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Sample records for reduced invasive capacity

  1. Global threats from invasive alien species in the twenty-first century and national response capacities

    PubMed Central

    Early, Regan; Bradley, Bethany A.; Dukes, Jeffrey S.; Lawler, Joshua J.; Olden, Julian D.; Blumenthal, Dana M.; Gonzalez, Patrick; Grosholz, Edwin D.; Ibañez, Ines; Miller, Luke P.; Sorte, Cascade J. B.; Tatem, Andrew J.

    2016-01-01

    Invasive alien species (IAS) threaten human livelihoods and biodiversity globally. Increasing globalization facilitates IAS arrival, and environmental changes, including climate change, facilitate IAS establishment. Here we provide the first global, spatial analysis of the terrestrial threat from IAS in light of twenty-first century globalization and environmental change, and evaluate national capacities to prevent and manage species invasions. We find that one-sixth of the global land surface is highly vulnerable to invasion, including substantial areas in developing economies and biodiversity hotspots. The dominant invasion vectors differ between high-income countries (imports, particularly of plants and pets) and low-income countries (air travel). Uniting data on the causes of introduction and establishment can improve early-warning and eradication schemes. Most countries have limited capacity to act against invasions. In particular, we reveal a clear need for proactive invasion strategies in areas with high poverty levels, high biodiversity and low historical levels of invasion. PMID:27549569

  2. Global threats from invasive alien species in the twenty-first century and national response capacities.

    PubMed

    Early, Regan; Bradley, Bethany A; Dukes, Jeffrey S; Lawler, Joshua J; Olden, Julian D; Blumenthal, Dana M; Gonzalez, Patrick; Grosholz, Edwin D; Ibañez, Ines; Miller, Luke P; Sorte, Cascade J B; Tatem, Andrew J

    2016-08-23

    Invasive alien species (IAS) threaten human livelihoods and biodiversity globally. Increasing globalization facilitates IAS arrival, and environmental changes, including climate change, facilitate IAS establishment. Here we provide the first global, spatial analysis of the terrestrial threat from IAS in light of twenty-first century globalization and environmental change, and evaluate national capacities to prevent and manage species invasions. We find that one-sixth of the global land surface is highly vulnerable to invasion, including substantial areas in developing economies and biodiversity hotspots. The dominant invasion vectors differ between high-income countries (imports, particularly of plants and pets) and low-income countries (air travel). Uniting data on the causes of introduction and establishment can improve early-warning and eradication schemes. Most countries have limited capacity to act against invasions. In particular, we reveal a clear need for proactive invasion strategies in areas with high poverty levels, high biodiversity and low historical levels of invasion.

  3. Protosemiosis: agency with reduced representation capacity

    PubMed Central

    Sharov, Alexei A.; Vehkavaara, Tommi

    2014-01-01

    Life has semiotic nature; and as life forms differ in their complexity, functionality, and adaptability, we assume that forms of semiosis also vary accordingly. Here we propose a criterion to distinguish between the primitive kind of semiosis, which we call “protosemiosis” (following Prodi) from the advanced kind of semiosis, or “eusemiosis”. In protosemiosis, agents associate signs directly with actions without considering objects, whereas in eusemiosis, agents associate signs with objects and only then possibly with actions. Protosemiosis started from the origin of life, and eusemiosis started when evolving agents acquired the ability to track and classify objects. Eusemiosis is qualitatively different from protosemiosis because it can not be reduced to a small number of specific signaling pathways. Proto-signs can be classified into proto-icons that signal via single specific interaction, proto-indexes that combine several functions, and proto-symbols that are processed by a universal subagent equipped with a set of heritable adapters. Prefix “proto” is used here to characterize signs at the protosemiotic level. Although objects are not recognized by protosemiotic agents, they can be reliably reconstructed by human observers. In summary, protosemiosis is a primitive kind of semiosis that supports “know-how” without “know-what”. Without studying protosemiosis, the biosemiotics theory would be incomplete. PMID:25937852

  4. Protosemiosis: agency with reduced representation capacity.

    PubMed

    Sharov, Alexei A; Vehkavaara, Tommi

    2015-04-01

    Life has semiotic nature; and as life forms differ in their complexity, functionality, and adaptability, we assume that forms of semiosis also vary accordingly. Here we propose a criterion to distinguish between the primitive kind of semiosis, which we call "protosemiosis" (following Prodi) from the advanced kind of semiosis, or "eusemiosis". In protosemiosis, agents associate signs directly with actions without considering objects, whereas in eusemiosis, agents associate signs with objects and only then possibly with actions. Protosemiosis started from the origin of life, and eusemiosis started when evolving agents acquired the ability to track and classify objects. Eusemiosis is qualitatively different from protosemiosis because it can not be reduced to a small number of specific signaling pathways. Proto-signs can be classified into proto-icons that signal via single specific interaction, proto-indexes that combine several functions, and proto-symbols that are processed by a universal subagent equipped with a set of heritable adapters. Prefix "proto" is used here to characterize signs at the protosemiotic level. Although objects are not recognized by protosemiotic agents, they can be reliably reconstructed by human observers. In summary, protosemiosis is a primitive kind of semiosis that supports "know-how" without "know-what". Without studying protosemiosis, the biosemiotics theory would be incomplete.

  5. Invasive lionfish reduce native fish abundance on a regional scale.

    PubMed

    Ballew, Nicholas G; Bacheler, Nathan M; Kellison, G Todd; Schueller, Amy M

    2016-08-31

    Invasive lionfish pose an unprecedented threat to biodiversity and fisheries throughout Atlantic waters off of the southeastern United States, the Caribbean, and the Gulf of Mexico. Here, we employ a spatially replicated Before-After-Control-Impact analysis with temporal pairing to quantify for the first time the impact of the lionfish invasion on native fish abundance across a broad regional scale and over the entire duration of the lionfish invasion (1990-2014). Our results suggest that 1) lionfish-impacted areas off of the southeastern United States are most prevalent off-shore near the continental shelf-break but are also common near-shore and 2) in impacted areas, lionfish have reduced tomtate (a native forage fish) abundance by 45% since the invasion began. Tomtate served as a model native fish species in our analysis, and as such, it is likely that the lionfish invasion has had similar impacts on other species, some of which may be of economic importance. Barring the development of a control strategy that reverses the lionfish invasion, the abundance of lionfish in the Atlantic, Caribbean, and Gulf of Mexico will likely remain at or above current levels. Consequently, the effect of lionfish on native fish abundance will likely continue for the foreseeable future.

  6. Invasive lionfish reduce native fish abundance on a regional scale

    PubMed Central

    Ballew, Nicholas G.; Bacheler, Nathan M.; Kellison, G. Todd; Schueller, Amy M.

    2016-01-01

    Invasive lionfish pose an unprecedented threat to biodiversity and fisheries throughout Atlantic waters off of the southeastern United States, the Caribbean, and the Gulf of Mexico. Here, we employ a spatially replicated Before-After-Control-Impact analysis with temporal pairing to quantify for the first time the impact of the lionfish invasion on native fish abundance across a broad regional scale and over the entire duration of the lionfish invasion (1990–2014). Our results suggest that 1) lionfish-impacted areas off of the southeastern United States are most prevalent off-shore near the continental shelf-break but are also common near-shore and 2) in impacted areas, lionfish have reduced tomtate (a native forage fish) abundance by 45% since the invasion began. Tomtate served as a model native fish species in our analysis, and as such, it is likely that the lionfish invasion has had similar impacts on other species, some of which may be of economic importance. Barring the development of a control strategy that reverses the lionfish invasion, the abundance of lionfish in the Atlantic, Caribbean, and Gulf of Mexico will likely remain at or above current levels. Consequently, the effect of lionfish on native fish abundance will likely continue for the foreseeable future. PMID:27578096

  7. Invasive lionfish reduce native fish abundance on a regional scale

    NASA Astrophysics Data System (ADS)

    Ballew, Nicholas G.; Bacheler, Nathan M.; Kellison, G. Todd; Schueller, Amy M.

    2016-08-01

    Invasive lionfish pose an unprecedented threat to biodiversity and fisheries throughout Atlantic waters off of the southeastern United States, the Caribbean, and the Gulf of Mexico. Here, we employ a spatially replicated Before-After-Control-Impact analysis with temporal pairing to quantify for the first time the impact of the lionfish invasion on native fish abundance across a broad regional scale and over the entire duration of the lionfish invasion (1990–2014). Our results suggest that 1) lionfish-impacted areas off of the southeastern United States are most prevalent off-shore near the continental shelf-break but are also common near-shore and 2) in impacted areas, lionfish have reduced tomtate (a native forage fish) abundance by 45% since the invasion began. Tomtate served as a model native fish species in our analysis, and as such, it is likely that the lionfish invasion has had similar impacts on other species, some of which may be of economic importance. Barring the development of a control strategy that reverses the lionfish invasion, the abundance of lionfish in the Atlantic, Caribbean, and Gulf of Mexico will likely remain at or above current levels. Consequently, the effect of lionfish on native fish abundance will likely continue for the foreseeable future.

  8. Are Vegetative Reproduction Capacities the Cause of Widespread Invasion of Eurasian Salicaceae in Patagonian River Landscapes?

    PubMed Central

    Thomas, Lisa K.; Tölle, Lena; Ziegenhagen, Birgit; Leyer, Ilona

    2012-01-01

    In recent decades, invasive willows and poplars (Salicaceae) have built dense floodplain forests along most of the rivers in Patagonia, Argentina. These invasion processes may affect Salix humboldtiana as the only native floodplain tree species in this region. It is assumed, that the property to reproduce vegetatively can play an important role in the establishment of invasive species in their new range. Thus, in order to contribute to a better understanding of willow and poplar invasions in riparian systems and to assess the potential impacts on S. humboldtiana the vegetative reproduction capacities of native and invasive Salicaceae were analysed. In a greenhouse experiment, we studied cutting survival and growth performance of the three most dominant invasive Salicaceae of the Patagonian Río Negro region (two Salix hybrids and Populus spec.), as well as S. humboldtiana, taking into account three different moisture and two different soil conditions. In a subsequent experiment, the shoot and root biomass of cuttings from the former experiment were removed and the bare cuttings were replanted to test their ability to re-sprout. The two invasive willow hybrids performed much better than S. humboldtiana and Populus spec. under all treatment combinations and tended to re-sprout more successfully after repeated biomass loss. Taking into account the ecology of vegetative and generative recruits of floodplain willows, the results indicate that the more vigorous vegetative reproduction capacity can be a crucial property for the success of invasive willow hybrids in Patagonia being a potential threat for S. humboldtiana. PMID:23226531

  9. Reduced visual processing capacity in sleep deprived persons.

    PubMed

    Kong, Danyang; Soon, Chun Siong; Chee, Michael W L

    2011-03-15

    Multiple experiments have found sleep deprivation to lower task-related parietal and extrastriate visual activation, suggesting a reduction of visual processing capacity in this state. The perceptual load theory of attention (Lavie, 1995) predicts that our capacity to process unattended distractors will be reduced by increasing perceptual difficulty of task-relevant stimuli. Here, we evaluated the effects of sleep deprivation and perceptual load on visual processing capacity by measuring neural repetition-suppression to unattended scenes while healthy volunteers attended to faces embedded in face-scene pictures. Perceptual load did not affect repetition suppression after a normal night of sleep. Sleep deprivation reduced repetition suppression in the parahippocampal place area (PPA) in the high but not low perceptual load condition. Additionally, the extent to which task-related fusiform face area (FFA) activation was reduced after sleep deprivation correlated with behavioral performance and lowered repetition suppression in the PPA. The findings concerning correct responses indicate that a portion of stimulus related activation following a normal night of sleep contributes to potentially useful visual processing capacity that is attenuated following sleep deprivation. Finally, when unattended stimuli are not highly intrusive, sleep deprivation does not appear to increase distractibility.

  10. Plasma antioxidant capacity is reduced in Asperger syndrome.

    PubMed

    Parellada, Mara; Moreno, Carmen; Mac-Dowell, Karina; Leza, Juan Carlos; Giraldez, Marisa; Bailón, Concepción; Castro, Carmen; Miranda-Azpiazu, Patricia; Fraguas, David; Arango, Celso

    2012-03-01

    Recent evidence suggests that children with autism have impaired detoxification capacity and may suffer from chronic oxidative stress. To our knowledge, there has been no study focusing on oxidative metabolism specifically in Asperger syndrome (a milder form of autism) or comparing this metabolism with other psychiatric disorders. In this study, total antioxidant status (TAOS), non-enzymatic (glutathione and homocysteine) and enzymatic (catalase, superoxide dismutase, and glutathione peroxidase) antioxidants, and lipid peroxidation were measured in plasma or erythrocyte lysates in a group of adolescent patients with Asperger syndrome, a group of adolescents with a first episode of psychosis, and a group of healthy controls at baseline and at 8-12 weeks. TAOS was also analyzed at 1 year. TAOS was reduced in Asperger individuals compared with healthy controls and psychosis patients, after covarying by age and antipsychotic treatment. This reduced antioxidant capacity did not depend on any of the individual antioxidant variables measured. Psychosis patients had increased homocysteine levels in plasma and decreased copper and ceruloplasmin at baseline. In conclusion, Asperger patients seem to have chronic low detoxifying capacity. No impaired detoxifying capacity was found in the first-episode psychosis group in the first year of illness.

  11. Invasive crayfish reduce food limitation of alien American mink and increase their resilience to control.

    PubMed

    Melero, Yolanda; Palazón, Santiago; Lambin, Xavier

    2014-02-01

    Trophic relationships between invasive species in multiply invaded ecosystems may reduce food limitation relative to more pristine ecosystems and increase resilience to control. Here, we consider whether invasive predatory American mink Neovison vison are trophically subsidized by invasive crayfish. We collated data from the literature on density and home range size of mink populations in relation to the prevalence of crayfish in the diet of mink. We then tested the hypothesis that populations of an invasive predator reach higher densities and are more resilient to lethal control when they have access to super-abundant non-native prey, even in the absence of changes in density dependence, hence compensatory capacity. We found a strong positive relationship between the proportion of crayfish in mink diet and mink population density, and a negative relationship between the proportion of crayfish in mink diet and mink home range size, with crayfish contribution to mink diet reflecting their abundance in the ecosystem. We then explored the consequence of elevated mink density by simulating a hypothetical eradication program with a constant harvest in a Ricker model. We found that mink populations were more resilient to harvest in the presence of crayfish. As a result, the simulated number of mink harvested to achieve eradication increased by 500% in the presence of abundant crayfish if carrying capacity increased by 630%. This led to a threefold increase in time to eradication under a constant harvest and an approximately 20-fold increase in the cumulative management cost. Our results add to evidence of inter-specific positive interactions involving invasive species, and our simple model illustrates how this increases management cost.

  12. Reducing proactive aggression through non-invasive brain stimulation.

    PubMed

    Dambacher, Franziska; Schuhmann, Teresa; Lobbestael, Jill; Arntz, Arnoud; Brugman, Suzanne; Sack, Alexander T

    2015-10-01

    Aggressive behavior poses a threat to human collaboration and social safety. It is of utmost importance to identify the functional mechanisms underlying aggression and to develop potential interventions capable of reducing dysfunctional aggressive behavior already at a brain level. We here experimentally shifted fronto-cortical asymmetry to manipulate the underlying motivational emotional states in both male and female participants while assessing the behavioral effects on proactive and reactive aggression. Thirty-two healthy volunteers received either anodal transcranial direct current stimulation to increase neural activity within right dorsolateral prefrontal cortex, or sham stimulation. Aggressive behavior was measured with the Taylor Aggression Paradigm. We revealed a general gender effect, showing that men displayed more behavioral aggression than women. After the induction of right fronto-hemispheric dominance, proactive aggression was reduced in men. This study demonstrates that non-invasive brain stimulation can reduce aggression in men. This is a relevant and promising step to better understand how cortical brain states connect to impulsive actions and to examine the causal role of the prefrontal cortex in aggression. Ultimately, such findings could help to examine whether the brain can be a direct target for potential supportive interventions in clinical settings dealing with overly aggressive patients and/or violent offenders.

  13. RhoC is essential for TGF-{beta}1-induced invasive capacity of rat ascites hepatoma cells

    SciTech Connect

    Mukai, M.; Endo, H.; Iwasaki, T.; Tatsuta, M.; Togawa, A.; Nakamura, H.; Inoue, M. . E-mail: inoue-ma2@mc.pref.osaka.jp

    2006-07-21

    Transforming growth factor-{beta}1 (TGF-{beta}1) is a multifunctional growth factor that plays a role in cell proliferation, differentiation, extracellular matrix production, apoptosis, and cell motility. We show here that TGF-{beta}1 increased the invasiveness of MM1 cells, which are a highly invasive clone of rat ascites hepatoma cells. Both mRNA and protein levels of RhoC but not RhoA in TGF-{beta}1-treated MM1 cells increased. In parallel with this increase in expression, RhoC activity was induced by TGF-{beta}1 treatment. When RhoC was overexpressed in MM1 cells, the invasive capacity increased. The RhoC-overexpressing cells formed more nodules than did mock cells when injected into rat peritoneum. Furthermore, when RhoC expression was reduced by transfection with shRNA/RhoC, the invasiveness of MM1 cells decreased with concomitant suppression of RhoC expression. Thus, the induced expression of RhoC by TGF-{beta}1 in MM1 cells plays a critical role in TGF-{beta}1-induced cell migration.

  14. Capacity of management plans for aquatic invasive species to integrate climate change.

    PubMed

    Bierwagen, Britta G; Thomas, Roxanne; Kane, Austin

    2008-06-01

    The consequences of climate change will affect aquatic ecosystems, including aquatic invasive species (AIS) that are already affecting these ecosystems. Effects on AIS include range shifts and more frequent overwintering of species. These effects may create new challenges for AIS management. We examined available U.S. state AIS management plans to assess each program's capacity to adapt to climate-change effects. We scored the adaptive capacity of AIS management plans on the basis of whether they addressed potential impacts resulting from climate change; demonstrated a capacity to adapt to changing conditions; provided for monitoring strategies; provided for plan revisions; and described funding for implementation. Most plans did not mention climate change specifically, but some did acknowledge climatic boundaries of species and ecosystem sensitivities to changing conditions. Just under half the plans mentioned changing environmental conditions as a factor, most frequently as part of research activities. Activities associated with monitoring showed the highest capacity to include information on changing conditions, and future revisions to management plans are likely to be the easiest avenue through which to address climate-change effects on AIS management activities. Our results show that programs have the capacity to incorporate information about climate-change effects and that the adaptive-management framework may be an appropriate approach.

  15. SNAIL transcription factor increases the motility and invasive capacity of prostate cancer cells

    PubMed Central

    OSORIO, LUIS A.; FARFÁN, NANCY M.; CASTELLÓN, ENRIQUE A.; CONTRERAS, HÉCTOR R.

    2016-01-01

    The incidence and mortality rates of prostate cancer (PCa) are increasing, and PCa is almost the second-leading cause of cancer-associated mortality in men. During tumor progression, epithelial cells decrease the number of adhesion molecules, change their polarity and position, rearrange their cytoskeleton and increase their migratory and invasive capacities. These changes are known under the concept of epithelial-mesenchymal transition (EMT). EMT is characterized by an upregulation of certain transcription factors, including SNAIL1, which represses genes that are characteristic of an epithelial phenotype, including E-cadherin, and indirectly increase the expression levels of genes, which are associated with the mesenchymal phenotype. It has been suggested that the transcription factor, SNAIL1, decreases the proliferation and increases the migratory and invasive capacities of PCa cell lines. The present study was performed using LNCaP and PC3 cell lines, in which the expression levels of SNAIL1 were increased or silenced through the use of lentiviral vectors. The expression levels of EMT markers were quantified using reverse transcription-quantitative polymerase chain reaction and western blot analysis. In addition, cell survival was analyzed using an MTS assay; cell proliferation was examined using an antibody targeting Ki-67; migration on plates with 8 µm pores to allow the passage of cells; and invasiveness was analyzed using a membrane chamber covered in dried basement membrane matrix solution. The levels of apoptosis were determined using a Caspase 3/7 assay containing a substrate modified by caspases 3 and 7. The results demonstrated that the overexpression and silencing of SNAIL1 decreased cell proliferation and survival. However, the overexpression of SNAIL1 decreased apoptosis, compared with cells with the SNAIL1-silenced cells, in which cell apoptosis increased. The migration and invasive capacities increased in the cells overexpressing SNAIL1, and

  16. Reduced Expression of the ROCK Inhibitor Rnd3 Is Associated with Increased Invasiveness and Metastatic Potential in Mesenchymal Tumor Cells

    PubMed Central

    Belgiovine, Cristina; Frapolli, Roberta; Bonezzi, Katiuscia; Chiodi, Ilaria; Favero, Francesco; Mello-Grand, Maurizia; Dei Tos, Angelo P.; Giulotto, Elena; Taraboletti, Giulia; D'Incalci, Maurizio; Mondello, Chiara

    2010-01-01

    Background Mesenchymal and amoeboid movements are two important mechanisms adopted by cancer cells to invade the surrounding environment. Mesenchymal movement depends on extracellular matrix protease activity, amoeboid movement on the RhoA-dependent kinase ROCK. Cancer cells can switch from one mechanism to the other in response to different stimuli, limiting the efficacy of antimetastatic therapies. Methodology and Principal Findings We investigated the acquisition and molecular regulation of the invasion capacity of neoplastically transformed human fibroblasts, which were able to induce sarcomas and metastases when injected into immunocompromised mice. We found that neoplastic transformation was associated with a change in cell morphology (from fibroblastic to polygonal), a reorganization of the actin cytoskeleton, a decrease in the expression of several matrix metalloproteases and increases in cell motility and invasiveness. In a three-dimensional environment, sarcomagenic cells showed a spherical morphology with cortical actin rings, suggesting a switch from mesenchymal to amoeboid movement. Accordingly, cell invasion decreased after treatment with the ROCK inhibitor Y27632, but not with the matrix protease inhibitor Ro 28-2653. The increased invasiveness of tumorigenic cells was associated with reduced expression of Rnd3 (also known as RhoE), a cellular inhibitor of ROCK. Indeed, ectopic Rnd3 expression reduced their invasive ability in vitro and their metastatic potential in vivo. Conclusions These results indicate that, during neoplastic transformation, cells of mesenchymal origin can switch from a mesenchymal mode of movement to an amoeboid one. In addition, they point to Rnd3 as a possible regulator of mesenchymal tumor cell invasion and to ROCK as a potential therapeutic target for sarcomas. PMID:21209796

  17. Does seeding after wildfires in rangelands reduce erosion or invasive species?

    USGS Publications Warehouse

    Pyke, David A.; Wirth, Troy A.; Beyers, Jan L.

    2013-01-01

    Mitigation of ecological damage caused by rangeland wildfires has historically been an issue restricted to the western United States. It has focused on conservation of ecosystem function through reducing soil erosion and spread of invasive plants. Effectiveness of mitigation treatments has been debated recently. We reviewed recent literature to conduct a meta-analysis of seeding after wildfires to determine if seedings may (1) protect ecosystems against soil erosion and (2) reduce invasion or abundance of undesirable nonnative plant species. Effectiveness of postfire seedings was examined in 8 erosion and 19 invasive species cases. Seeding has little effect on erosion during the first year after fire and is highly dependent upon initial establishment and coverage of species in successive years. Among all seeding cases, 28% reduced, 67% were neutral, and 5% increased invasive species abundance. Older seedings were more likely to show reductions in invasives than younger seedings. Seedings with high plant establishment were more likely to reduce invasives than those with low establishment. Studies are needed that examine (1) frequency of adequate establishment of postfire seedings and causal factors of success or failure, (2) long-term impacts of seeding along a range of initial establishment and concomitant plant coverage over time as it relates to erosion and abundance of invasive plant species, and (3) auxiliary treatments designed to increase likelihood of germination and establishment given the inevitable variability of environmental conditions. These studies would aid land managers in deciding when postfire treatments are required and their likely level of success.

