative stress injury: nephroprotective effects of a hyaluronan ester with butyric acid on mesangial cells

    Directory of Open Access Journals (Sweden)

    Baraldi O


    thiazolyl blue assay and flow cytometry analysis of cell cycle with propidium iodide.Results: HB treatment promoted apoptosis of mesangial cells after H2O2-induced damage, decreased cellular proliferation and activated p38 pathway, increasing expression of its target gene MPP-9.Conclusion: This in vitro model shows that HB treatment seems to redirect mesangial cells toward apoptosis after oxidative damage and to reduce cell proliferation through p38 MAPK pathway activation and upregulation of MPP-9 gene expression involved in mesangial matrix remodeling. Keywords: acute kidney injury, apoptosis, hyaluronan ester of butyric acid, mesangial cells

  19. HIV-1 and hijacking of the host immune system: the current scenario. (United States)

    Imran, Muhammad; Manzoor, Sobia; Saalim, Muhammad; Resham, Saleha; Ashraf, Javed; Javed, Aneela; Waqar, Ahmed Bilal


    Human immunodeficiency virus (HIV) infection is a major health burden across the world which leads to the development of acquired immune deficiency syndrome (AIDS). This review article discusses the prevalence of HIV, its major routes of transmission, natural immunity, and evasion from the host immune system. HIV is mostly prevalent in Sub-Saharan Africa and low income countries. It is mostly transmitted by sharing syringe needles, blood transfusion, and sexual routes. The host immune system is categorized into three main types; the innate, the adaptive, and the intrinsic immune system. Regarding the innate immune system against HIV, the key players are mucosal membrane, dendritic cells (DCs), complement system, interferon, and host Micro RNAs. The major components of the adaptive immune system exploited by HIV are T cells mainly CD4+ T cells and B cells. The intrinsic immune system confronted by HIV involves (apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3G) APOBEC3G, tripartite motif 5-α (TRIM5a), terherin, and (SAM-domain HD-domain containing protein) SAMHD1. HIV-1 efficiently interacts with the host immune system, exploits the host machinery, successfully replicates and transmits from one cell to another. Further research is required to explore evasion strategies of HIV to develop novel therapeutic approaches against HIV. © 2016 APMIS. Published by John Wiley & Sons Ltd.

  20. Tick salivary compounds: their role in modulation of host defences and pathogen transmission (United States)

    Kazimírová, Mária; Štibrániová, Iveta


    Ticks require blood meal to complete development and reproduction. Multifunctional tick salivary glands play a pivotal role in tick feeding and transmission of pathogens. Tick salivary molecules injected into the host modulate host defence responses to the benefit of the feeding ticks. To colonize tick organs, tick-borne microorganisms must overcome several barriers, i.e., tick gut membrane, tick immunity, and moulting. Tick-borne pathogens co-evolved with their vectors and hosts and developed molecular adaptations to avoid adverse effects of tick and host defences. Large gaps exist in the knowledge of survival strategies of tick-borne microorganisms and on the molecular mechanisms of tick-host-pathogen interactions. Prior to transmission to a host, the microorganisms penetrate and multiply in tick salivary glands. As soon as the tick is attached to a host, gene expression and production of salivary molecules is upregulated, primarily to facilitate feeding and avoid tick rejection by the host. Pathogens exploit tick salivary molecules for their survival and multiplication in the vector and transmission to and establishment in the hosts. Promotion of pathogen transmission by bioactive molecules in tick saliva was described as saliva-assisted transmission (SAT). SAT candidates comprise compounds with anti-haemostatic, anti-inflammatory and immunomodulatory functions, but the molecular mechanisms by which they mediate pathogen transmission are largely unknown. To date only a few tick salivary molecules associated with specific pathogen transmission have been identified and their functions partially elucidated. Advanced molecular techniques are applied in studying tick-host-pathogen interactions and provide information on expression of vector and pathogen genes during pathogen acquisition, establishment and transmission. Understanding the molecular events on the tick-host-pathogen interface may lead to development of new strategies to control tick-borne diseases. PMID

  1. White Sharks Exploit the Sun during Predatory Approaches. (United States)

    Huveneers, Charlie; Holman, Dirk; Robbins, Rachel; Fox, Andrew; Endler, John A; Taylor, Alex H


    There is no conclusive evidence of any nonhuman animal using the sun as part of its predation strategy. Here, we show that the world's largest predatory fish-the white shark (Carcharodon carcharias)-exploits the sun when approaching baits by positioning the sun directly behind them. On sunny days, sharks reversed their direction of approach along an east-west axis from morning to afternoon but had uniformly distributed approach directions during overcast conditions. These results show that white sharks have sufficient behavioral flexibility to exploit fluctuating environmental features when predating. This sun-tracking predation strategy has a number of potential functional roles, including improvement of prey detection, avoidance of retinal overstimulation, and predator concealment.