  18. Serum-Induced Differentiation of Glioblastoma Neurospheres Leads to Enhanced Migration/Invasion Capacity That Is Associated with Increased MMP9

    PubMed Central

    Joseph, Justin V.; Tomar, Tushar; Conroy, Siobhan; Eggens-Meijer, Ellie; Peñaranda Fajardo, Natalia; Pore, Milind M.; Balasubramanyian, Veerakumar; Wagemakers, Michiel; Copray, Sjef; den Dunnen, Wilfred F. A.; Kruyt, Frank A. E.

    2015-01-01

    Glioblastoma (GBM) is a highly infiltrative brain tumor in which cells with properties of stem cells, called glioblastoma stem cells (GSCs), have been identified. In general, the dominant view is that GSCs are responsible for the initiation, progression, invasion and recurrence of this tumor. In this study, we addressed the question whether the differentiation status of GBM cells is associated with their invasive capacity. For this, several primary GBM cell lines were used, cultured either as neurospheres known to enrich for GSCs or in medium supplemented with 10% FCS that promotes differentiation. The differentiation state of the cells was confirmed by determining the expression of stem cell and differentiation markers. The migration/invasion potential of these cells was tested using in vitro assays and intracranial mouse models. Interestingly, we found that serum-induced differentiation enhanced the invasive potential of GBM cells, which was associated with enhanced MMP9 expression. Chemical inhibition of MMP9 significantly reduced the invasive potential of differentiated cells in vitro. Furthermore, the serum-differentiated cells could revert back to an undifferentiated/stem cell state that were able to form neurospheres, although with a reduced efficiency as compared to non-differentiated counterparts. We propose a model in which activation of the differentiation program in GBM cells enhances their infiltrative potential and that depending on microenvironmental cues a significant portion of these cells are able to revert back to an undifferentiated state with enhanced tumorigenic potential. Thus, effective therapy should target both GSCs and differentiated offspring and targeting of differentiation-associated pathways may offer therapeutic opportunities to reduce invasive growth of GBM. PMID:26700636

  19. Vegetative propagation capacity of invasive alligator weed through small stolon fragments under different treatments

    PubMed Central

    Peng, Xuemei; Li, Haiyan; Yang, Yunfei; Zhi, Heng; Li, Chengcheng; Guo, Jian

    2017-01-01

    The ability to propagate via small diaspores is crucial for the invasion of a clone plant that does not reproduce sexually in its introduced range. We investigated the effects of node and internode adjacent mode, fragment type, burial orientation and position of the node in relation to the soil surface on the sprouting and growth of alligator weed (Alternanthera philoxeroides (Martius) Griseb.). All the factors had effects and interaction effects on the sprouting rate and growth. As a whole fragment in all treatments, the fragments with basal node buried upward on the soil surface, exhibited the best above-ground growth and root growth. The one-node fragment with basal node buried downward above the soil surface and upward under the soil surface significantly decreased the above-ground growth and root growth compared to that of the two-node fragment. Therefore, the one-node fragments were more affected by environmental conditions than the two-node fragments. The results indicated that reducing the number of nodes of a fragment and burying the node under the soil or orienting it downward above the soil surface could be applied to control the invasion of alligator weed. PMID:28262788

  20. Vegetative propagation capacity of invasive alligator weed through small stolon fragments under different treatments.

    PubMed

    Peng, Xuemei; Li, Haiyan; Yang, Yunfei; Zhi, Heng; Li, Chengcheng; Guo, Jian

    2017-03-06

    The ability to propagate via small diaspores is crucial for the invasion of a clone plant that does not reproduce sexually in its introduced range. We investigated the effects of node and internode adjacent mode, fragment type, burial orientation and position of the node in relation to the soil surface on the sprouting and growth of alligator weed (Alternanthera philoxeroides (Martius) Griseb.). All the factors had effects and interaction effects on the sprouting rate and growth. As a whole fragment in all treatments, the fragments with basal node buried upward on the soil surface, exhibited the best above-ground growth and root growth. The one-node fragment with basal node buried downward above the soil surface and upward under the soil surface significantly decreased the above-ground growth and root growth compared to that of the two-node fragment. Therefore, the one-node fragments were more affected by environmental conditions than the two-node fragments. The results indicated that reducing the number of nodes of a fragment and burying the node under the soil or orienting it downward above the soil surface could be applied to control the invasion of alligator weed.

  1. Detection capacity, information gaps and the design of surveillance programs for invasive forest pests.

    PubMed

    Yemshanov, Denys; Koch, Frank H; Ben-Haim, Yakov; Smith, William D

    2010-12-01

    Integrated pest risk maps and their underlying assessments provide broad guidance for establishing surveillance programs for invasive species, but they rarely account for knowledge gaps regarding the pest of interest or how these can be reduced. In this study we demonstrate how the somewhat competing notions of robustness to uncertainty and potential knowledge gains could be used in prioritizing large-scale surveillance activities. We illustrate this approach with the example of an invasive pest recently detected in North America, Sirex noctilio Fabricius. First, we formulate existing knowledge about the pest into a stochastic model and use the model to estimate the expected utility of surveillance efforts across the landscape. The expected utility accounts for the distribution, abundance and susceptibility of the host resource as well as the value of timely S. noctilio detections. Next, we make use of the info-gap decision theory framework to explore two alternative pest surveillance strategies. The first strategy aims for timely, certain detections and attempts to maximize the robustness to uncertainty about S. noctilio behavior; the second strategy aims to maximize the potential knowledge gain about the pest via unanticipated (i.e., opportune) detections. The results include a set of spatial outputs for each strategy that can be used independently to prioritize surveillance efforts. However, we demonstrate an alternative approach in which these outputs are combined via the Pareto ranking technique into a single priority map that outlines the survey regions with the best trade-offs between both surveillance strategies.

  2. An invasive plant-fungal mutualism reduces arthropod diversity.

    PubMed

    Rudgers, Jennifer A; Clay, Keith

    2008-08-01

    Ecological theory holds that competition and predation are the most important biotic forces affecting the composition of communities. Here, we expand this framework by demonstrating that mutualism can fundamentally alter community and food web structure. In large, replicated field plots, we manipulated the mutualism between a dominant plant (Lolium arundinaceum) and symbiotic fungal endophyte (Neotyphodium coenophialum). The presence of the mutualism reduced arthropod abundance up to 70%, reduced arthropod diversity nearly 20%, shifted arthropod species composition relative to endophyte-free plots and suppressed the biomass and richness of other plant species in the community. Herbivorous arthropods were more strongly affected than carnivores, and for both herbivores and carnivores, effects of the mutualism appeared to propagate indirectly via organisms occurring more basally in the food web. The influence of the mutualism was as great or greater than previously documented effects of competition and predation on arthropod communities. Our work demonstrates that a keystone mutualism can significantly reduce arthropod biodiversity at a broad community scale.

  3. Structural basis for reduced glomerular filtration capacity in nephrotic humans.

    PubMed Central

    Drumond, M C; Kristal, B; Myers, B D; Deen, W M

    1994-01-01

    Previous studies have established that in a variety of human glomerulopathies the reduced glomerular filtration rate (GFR) is due to a marked lowering of the ultrafiltration coefficient (Kf). To identify the factors which lower Kf, we measured the filtering surface area per glomerulus, filtration slit frequency, basement membrane thickness, and GFR and its determinants in patients with minimal change and membraneous nephropathies and in age-matched healthy controls. Overall values of Kf for the two kidneys were calculated from GFR, renal plasma flow rate, systemic colloid osmotic pressure, and three assumed values for the transcapillary pressure difference. "Experimental" values of the glomerular hydraulic permeability (kexp) were then calculated from Kf, glomerular filtering surface area, and estimates of the total number of nephrons of the two kidneys. Independent estimates of the glomerular hydraulic permeability (kmodel) were obtained using a recent mathematical model that is based on analyses of viscous flow through the various structural components of the glomerular capillary wall. Individual values of basement membrane thickness and filtration slit frequency were used as inputs in this model. The results indicate that the reductions of Kf in both nephropathies can be attributed entirely to reduced glomerular hydraulic permeability. The mean values of kexp and kmodel were very similar in both disorders and much smaller in the nephrotic groups than in healthy controls. There was good agreement between kexp and kmodel for any given group of subjects. It was shown that, in both groups of nephrotics, filtration slit frequency was a more important determinant of the water flow resistance than was basement membrane thickness. The decrease in filtration slit frequency observed in both disorders caused the average path length for the filtrate to increase, thereby explaining the decreased hydraulic permeability. Images PMID:8083359

  4. Reduced expression of AMPK-β1 during tumor progression enhances the oncogenic capacity of advanced ovarian cancer

    PubMed Central

    2014-01-01

    AMP-activated protein kinase (AMPK) is a key energy sensor that is involved in regulating cell metabolism. Our previous study revealed that the subunits of the heterotimeric AMPK enzyme are diversely expressed during ovarian cancer progression. However, the impact of the variable expression of these AMPK subunits in ovarian cancer oncogenesis remains obscure. Here, we provide evidence to show that reduced expression of the AMPK-β1 subunit during tumor progression is associated with the increased oncogenic capacity of advanced ovarian cancer cells. Immunohistochemical analysis revealed that AMPK-β1 levels were reduced in advanced-stage (P = 0.008), high-grade (P = 0.013) and metastatic ovarian cancers (P = 0.008). Intriguingly, down-regulation of AMPK-β1 was progressively reduced from tumor stages 1 to 3 of ovarian cancer. Functionally, enforced expression of AMPK-β1 inhibited ovarian-cancer-cell proliferation, anchorage-independent cell growth, cell migration and invasion. Conversely, depletion of AMPK-β1 by siRNA enhanced the oncogenic capacities of ovarian cancer cells, suggesting that the loss of AMPK-β1 favors the aggressiveness of ovarian cancer. Mechanistically, enforced expression of AMPK-β1 increased AMPK activity, which, in turn, induced cell-cycle arrest via inhibition of AKT/ERK signaling activity as well as impaired cell migration/invasion through the suppression of JNK signaling in ovarian cancer cells. Taken together, these findings suggest that the reduced expression of AMPK-β1 confers lower AMPK activity, which enhances the oncogenic capacity of advanced-stage ovarian cancer. PMID:24602453

  5. 8-Iso-prostaglandin f(2alpha) reduces trophoblast invasion and matrix metalloproteinase activity.

    PubMed

    Staff, A C; Ranheim, T; Henriksen, T; Halvorsen, B

    2000-06-01

    Preeclampsia is a common pregnancy complication in the latter half of gestation diagnosed by hypertension and proteinuria. A key feature of preeclampsia is an altered placentation with reduced trophoblast invasion. Normal placentation requires controlled invasion of trophoblasts into the maternal uterine wall, with secretion of specific proteolytic enzymes able to degrade basement membranes and extracellular matrix, such as the matrix metalloproteinases (MMPs). 8-Iso-prostaglandin F(2alpha) (8-iso-PGF(2alpha)) is a marker of oxidative stress in vivo and is biologically active. We have recently reported an elevated content of free 8-iso-PGF(2alpha) in preeclamptic gestational tissue at delivery. Assuming an elevated level of 8-iso-PGF(2alpha) during the invasion period of the pregnancy, we hypothesized that 8-iso-PGF(2alpha) could reduce invasion of JAR cells, a choriocarcinoma cell line. We investigated JAR cell invasion with 2 types of Transwell assays and demonstrated that 8-iso-PGF(2alpha) (10 micromol/L) resulted in reduced cell invasion in both the colorimetric and radioactivity Transwell assays (P<0.01). Zymograms revealed reduced MMP-2 and MMP-9 activity in conditioned media from JAR cells incubated with 8-iso-PGF(2alpha) (10 micromol/L) (P<0.02). 8-Iso-PGF(2alpha) (10 micromol/L) also reduced the collagenase type IV activity in the conditioned media of JAR cells (P=0.04). No effects on MMP-2 and MMP-9 mRNA levels were observed after incubation with 8-iso-PGF(2alpha) (10 micromol/L), whereas protein levels were significantly decreased (P<0.02), suggesting a posttranscriptional regulation. We hypothesize a potential role for 8-iso-PGF(2alpha) in the reduced trophoblast invasion in preeclampsia.

  6. An unpleasant emotional state reduces working memory capacity: electrophysiological evidence.

    PubMed

    Figueira, Jessica S B; Oliveira, Leticia; Pereira, Mirtes G; Pacheco, Luiza B; Lobo, Isabela; Motta-Ribeiro, Gabriel C; David, Isabel A

    2017-04-11

    Emotional states can guide the actions and decisions we make in our everyday life through their influence on cognitive processes such as working memory (WM). We investigated the long-lasting interference that an unpleasant emotional state had on goal-relevant WM representations from an electrophysiological perspective. Participants performed a change detection task that was preceded by the presentation of unpleasant or neutral task-irrelevant pictures in a blocked fashion. We focused on the contralateral delay activity (CDA), an event-related potential that is sensitive to the number of task-relevant items stored in WM. We found that the asymptotic limit for the CDA amplitude was lower during the unpleasant emotional state than during the neutral one; that is, an emotional state was capable of reducing how many task-relevant items the participants could hold in WM. Furthermore, both the individuals who experienced more intrusive thoughts and those who were dispositionally anxious were more susceptible to the influence of the emotional state. We provide evidence that an unpleasant emotional state diminished visual WM for task-relevant items, particularly in susceptible individuals. These results open new avenues to uncover the emotional-cognitive processing that underlies maladaptive WM representations and the role of such processing in the development of mental illness.

  7. Interaction with host factors exacerbates Trypanosoma cruzi cell invasion capacity upon oral infection.

    PubMed

    Covarrubias, Charles; Cortez, Mauro; Ferreira, Daniele; Yoshida, Nobuko

    2007-12-01

    Outbreaks of severe acute Chagas' disease acquired by oral infection, leading to death in some cases, have occurred in recent years. Using the mouse model, we investigated the basis of such virulence by analyzing a Trypanosoma cruzi isolate, SC, from a patient with severe acute clinical symptoms, who was infected by oral route. It has previously been shown that, upon oral inoculation into mice, T. cruzi metacyclic trypomastigotes invade the gastric mucosal epithelium by engaging the stage-specific surface glycoprotein gp82, whereas the surface molecule gp90 functions as a down-modulator of cell invasion. We found that, when orally inoculated into mice, metacyclic forms of the SC isolate, which express high levels of gp90, produced high parasitemias and high mortality, in sharp contrast with the reduced infectivity in vitro. Upon recovery from the mouse stomach 1h after oral inoculation, the gp90 molecule of the parasites was completely degraded, and their entry into HeLa cells, as well as into Caco-2 cells, was increased. The gp82 molecule was more resistant to digestive action of the gastric juice. Host cell invasion of SC isolate metacyclic trypomastigotes was augmented in the presence of gastric mucin. No alteration in infectivity was observed in T. cruzi strains CL and G which were used as references and which express gp90 molecules resistant to degradation by gastric juice. Taken together, our findings suggest that the exacerbation of T. cruzi infectivity, such as observed upon interaction of the SC isolate with the mouse stomach components, may be responsible for the severity of acute Chagas' disease that has been reported in outbreaks of oral T. cruzi infection.

  8. Atorvastatin suppresses glioma invasion and migration by reducing microglial MT1-MMP expression.

    PubMed

    Yongjun, Yi; Shuyun, Huang; Lei, Chen; Xiangrong, Chen; Zhilin, Yang; Yiquan, Ke

    2013-07-15

    Microglia, the immune cells of the brain, often present in large numbers in gliomas, where they promote tumor growth and invasiveness. This study found that atorvastatin reduced the pro-tumorigenic effects of microglia on glioma migration and invasion by reducing the microglial expression of membrane type 1 metalloproteinase (MT1-MMP). The results suggest that down-regulation of MT1-MMP is controlled by a p38 MAPK pathway in microglia. Taken together, the results support further research on atorvastatin as a candidate for glioma therapy by targeting microglia.

  9. Exacerbated Vulnerability in Existential Changes: The Essence of Dealing with Reduced Working Capacity

    ERIC Educational Resources Information Center

    Steingrímsdóttir, Sigrún Hulda; Halldórsdóttir, Sigríður

    2016-01-01

    The purpose of this phenomenological study was to explore people's experience of reduced working capacity and their encounters with professionals in that life situation. We collected data through in-depth interviews with eight individuals. The main finding of the current research is how illness and accident impairing work capacity "exacerbate…

  10. An invasive riparian tree reduces stream ecosystem efficiency via a recalcitrant organic matter subsidy.

    PubMed

    Mineau, Madeleine M; Baxter, Golden V; Marcarelli, Amy M; Minshall, G Wayne

    2012-07-01

    A disturbance, such as species invasion, can alter the exchange of materials and organisms between ecosystems, with potential consequences for the function of both ecosystems. Russian olive (Elaeagnus angustifolia) is an exotic tree invading riparian corridors in the western United States, and may alter stream organic matter budgets by increasing allochthonous litter and by reducing light via shading, in turn decreasing in-stream primary production. We used a before-after invasion comparison spanning 35 years to show that Russian olive invasion increased allochthonous litter nearly 25-fold to an invaded vs. a control reach of a stream, and we found that this litter decayed more slowly than native willow. Despite a mean 50% increase in canopy cover by Russian olive and associated shading, there were no significant changes in gross primary production. Benthic organic matter storage increased fourfold after Russian olive invasion compared to pre-invasion conditions, but there were no associated changes in stream ecosystem respiration or organic matter export. Thus, estimated stream ecosystem efficiency (ratio of ecosystem respiration to organic matter input) decreased 14%. These findings show that invasions of nonnative plant species in terrestrial habitats can alter resource fluxes to streams with consequences for whole-ecosystem functions.

  11. LIM kinase inhibition reduces breast cancer growth and invasiveness but systemic inhibition does not reduce metastasis in mice.

    PubMed

    Li, Rong; Doherty, Judy; Antonipillai, Juliana; Chen, Sheng; Devlin, Mark; Visser, Kathryn; Baell, Jonathan; Street, Ian; Anderson, Robin L; Bernard, Ora

    2013-04-01

    Metastasis is the major cause of morbidity and mortality in cancer patients. An understanding of the genes that regulate metastasis and development of therapies to target these genes is needed urgently. Since members of the LIM kinase (LIMK) family are key regulators of the actin cytoskeleton and are involved in cell motility and invasion, LIMK is considered to be a good therapeutic target for metastatic disease. Here we investigated the consequences of LIMK inhibition on growth and metastasis of human and mouse mammary tumors. LIMK activity was reduced in tumor cells by expression of dominant-negative LIMK1, by RNA interference or with a selective LIMK inhibitor. The extent of phosphorylation of the LIMK substrate, cofilin, of proliferation and invasion in 2D and 3D culture and of tumor growth and metastasis in mice were assessed. Inhibition of LIMK activity efficiently reduced the pro-invasive properties of tumor cells in vitro. Tumors expressing dominant-negative LIMK1 grew more slowly and were less metastatic in mice. However, systemic administration of a LIMK inhibitor did not reduce either primary tumor growth or spontaneous metastasis. Surprisingly, metastasis to the liver was increased after administration of the inhibitor. These data raise a concern about the use of systemic LIMK inhibitors for the treatment of metastatic breast cancer.

  12. Overexpression of gelsolin reduces the proliferation and invasion of colon carcinoma cells

    PubMed Central

    Li, Wen-Xiang; Yang, Meng-Xuan; Hong, Xin-Qiang; Dong, Tian-Geng; Yi, Tuo; Lin, Sheng-Li; Qin, Xin-Yu; Niu, Wei-Xin

    2016-01-01

    The enhanced motility of cancer cells via the remodeling of the actin cytoskeleton is crucial in the process of cancer cell invasion and metastasis. It was previously demonstrated that gelsolin (GSN) may be involved as a tumor or a metastasis suppressor, depending on the cell lines and model systems used. In the present study, the effect of GSN on the growth and invasion of human colon carcinoma (CC) cells was investigated using reverse transcription quantitative polymerase chain reaction and western blotting. It was observed that upregulation of the expression of GSN in human CC cells significantly reduced the invasiveness of these cells. The expression levels of GSN were observed to be reduced in CC cells, and the reduced expression level of GSN was often associated with a poorer metastasis-free survival rate in patients with CC (P=0.04). In addition, the overexpression of GSN inhibited the invasion of CC cells in vitro. Furthermore, GSN was observed to inhibit signal transducer and activator of transcription (STAT) 3 signaling in CC cells. Together, these results suggested that GSN is critical in regulating cytoskeletal events and inhibits the invasive and/or metastatic potential of CC cells. The results obtained in the present study may improve understanding of the functional and mechanistic links between GSN as a possible tumor suppressor and the STAT3 signaling pathway, with respect to the aggressive nature of CC. In addition, the present study demonstrated the importance of GSN in regulating the invasion and metastasis of CC cells at the molecular level, suggesting that GSN may be a potential predictor of prognosis and treatment success in CC. PMID:27573444

  13. Resveratrol inhibits development of experimental endometriosis in vivo and reduces endometrial stromal cell invasiveness in vitro.

    PubMed

    Bruner-Tran, Kaylon L; Osteen, Kevin G; Taylor, Hugh S; Sokalska, Anna; Haines, Kaitlin; Duleba, Antoni J

    2011-01-01

    Endometriosis is a common gynecologic disorder characterized by ectopic attachment and growth of endometrial tissues. Resveratrol is a natural polyphenol with antiproliferative and anti-inflammatory properties. Our objective was to study the effects of resveratrol on human endometriotic implants in a nude mouse model and to examine its impact on human endometrial stromal (HES) cell invasiveness in vitro. Human endometrial tissues were obtained from healthy donors. Endometriosis was established in oophorectomized nude mice by intraperitoneal injection of endometrial tissues. Mice were treated with 17β-estradiol (8 mg, silastic capsule implants) alone (n = 16) or with resveratrol (6 mg/mouse; n = 20) for 10-12 and 18-20 days beginning 1 day after tissue injection. Mice were killed and endometrial implants were evaluated. A Matrigel invasion assay was used to examine the effects of resveratrol on HES cells. We assessed number and size of endometriotic implants in vivo and Matrigel invasion in vitro. Resveratrol decreased the number of endometrial implants per mouse by 60% (P < 0.001) and the total volume of lesions per mouse by 80% (P < 0.001). Resveratrol (10-30 μM) also induced a concentration-dependent reduction of invasiveness of HES by up to 78% (P < 0.0001). Resveratrol inhibits development of endometriosis in the nude mouse and reduces invasiveness of HES cells. These observations may aid in the development of novel treatments of endometriosis.

  14. Experimental evidence that ecological effects of an invasive fish are reduced at high densities.

    PubMed

    Kornis, Matthew S; Carlson, Jedchada; Lehrer-Brey, Gabrielle; Vander Zanden, M Jake

    2014-05-01

    Understanding the relationship between invasive species density and ecological impact is a pressing topic in ecology, with implications for environmental management and policy. Although it is widely assumed that invasive species impact will increase with density, theory suggests interspecific competition may diminish at high densities due to increased intraspecific interactions. To test this theory, we experimentally examined intra- and interspecific interactions between a globally invasive fish, round goby (Neogobius melanostomus), and three native species at different round goby densities in a tributary of the Laurentian Great Lakes. Eighteen 2.25 m(2) enclosures were stocked with native fish species at natural abundances, while round gobies were stocked at three different densities: 0 m(-2), 2.7 m(-2), and 10.7 m(-2). After 52 days, native fish growth rate was significantly reduced in the low density goby treatment, while growth in the high density goby treatment mirrored the goby-free treatment for two of three native species. Invertebrate density and gut content weight of native fishes did not differ among treatments. Conversely, gut content weight and growth of round gobies were lower in the high goby density treatment, suggesting interactions between round gobies and native fishes are mediated by interference competition amongst gobies. Our experiment provides evidence that invasive species effects may diminish at high densities, possibly due to increased intraspecific interactions. This is consistent with some ecological theory, and cautions against the assumption that invasive species at moderate densities have low impact.

  15. Tomatidine inhibits invasion of human lung adenocarcinoma cell A549 by reducing matrix metalloproteinases expression.

    PubMed

    Yan, Kun-Huang; Lee, Liang-Ming; Yan, Shao-Han; Huang, Hsiang-Ching; Li, Chia-Chen; Lin, Hui-Ting; Chen, Pin-Shern

    2013-05-25

    Tomatidine is an aglycone of glycoalkaloid tomatine in tomato. Tomatidine is found to possess anti-inflammatory properties and may serve as a chemosensitizer in multidrug-resistant tumor cells. However, the effect of tomatidine on cancer cell metastasis remains unclear. This study examines the effect of tomatidine on the migration and invasion of human lung adenocarcinoma A549 cell in vitro. The data demonstrates that tomatidine does not effectively inhibit the viability of A549 cells. When treated with non-toxic doses of tomatidine, cell invasion is markedly suppressed by Boyden chamber invasion assay, while cell migration is not affected. Tomatidine reduces the mRNA level of matrix metalloproteinase-2 (MMP-2), MMP-9 and increases the expression of reversion-inducing cysteine-rich protein with kazal motifs (RECK), as well as tissue inhibitor of metalloproteinase-1 (TIMP-1). The immunoblotting assays indicate that tomatidine is very effective in suppressing the phosphorylation of Akt and extracellular signal regulating kinase (ERK). In addition, tomatidine significantly decreases the nuclear level of nuclear factor kappa B (NF-κB), which suggests that tomatidine inhibits NF-κB activity. Furthermore, the treatment of inhibitors specific for PI3K/Akt (LY294002), ERK (U0126), or NF-κB (pyrrolidine dithiocarbamate) to A549 cells reduced cell invasion and MMP-2/9 expression. The results suggest that tomatidine inhibits the invasion of A549 cells by reducing the expression of MMPs. It also inhibits ERK and Akt signaling pathways and NF-κB activity. These findings demonstrate a new therapeutic potential for tomatidine in anti-metastatic therapy.

  16. Fucoidan reduced the invasion of oral squamous cell carcinoma cells and modified their effects to macrophages.

    PubMed

    Lin, Junda; Wang, Ketao; Wang, Huayang; Shao, Qianqian; Luan, Yijun; Xu, Yan; Song, Xiaobin; Tan, Wanye; Liu, Shaohua; Wei, Fengcai; Qu, Xun

    2017-01-01

    Fucoidan is a complex of polysaccharides showing antitumor and immunomodulation properties. Our previous studies found its regulation to myeloid immune cells, including macrophages. Aberrant infiltration and functions of macrophages are commonly found in oral squamous cell carcinoma (OSCC). In this study, we analyzed the effects of fucoidan on invasion of OSCC cells, and their regulation to macrophages, trying to evaluate its role as a potential therapy for OSCC. CAL27 and THP-1-derived macrophages were used as models for OSCC cells and tumor-infiltrated macrophages in the in vitro study, respectively. The effects of fucoidan on invasion of OSCC cells and their recruitment to macrophages were analyzed by transwell assay. KIF4A siRNA transfection was performed to investigate its role in fucoidan-modulated OSCC cells invasion. CCL3-neutralizing antibody was added into the conditioned medium of OSCC cells to evaluate its role in fucoidan-mediated macrophages recruitment and re-education. Fucoidan reduced the invasive potential of CAL27 cells with a decrease of MMP-2 and KIF4A transcription. KIF4A knockdown in CAL27 cells led to decreased invasion and MMP-2 expression. The conditioned medium of fucoidan-treated CAL27 cells promoted recruitment and inflammatory cytokines secretion on THP-1-derived macrophages. Further analysis found that fucoidan increased CCL3 production in CAL27 cells. Blocking CCL3 expression reversed the effects of fucoidan on macrophage recruitment and re-education. Our study found that fucoidan regulated the invasion of OSCC cells and also their recruiting and re-educating effects on macrophages, suggesting it could be a complementary approach in the treatment of OSCC.

  17. Reduced seed predation after invasion supports enemy release in a broad biogeographical survey.

    PubMed

    Castells, Eva; Morante, Maria; Blanco-Moreno, José M; Sans, F Xavier; Vilatersana, Roser; Blasco-Moreno, Anabel

    2013-12-01

    The Enemy Release (ER) hypothesis predicts an increase in the plant invasive capacity after being released from their associated herbivores or pathogens in their area of origin. Despite the large number of studies on biological invasions addressing this hypothesis, tests evaluating changes in herbivory on native and introduced populations and their effects on plant reproductive potential at a biogeographical level are relatively rare. Here, we tested the ER hypothesis on the South African species Senecio pterophorus (Asteraceae), which is native to the Eastern Cape, has expanded into the Western Cape, and was introduced into Australia (>70-100 years ago) and Europe (>30 years ago). Insect seed predation was evaluated to determine whether plants in the introduced areas were released from herbivores compared to plants from the native range. In South Africa, 25 % of the seedheads of sampled plants were damaged. Plants from the introduced populations suffered lower seed predation compared to those from the native populations, as expected under the ER hypothesis, and this release was more pronounced in the region with the most recent introduction (Europe 0.2 % vs. Australia 15 %). The insect communities feeding on S. pterophorus in Australia and Europe differed from those found in South Africa, suggesting that the plants were released from their associated fauna after invasion and later established new associations with local herbivore communities in the novel habitats. Our study is the first to provide strong evidence of enemy release in a biogeographical survey across the entire known distribution of a species.

  18. Temperature and functional traits influence differences in nitrogen uptake capacity between native and invasive grasses.

    PubMed

    Leffler, A Joshua; James, Jeremy J; Monaco, Thomas A

    2013-01-01

    Performance differences between native and exotic invasive plants are often considered static, but invasive grasses may achieve growth advantages in western North America shrublands and steppe under only optimal growing conditions. We examine differences in N uptake and several morphological variables that influence uptake at temperatures between 5 and 25 °C. We contrast two native perennial grasses in western North America: Elymus elymoides and Pseudoroegneria spicata; two invasive annual grasses: Bromus tectorum and Taeniatherum caput-medusae; and one highly selected non-native perennial grass: Agropyron cristatum. The influence of temperature on N uptake is poorly characterized, yet these invasive annual grasses are known to germinate in warm soils in the autumn, and both experience cool soils during the short growing season following snowmelt in the spring. To further explore the influence of temperature on the correlation between morphological variables and N uptake, our data are applied to a previously published path model and one proposed here. Differences in N uptake between native and invasive grasses were small at the lowest temperature, but were large at the highest temperature. At lower temperatures, uptake of N by annuals and perennials was correlated with leaf N and mass. At higher temperatures, uptake by annuals was correlated only with these leaf traits, but uptake by perennials was correlated with these leaf traits as well as root N and mass. Consequently, our results imply that annual grasses face fewer morphological constraints on N uptake than perennial grasses, and annual grasses may gain further advantage in warmer temperature conditions or during more frequent warm periods.

  19. Use of Intraoperative Temporary Invasive Distraction to Reduce a Chronic Talar Neck Fracture-Dislocation

    DTIC Science & Technology

    2011-04-01

    medial approaches with a medial malleolar osteotomy . The talus was approximately 60° externally rotated in the mortise with the talar head pointing... TYPE N/A 3. DATES COVERED - 4. TITLE AND SUBTITLE Use of intraoperative temporary invasive distraction to reduce a chronic talar neck...if needed (this pin was not available in the external fixator set used in this procedure ). The construct was then assembled using four 4.0-mm

  20. MicroRNA-150 upregulation reduces osteosarcoma cell invasion and metastasis by downregulating Ezrin

    PubMed Central

    Zhan, Ce; Li, Cheng; Zhang, Hao; Tang, Hao; Ji, Fang; Qiao, Su-Chi; Xu, Wei-Dong; Wang, Zhi-Wei

    2016-01-01

    The present study aimed to investigate the effect of microRNA-150 (miRNA/miR-150) in osteosarcoma (OS) cell invasion and metastasis by the regulation of Ezrin. To compare the differences in the expression of miR-150 and Ezrin, cell models of OS metastasis were established by exogenous transfection of miR-150 on the basis of different expression levels of miR-150. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to estimate these expression levels. Ezrin expression was detected by western blot assay. Methylthiazolyldiphenyl-tetrazolium bromide assay was performed to determine cells proliferation. Cell invasion and migration were measured in vitro by Transwell migration assays. Detection of apoptosis adopted flow cytometry. The results of RT-qPCR showed that the miR-150 expression in OS F5M2 cells was significantly increased following exogenous transfection of miR-150 mimics, and the expression of miR-150 was positively correlated with the concentration of the miR-150 mimics. Western blot assay indicated that the Ezrin expression in the F5M2 cells was decreased with the exogenous overexpression of miR-150. Additionally, Transwell assays revealed that the overexpression of miR-150 significantly suppressed the invasion and metastasis ability of the F5M2 cells. miR-150 upregulation may reduce OS cell invasion and metastasis by downregulating the expression of Ezrin. PMID:27900020

  1. Blooming reduces the antioxidant capacity of dark chocolate in rats without lowering its capacity to improve lipid profiles.

    PubMed

    Shadwell, Naomi; Villalobos, Fatima; Kern, Mark; Hong, Mee Young

    2013-05-01

    Dark chocolate contains high levels of antioxidants which are linked to a reduced risk of cardiovascular disease. Chocolate blooming occurs after exposure to high temperatures. Although bloomed chocolate is safe for human consumption, it is not known whether or not the biological function of bloomed chocolate is affected. We hypothesized that bloomed chocolate would reduce the antioxidant potential and lipid-lowering properties of chocolate through altered expression of related genes. Thirty Sprague-Dawley rats were divided into 3 groups and fed either the control (CON), regular dark chocolate (RDC), or bloomed dark chocolate (BDC) diet. After 3 weeks, serum lipid levels and antioxidant capacity were measured. Hepatic expression of key genes was determined by real time polymerase chain reaction (PCR). Sensory characteristics of bloomed versus regular chocolate were assessed in 28 semi-trained panelists. Rats fed RDC exhibited greater serum antioxidant capacities compared to the CON (P < .05). Antioxidant levels of BDC were not different from RDC or CON. Both RDC and BDC lowered TG compared to CON (P < .05). The rats fed RDC had higher high-density lipoprotein levels compared to the CON (P < .05). In rats given RDC, fatty acid synthase gene expression was down-regulated and low-density lipoprotein receptor transcription was up-regulated (P < .05). Sensory panelists preferred the appearance and surface smoothness of the regular chocolate compared to bloomed chocolate (P < .001). Although blooming blunted the robust antioxidant response produced by regular dark chocolate, these results suggest that bloomed dark chocolate yields similarly beneficial effects on most blood lipid parameters or biomarkers. However, regular dark chocolate may be more beneficial for the improvement of antioxidant status and modulation of gene expression involved in lipid metabolism and promoted greater sensory ratings.

  2. Adhesive and invasive capacities of Edwarsiella tarda isolated from South American sea lion

    PubMed Central

    Fernández, Araceli; Villanueva, María Paz; González, Mario; Fernández, Fabiola; Latif, Fadua; Flores, Sandra Nonier; Fernández, Heriberto

    2014-01-01

    Edwarsiella tarda is a zoonotic bacterium that can be isolated from humans, animals and the environment. Although E. tarda is primarily considered a fish pathogen, it is the only species of its genus considered to be pathogenic for humans as well. A survey of zoonotic intestinal bacteria in fresh feces from South American sea lions (SASL) Otaria flavescens, reported E. tarda as the most frequently isolated species. In this study, we used HEp-2 cells to establish in vitro the adherence and invasive ability of 17 E. tarda strains isolated from SASL fecal material. All the strains were able to adhere and invade HEp-2 cells with adhesion and invasion percentages ranging from 56 to 100% and 21 to 74%, respectively. Despite the expression of these pathogenic factors, further investigation is needed to determine whether this bacterium could play a role as primary pathogen for this and other species of pinnipeds. PMID:25477948

  3. Adhesive and invasive capacities of Edwardsiella tarda isolated from South American sea lion.

    PubMed

    Fernández, Araceli; Villanueva, María Paz; González, Mario; Fernández, Fabiola; Latif, Fadua; Flores, Sandra Nonier; Fernández, Heriberto

    2014-01-01

    Edwarsiella tarda is a zoonotic bacterium that can be isolated from humans, animals and the environment. Although E. tarda is primarily considered a fish pathogen, it is the only species of its genus considered to be pathogenic for humans as well. A survey of zoonotic intestinal bacteria in fresh feces from South American sea lions (SASL) Otaria flavescens, reported E. tarda as the most frequently isolated species. In this study, we used HEp-2 cells to establish in vitro the adherence and invasive ability of 17 E. tarda strains isolated from SASL fecal material. All the strains were able to adhere and invade HEp-2 cells with adhesion and invasion percentages ranging from 56 to 100% and 21 to 74%, respectively. Despite the expression of these pathogenic factors, further investigation is needed to determine whether this bacterium could play a role as primary pathogen for this and other species of pinnipeds.

  4. Incentivizing the public to support invasive species management: eurasian milfoil reduces lakefront property values.

    PubMed

    Olden, Julian D; Tamayo, Mariana

    2014-01-01

    Economic evaluations of invasive species are essential for providing comprehensive assessments of the benefits and costs of publicly-funded management activities, yet many previous investigations have focused narrowly on expenditures to control spread and infestation. We use hedonic modeling to evaluate the economic effects of Eurasian milfoil (Myriophyllum spicatum) invasions on lakefront property values of single-family homes in an urban-suburban landscape. Milfoil often forms dense canopies at the water surface, diminishing the value of ecosystem services (e.g., recreation, fishing) and necessitating expensive control and management efforts. We compare 1,258 lakeshore property sale transactions (1995-2006) in 17 lakes with milfoil and 24 un-invaded lakes in King County, Washington (USA). After accounting for structural (e.g., house size), locational (e.g., boat launch), and environmental characteristics (e.g., water clarity) of lakes, we found that milfoil has a significant negative effect on property sales price ($94,385 USD lower price), corresponding to a 19% decline in mean property values. The aggregate cost of milfoil invading one additional lake in the study area is, on average, $377,542 USD per year. Our study illustrates that invasive aquatic plants can significantly impact property values (and associated losses in property taxes that reduce local government revenue), justifying the need for management strategies that prevent and control invasions. We recommend coordinated efforts across Lake Management Districts to focus institutional support, funding, and outreach to prevent the introduction and spread of milfoil. This effort will limit opportunities for re-introduction from neighboring lakes and incentivize private landowners and natural resource agencies to commit time and funding to invasive species management.

  5. Incentivizing the Public to Support Invasive Species Management: Eurasian Milfoil Reduces Lakefront Property Values

    PubMed Central

    Olden, Julian D.; Tamayo, Mariana

    2014-01-01

    Economic evaluations of invasive species are essential for providing comprehensive assessments of the benefits and costs of publicly-funded management activities, yet many previous investigations have focused narrowly on expenditures to control spread and infestation. We use hedonic modeling to evaluate the economic effects of Eurasian milfoil (Myriophyllum spicatum) invasions on lakefront property values of single-family homes in an urban-suburban landscape. Milfoil often forms dense canopies at the water surface, diminishing the value of ecosystem services (e.g., recreation, fishing) and necessitating expensive control and management efforts. We compare 1,258 lakeshore property sale transactions (1995–2006) in 17 lakes with milfoil and 24 un-invaded lakes in King County, Washington (USA). After accounting for structural (e.g., house size), locational (e.g., boat launch), and environmental characteristics (e.g., water clarity) of lakes, we found that milfoil has a significant negative effect on property sales price ($94,385 USD lower price), corresponding to a 19% decline in mean property values. The aggregate cost of milfoil invading one additional lake in the study area is, on average, $377,542 USD per year. Our study illustrates that invasive aquatic plants can significantly impact property values (and associated losses in property taxes that reduce local government revenue), justifying the need for management strategies that prevent and control invasions. We recommend coordinated efforts across Lake Management Districts to focus institutional support, funding, and outreach to prevent the introduction and spread of milfoil. This effort will limit opportunities for re-introduction from neighboring lakes and incentivize private landowners and natural resource agencies to commit time and funding to invasive species management. PMID:25333619

  6. Keystone predators (eastern newts, Notophthalmus viridescens) reduce the impacts of an aquatic invasive species

    USGS Publications Warehouse

    Smith, Kimberly G.

    2006-01-01

    Predation, competition, and their interaction are known to be important factors that influence the structure of ecological communities. In particular, in those cases where a competitive hierarchy exists among prey species, the presence of certain keystone predators can result in enhanced diversity in the prey community. However, little is known regarding the influence of keystone predator presence on invaded prey communities. Given the widespread occurrence of invasive species and substantial concern regarding their ecological impacts, studies on this topic are needed. In this study I used naturalistic replications of an experimental tadpole assemblage to assess the influence of predatory eastern newts, Notophthalmus viridescens, on the outcome of interspecific competition among native and nonindigenous tadpoles. When newts were absent, the presence of the tadpoles of one invasive species, the Cuban treefrog, Osteopilus septentrionalis, resulted in decreased survival and growth rate of the dominant native species, Bufo terrestris, and dominance of the tadpole assemblage by O. septentrionalis. However, the presence of one adult newt generally reduced or eliminated the negative impacts of O. septentrionalis tadpoles, resulting in comparable survival and performance of native species in invaded and noninvaded treatments. Differential mortality among the tadpole species suggests that newts preyed selectively on O. septentrionalis tadpoles, supporting the hypothesis that newts acted as keystone predators in the invaded assemblage. The presence of nonindigenous larval cane toads, Bufo marinus, did not significantly affect native species, and this species was not negatively affected by the presence of newts. Collectively, these results suggest that eastern newts significantly modified the competitive hierarchy of the invaded tadpole assemblage and reduced the impacts of a competitively superior invasive species. If general, these results suggest that the presence of

  7. Reducing hypoxia and inflammation during invasive pulmonary aspergillosis by targeting the Interleukin-1 receptor

    PubMed Central

    Gresnigt, Mark S.; Rekiki, Abdessalem; Rasid, Orhan; Savers, Amélie; Jouvion, Grégory; Dannaoui, Eric; Parlato, Marianna; Fitting, Catherine; Brock, Matthias; Cavaillon, Jean-Marc; van de Veerdonk, Frank L.; Ibrahim-Granet, Oumaïma

    2016-01-01

    Hypoxia as a result of pulmonary tissue damage due to unresolved inflammation during invasive pulmonary aspergillosis (IPA) is associated with a poor outcome. Aspergillus fumigatus can exploit the hypoxic microenvironment in the lung, but the inflammatory response required for fungal clearance can become severely disregulated as a result of hypoxia. Since severe inflammation can be detrimental to the host, we investigated whether targeting the interleukin IL-1 pathway could reduce inflammation and tissue hypoxia, improving the outcome of IPA. The interplay between hypoxia and inflammation was investigated by in vivo imaging of hypoxia and measurement of cytokines in the lungs in a model of corticosteroid immunocompromised and in Cxcr2 deficient mice. Severe hypoxia was observed following Aspergillus infection in both models and correlated with development of pulmonary inflammation and expression of hypoxia specific transcripts. Treatment with IL-1 receptor antagonist reduced hypoxia and slightly, but significantly reduced mortality in immunosuppressed mice, but was unable to reduce hypoxia in Cxcr2−/− mice. Our data provides evidence that the inflammatory response during invasive pulmonary aspergillosis, and in particular the IL-1 axis, drives the development of hypoxia. Targeting the inflammatory IL-1 response could be used as a potential immunomodulatory therapy to improve the outcome of aspergillosis. PMID:27215684

  8. Invasive warm-season grasses reduce mycorrhizal root colonization and biomass production of native prairie grasses.

    PubMed

    Wilson, Gail W T; Hickman, Karen R; Williamson, Melinda M

    2012-07-01

    Soil organisms play important roles in regulating ecosystem-level processes and the association of arbuscular mycorrhizal (AM) fungi with a plant species can be a central force shaping plant species' ecology. Understanding how mycorrhizal associations are affected by plant invasions may be a critical aspect of the conservation and restoration of native ecosystems. We examined the competitive ability of old world bluestem, a non-native grass (Caucasian bluestem [Bothriochloa bladhii]), and the influence of B. bladhii competition on AM root colonization of native warm-season prairie grasses (Andropogon gerardii or Schizachyrium scoparium), using a substitutive design greenhouse competition experiment. Competition by the non-native resulted in significantly reduced biomass production and AM colonization of the native grasses. To assess plant-soil feedbacks of B. bladhii and Bothriochloa ischaemum, we conducted a second greenhouse study which examined soil alterations indirectly by assessing biomass production and AM colonization of native warm-season grasses planted into soil collected beneath Bothriochloa spp. This study was conducted using soil from four replicate prairie sites throughout Kansas and Oklahoma, USA. Our results indicate that a major mechanism in plant growth suppression following invasion by Bothriochloa spp. is the alteration in soil microbial communities. Plant growth was tightly correlated with AM root colonization demonstrating that mycorrhizae play an important role in the invasion of these systems by Bothriochloa spp. and indicating that the restoration of native AM fungal communities may be a fundamental consideration for the successful establishment of native grasses into invaded sites.

  9. Invasive fungal infection following reduced-intensity cord blood transplantation for adult patients with hematologic diseases.

    PubMed

    Miyakoshi, Shigesaburo; Kusumi, Eiji; Matsumura, Tomoko; Hori, Akiko; Murashige, Naoko; Hamaki, Tamae; Yuji, Koichiro; Uchida, Naoyuki; Masuoka, Kazuhiro; Wake, Atsushi; Kanda, Yoshinobu; Kami, Masahiro; Tanaka, Yuji; Taniguchi, Shuichi

    2007-07-01

    Invasive fungal infection (IFI) is a significant complication after allogeneic hematopoietic stem cell transplantation (HSCT); however, we have little information on its clinical features after reduced intensity cord blood transplantation (RICBT) for adults. We reviewed medical records of 128 patients who underwent RICBT at Toranomon Hospital between March 2002 and November 2005. Most of the patients received purine-analogbased preparative regimens. Graft-versus-host disease (GVHD) prophylaxis was a continuous infusion of either tacrolimus 0.03 mg/kg or cyclosporine 3 mg/kg. IFI was diagnosed according to the established EORTC/NIH-MSG criteria. IFI was diagnosed in 14 patients. Thirteen of the 14 had probable invasive pulmonary aspergillosis and the other had fungemia resulting from Trichosporon spp. Median onset of IFI was day 20 (range: 1-82), and no patients developed IFI after day 100. Three-year cumulative incidence of IA was 10.2%. Four of the 13 patients with invasive aspergillosis (IA) developed grade II-IV acute GVHD, and their IA was diagnosed before the onset of acute GVHD. The mortality rate of IFI was 86%. Multivariate analysis revealed that the use of prednisolone >0.2 mg/kg (relative risk 7.97, 95% confidence interval 2.24-28.4, P = .0014) was a significant risk factor for IA. This study suggests that IFI is an important cause of deaths after RICBT, and effective strategies are warranted to prevent IFI.