  2. Commodification and exploitation: arguments in favour of compensated organ donation. (United States)

    de Castro, L D


    This paper takes the view that compensated donation and altruism are not incompatible. In particular, it holds that the arguments against giving compensation stand on weak rational grounds: (1) the charge that compensation fosters "commodification" has neither been specific enough to account for different types of monetary transactions nor sufficiently grounded in reality to be rationally convincing; (2) although altruism is commendable, organ donors should not be compelled to act purely on the basis of altruistic motivations, especially if there are good reasons to believe that significantly more lives can be saved and enhanced if incentives are put in place, and (3) offering compensation for organs does not necessarily lead to exploitation-on the contrary, it may be regarded as a necessity in efforts to minimise the level of exploitation that already exists in current organ procurement systems.

  3. Analysis Of Damage Arising From Exploitation Of The Aircraft

    Directory of Open Access Journals (Sweden)

    Woźny Piotr


    Full Text Available During exploitation, due to a variety of reasons, aircrafts are damaged or suffer from different failures. In the process of operation, using appropriate methods of diagnosis, failure, damage, and relative deregulation of individual elements or units can be detected. For this purpose, one can apply a number of indirect diagnostic methods with the use of recorded diagnostic signals or a direct diagnosis with the use of non-destructive methods. The proper identification of the technical condition allows to determine the causes of irregularities and take actions aimed at preventing their occurrence. The article presents the types of exploitation damage of a multi-purpose aircraft. In addition, the criteria for the division of damage and research methods of the causes of damage are presented. Furthermore, an analysis of the scope of activities to be performed during the research of causes of damage to the aircraft is made.

  4. Exploration and Exploitation Fit and Performance in International Strategic Alliances

    DEFF Research Database (Denmark)

    Nielsen, Bo Bernhard; Gudergan, Siegfried


    Exploration and exploitation constitute two separate, potentially conflicting strategic choices for firms engaged in international strategic alliances. Our empirical study challenges the ambidexterity argument and demonstrates that exploration and exploitation are separate (though not necessarily...... antithetical) strategies with different antecedents and performance consequences. Our results show that while competency similarity is conducive to upstream innovative performance, prior experience with the partner is potentially damaging for this type of performance and trust and cultural distance do not play...... significant roles. When the motive is efficiency and downstream market performance, prior experience with the partner instead is beneficial, as are high levels of trust and low levels of cultural distance. These findings have key implications for literature on strategic fit and alliance performance....

  5. Exploiting cantilever curvature for noise reduction in atomic force microscopy. (United States)

    Labuda, Aleksander; Grütter, Peter H


    Optical beam deflection is a widely used method for detecting the deflection of atomic force microscope (AFM) cantilevers. This paper presents a first order derivation for the angular detection noise density which determines the lower limit for deflection sensing. Surprisingly, the cantilever radius of curvature, commonly not considered, plays a crucial role and can be exploited to decrease angular detection noise. We demonstrate a reduction in angular detection shot noise of more than an order of magnitude on a home-built AFM with a commercial 450 μm long cantilever by exploiting the optical properties of the cantilever curvature caused by the reflective gold coating. Lastly, we demonstrate how cantilever curvature can be responsible for up to 45% of the variability in the measured sensitivity of cantilevers on commercially available AFMs.

  6. Exploiting the Errors: A Simple Approach for Improved Volatility Forecasting

    DEFF Research Database (Denmark)

    Bollerslev, Tim; Patton, Andrew J.; Quaedvlieg, Rogier

    We propose a new family of easy-to-implement realized volatility based forecasting models. The models exploit the asymptotic theory for high-frequency realized volatility estimation to improve the accuracy of the forecasts. By allowing the parameters of the models to vary explicitly with the (est......We propose a new family of easy-to-implement realized volatility based forecasting models. The models exploit the asymptotic theory for high-frequency realized volatility estimation to improve the accuracy of the forecasts. By allowing the parameters of the models to vary explicitly...... with the (estimated) degree of measurement error, the models exhibit stronger persistence, and in turn generate more responsive forecasts, when the measurement error is relatively low. Implementing the new class of models for the S&P500 equity index and the individual constituents of the Dow Jones Industrial Average...

  7. Mathematical modeling of the behavior of geothermal systems under exploitation

    Energy Technology Data Exchange (ETDEWEB)

    Bodvarsson, G.S.