  10. Self-Disorders in Individuals with Autistic Traits: Contribution of Reduced Autobiographical Reasoning Capacities.

    PubMed

    Berna, Fabrice; Göritz, Anja S; Schröder, Johanna; Coutelle, Romain; Danion, Jean-Marie; Cuervo-Lombard, Christine V; Moritz, Steffen

    2016-08-01

    The present web-based study (N = 840) aimed to illuminate the cognitive mechanisms underlying self-disorders in autism. Initially, participants selected three self-defining memories. Then, we assessed their capacity to give meaning to these events (i.e., meaning making), their tendency to scrutinize autobiographical memory to better understand themselves (i.e., self-continuity function of autobiographical memory) and their clarity of self-concept. The results showed that individuals with high autistic traits (ATs) had a lower clarity of self-concept than control participants. Meaning making was also reduced in AT individuals and mediated the relation between AT and self-concept clarity. Our results suggest that the reduced clarity of self-concept in AT individuals is related to an impaired capacity to make meaning of important past life events.

  11. Tauroursodeoxycholic acid reduces the invasion of MDA-MB-231 cells by modulating matrix metalloproteinases 7 and 13

    PubMed Central

    Park, Ga-Young; Han, Yu Kyeong; Han, Jeong Yoon; Lee, Chang Geun

    2016-01-01

    Tauroursodeoxycholic acid (TUDCA) is a conjugated form of UDCA that modulates several signaling pathways and acts as a chemical chaperone to relieve endoplasmic reticulum (ER) stress. The present study showed that TUDCA reduced the invasion of the MDA-MB-231 metastatic breast cancer cell line under normoxic and hypoxic conditions using an in vitro invasion assay. Quantitative polymerase chain reaction assay revealed that the reduced invasion following TUDCA treatment was associated with a decreased expression of matrix metalloproteinase (MMP)-7 and −13, which play important roles in invasion and metastasis. Inhibitors and short hairpin RNAs were used to show that the effect of TUDCA in the reduction of invasion appeared to be dependent on the protein kinase RNA-like ER kinase pathway, a downstream ER stress signaling pathway. Thus, TUDCA is a candidate anti-metastatic agent to target the ER stress pathway. PMID:27602168

  12. Interaction between Varroa destructor and imidacloprid reduces flight capacity of honeybees

    PubMed Central

    Blanken, Lisa J.; van Dooremalen, Coby

    2015-01-01

    Current high losses of honeybees seriously threaten crop pollination. Whereas parasite exposure is acknowledged as an important cause of these losses, the role of insecticides is controversial. Parasites and neonicotinoid insecticides reduce homing success of foragers (e.g. by reduced orientation), but it is unknown whether they negatively affect flight capacity. We investigated how exposing colonies to the parasitic mite Varroa destructor and the neonicotinoid insecticide imidacloprid affect flight capacity of foragers. Flight distance, time and speed of foragers were measured in flight mills to assess the relative and interactive effects of high V. destructor load and a field-realistic, chronic sub-lethal dose of imidacloprid. Foragers from colonies exposed to high levels of V. destructor flew shorter distances, with a larger effect when also exposed to imidacloprid. Bee body mass partly explained our results as bees were heavier when exposed to these stressors, possibly due to an earlier onset of foraging. Our findings contribute to understanding of interacting stressors that can explain colony losses. Reduced flight capacity decreases the food-collecting ability of honeybees and may hamper the use of precocious foraging as a coping mechanism during colony (nutritional) stress. Ineffective coping mechanisms may lead to destructive cascading effects and subsequent colony collapse. PMID:26631559

  13. The role of miR-21 in proliferation and invasion capacity of human tongue squamous cell carcinoma in vitro

    PubMed Central

    Wang, Yin; Zhu, Yu; Lv, Pin; Li, Longjiang

    2015-01-01

    Tongue squamous cell carcinoma is one of the most common cancers, which has the highest incidence in oral maxillofacial malignant tumors. MiR-21 may promote tumorigeness by down-regulating tumor suppressing genes and/or controlling the genes for cell differentiation and apoptosis, and it has been identified as the most expressive and unusual in a number of profiling experiments. The study shows there are high expressions of miR-21 in tongue squamous cell carcinoma cell lines (Tca8113 and its high metastatic lines), especially in high metastatic lines. miR-21 silencing could suppress the capacity of proliferation, migration and invasion, arrest the cell cycle and induce apoptosis of tongue squamous cell carcinoma cell lines (Tca8113 and its high metastatic lines). All the results indicate that miR-21 will probably open a new path to the gene therapy for oral squamous cell carcinoma. PMID:26191145

  14. The HIV-protease inhibitor saquinavir reduces proliferation, invasion and clonogenicity in cervical cancer cell lines

    PubMed Central

    Bandiera, Elisabetta; Todeschini, Paola; Romani, Chiara; Zanotti, Laura; Erba, Eugenio; Colmegna, Benedetta; Bignotti, Eliana; Santin, Alessandro Davide; Sartori, Enrico; Odicino, Franco Edoardo; Pecorelli, Sergio; Tassi, Renata Alessandra; Ravaggi, Antonella

    2016-01-01

    Innovative therapies in cervical cancer (CC) remain a priority. Recent data indicate that human immunodeficiency virus (HIV)-protease inhibitors used in highly active antiretroviral therapy can exert direct antitumor activities also in HIV-free preclinical and clinical models. The aim of the present study was to evaluate the antineoplastic effects of various HIV-protease inhibitors (indinavir, ritonavir and saquinavir) on primary and established CC cell lines. Two CC cell lines established in our laboratory and four commercially available CC cell lines were treated with indinavir, ritonavir and saquinavir at different concentrations and for different times. Proliferation, clonogenicity and radiosensitivity were evaluated by crystal violet staining. Proteasomal activities were assessed using a cell-based assay and immunoblotting. Cell cycle was analyzed by propidium iodide staining and flow cytometric analysis. Invasion was tested with Matrigel chambers. A t-test for paired samples was used for statistical analysis. In all cell lines, saquinavir was more effective than ritonavir in reducing cell proliferation and inhibiting proteasomal activities (P≤0.05). Conversely, indinavir exerted a negligible effect. The saquinavir concentrations required to modulate the proteasome activities were higher than those observed to be effective in inhibiting cell proliferation. In HeLa cells, saquinavir was strongly effective in inhibiting cell invasion and clonogenicity (P≤0.05) at concentrations much lower than those required to perturb proteasomal activities. Saquinavir did not contribute to increase the sensitivity of HeLa cells to X-rays. In conclusion, the present results demonstrate that saquinavir is able to significantly reduce cell proliferation, cell invasion and clonogenicity in a proteasome-independent manner in in vitro models of CC, and suggest that saquinavir could be a promising CC therapeutic agent. PMID:27698818

  15. Retracted: Glabridin attenuates the migratory and invasive capacity of breast cancer cells by activating microRNA-200c

    PubMed Central

    Ye, Xianqing; Jiang, Fei; Li, Yuan; Mu, Juan; Si, Lu; Wang, Xingxing; Ning, Shilong; Li, Zhong

    2014-01-01

    Current treatments for breast cancer, a common malignancy in human females, are less than satisfactory because of high rates of metastasis. Glabridin (GLA), which acts through the FAK/ROS signaling pathway, has been used as an antioxidant and anti-metastatic agent. However, little is known regarding the effect of microRNA (miRNA) on GLA's anti-metastatic activity. The miRNA-200 family, which is frequently expressed at low levels in triple negative breast cancers, inhibits metastasis by blocking the epithelial–mesenchymal transition. Here, we found that GLA attenuated the migratory and invasive capacity of breast cancer cells by activating miR-200c. GLA induced the mesenchymal–epithelial transition in vitro and in vivo, as determined by increased expression of the epithelial marker, E-cadherin, and decreased expression of the mesenchymal marker, vimentin. Overexpression of miR-200c enhanced the expression of E-cadherin and decreased the expression of vimentin. Furthermore, in MDA-MB-231 and BT-549 breast cancer cells exposed to GLA, knockdown of miR-200c blocked the GLA-induced mesenchymal–epithelial transition and alleviated the GLA-induced inhibition of migration and invasion. Thus, elevation of miR-200c by GLA has considerable therapeutic potential for anti-metastatic therapy for breast cancer patients. PMID:24754877

  16. The cupric ion reducing antioxidant capacity and polyphenolic content of some herbal teas.

    PubMed

    Apak, Reşat; Güçlü, Kubilay; Ozyürek, Mustafa; Esin Karademir, Saliha; Erçağ, Erol

    2006-01-01

    The total antioxidant capacity of the aqueous extracts of some endemic herbs-prepared as infusions by steeping these herbs in hot water--was assayed with bis(neocuproine)copper(II) chloride, also known as the cupric ion reducing antioxidant capacity (CUPRAC) reagent, which was easily accessible, rapid, stable and responsive to both hydrophilic and lipophilic antioxidants. The highest antioxidant capacities of some herbal teas available in the Turkish market were observed for scarlet pimpernel (Anagallis arvensis), sweet basil (Ocimum basilicum), green tea (Camellia sinensis) and lemon balm (Melissa officinalis), in this order (1.63, 1.18, 1.07, and 0.99 mmol trolox equivalent (TR)/g, respectively). For infusions prepared from ready-to-use tea bags, the CUPRAC values were highest for Ceylon blended ordinary tea (4.41), green tea with lemon (1.61), English breakfast ordinary tea (1.26) and green tea (0.94), all of which were manufactured types of C. sinensis. Following the strongest antioxidant herbs with capacities close to or slightly exceeding 1.0 mmol TR/g, sage, thyme, coriander, coltsfoot, blackberry and immortelle (Helichrysum) exhibited capacities around 0.5 mmol TR/g. The correlation of the Folin total phenolic content of herbal teas with their CUPRAC and ABTS (2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt) total antioxidant capacities gave linear curves with correlation coefficients of 0.966 and 0.936, respectively, showing that the CUPRAC assay results better correlated with total phenolic content of herbal teas. Absorbance versus concentration data at different dilutions and upon standard additions of model antioxidant compounds (trolox and quercetin) to herbal tea infusions showed that the absorbances (at 450 nm of the CUPRAC method) due to different antioxidant compounds in herbal tea infusions were additive; that is, the tested antioxidants did not chemically interact to cause apparent deviations from Beer's law.

  17. Archipelago-wide island restoration in the Galápagos Islands: reducing costs of invasive mammal eradication programs and reinvasion risk.

    PubMed

    Carrion, Victor; Donlan, C Josh; Campbell, Karl J; Lavoie, Christian; Cruz, Felipe

    2011-05-11

    Invasive alien mammals are the major driver of biodiversity loss and ecosystem degradation on islands. Over the past three decades, invasive mammal eradication from islands has become one of society's most powerful tools for preventing extinction of insular endemics and restoring insular ecosystems. As practitioners tackle larger islands for restoration, three factors will heavily influence success and outcomes: the degree of local support, the ability to mitigate for non-target impacts, and the ability to eradicate non-native species more cost-effectively. Investments in removing invasive species, however, must be weighed against the risk of reintroduction. One way to reduce reintroduction risks is to eradicate the target invasive species from an entire archipelago, and thus eliminate readily available sources. We illustrate the costs and benefits of this approach with the efforts to remove invasive goats from the Galápagos Islands. Project Isabela, the world's largest island restoration effort to date, removed >140,000 goats from >500,000 ha for a cost of US$10.5 million. Leveraging the capacity built during Project Isabela, and given that goat reintroductions have been common over the past decade, we implemented an archipelago-wide goat eradication strategy. Feral goats remain on three islands in the archipelago, and removal efforts are underway. Efforts on the Galápagos Islands demonstrate that for some species, island size is no longer the limiting factor with respect to eradication. Rather, bureaucratic processes, financing, political will, and stakeholder approval appear to be the new challenges. Eradication efforts have delivered a suite of biodiversity benefits that are in the process of revealing themselves. The costs of rectifying intentional reintroductions are high in terms of financial and human resources. Reducing the archipelago-wide goat density to low levels is a technical approach to reducing reintroduction risk in the short-term, and is being

  18. Prolonged head-down tilt exposure reduces maximal cutaneous vasodilator and sweating capacity in humans

    NASA Technical Reports Server (NTRS)

    Crandall, C. G.; Shibasaki, M.; Wilson, T. E.; Cui, J.; Levine, B. D.

    2003-01-01

    Cutaneous vasodilation and sweat rate are reduced during a thermal challenge after simulated and actual microgravity exposure. The effects of microgravity exposure on cutaneous vasodilator capacity and on sweat gland function are unknown. The purpose of this study was to test the hypothesis that simulated microgravity exposure, using the 6 degrees head-down tilt (HDT) bed rest model, reduces maximal forearm cutaneous vascular conductance (FVC) and sweat gland function and that exercise during HDT preserves these responses. To test these hypotheses, 20 subjects were exposed to 14 days of strict HDT bed rest. Twelve of those subjects exercised (supine cycle ergometry) at 75% of pre-bed rest heart rate maximum for 90 min/day throughout HDT bed rest. Before and after HDT bed rest, maximal FVC was measured, via plethysmography, by heating the entire forearm to 42 degrees C for 45 min. Sweat gland function was assessed by administering 1 x 10(-6) to 2 M acetylcholine (9 doses) via intradermal microdialysis while simultaneously monitoring sweat rate over the microdialysis membranes. In the nonexercise group, maximal FVC and maximal stimulated sweat rate were significantly reduced after HDT bed rest. In contrast, these responses were unchanged in the exercise group. These data suggest that 14 days of simulated microgravity exposure, using the HDT bed rest model, reduces cutaneous vasodilator and sweating capacity, whereas aerobic exercise training during HDT bed rest preserves these responses.

  19. Invasive surgery reduces infarct size and preserves cardiac function in a porcine model of myocardial infarction

    PubMed Central

    van Hout, Gerardus PJ; Teuben, Michel PJ; Heeres, Marjolein; de Maat, Steven; de Jong, Renate; Maas, Coen; Kouwenberg, Lisanne HJA; Koenderman, Leo; van Solinge, Wouter W; de Jager, Saskia CA; Pasterkamp, Gerard; Hoefer, Imo E

    2015-01-01

    Reperfusion injury following myocardial infarction (MI) increases infarct size (IS) and deteriorates cardiac function. Cardioprotective strategies in large animal MI models often failed in clinical trials, suggesting translational failure. Experimentally, MI is induced artificially and the effect of the experimental procedures may influence outcome and thus clinical applicability. The aim of this study was to investigate if invasive surgery, as in the common open chest MI model affects IS and cardiac function. Twenty female landrace pigs were subjected to MI by transluminal balloon occlusion. In 10 of 20 pigs, balloon occlusion was preceded by invasive surgery (medial sternotomy). After 72 hrs, pigs were subjected to echocardiography and Evans blue/triphenyl tetrazoliumchloride double staining to determine IS and area at risk. Quantification of IS showed a significant IS reduction in the open chest group compared to the closed chest group (IS versus area at risk: 50.9 ± 5.4% versus 69.9 ± 3.4%, P = 0.007). End systolic LV volume and LV ejection fraction measured by echocardiography at follow-up differed significantly between both groups (51 ± 5 ml versus 65 ± 3 ml, P = 0.033; 47.5 ± 2.6% versus 38.8 ± 1.2%, P = 0.005). The inflammatory response in the damaged myocardium did not differ between groups. This study indicates that invasive surgery reduces IS and preserves cardiac function in a porcine MI model. Future studies need to elucidate the effect of infarct induction technique on the efficacy of pharmacological therapies in large animal cardioprotection studies. PMID:26282710

  20. Combined HPLC-CUPRAC (cupric ion reducing antioxidant capacity) assay of parsley, celery leaves, and nettle.

    PubMed

    Yildiz, Leyla; Başkan, Kevser Sözgen; Tütem, Esma; Apak, Reşat

    2008-10-19

    This study aims to identify the essential antioxidant compounds present in parsley (Petroselinum sativum) and celery (Apium graveolens) leaves belonging to the Umbelliferae (Apiaceae) family, and in stinging nettle (Urtica dioica) belonging to Urticaceae family, to measure the total antioxidant capacity (TAC) of these compounds with CUPRAC (cupric ion reducing antioxidant capacity) and ABTS spectrophotometric methods, and to correlate the TAC with high performance liquid chromatography (HPLC) findings. The CUPRAC spectrophotometric method of TAC assay using copper(II)-neocuproine (2,9-dimethyl-1,10-phenanthroline) as the chromogenic oxidant was developed in our laboratories. The individual antioxidant constituents of plant extracts were identified and quantified by HPLC on a C18 column using a modified mobile phase of gradient elution comprised of MeOH-0.2% o-phosphoric acid and UV detection for polyphenols at 280 nm. The TAC values of HPLC-quantified antioxidant constituents were found, and compared for the first time with those found by CUPRAC. The TAC of HPLC-quantified compounds accounted for a relatively high percentage of the observed CUPRAC capacities of plant extracts, namely 81% of nettle, 60-77% of parsley (in different hydrolyzates of extract and solid sample), and 41-57% of celery leaves (in different hydrolyzates). The CUPRAC total capacities of the 70% MeOH extracts of studied plants (in the units of mmol trolox g(-1)plant) were in the order: celery leaves>nettle>parsley. The TAC calculated with the aid of HPLC-spectrophotometry did not compensate for 100% of the CUPRAC total capacities, because all flavonoid glycosides subjected to hydrolysis were either not detectable with HPLC, or not converted to the corresponding aglycons (i.e., easily detectable and quantifiable with HPLC) during the hydrolysis step.

  1. Invasive floating macrophytes reduce greenhouse gas emissions from a small tropical lake.

    PubMed

    Attermeyer, K; Flury, S; Jayakumar, R; Fiener, P; Steger, K; Arya, V; Wilken, F; van Geldern, R; Premke, K

    2016-02-05

    Floating macrophytes, including water hyacinth (Eichhornia crassipes), are dominant invasive organisms in tropical aquatic systems, and they may play an important role in modifying the gas exchange between water and the atmosphere. However, these systems are underrepresented in global datasets of greenhouse gas (GHG) emissions. This study investigated the carbon (C) turnover and GHG emissions from a small (0.6 km(2)) water-harvesting lake in South India and analysed the effect of floating macrophytes on these emissions. We measured carbon dioxide (CO2) and methane (CH4) emissions with gas chambers in the field as well as water C mineralization rates and physicochemical variables in both the open water and in water within stands of water hyacinths. The CO2 and CH4 emissions from areas covered by water hyacinths were reduced by 57% compared with that of open water. However, the C mineralization rates were not significantly different in the water between the two areas. We conclude that the increased invasion of water hyacinths and other floating macrophytes has the potential to change GHG emissions, a process that might be relevant in regional C budgets.

  2. Loxoribine pretreatment reduces Salmonella Enteritidis organ invasion in 1-day-old chickens.

    PubMed

    Swaggerty, C L; He, H; Genovese, K J; Duke, S E; Kogut, M H

    2012-04-01

    Young poultry exhibit a transient colonization by some food-borne pathogens, including Salmonella, during the first week of life that stems from immature innate and acquired defense mechanisms. Consequently, modulation of the hosts' natural immune response is emerging as an important area of interest for food animal producers, including the poultry industry. Toll-like receptor (TLR) agonists have been shown to boost the innate immune response in young chickens and increase their resistance to colonization by Salmonella enterica serovar Enteritidis. The objective of the present study was to determine if pretreatment with loxoribine, a TLR7 agonist and immune modulator, protects young chicks from Salmonella Enteritidis organ invasion. Loxoribine (0-100 μg) was administered intra-abdominally to 1-d-old broiler chicks, and 4 h later, the birds were challenged orally with Salmonella Enteritidis. Twenty-four hours postchallenge, birds were euthanized and the liver and spleen aseptically removed and cultured for Salmonella Enteritidis. This was carried out on 3 separate occasions using 26 to 50 chicks per dose per experiment. Pretreatment of chicks with loxoribine (6.25-25 μg) significantly (P ≤ 0.05) reduced liver and spleen organ invasion by Salmonella Enteritidis. Higher doses (50-100 μg) of loxoribine had no effect. The results obtained in this study indicate that there is a potential application for using loxoribine to increase protection of young chicks when they are most susceptible to infections with Salmonella.

  3. Invasive floating macrophytes reduce greenhouse gas emissions from a small tropical lake

    PubMed Central

    Attermeyer, K.; Flury, S.; Jayakumar, R.; Fiener, P.; Steger, K.; Arya, V.; Wilken, F.; van Geldern, R.; Premke, K.

    2016-01-01

    Floating macrophytes, including water hyacinth (Eichhornia crassipes), are dominant invasive organisms in tropical aquatic systems, and they may play an important role in modifying the gas exchange between water and the atmosphere. However, these systems are underrepresented in global datasets of greenhouse gas (GHG) emissions. This study investigated the carbon (C) turnover and GHG emissions from a small (0.6 km2) water-harvesting lake in South India and analysed the effect of floating macrophytes on these emissions. We measured carbon dioxide (CO2) and methane (CH4) emissions with gas chambers in the field as well as water C mineralization rates and physicochemical variables in both the open water and in water within stands of water hyacinths. The CO2 and CH4 emissions from areas covered by water hyacinths were reduced by 57% compared with that of open water. However, the C mineralization rates were not significantly different in the water between the two areas. We conclude that the increased invasion of water hyacinths and other floating macrophytes has the potential to change GHG emissions, a process that might be relevant in regional C budgets. PMID:26846590

  4. Invasive floating macrophytes reduce greenhouse gas emissions from a small tropical lake

    NASA Astrophysics Data System (ADS)

    Attermeyer, K.; Flury, S.; Jayakumar, R.; Fiener, P.; Steger, K.; Arya, V.; Wilken, F.; van Geldern, R.; Premke, K.

    2016-02-01

    Floating macrophytes, including water hyacinth (Eichhornia crassipes), are dominant invasive organisms in tropical aquatic systems, and they may play an important role in modifying the gas exchange between water and the atmosphere. However, these systems are underrepresented in global datasets of greenhouse gas (GHG) emissions. This study investigated the carbon (C) turnover and GHG emissions from a small (0.6 km2) water-harvesting lake in South India and analysed the effect of floating macrophytes on these emissions. We measured carbon dioxide (CO2) and methane (CH4) emissions with gas chambers in the field as well as water C mineralization rates and physicochemical variables in both the open water and in water within stands of water hyacinths. The CO2 and CH4 emissions from areas covered by water hyacinths were reduced by 57% compared with that of open water. However, the C mineralization rates were not significantly different in the water between the two areas. We conclude that the increased invasion of water hyacinths and other floating macrophytes has the potential to change GHG emissions, a process that might be relevant in regional C budgets.

  5. Genetic recapitulation of human pre-eclampsia risk during convergent evolution of reduced placental invasiveness in eutherian mammals.

    PubMed

    Elliot, Michael G; Crespi, Bernard J

    2015-03-05

    The relationship between phenotypic variation arising through individual development and phenotypic variation arising through diversification of species has long been a central question in evolutionary biology. Among humans, reduced placental invasion into endometrial tissues is associated with diseases of pregnancy, especially pre-eclampsia, and reduced placental invasiveness has also evolved, convergently, in at least 10 lineages of eutherian mammals. We tested the hypothesis that a common genetic basis underlies both reduced placental invasion arising through a developmental process in human placental disease and reduced placental invasion found as a derived trait in the diversification of Euarchontoglires (rodents, lagomorphs, tree shrews, colugos and primates). Based on whole-genome analyses across 18 taxa, we identified 1254 genes as having evolved adaptively across all three lineages exhibiting independent evolutionary transitions towards reduced placental invasion. These genes showed strong evidence of enrichment for associations with pre-eclampsia, based on genetic-association studies, gene-expression analyses and gene ontology. We further used in silico prediction to identify a subset of 199 genes that are likely targets of natural selection during transitions in placental invasiveness and which are predicted to also underlie human placental disorders. Our results indicate that abnormal ontogenies can recapitulate major phylogenetic shifts in mammalian evolution, identify new candidate genes for involvement in pre-eclampsia, imply that study of species with less-invasive placentation will provide useful insights into the regulation of placental invasion and pre-eclampsia, and recommend a novel comparative functional-evolutionary approach to the study of genetically based human disease and mammalian diversification.

  6. Genetic recapitulation of human pre-eclampsia risk during convergent evolution of reduced placental invasiveness in eutherian mammals

    PubMed Central

    Elliot, Michael G.; Crespi, Bernard J.

    2015-01-01

    The relationship between phenotypic variation arising through individual development and phenotypic variation arising through diversification of species has long been a central question in evolutionary biology. Among humans, reduced placental invasion into endometrial tissues is associated with diseases of pregnancy, especially pre-eclampsia, and reduced placental invasiveness has also evolved, convergently, in at least 10 lineages of eutherian mammals. We tested the hypothesis that a common genetic basis underlies both reduced placental invasion arising through a developmental process in human placental disease and reduced placental invasion found as a derived trait in the diversification of Euarchontoglires (rodents, lagomorphs, tree shrews, colugos and primates). Based on whole-genome analyses across 18 taxa, we identified 1254 genes as having evolved adaptively across all three lineages exhibiting independent evolutionary transitions towards reduced placental invasion. These genes showed strong evidence of enrichment for associations with pre-eclampsia, based on genetic-association studies, gene-expression analyses and gene ontology. We further used in silico prediction to identify a subset of 199 genes that are likely targets of natural selection during transitions in placental invasiveness and which are predicted to also underlie human placental disorders. Our results indicate that abnormal ontogenies can recapitulate major phylogenetic shifts in mammalian evolution, identify new candidate genes for involvement in pre-eclampsia, imply that study of species with less-invasive placentation will provide useful insights into the regulation of placental invasion and pre-eclampsia, and recommend a novel comparative functional-evolutionary approach to the study of genetically based human disease and mammalian diversification. PMID:25602073

  7. A highly invasive subpopulation of MDA-MB-231 breast cancer cells shows accelerated growth, differential chemoresistance, features of apocrine tumors and reduced tumorigenicity in vivo

    PubMed Central

    Mirisola, Valentina; Esposito, Alessia Isabella; Reverberi, Daniele; Matis, Serena; Maffei, Massimo; Giaretti, Walter; Viale, Maurizio; Gangemi, Rosaria; Emionite, Laura; Astigiano, Simonetta; Cilli, Michele; Bachmeier, Beatrice E.; Killian, Peter H.; Albini, Adriana; Pfeffer, Ulrich

    2016-01-01

    The acquisition of an invasive phenotype is a prerequisite for metastasization, yet it is not clear whether or to which extent the invasive phenotype is linked to other features characteristic of metastatic cells. We selected an invasive subpopulation from the triple negative breast cancer cell line MDA-MB-231, performing repeated cycles of preparative assays of invasion through Matrigel covered membranes. The invasive sub-population of MDA-MB-231 cells exhibits stronger migratory capacity as compared to parental cells confirming the highly invasive potential of the selected cell line. Prolonged cultivation of these cells did not abolish the invasive phenotype. ArrayCGH, DNA index quantification and karyotype analyses confirmed a common genetic origin of the parental and invasive subpopulations and revealed discrete structural differences of the invasive subpopulation including increased ploidy and the absence of a characteristic amplification of chromosome 5p14.1-15.33. Gene expression analyses showed a drastically altered expression profile including features of apocrine breast cancers and of invasion related matrix-metalloproteases and cytokines. The invasive cells showed accelerated proliferation, increased apoptosis, and an altered pattern of chemo-sensitivity with lower IC50 values for drugs affecting the mitotic apparatus. However, the invasive cell population is significantly less tumorigenic in orthotopic mouse xenografts suggesting that the acquisition of the invasive capacity and the achievement of metastatic growth potential are distinct events. PMID:27626697

  8. Biomarkers of oxidative stress and its association with the urinary reducing capacity in bus maintenance workers

    PubMed Central

    2011-01-01

    Background Exposure to particles (PM) induces adverse health effects (cancer, cardiovascular and pulmonary diseases). A key-role in these adverse effects seems to be played by oxidative stress, which is an excess of reactive oxygen species relative to the amount of reducing species (including antioxidants), the first line of defense against reactive oxygen species. The aim of this study was to document the oxidative stress caused by exposure to respirable particles in vivo, and to test whether exposed workers presented changes in their urinary levels for reducing species. Methods Bus depot workers (n = 32) exposed to particles and pollutants (respirable PM4, organic and elemental carbon, particulate metal content, polycyclic aromatic hydrocarbons, NOx, O3) were surveyed over two consecutive days. We collected urine samples before and after each shift, and quantified an oxidative stress biomarker (8-hydroxy-2'-deoxyguanosine), the reducing capacity and a biomarker of PAH exposure (1-hydroxypyrene). We used a linear mixed model to test for associations between the oxidative stress status of the workers and their particle exposure as well as with their urinary level of reducing species. Results Workers were exposed to low levels of respirable PM4 (range 25-71 μg/m3). However, urinary levels of 8-hydroxy-2'-deoxyguanosine increased significantly within each shift and between both days for non-smokers. The between-day increase was significantly correlated (p < 0.001) with the concentrations of organic carbon, NOx, and the particulate copper content. The within-shift increase in 8OHdG was highly correlated to an increase of the urinary reducing capacity (Spearman ρ = 0.59, p < 0.0001). Conclusions These findings confirm that exposure to components associated to respirable particulate matter causes a systemic oxidative stress, as measured with the urinary 8OHdG. The strong association observed between urinary 8OHdG with the reducing capacity is suggestive of protective

  9. Matrix metalloproteinase 8 degrades apolipoprotein A-I and reduces its cholesterol efflux capacity.

    PubMed

    Salminen, Aino; Åström, Pirjo; Metso, Jari; Soliymani, Rabah; Salo, Tuula; Jauhiainen, Matti; Pussinen, Pirkko J; Sorsa, Timo

    2015-04-01

    Various cell types in atherosclerotic lesions express matrix metalloproteinase (MMP)-8. We investigated whether MMP-8 affects the structure and antiatherogenic function of apolipoprotein (apo) A-I, the main protein component of HDL particles. Furthermore, we studied serum lipid profiles and cholesterol efflux capacity in MMP-8-deficient mouse model. Incubation of apoA-I (28 kDa) with activated MMP-8 yielded 22 kDa and 25 kDa apoA-I fragments. Mass spectrometric analyses revealed that apoA-I was cleaved at its carboxyl-terminal part. Treatment of apoA-I and HDL with MMP-8 resulted in significant reduction (up to 84%, P < 0.001) in their ability to facilitate cholesterol efflux from cholesterol-loaded THP-1 macrophages. The cleavage of apoA-I by MMP-8 and the reduction in its cholesterol efflux capacity was inhibited by doxycycline. MMP-8-deficient mice had significantly lower serum triglyceride (TG) levels (P = 0.003) and larger HDL particles compared with wild-type (WT) mice. However, no differences were observed in the apoA-I levels or serum cholesterol efflux capacities between the mouse groups. Proteolytic modification of apoA-I by MMP-8 may impair the first steps of reverse cholesterol transport, leading to increased accumulation of cholesterol in the vessel walls. Eventually, inhibition of MMPs by doxycycline may reduce the risk for atherosclerotic vascular diseases.

  10. Monocarboxylate transporter 8 modulates the viability and invasive capacity of human placental cells and fetoplacental growth in mice.

    PubMed

    Vasilopoulou, Elisavet; Loubière, Laurence S; Heuer, Heike; Trajkovic-Arsic, Marija; Darras, Veerle M; Visser, Theo J; Lash, Gendie E; Whitley, Guy S; McCabe, Christopher J; Franklyn, Jayne A; Kilby, Mark D; Chan, Shiao Y

    2013-01-01

    Monocarboxylate transporter 8 (MCT8) is a well-established thyroid hormone (TH) transporter. In humans, MCT8 mutations result in changes in circulating TH concentrations and X-linked severe global neurodevelopmental delay. MCT8 is expressed in the human placenta throughout gestation, with increased expression in trophoblast cells from growth-restricted pregnancies. We postulate that MCT8 plays an important role in placental development and transplacental TH transport. We investigated the effect of altering MCT8 expression in human trophoblast in vitro and in a Mct8 knockout mouse model. Silencing of endogenous MCT8 reduced T3 uptake into human extravillous trophoblast-like cells (SGHPL-4; 40%, P<0.05) and primary cytotrophoblast (15%, P<0.05). MCT8 over-expression transiently increased T3 uptake (SGHPL-4∶30%, P<0.05; cytotrophoblast: 15%, P<0.05). Silencing MCT8 did not significantly affect SGHPL-4 invasion, but with MCT8 over-expression T3 treatment promoted invasion compared with no T3 (3.3-fold; P<0.05). Furthermore, MCT8 silencing increased cytotrophoblast viability (∼20%, P<0.05) and MCT8 over-expression reduced cytotrophoblast viability independently of T3 (∼20%, P<0.05). In vivo, Mct8 knockout reduced fetal:placental weight ratios compared with wild-type controls at gestational day 18 (25%, P<0.05) but absolute fetal and placental weights were not significantly different. The volume fraction of the labyrinthine zone of the placenta, which facilitates maternal-fetal exchange, was reduced in Mct8 knockout placentae (10%, P<0.05). However, there was no effect on mouse placental cell proliferation in vivo. We conclude that MCT8 makes a significant contribution to T3 uptake into human trophoblast cells and has a role in modulating human trophoblast cell invasion and viability. In mice, Mct8 knockout has subtle effects upon fetoplacental growth and does not significantly affect placental cell viability probably due to compensatory mechanisms in vivo.

  11. Monocarboxylate Transporter 8 Modulates the Viability and Invasive Capacity of Human Placental Cells and Fetoplacental Growth in Mice

    PubMed Central

    Vasilopoulou, Elisavet; Loubière, Laurence S.; Heuer, Heike; Trajkovic-Arsic, Marija; Darras, Veerle M.; Visser, Theo J.; Lash, Gendie E.; Whitley, Guy S.; McCabe, Christopher J.; Franklyn, Jayne A.; Kilby, Mark D.; Chan, Shiao Y.

    2013-01-01

    Monocarboxylate transporter 8 (MCT8) is a well-established thyroid hormone (TH) transporter. In humans, MCT8 mutations result in changes in circulating TH concentrations and X-linked severe global neurodevelopmental delay. MCT8 is expressed in the human placenta throughout gestation, with increased expression in trophoblast cells from growth-restricted pregnancies. We postulate that MCT8 plays an important role in placental development and transplacental TH transport. We investigated the effect of altering MCT8 expression in human trophoblast in vitro and in a Mct8 knockout mouse model. Silencing of endogenous MCT8 reduced T3 uptake into human extravillous trophoblast-like cells (SGHPL-4; 40%, P<0.05) and primary cytotrophoblast (15%, P<0.05). MCT8 over-expression transiently increased T3 uptake (SGHPL-4∶30%, P<0.05; cytotrophoblast: 15%, P<0.05). Silencing MCT8 did not significantly affect SGHPL-4 invasion, but with MCT8 over-expression T3 treatment promoted invasion compared with no T3 (3.3-fold; P<0.05). Furthermore, MCT8 silencing increased cytotrophoblast viability (∼20%, P<0.05) and MCT8 over-expression reduced cytotrophoblast viability independently of T3 (∼20%, P<0.05). In vivo, Mct8 knockout reduced fetal:placental weight ratios compared with wild-type controls at gestational day 18 (25%, P<0.05) but absolute fetal and placental weights were not significantly different. The volume fraction of the labyrinthine zone of the placenta, which facilitates maternal-fetal exchange, was reduced in Mct8 knockout placentae (10%, P<0.05). However, there was no effect on mouse placental cell proliferation in vivo. We conclude that MCT8 makes a significant contribution to T3 uptake into human trophoblast cells and has a role in modulating human trophoblast cell invasion and viability. In mice, Mct8 knockout has subtle effects upon fetoplacental growth and does not significantly affect placental cell viability probably due to compensatory mechanisms in vivo. PMID

  12. Seed dispersal capacity and post-dispersal fate of the invasive Spartina alterniflora in saltmarshes of the Yangtze Estuary

    NASA Astrophysics Data System (ADS)

    Xiao, Derong; Zhang, Chao; Zhang, Liquan; Zhu, Zhenchang; Tian, Kun; Gao, Wei

    2016-02-01

    Spartina alterniflora is one of the most serious invasive species in the coastal saltmarshes of China. Seeds are generally considered to be the main method for this species to colonise new habitat, but little is known quantitatively about the seed dispersal capacity and post-dispersal fate (i.e., germination and survival time). We measured the duration of seed flotation, seed persistence and seed germination of S. alterniflora in three intertidal zones [low intertidal zone (LIT), middle intertidal zone (MIT) and high intertidal zone (HIT)] in the Yangtze Estuary on the eastern coast of China. The results showed that (1) the flotation time of S. alterniflora seeds ranged from 3 to 13 days, and the values were higher in HIT and MIT than in LIT; (2) the period of seed germination was from February to June, mainly in March and April, and seed source affected seed germination as the values for seeds from HIT and MIT were much higher than those from LIT, while burial sites had no effect on germination percentages, and (3) the seed persistence was less than a year regardless of seed source, which was characterised by a transient seed bank, with values being higher in HIT and MIT than in LIT. Our results suggested that low marsh plants were far less able to produce successful seeds, or conversely, that the mid-marsh location had plants with the greatest seed production and seed mass, and the high- and mid-marsh plants had good seed floatation ability, germination and survival. Thus, plants in the mid-and high-marsh may contribute disproportionally to an invasion.

  13. Inhibition of TRPC6 reduces non-small cell lung cancer cell proliferation and invasion

    PubMed Central

    Lu, Xiao-Yu; Yan, Yan; Zhai, Yu-Jia; Bao, Qing; Doetsch, Paul W.; Deng, Xingming; Thai, Tiffany L.; Alli, Abdel A.; Eaton, Douglas C.; Shen, Bao-Zhong; Ma, He-Ping

    2017-01-01

    Recent studies indicate that the transient receptor potential canonical 6 (TRPC6) channel is highly expressed in several types of cancer cells. However, it remains unclear whether TRPC6 contributes to the malignancy of human non-small cell lung cancer (NSCLC). We used a human NSCLC A549 cell line as a model and found that pharmacological blockade or molecular knockdown of TRPC6 channel inhibited A549 cell proliferation by arresting cell cycle at the S-G2M phase and caused a significant portion of cells detached and rounded-up, but did not induce any types of cell death. Western blot and cell cycle analysis show that the detached round cells at the S-G2M phase expressed more TRPC6 than the still attached polygon cells at the G1 phase. Patch-clamp data also show that TRPC whole-cell currents in the detached cells were significantly higher than in the still attached cells. Inhibition of Ca2+-permeable TRPC6 channels significantly reduced intracellular Ca2+ in A549 cells. Interestingly, either blockade or knockdown of TRPC6 strongly reduced the invasion of this NSCLC cell line and decreased the expression of an adherent protein, fibronectin, and a tight junction protein, zonula occluden protein-1 (ZO-1). These data suggest that TRPC6-mediated elevation of intracellular Ca2+ stimulates NSCLC cell proliferation by promoting cell cycle progression and that inhibition of TRPC6 attenuates cell proliferation and invasion. Therefore, further in vivo studies may lead to a consideration of using a specific TRPC6 blocker as a complement to treat NSCLC. PMID:28030826

  14. Reduced plantarflexor specific torque in the elderly is associated with a lower activation capacity.

    PubMed

    Morse, Christopher I; Thom, Jeanette M; Davis, Mark G; Fox, Ken R; Birch, Karen M; Narici, Marco V

    2004-06-01

    Previous studies have reported a decrease in muscle torque per cross-sectional area in old age. This investigation aimed at determining the influence of agonists muscle activation and antagonists co-activation on the specific torque of the plantarflexors (PF) in recreationally active elderly males (EM) and, for comparison, in young men (YM). Twenty-one EM, aged 70-82 years, and 14 YM, aged 19-35 years, performed isometric maximum voluntary contractions (MVC). Activation was assessed by comparing the amplitude of interpolated supramaximal twitch doublets at MVC, with post-tetanic doublet peak torque. Co-activation of the tibialis anterior (TA) was evaluated as the ratio of TA-integrated EMG (IEMG) activity during PF MVC compared to TA IEMG during maximal voluntary dorsiflexion. Triceps surae muscle volume (VOL) was assessed using magnetic resonance imaging (MRI), and PF peak torque was normalised to VOL (PT/VOL) since the later approximates physiological cross-sectional area (CSA) more closely than anatomical CSA. Also, physical activity level, assessed by accelerometry, was significantly lower (21%) in the elderly males. In comparison to the YM group, a greater difference in PT (39%) than VOL (19%) was found in the EM group. PT/VOL and activation capacity were respectively lower by 25% and 21% in EM compared to YM, whereas co-activation was not significantly different. In EM PT/VOL correlated with activation (R(2)=0.31, P<0.01). In conclusion, a reduction in activation capacity may contribute significantly to the decline in specific torque in the plantar flexors of elderly males. The hypothesis is put forward that reduced physical activity is partialy responsible for the reduced activation capacity in the elderly.

  15. MiR-134 regulates the proliferation and invasion of glioblastoma cells by reducing Nanog expression.

    PubMed

    Niu, Chao Shi; Yang, Yang; Cheng, Chuan-Dong

    2013-05-01

    MiR-134 is a brain-enriched miRNA that plays an essential role in the development of the embryonic stem cell-orientated differentiation to central nervous system by suppression of Nanog and neural development (including neurons, cylindraxile and dendrites) and has been shown to be downregulated in oligodendrogliomas (ODG) and glioblastomas (GBM), suggesting its possible involvement in brain tumor progression. In this study, we defined the expression and function of miR-134, which we found to be downregulated in glioma samples and the glioblastoma cell line U87 by SYBR green real-time quantitative reverse transcription-PCR (real-time PCR). Early reports have characterized Nanog as a direct target of miR-134 by a dual-luciferase reporter assay in 293T cells. In our study, overexpression of miR-134 in U87 glioblastoma cells resulted in significant downregulation of Nanog mRNA levels as well as protein levels. miR-134 overexpression reduced the proliferation, invasiveness and migration capability of U87 cells while promoted apoptosis of these cells in vitro and suppressed the growth of tumor xenografts in vivo. These findings demonstrated that miR-134 deregulation is common in human gliomas. Restoration of its function inhibits cell proliferation, invasion and migration capability and promotes apoptosis, which could be partly due to its inhibitory effect on Nanog protein expression in glioblastoma cells. MiR-134 could play an important role as a tumor suppressor relying on its direct translational attenuation of Nanog.

  16. PreImplantation Factor (PIF*) endogenously prevents preeclampsia: Promotes trophoblast invasion and reduces oxidative stress.

    PubMed

    Barnea, E R; Vialard, F; Moindjie, H; Ornaghi, S; Dieudonne, M N; Paidas, M J

    2016-04-01

    Preeclampsia is a unique pregnancy disorder whose patho-physiology is initiated early in gestation, while clinical manifestations typically occur in mid-to-late pregnancy. Thus, prevention should optimally be initiated in early gestation. The intimate interaction between PIF, secreted early by viable embryos, and its host-mother provides insight into putative mechanisms of preeclampsia prevention. PIF is instrumental at the two critical events underlying preeclampsia. At first, shallow implantation leads to impaired placentation, oxidative stress, protein misfolding, and endothelial dysfunction. Later in gestation, hyper-oxygenation due to overflow of maternally derived oxygenated blood compromises the placenta. The first is likely involved in early preeclampsia occurrence due to reduced effectiveness of trophoblast/uterus interaction. The latter is observed with later-onset preeclampsia, caused by a breakdown in placental blood flow regulation. We reported that 1. PIF promotes implantation, endometrium receptivity, trophoblast invasion and increases pro-tolerance trophoblastic HLA-G expression and, 2. PIF protects against oxidative stress and protein misfolding, interacting with specific targets in embryo, 3. PIF regulates systemic immunity to reduce oxidative stress. Using PIF as an early preventative preeclampsia intervention could ameliorate or even prevent the disease, whose current main solution is early delivery.

  17. A co-invasive microsporidian parasite that reduces the predatory behaviour of its host Dikerogammarus villosus (Crustacea, Amphipoda).

    PubMed

    Bacela-Spychalska, K; Rigaud, T; Wattier, R A

    2014-02-01

    Parasites are known to affect the predatory behaviour or diet of their hosts. In relation to biological invasions, parasites may significantly influence the invasiveness of the host population and/or mediate the relationships between the invader and the invaded community. Dikerogammarus villosus, a recently introduced species, has had a major impact in European rivers. Notably, its high position in trophic web and high predatory behaviour, have both facilitated its invasive success, and affected other macroinvertebrate taxa in colonized habitats. The intracellular parasite Cucumispora dikerogammari, specific to D. villosus, has successfully dispersed together with this amphipod. Data presented here have shown that D. villosus infected by this parasite have a reduced predatory behaviour compared with healthy individuals, and are much more active suggesting that the co-invasive parasite may diminish the predatory pressure of D. villosus on newly colonized communities.

  18. CXCR4 increases in-vivo glioma perivascular invasion, and reduces radiation induced apoptosis: A genetic knockdown study

    PubMed Central

    Yadav, Viveka Nand; Zamler, Daniel; Baker, Gregory J.; Kadiyala, Padma; Erdreich-Epstein, Anat; DeCarvalho, Ana C.; Mikkelsen, Tom; Castro, Maria G.; Lowenstein, Pedro R.

    2016-01-01

    Glioblastoma (GBM) is a highly invasive brain tumor. Perivascular invasion, autovascularization and vascular co-option occur throughout the disease and lead to tumor invasion and progression. The molecular basis for perivascular invasion, i.e., the interaction of glioma tumor cells with endothelial cells is not well characterized. Recent studies indicate that glioma cells have increased expression of CXCR4. We investigated the in-vivo role of CXCR4 in perivascular invasion of glioma cells using shRNA-mediated knock down of CXCR4. We show that primary cultures of human glioma stem cells HF2303 and mouse glioma GL26-Cit cells exhibit significant migration towards human (HBMVE) and mouse (MBVE) brain microvascular endothelial cells. Blocking CXCR4 on tumor cells with AMD3100 in-vitro, inhibits migration of GL26-Cit and HF2303 toward MBVE and HBMVE cells. Additionally, genetic down regulation of CXCR4 in mouse glioma GL26-Cit cells inhibits their in-vitro migration towards MBVE cells; in an in-vivo intracranial mouse model, these cells display reduced tumor growth and perivascular invasion, leading to increased survival. Quantitative analysis of brain sections showed that CXCR4 knockdown tumors are less invasive. Lastly, we tested the effects of radiation on CXCR4 knock down GL26-Cit cells in an orthotopic brain tumor model. Radiation treatment increased apoptosis of CXCR4 downregulated tumor cells and prolonged median survival. In summary, our data suggest that CXCR4 signaling is critical for perivascular invasion of GBM cells and targeting this receptor makes tumors less invasive and more sensitive to radiation therapy. Combination of CXCR4 knock down and radiation treatment might improve the efficacy of GBM therapy. PMID:27863376

  19. Total Reducing Capacity in Aquifer Minerals and Sediments: Quantifying the Potential to Attenuate Cr(VI) in Groundwater

    SciTech Connect

    Sisman, S. Lara

    2015-07-20

    Hexavalent chromium, Cr(VI), is present in the environment as a byproduct of industrial processes. Due to its mobility and toxicity, it is crucial to attenuate or remove Cr(VI) from the environment. The objective of this investigation was to quantify potential natural attenuation, or reduction capacity, of reactive minerals and aquifer sediments. Samples of reduced-iron containing minerals such as ilmenite, as well as Puye Formation sediments representing a contaminated aquifer in New Mexico, were reacted with chromate. The change in Cr(VI) during the reaction was used to calculate reduction capacity. This study found that minerals that contain reduced iron, such as ilmenite, have high reducing capacities. The data indicated that sample history may impact reduction capacity tests due to surface passivation. Further, this investigation identified areas for future research including: a) refining the relationships between iron content, magnetic susceptibility and reduction capacity, and b) long term kinetic testing using fresh aquifer sediments.