    Analytical and numerical methods have been used in this investigation to model the behavior of geothermal systems under exploitation. The work is divided into three parts: (1) development of a numerical code, (2) theoretical studies of geothermal systems, and (3) field applications. A new single-phase three-dimensional simulator, capable of solving heat and mass flow problems in a saturated, heterogeneous porous or fractured medium has been developed. The simulator uses the integrated finite difference method for formulating the governing equations and an efficient sparse solver for the solution of the linearized equations. In the theoretical studies, various reservoir engineering problems have been examined. These include (a) well-test analysis, (b) exploitation strategies, (c) injection into fractured rocks, and (d) fault-charged geothermal reservoirs.

  8. Information source exploitation/exploration and NPD decision-making

    DEFF Research Database (Denmark)

    Jespersen, Kristina Risom

    of gate decision-making and information sources was developed across five generic stages (idea, concept, design, test, and commercialization). Our data was generated with a participatory agent-based simulation of NPD gate decision-points in the development process. The sample consists of 134 managers from......The purpose of this study is to examine how the exploration/exploitation continuum is applied by decision-makers in new product gate decision-making. Specifically, we analyze at gate decision-points how the evaluation of a new product project is affected by the information source exploitation....../exploration search behavior of decision-makers. In addition, overexploitation and overexploration in new product development decision-making is investigated through mediating effects of perceived information usefulness and applied performance criteria by decision-makers at gates. To this end a conceptual model...

  9. Design and Exploitation Problems of Drill String in Directional Drilling

    Directory of Open Access Journals (Sweden)

    Bednarz Stanislaw


    Full Text Available Drill string design for directional drilling requires accounting for a number of factors. First, types and expected values of loads should be determined. Then, elements of the drill string should be so selected as to enable realization of the plan at specified loads. Some of additional factors, e. g. purchase, exploitation cost, geological conditions in the bore-hole, washing of the bore-hole, stability, trajectory, rig parameters, accuracy of gauges, pumps parameters remain in conflict. Drill pipes are made of rolled pipes, upset and welded with tool joints to 9,5 m long; the shorter ones can be made of hot forged rods. Exploitation requirements, being a result of practical experience supported by theoretical and laboratory analyses should be a part of syllabuses of technical staff educational programs. Apart from designing the string, it is also vital to lower the risk of a drilling failure. The significance of these aspects seems to be unquestionable.

  10. Environmental Impacts of Sand Exploitation. Analysis of Sand Market

    Directory of Open Access Journals (Sweden)

    Marius Dan Gavriletea


    Full Text Available Sand is an indispensable natural resource for any society. Despite society’s increasing dependence on sand, there are major challenges that this industry needs to deal with: limited sand resources, illegal mining, and environmental impact of sand mining. The purpose of this paper is twofold: to present an overview of the sand market, highlighting the main trends and actors for production, export and import, and to review the main environmental impacts associated with sand exploitation process. Based on these findings, we recommend different measures to be followed to reduce negative impacts. Sand mining should be done in a way that limits environmental damage during exploitation and restores the land after mining operations are completed.

  11. Exploitation of Natural Resources and the Public Sector in Greenland

    DEFF Research Database (Denmark)

    Nielsen, Søren Bo

    This paper considers the role of the public sector in future exploitation of non-renewable resources, especially minerals, in Greenland. The focus is on fiscal sustainability, principles for public sector involvement and the form of government take from mining activities. At present, the public...... to GDP. Hence, fiscal policy is quite far from being sustainable. Apart from a need for reforms, these facts also constrain the possible role of the public sector in future resource exploitation. In any case, the government should preferably adhere to strict principles when developing the mineral sector...... in Greenland. Furthermore, serious attention should be given to how to secure an appropriate government take from mineral activities. The paper discusses several types of taxes as well as financing models....

  12. Target Localization with a Single Antenna via Directional Multipath Exploitation

    Directory of Open Access Journals (Sweden)

    Ali H. Muqaibel


    Full Text Available Target localization in urban sensing can benefit from angle dependency of the pulse shape at a radar receiver antenna. We propose a localization approach that utilizes the embedded directivity in ultra-wideband (UWB antennas to estimate target positions. A single radar unit sensing operation of indoor targets surrounded by interior walls is considered, where interior wall multipaths are exploited to provide target cross-range. This exploitation assumes resolvability of the multipath components, which is made possible by the virtue of using UWB radar signals. The proposed approach is most attractive when only few multipaths are detectable due to propagation obstructions or owing to low signal-to-noise ratios. Both simulated and experimental data are used to demonstrate the effectiveness of the proposed approach.