  20. Highlights Regarding Host Predisposing Factors to Recurrent Vulvovaginal Candidiasis: Chronic Stress and Reduced Antioxidant Capacity

    PubMed Central

    Akimoto-Gunther, Luciene; Bonfim-Mendonça, Patrícia de Souza; Takahachi, Gisele; Irie, Mary Mayumi T.; Miyamoto, Sônia; Consolaro, Márcia Edilaine Lopes; Svidzinsk, Terezinha I. Estivalet

    2016-01-01

    We studied host factors that could predispose women to develop recurrent vulvovaginal candidiasis (RVVC), including glycemia, insulin resistance, chronic stress, antioxidant capacity, overall immune status, local inflammation and vaginal microbiota. The presence of yeasts in vaginal culture was screened in 277 women, with or without signs and symptoms of VVC and RVVC. The presence of an inflammatory process and microbiota were analyzed through vaginal bacterioscopy and cervical-vaginal cytology, respectively. Fasting-blood samples were collected by standard venipuncture for biochemical analyses. Flow cytometry was employed to obtain the T helper/T cytotoxic lymphocyte ratio, and insulin resistance was assessed by the HOMA index (HI). Yeasts were isolated from 71 (26%) women: 23 (32.4%) with a positive culture but without symptoms (COL), 22 (31%) in an acute episode (VVC), and 26 (36.6%) with RVVC. C. albicans was the main yeast isolated in all clinical profiles. The control group (negative culture) comprised 206 women. Diabetes mellitus and insulin resistance were more associated with the positive-culture groups (COL, VVC and RVVC) than with negative ones. The RVVC group showed lower mean levels of cortisol than the control group and lower antioxidant capacity than all other groups. The T Helper/T cytotoxic lymphocyte ratio was similar in all groups. The RVVC group showed a similar level of vaginal inflammation to the control group, and lower than in the COL and VVC groups. Only the CVV group showed a reduction in vaginal lactobacillus microbiota. Our data suggest that both chronic stress (decreased early-morning cortisol levels) and reduced antioxidant capacity can be host predisposing factors to RVVC. PMID:27415762

  1. Interpretation of spirometric tests in asthmatic patients with reduced forced vital capacity.

    PubMed

    Almirall, J J; Páez, I

    1994-01-01

    We have studied 175 consecutive asthmatic patients presenting with: 1) a reversible airflow obstruction, demonstrated by an increase in the forced expiratory volume in 1 second (FEV1) or in the forced vital capacity (FVC) by at least 12% along with an absolute increase of 200 ml versus prebronchodilator values after inhalation of salbutamol; 2) FVC below the lower normal limit before administration of the bronchodilator; and 3) normal FVC or slow vital capacity after bronchodilator. Two different criteria for the lower normal limit of the FEV1/FVC ratio were used to determine whether prebronchodilator spirometric patterns could be considered obstructive or not. The use of the predicted FEV1/FVC ratio as the lower normal limit allowed correct identification of obstruction in 94.9% of the patients, whereas taking the estimated fifth percentile as the lower normal limit of the FEV1/FVC correctly identified obstruction in only 78.9% of the asthmatics. Our results suggest that the predicted FEV1/FVC ratio is an adequate estimate of the lower normal limit in asthmatic patients with reduced FVC in order to distinguish obstructive from nonobstructive patterns.

  2. Maternal obesity reduces oxidative capacity in fetal skeletal muscle of Japanese macaques

    PubMed Central

    McCurdy, Carrie E.; Hetrick, Byron; Houck, Julie; Drew, Brian G.; Kaye, Spencer; Lashbrook, Melanie; Bergman, Bryan C.; Takahashi, Diana L.; Dean, Tyler A.; Gertsman, Ilya; Hansen, Kirk C.; Philp, Andrew; Hevener, Andrea L.; Chicco, Adam J.; Aagaard, Kjersti M.; Grove, Kevin L.; Friedman, Jacob E.

    2016-01-01

    Maternal obesity is proposed to alter the programming of metabolic systems in the offspring, increasing the risk for developing metabolic diseases; however, the cellular mechanisms remain poorly understood. Here, we used a nonhuman primate model to examine the impact of a maternal Western-style diet (WSD) alone, or in combination with obesity (Ob/WSD), on fetal skeletal muscle metabolism studied in the early third trimester. We find that fetal muscle responds to Ob/WSD by upregulating fatty acid metabolism, mitochondrial complex activity, and metabolic switches (CPT-1, PDK4) that promote lipid utilization over glucose oxidation. Ob/WSD fetuses also had reduced mitochondrial content, diminished oxidative capacity, and lower mitochondrial efficiency in muscle. The decrease in oxidative capacity and glucose metabolism was persistent in primary myotubes from Ob/WSD fetuses despite no additional lipid-induced stress. Switching obese mothers to a healthy diet prior to pregnancy did not improve fetal muscle mitochondrial function. Lastly, while maternal WSD alone led only to intermediary changes in fetal muscle metabolism, it was sufficient to increase oxidative damage and cellular stress. Our findings suggest that maternal obesity or WSD, alone or in combination, leads to programmed decreases in oxidative metabolism in offspring muscle. These alterations may have important implications for future health. PMID:27734025

  3. Reduced Efficiency and Capacity of Cognitive Control in Autism Spectrum Disorder.

    PubMed

    Mackie, Melissa-Ann; Fan, Jin

    2016-03-01

    Cognitive control constrains mental operations to prioritize information that reaches conscious awareness and is essential to flexible, adaptive behavior under conditions of uncertainty. Cognitive control can be compromised by neurodevelopmental disorders such as autism spectrum disorder (ASD), which is characterized by the presence of social and communicative deficits, and restricted interests/repetitive behaviors. Although prior investigations have attempted to elucidate the nature of cognitive control in ASD, whether there is an underlying information processing deficit associated with cognitive control remains unclear. This study challenged cognitive control in 15 high-functioning adults with ASD and 15 typically developing (TD) controls using three novel tasks designed to systematically manipulate uncertainty. We aimed to investigate the efficiency of cognitive control in sequential information processing, cognitive control of nonsequential information processing across a range of cognitive loads and cognitive control capacity under time constraint. Results demonstrated that the ASD group performed less efficiently on sequential and nonsequential information processing, and had reduced cognitive control capacity under time constraint relative to the TD group. These findings suggest that inefficient cognitive control of information processing may be a fundamental deficit in ASD.

  4. Water-borne pharmaceuticals reduce phenotypic diversity and response capacity of natural phytoplankton communities

    PubMed Central

    Jokela, Jukka; Castiglioni, Sara; Thomas, Mridul K.; Nizzetto, Luca

    2017-01-01

    Chemical micropollutants occur worldwide in the environment at low concentrations and in complex mixtures, and how they affect the ecology of natural systems is still uncertain. Dynamics of natural communities are driven by the interaction between individual organisms and their growth environment, which is mediated by the organisms’ expressed phenotypic traits. We tested whether exposure to a mixture of 12 pharmaceuticals and personal care products (PPCP) influences phenotypic trait diversity in lake phytoplankton communities and their ability to regulate biomass production to fit environmental changes (response capacity). We exposed natural phytoplankton assemblages to three mixture levels in permeable microcosms maintained at three depths in a eutrophic lake for one week, during which the environmental conditions were fluctuating. We studied individual-level traits, phenotypic diversity and community biomass. PPCP reduced individual-level trait variance and overall community phenotypic diversity, but maintained higher standing phytoplankton biomass compared to untreated controls. Estimated effect sizes of PPCP on traits and community properties were very large (partial Eta-squared > 0.15). The PPCP mixture antagonistically interacted with the natural environmental gradient in habitats offered by different depths and, at concentrations comparable to those in waste-water effluents, prevented communities from converging to the same phenotypic structure and total biomass of unexposed controls. We show that micropollutants can alter individual-level trait diversity of lake phytoplankton communities and therefore their capacity to respond to natural environmental gradients, potentially affecting aquatic ecosystem processes. PMID:28328933

  5. Automatic method for the determination of Folin-Ciocalteu reducing capacity in food products.

    PubMed

    Magalhães, Luís M; Segundo, Marcela A; Reis, Salette; Lima, José L F C; Rangel, António O S S

    2006-07-26

    In the present work, an automatic flow procedure based on multi-syringe flow injection analysis was developed for the assessment of Folin-Ciocalteu reagent (FCR) reducing capacity in several types of food products using gallic acid as the standard. Different strategies for mixing of sample and reagent were tested (continuous flow of FCR, merging zones, and intercalated zones approaches); lower reagent consumption and higher determination throughput were attained for the merging zones approach (100 microL of sample+100 microL of FCR). The application of the proposed method to compounds with known antioxidant activity (both phenolic and nonphenolic) and to samples (wines, beers, teas, soft drinks, and fruit juices) provided results similar to those obtained by the conventional batch method. The detection limit was 0.6 mg L-1, and the determination frequency was about 12 h-1. Good repeatability was attained (RSD<1.3%, n=10).

  6. Aminopyrald and Picloram reduce seed production of the invasive annual grasses Medusahead and Ventenata

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Invasive annual grasses are negatively impacting millions of hectares of U.S. rangelands. Sulfonylurea, amino acid synthesis inhibitor and photosynthesis inhibitor herbicides are sometimes used to control invasive annual grasses. On the other hand, growth regulator herbicides are widely used to co...

  7. Landscape corridors can increase invasion by an exotic species and reduce diversity of native species

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Although corridors have become commonplace in conservation to mitigate negative effects of habitat fragmentation, concerns persist that they may facilitate spread of invasive species. In a large-scale experiment, we measured effects of corridors on invasive fire ants, Solenopsis invicta, and on comm...

  8. Cupric ion reducing antioxidant capacity assay for antioxidants in human serum and for hydroxyl radical scavengers.

    PubMed

    Apak, Reşat; Güçlü, Kubilay; Ozyürek, Mustafa; Bektaşoğlu, Burcu; Bener, Mustafa

    2010-01-01

    Tests measuring the combined antioxidant effect of the nonenzymatic defenses in biological fluids may be useful in providing an index of the organism's capability to counteract reactive species known as pro-oxidants, resist oxidative damage, and combat oxidative stress-related diseases. The selected chromogenic redox reagent for the assay of human serum should be easily accessible, stable, selective, and respond to all types of biologically important antioxidants such as ascorbic acid, alpha-tocopherol, beta-carotene, reduced glutathione (GSH), uric acid, and bilirubin, regardless of chemical type or hydrophilicity. Our recently developed cupric reducing antioxidant capacity (CUPRAC) spectrophotometric method for a number of polyphenols and flavonoids using the copper(II)-neocuproine reagent in ammonium acetate buffer is now applied to a complete series of plasma antioxidants for the assay of total antioxidant capacity of serum, and the resulting absorbance at 450 nm is recorded either directly (e.g., for ascorbic acid, alpha-tocopherol, and glutathione) or after incubation at 50 degrees C for 20 min (e.g., for uric acid, bilirubin, and albumin), quantitation being made by means of a calibration curve. The lipophilic antioxidants, alpha-tocopherol and beta-carotene, are assayed in dichloromethane. Lipophilic antioxidants of serum are extracted with n-hexane from an ethanolic solution of serum subjected to centrifugation. Hydrophilic antioxidants of serum are assayed in the centrifugate after perchloric acid precipitation of proteins. The CUPRAC molar absorptivities, linear ranges, and TEAC (trolox equivalent antioxidant capacity) coefficients of the serum antioxidants are established, and the results are evaluated in comparison with the findings of the ABTS/TEAC reference method. The intra- and inter-assay coefficients of variation (CVs) are 0.7 and 1.5%, respectively, for serum. The CUPRAC assay proved to be efficient for glutathione and thiol-type antioxidants

  9. Building capacity for national carbon measurements for reducing emissions from deforestation and forest degradation

    NASA Astrophysics Data System (ADS)

    Goetz, S. J.; Laporte, N.; Horning, N.; Pelletier, J.; Jantz, P.; Ndunda, P.

    2014-12-01

    Many tropical countries are now working on developing their strategies for reducing emissions from deforestation and forest degradation, including activities that result in conservation or enhancement of forest carbon stocks and sustainable management of forests to effectively decrease atmospheric carbon emissions (i.e. REDD+). A new international REDD+ agreement is at the heart of recent negotiations of the parties to the UN Framework Convention on Climate Change (UNFCCC). REDD+ mechanisms could provide an opportunity to not only diminish an important source of emissions, but also to promote large-scale conservation of tropical forests and establish incentives and opportunities to alleviate poverty. Most tropical countries still lack basic information for developing and implementing their forest carbon stock assessments, including the extent of forest area and the rate at which forests are being cleared and/or degraded, and the carbon amounts associated with these losses. These same countries also need support to conduct integrated assessments of the most promising approaches for reducing emissions, and in identifying those policy options that hold the greatest potential while minimizing potential negative impacts of REDD+ policies. The WHRC SERVIR project in East Africa is helping to provide these data sets to countries via best practice tools and methods to support cost effective forest carbon monitoring solutions and more informed decision making processes under REDD+. We will present the results of our capacity building activites in the region and planned future efforts being coordinated with the NASA-SERVIR Hub in Kenya to support to REDD+ decision support.

  10. Reduced aerobic capacity causes leaky ryanodine receptors that trigger arrhythmia in a rat strain artificially selected and bred for low aerobic running capacity

    PubMed Central

    Høydal, MA; Stølen, TO; Johnsen, AB; Alvez, M; Catalucci, D; Condorelli, G; Koch, LG; Britton, SL; Smith, GL; Wisløff, U

    2014-01-01

    Aim Rats selectively bred for inborn Low Capacity of Running (LCR) display a series of poor health indices where as rats selected for High Capacity of Running (HCR) display a healthy profile. We hypothesized that selection of low aerobic capacity over generations leads to a phenotype with increased diastolic Ca2+ leak that trigger arrhythmia. Methods We used rats selected for HCR (N=10) or LCR (N=10) to determine the effect of inborn aerobic capacity on Ca2+ leak and susceptibility of ventricular arrhythmia. We studied isolated FURA2/AM loaded cardiomyocytes to detect Ca2+-handling and function on an inverted epi-fluorescence microscope. To determine arrhythmogenicity we did a final experiment with electrical burst pacing in Langendorff perfused hearts. Results Ca2+-handling was impaired by reduced Ca2+ amplitude, prolonged time to 50% Ca2+ decay, and reduced sarcoplasmic reticulum (SR) Ca2+-content. Impaired Ca2+ removal was influenced by reduced SR Ca2+ ATP-ase 2a (SERCA2a) function and increased sodium/Ca2+-exchanger (NCX) in LCR rats. Diastolic Ca2 leak was 87% higher in LCR rats. The leak was reduced by CaMKII inhibition. Expression levels of phosphorylated theorine-286 CaMKII levels and increased RyR2 phosphorylation at the Serine-2814 site mechanistically support our findings of increased leak in LCR. LCR rats had significantly higher incidence of ventricular fibrillation. Conclusion Selection of inborn low aerobic capacity over generations leads to a phenotype with increased risk of ventricular fibrillation. Increased phosphorylation of CaMKII at serine-2814 at the cardiac ryanodine receptor appears as an important mechanism of impaired Ca2+ handling and diastolic Ca2+ leak that results in increased susceptibility to ventricular fibrillation. PMID:24444142

  11. A reduced genome decreases the host carrying capacity for foreign DNA

    PubMed Central

    2014-01-01

    Background Host-plasmid interactions have been discussed largely in terms of the influences of plasmids, whereas the contributions of variations in host genomes to host interactions with foreign DNA remain unclear. A strain with a so-called “clean genome” (i.e., MDS42) of reduced genome size has recently been generated from the wild-type strain MG1655, a commonly used host strain. A quantitative evaluation of the influence of plasmid burdens in these two Escherichia coli strains can not only provide an understanding of how a reduced genome responds to foreign DNA but also offer insights into the proper application of these strains. Results The decreases in growth caused by the cost of carrying foreign DNA were similar for the wild-type and clean-genome strains. A negative correlation between the growth rate and the total amount of exogenous DNA was observed in both strains, but a better theoretical fit with a higher statistical significance was found for the strain with the clean genome. Compared to the wild-type strain, the clean-genome strain exhibited a reduced carrying capacity for exogenous DNA, which was largely attributed to its ability to restrict the replication of foreign DNA. A tendency to allocate energy and resources toward gene expression, but not DNA replication, was observed in the strain with the clean genome. Conclusions The possession of a clean genome constrained the plasmid copy number to a wild-type-equivalent load. The results indicate that the wild-type strain possesses a greater tolerance for foreign DNA, as in endosymbiosis, and that the use of strains with clean genomes will be favorable in the applications that require precise control and theoretical prediction. PMID:24685185

  12. Overexpression of NaV 1.6 channels is associated with the invasion capacity of human cervical cancer.

    PubMed

    Hernandez-Plata, Everardo; Ortiz, Cindy S; Marquina-Castillo, Brenda; Medina-Martinez, Ingrid; Alfaro, Ana; Berumen, Jaime; Rivera, Manuel; Gomora, Juan C

    2012-05-01

    Functional activity of voltage-gated sodium channels (VGSC) has been associated to the invasion and metastasis behaviors of prostate, breast and some other types of cancer. We previously reported the functional expression of VGSC in primary cultures and biopsies derived from cervical cancer (CaC). Here, we investigate the relative expression levels of VGSC subunits and its possible role in CaC. Quantitative real-time PCR revealed that mRNA levels of Na(V) 1.6 α-subunit in CaC samples were ∼40-fold higher than in noncancerous cervical (NCC) biopsies. A Na(V) 1.7 α-subunit variant also showed increased mRNA levels in CaC (∼20-fold). All four Na(V) β subunits were also detected in CaC samples, being Na(V) β1 the most abundant. Proteins of Na(V) 1.6 and Na(V) 1.7 α-subunits were immunolocalized in both NCC and CaC biopsies and in CaC primary cultures as well; however, although in NCC sections proteins were mainly relegated to the plasma membrane, in CaC biopsies and primary cultures the respective signal was stronger and widely distributed in both cytoplasm and plasma membrane. Functional activity of Na(V) 1.6 channels in the plasma membrane of CaC cells was confirmed by whole-cell patch-clamp experiments using Cn2, a Na(V) 1.6-specific toxin, which blocked ∼30% of the total sodium current. Blocking of sodium channels VGSC with tetrodotoxin and Cn2 did not affect proliferation neither migration, but reduced by ∼20% the invasiveness of CaC primary culture cells in vitro assays. We conclude that Na(V) 1.6 is upregulated in CaC and could serve as a novel molecular marker for the metastatic behavior of this carcinoma.

  13. Mechanism and capacities of reducing ecological cost through rice–duck cultivation

    PubMed Central

    Long, Pan; Huang, Huang; Liao, Xiaolan; Fu, Zhiqiang; Zheng, Huabin; Chen, Aiwu; Chen, Can

    2013-01-01

    BACKGROUND: Rice–duck cultivation is the essence of Chinese traditional agriculture. A scientific assessment of the mechanism and its capacity is of theoretical significance and practical value in improving modern agricultural technology. RESULTS: The duck’s secretions, excreta and their treading, pecking and predation decrease the occurrence of plant diseases, pests and weeds, enrich species diversity and improve the field environment. The rice–duck intergrowth system effectively prevents rice planthoppers and rice leafhoppers. The control effects can be up to 98.47% and 100% respectively; it also has effects on the control of Chilo suppressalis, Tryporyza incertulas and the rice leafrollers. Notable control results are found on sheath blight, while the effects on other diseases are about 50%. Harm from weeds is placed under primary control; prevention of weeds is sequenced by broadleaf weeds > sedge weeds > Gramineae weeds. Contents of soil organic matter, N, P and K are improved by the system; nutrient utilization is accelerated, resulting in decreased fertilizer application. Greenhouse gas emissions are reduced by 1–2% and duck fodder is saved in this system. There is also an obvious economic benefit. CONCLUSION: Compared to conventional rice cultivation, rice–duck cultivation shows great benefits to ecologic cost and economic income. © 2013 The Authors. Journal of the Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry. PMID:23703299

  14. Synergy of extreme drought and shrub invasion reduce ecosystem functioning and resilience in water-limited climates

    NASA Astrophysics Data System (ADS)

    Caldeira, Maria C.; Lecomte, Xavier; David, Teresa S.; Pinto, Joaquim G.; Bugalho, Miguel N.; Werner, Christiane

    2015-10-01

    Extreme drought events and plant invasions are major drivers of global change that can critically affect ecosystem functioning and alter ecosystem-atmosphere exchange. Invaders are expanding worldwide and extreme drought events are projected to increase in frequency and intensity. However, very little is known on how these drivers may interact to affect the functioning and resilience of ecosystems to extreme events. Using a manipulative shrub removal experiment and the co-occurrence of an extreme drought event (2011/2012) in a Mediterranean woodland, we show that native shrub invasion and extreme drought synergistically reduced ecosystem transpiration and the resilience of key-stone oak tree species. Ecosystem transpiration was dominated by the water use of the invasive shrub Cistus ladanifer, which further increased after the extreme drought event. Meanwhile, the transpiration of key-stone tree species decreased, indicating a competitive advantage in favour of the invader. Our results suggest that in Mediterranean-type climates the invasion of water spending species and projected recurrent extreme drought events may synergistically cause critical drought tolerance thresholds of key-stone tree species to be surpassed, corroborating observed higher tree mortality in the invaded ecosystems. Ultimately, this may shift seasonally water limited ecosystems into less desirable alternative states dominated by water spending invasive shrubs.

  15. Parasites reduce food web robustness because they are sensitive to secondary extinction as illustrated by an invasive estuarine snail.

    PubMed

    Lafferty, Kevin D; Kuris, Armand M

    2009-06-27

    A robust food web is one in which few secondary extinctions occur after removing species. We investigated how parasites affected the robustness of the Carpinteria Salt Marsh food web by conducting random species removals and a hypothetical, but plausible, species invasion. Parasites were much more likely than free-living species to suffer secondary extinctions following the removal of a free-living species from the food web. For this reason, the food web was less robust with the inclusion of parasites. Removal of the horn snail, Cerithidea californica, resulted in a disproportionate number of secondary parasite extinctions. The exotic Japanese mud snail, Batillaria attramentaria, is the ecological analogue of the native California horn snail and can completely replace it following invasion. Owing to the similarities between the two snail species, the invasion had no effect on predator-prey interactions. However, because the native snail is host for 17 host-specific parasites, and the invader is host to only one, comparison of a food web that includes parasites showed significant effects of invasion on the native community. The hypothetical invasion also significantly reduced the connectance of the web because the loss of 17 native trematode species eliminated many links.

  16. Synergy of extreme drought and shrub invasion reduce ecosystem functioning and resilience in water-limited climates.

    PubMed

    Caldeira, Maria C; Lecomte, Xavier; David, Teresa S; Pinto, Joaquim G; Bugalho, Miguel N; Werner, Christiane

    2015-10-13

    Extreme drought events and plant invasions are major drivers of global change that can critically affect ecosystem functioning and alter ecosystem-atmosphere exchange. Invaders are expanding worldwide and extreme drought events are projected to increase in frequency and intensity. However, very little is known on how these drivers may interact to affect the functioning and resilience of ecosystems to extreme events. Using a manipulative shrub removal experiment and the co-occurrence of an extreme drought event (2011/2012) in a Mediterranean woodland, we show that native shrub invasion and extreme drought synergistically reduced ecosystem transpiration and the resilience of key-stone oak tree species. Ecosystem transpiration was dominated by the water use of the invasive shrub Cistus ladanifer, which further increased after the extreme drought event. Meanwhile, the transpiration of key-stone tree species decreased, indicating a competitive advantage in favour of the invader. Our results suggest that in Mediterranean-type climates the invasion of water spending species and projected recurrent extreme drought events may synergistically cause critical drought tolerance thresholds of key-stone tree species to be surpassed, corroborating observed higher tree mortality in the invaded ecosystems. Ultimately, this may shift seasonally water limited ecosystems into less desirable alternative states dominated by water spending invasive shrubs.

  17. Parasites reduce food web robustness because they are sensitive to secondary extinction as illustrated by an invasive estuarine snail

    USGS Publications Warehouse

    Lafferty, Kevin D.; Kuris, Armand M.

    2009-01-01

    A robust food web is one in which few secondary extinctions occur after removing species. We investigated how parasites affected the robustness of the Carpinteria Salt Marsh food web by conducting random species removals and a hypothetical, but plausible, species invasion. Parasites were much more likely than free-living species to suffer secondary extinctions following the removal of a free-living species from the food web. For this reason, the food web was less robust with the inclusion of parasites. Removal of the horn snail, Cerithidea californica, resulted in a disproportionate number of secondary parasite extinctions. The exotic Japanese mud snail, Batillaria attramentaria, is the ecological analogue of the native California horn snail and can completely replace it following invasion. Owing to the similarities between the two snail species, the invasion had no effect on predator–prey interactions. However, because the native snail is host for 17 host-specific parasites, and the invader is host to only one, comparison of a food web that includes parasites showed significant effects of invasion on the native community. The hypothetical invasion also significantly reduced the connectance of the web because the loss of 17 native trematode species eliminated many links.

  18. Synergy of extreme drought and shrub invasion reduce ecosystem functioning and resilience in water-limited climates

    PubMed Central

    Caldeira, Maria C.; Lecomte, Xavier; David, Teresa S.; Pinto, Joaquim G.; Bugalho, Miguel N.; Werner, Christiane

    2015-01-01

    Extreme drought events and plant invasions are major drivers of global change that can critically affect ecosystem functioning and alter ecosystem-atmosphere exchange. Invaders are expanding worldwide and extreme drought events are projected to increase in frequency and intensity. However, very little is known on how these drivers may interact to affect the functioning and resilience of ecosystems to extreme events. Using a manipulative shrub removal experiment and the co-occurrence of an extreme drought event (2011/2012) in a Mediterranean woodland, we show that native shrub invasion and extreme drought synergistically reduced ecosystem transpiration and the resilience of key-stone oak tree species. Ecosystem transpiration was dominated by the water use of the invasive shrub Cistus ladanifer, which further increased after the extreme drought event. Meanwhile, the transpiration of key-stone tree species decreased, indicating a competitive advantage in favour of the invader. Our results suggest that in Mediterranean-type climates the invasion of water spending species and projected recurrent extreme drought events may synergistically cause critical drought tolerance thresholds of key-stone tree species to be surpassed, corroborating observed higher tree mortality in the invaded ecosystems. Ultimately, this may shift seasonally water limited ecosystems into less desirable alternative states dominated by water spending invasive shrubs. PMID:26461978

  19. Reducing Adverse Childhood Experiences (ACE) by Building Community Capacity: A Summary of Washington Family Policy Council Research Findings

    PubMed Central

    Hall, Judy; Porter, Laura; Longhi, Dario; Becker-Green, Jody; Dreyfus, Susan

    2012-01-01

    Community capacity for organization and collaboration has been shown to be a powerful tool for improving the health and well-being of communities. Since 1994 the Washington State Family Policy Council has supported the development of community capacity in 42 community public health and safety networks. Community networks bring local communities together to restructure natural supports and local resources to meet the needs of families and children, and increase cross-system coordination and flexible funding streams to improve local services and policy. In this study, researchers sought to demonstrate the strong impact of the community networks’ capacity to interrupt health and social problems. Findings suggest that community networks reduce health and safety problems for the entire community population. Further, community networks with high community capacity reduced adverse childhood experiences (ACE) in young adults ages 18–34. PMID:22970785

  20. Nasturtium officinale reduces oxidative stress and enhances antioxidant capacity in hypercholesterolaemic rats.

    PubMed

    Yazdanparast, Razieh; Bahramikia, Seifollah; Ardestani, Amin

    2008-04-15

    Nasturtium officinale R. Br. (Brassicaceae) has been used as a home remedy by the people of south eastern (SE) region of Iran as a medicinal plant. This therapeutical application has been attributed to Nasturtium officinale (N. officinale) antioxidant capacity which is mostly tested by means of cell-free assays: 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP). In addition, the antioxidant effect of N. officinale extract has been investigated in hypercholesterolaemic rats in vivo. The results revealed that the extract has notable scavenging activity against DPPH radicals as well as potent reducing power in FRAP assay. Intragastric administration of N. officinale (500 mg/kg body weight per day) to groups of hypercholesterolaemic rats for 30 days lowered their blood total cholesterol (TC), triglyceride (TG), and low density lipoprotein cholesterol (LDL-C) levels by 37, 44 and 48%, respectively. However, the blood high density lipoprotein cholesterol (HDL-C) levels in the same treated rats increased by 16%. To evaluate the mechanism(s) of action, we studied the antioxidative potential of N. officinale extract in terms of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione reductase (GR) activities and also the level of reduced glutathione (GSH) in the liver tissues. In addition, hepatic tissue malondialdehyde level (MDA, an index of lipid peroxidation) was also determined. Under hypercholesterolaemic condition, hepatic MDA was increased. Moreover, our data indicated GSH depletion along with significant reduction in the activities of CAT and SOD in rats fed high-fat diet rats. On the other hand, significant elevation in the activities of GPx and GR were seen in the same group of rats. Treatment of hypercholesterolaemic rats with N. officinale extract significantly increased the GSH level along with enhanced CAT and SOD activities in liver tissues. Furthermore, N. officinale extract significantly

  1. Losartan reduces oxidative damage to renal DNA and conserves plasma antioxidant capacity in diabetic rats.

    PubMed

    Lodovici, Maura; Bigagli, Elisabetta; Tarantini, Francesca; Di Serio, Claudia; Raimondi, Laura

    2015-11-01

    Increased reactive oxygen species (ROS) levels produced by hyperglycemia and angiotensin-II (AT-II) are considered among the pathogenic factors in the malignant transformation of diabetic renal cells. We aimed to investigate the potential role of AT-II in the increased cancer risk seen in diabetes; measuring oxidative damage to renal DNA and protective antioxidant defenses, including adiponectin (Adp) and plasma antioxidant capacity by the Ferric Reducing Ability of Plasma (FRAP) method. In the kidney of streptozotocin (STZ)-induced (55 mg/kg) diabetic rats either treated or not treated for 3 weeks with losartan, an AT-II type 1 receptor antagonist (20 mg/kg/day); we measured 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) levels, as an index of oxidative DNA damage, circulating Adp and FRAP. Diabetic rats showed significantly higher 8-oxodGuo levels in renal DNA (8.48 ± 0.98 × 10(-6) dG, mean ± SEM n = 11) than normoglycemic ones (1.18 ± 0.04 × 10(-6) dG, mean ± SEM, n=7) and lower plasma Adp and FRAP levels in comparison to normoglycemics. The treatment of diabetic rats with losartan significantly (P < 0.01) reduced 8-oxodGuo levels (5.4 ± 0.58 × 10(-6) dG, mean ± SEM n=9) in renal DNA and conserved FRAP values. Moreover, an inverse correlation was found between 8-oxodGuo in kidney DNA and circulating Adp levels in normoglycemic and diabetic rats. Losartan treatment preserves FRAP levels, reduces DNA oxidative injury and thus the carcinogenesis risk. Furthermore, our results indicate that Adp plasma levels are a further marker of oxidative injury to the kidney and confirm that it is an important part of the plasma antioxidant defense.

  2. n-Butylidenephthalide Regulated Tumor Stem Cell Genes EZH2/AXL and Reduced Its Migration and Invasion in Glioblastoma

    PubMed Central

    Yen, Ssu-Yin; Chuang, Hong-Meng; Huang, Mao-Hsuan; Lin, Shinn-Zong; Chiou, Tzyy-Wen; Harn, Horng-Jyh

    2017-01-01

    Glioblastoma (GBM) is one of the most common and aggressive types of brain tumor. Due to its highly recurrent rate and poor prognosis, the overall survival time with this type of tumor is only 20–21 months. Recent knowledge suggests that its recurrence is in part due to the presence of cancer stem cells (CSCs), which display radioresistant, chemoresistant, self-renewal and tumorigenic potential. Enhancers of Zeste 2 (EZH2) and AXL receptor tyrosine kinase (AXL) are both highly expressed in GBM. Additionally, they are an essential regulator involved in CSCs maintenance, migration, invasion, epithelial-to-mesenchymal transition (EMT), stemness, metastasis and patient survival. In this study, we used a small molecule, n-butylidenephthalide (BP), to assess the anti-GBM stem-like cells potential, and then tried to find out the associated genes involved with regulation in migration and invasion. We demonstrated that BP reduced the expression of AXL and stemness related genes in a dose-dependent manner. The migratory and invasive capabilities of GBM stem-like cells could be reduced by AXL/EZH2. Finally, in the overexpression of AXL, EZH2 and Sox2 by transfection in GBM stem-like cells, we found that AXL/EZH2/TGF-β1, but not Sox2, might be a key regulator in tumor invasion, migration and EMT. These results might help in the development of a new anticancer compound and can be a target for treating GBM. PMID:28208648

  3. n-Butylidenephthalide Regulated Tumor Stem Cell Genes EZH2/AXL and Reduced Its Migration and Invasion in Glioblastoma.

    PubMed

    Yen, Ssu-Yin; Chuang, Hong-Meng; Huang, Mao-Hsuan; Lin, Shinn-Zong; Chiou, Tzyy-Wen; Harn, Horng-Jyh

    2017-02-10

    Glioblastoma (GBM) is one of the most common and aggressive types of brain tumor. Due to its highly recurrent rate and poor prognosis, the overall survival time with this type of tumor is only 20-21 months. Recent knowledge suggests that its recurrence is in part due to the presence of cancer stem cells (CSCs), which display radioresistant, chemoresistant, self-renewal and tumorigenic potential. Enhancers of Zeste 2 (EZH2) and AXL receptor tyrosine kinase (AXL) are both highly expressed in GBM. Additionally, they are an essential regulator involved in CSCs maintenance, migration, invasion, epithelial-to-mesenchymal transition (EMT), stemness, metastasis and patient survival. In this study, we used a small molecule, n-butylidenephthalide (BP), to assess the anti-GBM stem-like cells potential, and then tried to find out the associated genes involved with regulation in migration and invasion. We demonstrated that BP reduced the expression of AXL and stemness related genes in a dose-dependent manner. The migratory and invasive capabilities of GBM stem-like cells could be reduced by AXL/EZH2. Finally, in the overexpression of AXL, EZH2 and Sox2 by transfection in GBM stem-like cells, we found that AXL/EZH2/TGF-ꞵ1, but not Sox2, might be a key regulator in tumor invasion, migration and EMT. These results might help in the development of a new anticancer compound and can be a target for treating GBM.

  4. Characteristics of invasion-reduced hilA gene mutant of Salmonella Enteritidis in vitro and in vivo.

    PubMed

    Lv, Shuang; Si, Wei; Yu, Shenye; Li, Zhaoli; Wang, Xiumei; Chen, Liping; Zhang, Wanjiang; Liu, Siguo

    2015-08-01

    Salmonella enterica serovar Enteritidis (Salmonella Enteritidis) is a facultative intracellular pathogen that causes huge losses in poultry industry and also food poisoning in humans due to its being a food-borne pathogen. Functions of Invasion-related genes need to be explored, as invasion is a key step for Salmonella infection. In this study, a transposon mutant library of Salmonella Enteritidis isolate SM6 was constructed and screened for the invasion-related genes via incubation with Caco-2 cells. Three stably attenuated mutants were identified for significantly reduced invasion with insertions all in hilA (hyperinvasive locus A) gene. We constructed and evaluated the hilA deletion mutant in vivo and in vitro. SM6△hilA showed significantly reduced ability to invade Caco-2 cells and decreased pathogenicity in chicks. However, the bacterial load and pathological damage in the cecum were significantly higher than those in the SM6 in vivo. Present results provide new evidences for pathogenicity research on Salmonella Enteritidis.

  5. Application of visible and near infrared hyperspectral imaging for non-invasively measuring distribution of water-holding capacity in salmon flesh.

    PubMed

    Wu, Di; Sun, Da-Wen

    2013-11-15

    Water-holding capacity (WHC) is a primary quality determinant of salmon flesh. One of the limiting factors for not having a direct measurement of WHC for salmon quality grading is that current WHC measurements are destructive, time-consuming, and inefficient. In this study, two hyperspectral image systems operated in the visible and short-wave near infrared range (400-1000 nm) and the long-wave near infrared range (897-1753 nm) were applied for non-invasive determination of four WHC indices, namely percentage liquid loss (PLL), percentage water loss (PWL), percentage fat loss (PFL), and percentage water remained (PWR) of salmon flesh. Two calibration methods of partial least square regression (PLSR) and least-squares support vector machines (LS-SVM) were applied, respectively, to establish calibration models of WHC indices based on the spectral signatures of salmon flesh, and the performances of these two methods were compared to determine the optimal spectral calibration strategy. The performances were also compared between two hyperspectral image systems, when full range spectra were considered. Out of 121 wavelength variables, only thirteen (PLL), twelve (PWL), nine (PFL), and twelve variables (PWR) were selected as important variables by using competitive adaptive reweighted sampling (CARS) algorithm to reduce redundancy and collinearity of hyperspectral images. The CARS-PLSR combination was identified as the optimal method to calibrate the prediction models for WHC determination, resulting in good correlation coefficient of prediction (rP) of 0.941, 0.937, 0.815, and 0.970 for PLL, PWL, PFL, and PWR analysis, respectively. CARS-PLSR equations were obtained according to the regression coefficients of the CARS-PLSR models and were transferred to each pixel in the image for visualizing WHC indices in all portions of the salmon fillet. The overall results show that the laborious, time-consuming, and destructive traditional techniques could be replaced by

  6. Landscape corridors can increase invasion by an exotic species and reduce diversity of native species.

    SciTech Connect

    Resasco, Julian; et al,

    2014-04-01

    Abstract. Landscape corridors are commonly used to mitigate negative effects of habitat fragmentation, but concerns persist that they may facilitate the spread of invasive species. In a replicated landscape experiment of open habitat, we measured effects of corridors on the invasive fire ant, Solenopsis invicta, and native ants. Fire ants have two social forms: polygyne, which tend to disperse poorly but establish at high densities, and monogyne, which disperse widely but establish at lower densities. In landscapes dominated by polygyne fire ants, fire ant abundance was higher and native ant diversity was lower in habitat patches connected by corridors than in unconnected patches. Conversely, in landscapes dominated by monogyne fire ants, connectivity had no influence on fire ant abundance and native ant diversity. Polygyne fire ants dominated recently created landscapes, suggesting that these corridor effects may be transient. Our results suggest that corridors can facilitate invasion and they highlight the importance of considering species’ traits when assessing corridor utility.

  7. Landscape corridors can increase invasion by an exotic species and reduce diversity of native species.

    PubMed

    Resasco, Julian; Haddad, Nick M; Orrock, John L; Shoemaker, DeWayne; Brudvig, Lars A; Damschen, Ellen I; Tewksbury, Joshua J; Levey, Douglas J

    2014-08-01

    Landscape corridors are commonly used to mitigate negative effects of habitat fragmentation, but concerns persist that they may facilitate the spread of invasive species. In a replicated landscape experiment of open habitat, we measured effects of corridors on the invasive fire ant, Solenopsis invicta, and native ants. Fire ants have two social forms: polygyne, which tend to disperse poorly but establish at high densities, and monogyne, which disperse widely but establish at lower densities. In landscapes dominated by polygyne fire ants, fire ant abundance was higher and native ant diversity was lower in habitat patches connected by corridors than in unconnected patches. Conversely, in landscapes dominated by monogyne fire ants, connectivity had no influence on fire ant abundance and native ant diversity. Polygyne fire ants dominated recently created landscapes, suggesting that these corridor effects may be transient. Our results suggest that corridors can facilitate invasion and they highlight the importance of considering species' traits when assessing corridor utility.

  8. Reduced sensitizing capacity of epoxy resin systems: a structure-activity relationship study.

    PubMed

    Niklasson, Ida B; Broo, Kerstin; Jonsson, Charlotte; Luthman, Kristina; Karlberg, Ann-Therese

    2009-11-01

    Epoxy resins can be prepared from numerous chemical compositions. Until recently, alternatives to epoxy resins based on diglycidyl ethers of bisphenol A (DGEBA) or bisphenol F (DGEBF) monomers have not received commercial interest, but are presently doing so, as epoxy resins with various properties are desired. Epoxy resin systems are known to cause allergic contact dermatitis because of contents of uncured monomers, reactive diluents, and hardeners. Reactive diluents, for example, glycidyl ethers, which also contain epoxide moieties, are added to reduce viscosity and improve polymerization. We have investigated the contact allergenic properties of a series of six analogues to phenyl glycidyl ether (PGE), all with similar basic structures but with varying carbon chain lengths and degrees of saturation. The chemical reactivity of the compounds in the test series toward the hexapeptide H-Pro-His-Cys-Lys-Arg-Met-OH was investigated. All epoxides were shown to bind covalently to both cysteine and proline residues. The percent depletion of nonreacted peptide was also studied resulting in 88% depletion when using PGE and 46% when using butyl glycidyl ether (5) at the same time point, thus revealing a large difference between the fastest and the slowest reacting epoxide. The skin sensitization potencies of the epoxides using the murine local lymph node assay (LLNA) were evaluated in relation to the observed physicochemical and reactivity properties. To enable determination of statistical significance between structurally closely related compounds, a nonpooled LLNA was performed. It was found that the compounds investigated ranged from strong to weak sensitizers, congruent with the reactivity data, indicating that even small changes in chemical structure result in significant differences in sensitizing capacity.

  9. Thermal and refining processes, not fermentation, tend to reduce lipotropic capacity of plant-based foods.

    PubMed

    Fardet, Anthony; Martin, Jean-François; Chardigny, Jean-Michel

    2011-08-01

    Plant-based foods (PBF) are relevant and diversified sources of lipotropes, which are compounds preventing excess hepatic fat deposits. In a first study, we defined the lipotropic capacity (LC, %) of raw PBF as the means of 8 lipotrope densities (LD, mg/100 kcal), each expressed relative to that of a reference food ranking the highest considering its mean 8 LD ranks (LC(raw asparagus)=100%) (A. Fardet, J.-F. Martin and J. M. Chardigny, J. Food Comp. Anal., 2011, DOI: 10.1016/j.jfca.2011.1003.1013). We showed that vegetables appeared as the best source of lipotropes on a 100 kcal-basis compared to legumes, cereals, fruits and nuts. The main objective of this second study was to quantify the effect of processing on LD and LC of raw PBF based on lipotrope contents collected in a USDA (United State Department of Agriculture) database and the literature, i.e. betaine, choline, myo-inositol, methionine, magnesium, niacin, pantothenic acid and folate contents. Choline and betaine densities were not significantly affected by processing while methionine and lipotropic micronutrient densities were significantly decreased, especially for magnesium, pantothenate and folates. Myo-inositol density decreases were insignificant due to lower product number resulting from limited literature data. Lipotropic micronutrient densities were more affected by processing than other densities. Fermentations increased betaine (median change of +32%) and choline (+34%) densities. Canning and boiling vegetables increased choline densities (+26%). Globally, processing significantly reduced LC by ∼20%, fermentations being less drastic (median change of -5%) than refining (-33%) and thermal treatments (-16%). More specifically, canning increased LC of beetroot (536 vs 390%) and common bean (40 vs 36%) as fermentation towards LC grape (14 vs 7% for wine). Results were then mainly discussed based on percentages of lipotrope content changes on a dry-weight basis. Results of this study also showed

  10. No evolution of reduced resistance and compensation for psyllid herbivory by the invasive Genista monspessulana

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The evolution of redirecting resources from plant defense to growth or reproduction may explain why some exotic species are successful invaders in new environments. For example, the evolution of increased competitive ability hypothesis (EICA) posits that escape from herbivores by invasive plants re...

  11. Invasive mycosis due to species of Blastobotrys in immunocompromised patients with reduced susceptibility to antifungals.

    PubMed

    Kumar, Anil; Babu, Rachana; Bijulal, Swapna; Abraham, Mohan; Sasidharan, P; Kathuria, Shallu; Sharma, Cheshta; Meis, Jacques F; Chowdhary, Anuradha

    2014-11-01

    Cases of invasive mycosis due to Blastobotrys serpentis and B. proliferans identified by sequencing in a preterm patient and a rhabdomyosarcoma patient, respectively, are reported. Both species revealed elevated fluconazole and echinocandin MICs by the CLSI broth microdilution method. Additionally, B. serpentis exhibited high amphotericin B MICs, thus posing serious therapeutic challenges.

  12. ARE INVASIVE RIPARIAN PLANTS ASSOCIATED WITH REDUCED BIOTIC CONDITION OF FAUNA IN WESTERN US STREAMS?

    EPA Science Inventory

    Yes. Records on the presence or absence of 12 invasive riparian plant taxa and observations on macroinvertebrate and vertebrate communities within streams were collected at over 1000 stream reaches. The sampled reaches were selected on a probability basis to represent the populat...

  13. Soluble Fiber with High Water-Binding Capacity, Swelling Capacity, and Fermentability Reduces Food Intake by Promoting Satiety Rather Than Satiation in Rats.

    PubMed

    Tan, Chengquan; Wei, Hongkui; Zhao, Xichen; Xu, Chuanhui; Zhou, Yuanfei; Peng, Jian

    2016-10-02

    To understand whether soluble fiber (SF) with high water-binding capacity (WBC), swelling capacity (SC) and fermentability reduces food intake and whether it does so by promoting satiety or satiation or both, we investigated the effects of different SFs with these properties on the food intake in rats. Thirty-two male Sprague-Dawley rats were randomized to four equal groups and fed the control diet or diet containing 2% konjac flour (KF), pregelatinized waxy maize starch (PWMS) plus guar gum (PG), and PWMS starch plus xanthan gum (PX) for three weeks, with the measured values of SF, WBC, and SC in the four diets following the order of PG > KF > PX > control. Food intake, body weight, meal pattern, behavioral satiety sequence, and short-chain fatty acids (SCFAs) in cecal content were evaluated. KF and PG groups reduced the food intake, mainly due to the decreased feeding behavior and increased satiety, as indicated by decreased meal numbers and increased inter-meal intervals. Additionally, KF and PG groups increased concentrations of acetate acid, propionate acid, and SCFAs in the cecal contents. Our results indicate that SF with high WBC, SC, and fermentability reduces food intake-probably by promoting a feeling of satiety in rats to decrease their feeding behavior.