  13. Exploring, exploiting and evolving diversity of aquatic ecosystem models

    DEFF Research Database (Denmark)

    Janssen, Annette B. G.; Arhonditsis, George B.; Beusen, Arthur


    Here, we present a community perspective on how to explore, exploit and evolve the diversity in aquatic ecosystem models. These models play an important role in understanding the functioning of aquatic ecosystems, filling in observation gaps and developing effective strategies for water quality...... management. In this spirit, numerous models have been developed since the 1970s. We set off to explore model diversity by making an inventory among 42 aquatic ecosystem modellers, by categorizing the resulting set of models and by analysing them for diversity. We then focus on how to exploit model diversity...... by comparing and combining different aspects of existing models. Finally, we discuss how model diversity came about in the past and could evolve in the future. Throughout our study, we use analogies from biodiversity research to analyse and interpret model diversity. We recommend to make models publicly...

  14. Exploitation of the Virtual Worlds in Tourism and Tourism Education

    Directory of Open Access Journals (Sweden)

    Zejda Pavel


    Full Text Available Academics perceive a great potential of virtual worlds in various areas, including tourism and education. Efforts adapting the virtual worlds in practice are, however, still marginal. There is no clear definition of the virtual world. Therefore the author of this article attempts to provide one. The paper also focuses on the barriers of a wider exploitation of the virtual worlds and discusses the principles that might help to increase their potential in tourism area. One of the principles – gamification – favours a wider adaptation of the virtual worlds in tourism. Applying gamification principles provides visitors with some unique experiences while serving as a powerful marketing tool for institutions. The benefits of implementing tourism education activities based on cooperative principles set in an immersive environment of the virtual worlds are depicted afterwards. Finally, this paper includes successful case studies, which show advantages and drawbacks of some approaches in exploiting the virtual worlds in tourism and tourism education.

  15. Transformation-aware Exploit Generation using a HI-CFG (United States)


    buffer structure (the chain of buffers used between transformations) of a program, and use this structure to construct an exploit input by inverting one...make digital or hard copies of all or part of this work for personal or classroom use is granted without fee provided that copies are not made or... inverting one transformation at a time. We propose a new program representation, a hybrid information- and control-flow graph (HI-CFG), and give

  16. variabilite des productions et des revenus des exploitations ...

    African Journals Online (AJOL)

    diversification pratiquées sont les prestations de service, la foresterie et pisciculture, la migration, l'artisanat et autres (Tableau 7). Les activités de diversification ont rapporté assez de revenus aux exploitations agricoles familiales dans les villages étudiés. Il est estimé à plus de. 400 000 Fcfa dans les villages de Kokélé, ...

  17. Exploiting Network Topology Information to Mitigate Ambiguities in VMP Localization

    DEFF Research Database (Denmark)

    Pedersen, Claus; Pedersen, Troels; Fleury, Bernard Henri


    We investigate an extension to the probabilistic model of a wireless sensor network (WSN) in the variational message passing localization algorithm. This extension exploits network topology information to mitigate ambiguities in WSN localization schemes. In a simulation case study we show...... that this extension in some cases improves the location estimates produced by the algorithm. The final version of the paper will present quantitative results from more extensive investigations that will document the extent of this improvement....

  18. Enhanced surrogate models for statistical design exploiting space mapping technology

    DEFF Research Database (Denmark)

    Koziel, Slawek; Bandler, John W.; Mohamed, Achmed S.


    We present advances in microwave and RF device modeling exploiting Space Mapping (SM) technology. We propose new SM modeling formulations utilizing input mappings, output mappings, frequency scaling and quadratic approximations. Our aim is to enhance circuit models for statistical analysis...... and yield-driven design. We illustrate our results using a capacitively-loaded two-section impedance transformer, a single-resonator waveguide filter and a six-section H-plane waveguide filter....

  19. aspects economiques de l'exploitation des ressources halieutiques ...

    African Journals Online (AJOL)

    ECONOM/C ASPECTS OF THE EXPLOITATION OF HALIEUTIC RESSOURCES OF “PETITS BARRAGES”. INLAND ..... journalière du travail et la gestion familiale ou du comité de gestion,. TRF est le taux de rémunération des fonds propres,. BNE est le bénéfice net d'exploita- tien, ..... Ces bas prix de marché s'expliquent.

  20. Generalized image deconvolution by exploiting spatially variant point spread functions


    Lee, Sangyun; Lee, KyeoReh; Shin, Seungwoo; Park, YongKeun


    An optical imaging system forms an object image by recollecting light scattered by the object. However, intact optical information of the object delivered through the imaging system is deteriorated by imperfect optical elements and unwanted defects. Image deconvolution, also known as inverse filtering, has been widely exploited as a recovery technique because of its practical feasibility, and operates by assuming the linear shift-invariant property of the imaging system. However, shift invari...