  14. Soluble Fiber with High Water-Binding Capacity, Swelling Capacity, and Fermentability Reduces Food Intake by Promoting Satiety Rather Than Satiation in Rats

    PubMed Central

    Tan, Chengquan; Wei, Hongkui; Zhao, Xichen; Xu, Chuanhui; Zhou, Yuanfei; Peng, Jian

    2016-01-01

    To understand whether soluble fiber (SF) with high water-binding capacity (WBC), swelling capacity (SC) and fermentability reduces food intake and whether it does so by promoting satiety or satiation or both, we investigated the effects of different SFs with these properties on the food intake in rats. Thirty-two male Sprague-Dawley rats were randomized to four equal groups and fed the control diet or diet containing 2% konjac flour (KF), pregelatinized waxy maize starch (PWMS) plus guar gum (PG), and PWMS starch plus xanthan gum (PX) for three weeks, with the measured values of SF, WBC, and SC in the four diets following the order of PG > KF > PX > control. Food intake, body weight, meal pattern, behavioral satiety sequence, and short-chain fatty acids (SCFAs) in cecal content were evaluated. KF and PG groups reduced the food intake, mainly due to the decreased feeding behavior and increased satiety, as indicated by decreased meal numbers and increased inter-meal intervals. Additionally, KF and PG groups increased concentrations of acetate acid, propionate acid, and SCFAs in the cecal contents. Our results indicate that SF with high WBC, SC, and fermentability reduces food intake—probably by promoting a feeling of satiety in rats to decrease their feeding behavior. PMID:27706095

  15. Propofol induction reduces the capacity for neural information integration: implications for the mechanism of consciousness and general anesthesia.

    PubMed

    Lee, UnCheol; Mashour, George A; Kim, Seunghwan; Noh, Gyu-Jeong; Choi, Byung-Moon

    2009-03-01

    The cognitive unbinding paradigm suggests that the synthesis of neural information is attenuated by general anesthesia. Here, we analyzed the functional organization of brain activities in the conscious and anesthetized states, based on functional segregation and integration. Electroencephalography (EEG) recordings were obtained from 14 subjects undergoing induction of general anesthesia with propofol. We quantified changes in mean information integration capacity in each band of the EEG. After induction with propofol, mean information integration capacity was reduced most prominently in the gamma band of the EEG (p=.0001). Furthermore, we demonstrate that loss of consciousness is reflected by the breakdown of the spatiotemporal organization of gamma waves. We conclude that induction of general anesthesia with propofol reduces the capacity for information integration in the brain. These data directly support the information integration theory of consciousness and the cognitive unbinding paradigm of general anesthesia.

  16. Strengthening community capacity to participate in making decisions to reduce disproportionate environmental exposures.

    PubMed

    Freudenberg, Nicholas; Pastor, Manuel; Israel, Barbara

    2011-12-01

    Environmental exposures impose a disproportionate health burden on low-income populations and communities of color. One contributing factor may be the obstacles such communities face to full participation in making policy decisions about environmental health. This study described and analyzed the characteristics that contributed to communities' capacity to participate in making environmental decisions and suggested steps public agencies could take to achieve more meaningful participation. By strengthening community capacity, advancing authentic participation, and building democratic power, it might be possible to alter current patterns of health inequities. Strengthening participation by working with communities to develop the capacities needed to be effective in such processes is a key role for local, state, and national environmental agencies.

  17. NEUROPSYCHOLOGICAL PERFORMANCE WITHIN-PERSON VARIABILITY IS ASSOCIATED WITH REDUCED TREATMENT CONSENT CAPACITY

    PubMed Central

    Gurrera, Ronald J.; Karel, Michele J.; Azar, Armin R.; Moye, Jennifer

    2013-01-01

    OBJECTIVES The capacity of older adults to make health care decisions is often impaired in dementia and has been linked to performance on specific neuropsychological tasks. Within-person across-test neuropsychological performance variability has been shown to predict future dementia. This study examined the relationship of within-person across-test neuropsychological performance variability to a current construct of treatment decision (consent) capacity. DESIGN Participants completed a neuropsychological test battery and a standardized capacity assessment. Standard scores were used to compute mean neuropsychological performance and within-person across-test variability. SETTING Assessments were performed in the participant’s preferred location (e.g., outpatient clinic office, senior center, or home). PARTICIPANTS Participants were recruited from the community with fliers and advertisements, and consisted of men (N=79) and women (N=80) with (N=83) or without (N=76) significant cognitive impairment. MEASUREMENTS Participants completed the MacArthur Competence Assessment Tool - Treatment (MacCAT-T) and 11 neuropsychological tests commonly used in the cognitive assessment of older individuals. RESULTS Neuropsychological performance and within-person variability were independently associated with continuous and dichotomous measures of capacity, and within-person neuropsychological variability was significantly associated with within-person decisional ability variability. Prevalence of incapacity was greater than expected in participants with and without significant cognitive impairment when decisional abilities were considered separately. CONCLUSIONS These findings are consistent with an emerging construct of consent capacity in which discrete decisional abilities are differentially associated with cognitive processes, and indicate that the sensitivity and accuracy of consent capacity assessments can be improved by evaluating decisional abilities separately. PMID

  18. α-Solanine inhibits human melanoma cell migration and invasion by reducing matrix metalloproteinase-2/9 activities.

    PubMed

    Lu, Ming-Kun; Shih, Yuan-Wei; Chang Chien, Tzu-Tsung; Fang, Li-Heng; Huang, Hsiang-Ching; Chen, Pin-Shern

    2010-01-01

    α-Solanine, a naturally occurring steroidal glycoalkaloid in potato sprouts, was found to possess anti-carcinogenic properties, such as inhibiting proliferation and inducing apoptosis of tumor cells. However, the effect of α-solanine on cancer metastasis remains unclear. In the present study, we examined the effect of α-solanine on metastasis in vitro. Data demonstrated that α-solanine inhibited proliferation of human melanoma cell line A2058 in a dose-dependent manner. When treated with non-toxic doses of α-solanine, cell migration and invasion were markedly suppressed. Furthermore, α-solanine reduced the activity of matrix metalloproteinase-2 (MMP-2) and MMP-9, which are involved in the migration and invasion of cancer cells. Our biochemical assays indicated that α-solanine potently suppressed the phosphorylation of c-Jun N-terminal kinase (JNK), phosphatidylinositide-3 kinase (PI3K) and Akt, while it did not affect phosphorylation of extracellular signal regulating kinase (ERK). In addition, α-solanine significantly decreased the nuclear level of nuclear factor kappa B (NF-κB), suggesting that α-solanine inhibited NF-κB activity. Taken together, the results suggested that α-solanine inhibited migration and invasion of A2058 cells by reducing MMP-2/9 activities. It also inhibited JNK and PI3K/Akt signaling pathways as well as NF-κB activity. These findings reveal new therapeutic potential for α-solanine in anti-metastatic therapy.

  19. Self-Disorders in Individuals with Autistic Traits: Contribution of Reduced Autobiographical Reasoning Capacities

    ERIC Educational Resources Information Center

    Berna, Fabrice; Göritz, Anja S.; Schröder, Johanna; Coutelle, Romain; Danion, Jean-Marie; Cuervo-Lombard, Christine V.; Moritz, Steffen

    2016-01-01

    The present web-based study (N = 840) aimed to illuminate the cognitive mechanisms underlying self-disorders in autism. Initially, participants selected three self-defining memories. Then, we assessed their capacity to give meaning to these events (i.e., meaning making), their tendency to scrutinize autobiographical memory to better understand…

  20. Impaired Semantic Knowledge Underlies the Reduced Verbal Short-Term Storage Capacity in Alzheimer's Disease

    ERIC Educational Resources Information Center

    Peters, Frederic; Majerus, Steve; De Baerdemaeker, Julie; Salmon, Eric; Collette, Fabienne

    2009-01-01

    A decrease in verbal short-term memory (STM) capacity is consistently observed in patients with Alzheimer's disease (AD). Although this impairment has been mainly attributed to attentional deficits during encoding and maintenance, the progressive deterioration of semantic knowledge in early stages of AD may also be an important determinant of poor…

  1. Diosgenin, a Steroidal Saponin, Inhibits Migration and Invasion of Human Prostate Cancer PC-3 Cells by Reducing Matrix Metalloproteinases Expression

    PubMed Central

    Chen, Pin-Shern; Shih, Yuan-Wei; Huang, Hsiang-Ching; Cheng, Hsing-Wen

    2011-01-01

    Background Diosgenin, a steroidal saponin obtained from fenugreek (Trigonella foenum graecum), was found to exert anti-carcinogenic properties, such as inhibiting proliferation and inducing apoptosis in a variety of tumor cells. However, the effect of diosgenin on cancer metastasis remains unclear. The aim of the study is to examine the effect of diosgenin on migration and invasion in human prostate cancer PC-3 cells. Methods and Principal Findings Diosgenin inhibited proliferation of PC-3 cells in a dose-dependent manner. When treated with non-toxic doses of diosgenin, cell migration and invasion were markedly suppressed by in vitro wound healing assay and Boyden chamber invasion assay, respectively. Furthermore, diosgenin reduced the activities of matrix metalloproteinase-2 (MMP-2) and MMP-9 by gelatin zymography assay. The mRNA level of MMP-2, -9, -7 and extracellular inducer of matrix metalloproteinase (EMMPRIN) were also suppressed while tissue inhibitor of metalloproteinase-2 (TIMP-2) was increased by diosgenin. In addition, diosgenin abolished the expression of vascular endothelial growth factor (VEGF) in PC-3 cells and tube formation of endothelial cells. Our immunoblotting assays indicated that diosgenin potently suppressed the phosphorylation of phosphatidylinositide-3 kinase (PI3K), Akt, extracellular signal regulating kinase (ERK) and c-Jun N-terminal kinase (JNK). In addition, diosgenin significantly decreased the nuclear level of nuclear factor kappa B (NF-κB), suggesting that diosgenin inhibited NF-κB activity. Conclusion/Significance The results suggested that diosgenin inhibited migration and invasion of PC-3 cells by reducing MMPs expression. It also inhibited ERK, JNK and PI3K/Akt signaling pathways as well as NF-κB activity. These findings reveal new therapeutic potential for diosgenin in anti-metastatic therapy. PMID:21629786

  2. Ecosystem engineering by invasive exotic beavers reduces in-stream diversity and enhances ecosystem function in Cape Horn, Chile.

    PubMed

    Anderson, Christopher B; Rosemond, Amy D

    2007-11-01

    Species invasions are of global significance, but predicting their impacts can be difficult. Introduced ecosystem engineers, however, provide an opportunity to test the underlying mechanisms that may be common to all invasive engineers and link relationships between changes in diversity and ecosystem function, thereby providing explanatory power for observed ecological patterns. Here we test specific predictions for an invasive ecosystem engineer by quantifying the impacts of habitat and resource modifications caused by North American beavers (Castor canadensis) on aquatic macroinvertebrate community structure and stream ecosystem function in the Cape Horn Biosphere Reserve, Chile. We compared responses to beavers in three habitat types: (1) forested (unimpacted) stream reaches, (2) beaver ponds, and (3) sites immediately downstream of beaver dams in four streams. We found that beaver engineering in ponds created taxonomically simplified, but more productive, benthic macroinvertebrate assemblages. Specifically, macroinvertebrate richness, diversity and number of functional feeding groups were reduced by half, while abundance, biomass and secondary production increased three- to fivefold in beaver ponds compared to forested sites. Reaches downstream of beaver ponds were very similar to natural forested sections. Beaver invasion effects on both community and ecosystem parameters occurred predominantly via increased retention of fine particulate organic matter, which was associated with reduced macroinvertebrate richness and diversity (via homogenization of benthic microhabitat) and increased macroinvertebrate biomass and production (via greater food availability). Beaver modifications to macroinvertebrate community structure were largely confined to ponds, but increased benthic production in beaver-modified habitats adds to energy retention and flow for the entire stream ecosystem. Furthermore, the effects of beavers on taxa richness (negative) and measures of

  3. The Hedgehog Inhibitor Cyclopamine Reduces β-Catenin-Tcf Transcriptional Activity, Induces E-Cadherin Expression, and Reduces Invasion in Colorectal Cancer Cells

    PubMed Central

    Qualtrough, David; Rees, Phil; Speight, Beverley; Williams, Ann C.; Paraskeva, Christos

    2015-01-01

    Colorectal cancer is a major global health problem resulting in over 600,000 deaths world-wide every year with the majority of these due to metastatic disease. Wnt signalling, and more specifically β-catenin-related transcription, has been shown to drive both tumorigenesis and the metastatic process in colorectal neoplasia, yet its complex interactions with other key signalling pathways, such as hedgehog, remain to be elucidated. We have previously shown that the Hedgehog (HH) signalling pathway is active in cells from colorectal tumours, and that inhibition of the pathway with cyclopamine induces apoptosis. We now show that cyclopamine treatment reduces β-catenin related transcription in colorectal cancer cell lines, and that this effect can be reversed by addition of Sonic Hedgehog protein. We also show that cyclopamine concomitantly induces expression of the tumour suppressor and prognostic indicator E-cadherin. Consistent with a role for HH in regulating the invasive potential we show that cyclopamine reduces the expression of transcription factors (Slug, Snail and Twist) associated with the epithelial-mesenchymal transition and reduces the invasiveness of colorectal cancer cells in vitro. Taken together, these data show that pharmacological inhibition of the hedgehog pathway has therapeutic potential in the treatment of colorectal cancer. PMID:26393651

  4. Invasive Parasites, Habitat Change and Heavy Rainfall Reduce Breeding Success in Darwin's Finches

    PubMed Central

    Cimadom, Arno; Ulloa, Angel; Meidl, Patrick; Zöttl, Markus; Zöttl, Elisabet; Fessl, Birgit; Nemeth, Erwin; Dvorak, Michael; Cunninghame, Francesca; Tebbich, Sabine

    2014-01-01

    Invasive alien parasites and pathogens are a growing threat to biodiversity worldwide, which can contribute to the extinction of endemic species. On the Galápagos Islands, the invasive parasitic fly Philornis downsi poses a major threat to the endemic avifauna. Here, we investigated the influence of this parasite on the breeding success of two Darwin's finch species, the warbler finch (Certhidea olivacea) and the sympatric small tree finch (Camarhynchus parvulus), on Santa Cruz Island in 2010 and 2012. While the population of the small tree finch appeared to be stable, the warbler finch has experienced a dramatic decline in population size on Santa Cruz Island since 1997. We aimed to identify whether warbler finches are particularly vulnerable during different stages of the breeding cycle. Contrary to our prediction, breeding success was lower in the small tree finch than in the warbler finch. In both species P. downsi had a strong negative impact on breeding success and our data suggest that heavy rain events also lowered the fledging success. On the one hand parents might be less efficient in compensating their chicks' energy loss due to parasitism as they might be less efficient in foraging on days of heavy rain. On the other hand, intense rainfalls might lead to increased humidity and more rapid cooling of the nests. In the case of the warbler finch we found that the control of invasive plant species with herbicides had a significant additive negative impact on the breeding success. It is very likely that the availability of insects (i.e. food abundance)is lower in such controlled areas, as herbicide usage led to the removal of the entire understory. Predation seems to be a minor factor in brood loss. PMID:25248092

  5. Reducing wait times through operations research: optimizing the use of surge capacity.

    PubMed

    Patrick, Jonathan; Puterman, Martin L

    2008-01-01

    Widespread public demand for improved access, political pressure for shorter wait times, a stretched workforce, an aging population and overutilized equipment and facilities challenge healthcare leaders to adopt new management approaches. This paper highlights the significant benefits that can be achieved by applying operations research (OR) methods to healthcare management. It shows how queuing theory provides managers with insights into the causes for excessive wait times and the relationship between wait times and capacity. It provides a case study of the use of several OR methods, including Markov decision processes, linear programming and simulation, to optimize the scheduling of patients with multiple priorities. The study shows that by applying this approach, wait time targets can be attained with the judicious use of surge capacity in the form of overtime. It concludes with some policy insights.

  6. Reducing Wait Times through Operations Research: Optimizing the Use of Surge Capacity.

    PubMed

    Patrick, Jonathan; Puterman, Martin L

    2008-02-01

    Widespread public demand for improved access, political pressure for shorter wait times, a stretched workforce, an aging population and overutilized equipment and facilities challenge healthcare leaders to adopt new management approaches. This paper highlights the significant benefits that can be achieved by applying operations research (OR) methods to healthcare management. It shows how queuing theory provides managers with insights into the causes for excessive wait times and the relationship between wait times and capacity. It provides a case study of the use of several OR methods, including Markov decision processes, linear programming and simulation, to optimize the scheduling of patients with multiple priorities. The study shows that by applying this approach, wait time targets can be attained with the judicious use of surge capacity in the form of overtime. It concludes with some policy insights.

  7. Daucus carota Pentane/Diethyl Ether Fraction Inhibits Motility and Reduces Invasion of Cancer Cells.

    PubMed

    Zgheib, Perla; Daher, Costantine F; Mroueh, Mohamad; Nasrallah, Anita; Taleb, Robin I; El-Sibai, Mirvat

    2014-01-01

    Daucus carota (DC) is a herb used in folklore medicine in Lebanon to treat numerous diseases including cancer. Recent studies in our laboratory on DC oil and its fractions revealed potent anticancer activities in vitro and in vivo. The present study aims to investigate the effect of the most potent DC fraction, pentane/diethyl ether (50:50), on lung, skin, breast and glioblastoma cancer cell motility and invasion. Upon treatment, a pronounced decrease in cancer cell motility was observed in the 4 cell lines. The treatment also led to a decrease in cancer cell invasion and an increased cell adhesion. Additionally, the DC fraction caused a decrease in the activation of the ρ-GTPases Rac and CDC42, a finding that may partially explain the treatment-induced decrease in cell motility. The current study demonstrates a crucial effect of the DC pentane/diethyl ether fraction on cancer cell motility and metastasis, making it a potential candidate for cancer therapy specifically targeting cancer motility and metastasis.

  8. Reduced swim performance and aerobic capacity in adult zebrafish exposed to waterborne selenite.

    PubMed

    Massé, Anita J; Thomas, Jith K; Janz, David M

    2013-04-01

    Although dietary exposure of adult fish to organoselenium in contaminated aquatic ecosystems has been reported to bioaccumulate and cause larval deformities in offspring, subtle physiological effects produced through low level waterborne selenium exposure in fish such as swim performance and aerobic capacity have not been investigated. To evaluate potential effects of selenite on these responses, adult zebrafish (Danio rerio) were exposed to nominal aqueous concentrations of 0, 10 or 100 μg/L sodium selenite for 14 days. Upon completion of the exposure period, fish underwent two successive swim trials in a swim tunnel respirometer to determine critical swim speed (Ucrit), oxygen consumption (MO2), standard and active metabolic rates, aerobic scope (AS) and cost of transport (COT) followed by analysis of whole body triglyceride and glycogen concentrations. Selenite exposure had a significant negative effect on Ucrit and aerobic capacity. Active metabolic rates and AS significantly decreased in both selenite exposure groups after the second swim trial. No significant effect was observed in MO2, standard metabolic rate, COT, triglyceride and glycogen levels, or condition factor between groups. These results suggest that aqueous selenite exposure at environmentally relevant concentrations produces adverse effects on aerobic capacity that can diminish endurance and maximum swim speeds, which may lower fish survivability.

  9. Risk of COPD with obstruction in active smokers with normal spirometry and reduced diffusion capacity.

    PubMed

    Harvey, Ben-Gary; Strulovici-Barel, Yael; Kaner, Robert J; Sanders, Abraham; Vincent, Thomas L; Mezey, Jason G; Crystal, Ronald G

    2015-12-01

    Smokers are assessed for chronic obstructive pulmonary disease (COPD) using spirometry, with COPD defined by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) as airflow limitation that is not fully reversible with bronchodilators. There is a subset of smokers with normal spirometry (by GOLD criteria), who have a low diffusing capacity of the lung for carbon monoxide (DLCO), a parameter linked to emphysema and small airway disease. The natural history of these "normal spirometry/low DLCO" smokers is unknown.From a cohort of 1570 smokers in the New York City metropolitian area, all of whom had normal spirometry, two groups were randomly selected for lung function follow-up: smokers with normal spirometry/normal DLCO (n=59) and smokers with normal spirometry/low DLCO (n=46). All had normal history, physical examination, complete blood count, urinalysis, HIV status, α1-antitrypsin level, chest radiography, forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC ratio and total lung capacity. Throughout the study, all continued to be active smokers.In the normal spirometry/normal DLCO group assessed over 45±20 months, 3% developed GOLD-defined COPD. In contrast, in the normal spirometry/low DLCO group, followed over 41±31 months, 22% developed GOLD-defined COPD.Despite appearing "normal" according to GOLD, smokers with normal spirometry but low DLCO are at significant risk of developing COPD with obstruction to airflow.

  10. Impaired semantic knowledge underlies the reduced verbal short-term storage capacity in Alzheimer's disease.

    PubMed

    Peters, Frédéric; Majerus, Steve; De Baerdemaeker, Julie; Salmon, Eric; Collette, Fabienne

    2009-12-01

    A decrease in verbal short-term memory (STM) capacity is consistently observed in patients with Alzheimer's disease (AD). Although this impairment has been mainly attributed to attentional deficits during encoding and maintenance, the progressive deterioration of semantic knowledge in early stages of AD may also be an important determinant of poor STM performance. The aim of this study was to examine the influence of semantic knowledge on verbal short-term memory storage capacity in normal aging and in AD by exploring the impact of word imageability on STM performance. Sixteen patients suffering from mild AD, 16 healthy elderly subjects and 16 young subjects performed an immediate serial recall task using word lists containing high or low imageability words. All participant groups recalled more high imageability words than low imageability words, but the effect of word imageability on verbal STM was greater in AD patients than in both the young and the elderly control groups. More precisely, AD patients showed a marked decrease in STM performance when presented with lists of low imageability words, whereas recall of high imageability words was relatively well preserved. Furthermore, AD patients displayed an abnormal proportion of phonological errors in the low imageability condition. Overall, these results indicate that the support of semantic knowledge on STM performance was impaired for lists of low imageability words in AD patients. More generally, these findings suggest that the deterioration of semantic knowledge is partly responsible for the poor verbal short-term storage capacity observed in AD.

  11. Fortune favours the bold: a higher predator reduces the impact of a native but not an invasive intermediate predator.

    PubMed

    Barrios-O'Neill, Daniel; Dick, Jaimie T A; Emmerson, Mark C; Ricciardi, Anthony; MacIsaac, Hugh J; Alexander, Mhairi E; Bovy, Helene C

    2014-05-01

    Emergent multiple predator effects (MPEs) might radically alter predictions of predatory impact that are based solely on the impact of individuals. In the context of biological invasions, determining if and how the individual-level impacts of invasive predators relates to their impacts in multiple-individual situations will inform understanding of how such impacts might propagate through recipient communities. Here, we use functional responses (the relationship between prey consumption rate and prey density) to compare the impacts of the invasive freshwater mysid crustacean Hemimysis anomala with a native counterpart Mysis salemaai when feeding on basal cladoceran prey (i) as individuals, (ii) in conspecific groups and (iii) in conspecific groups in the presence of a higher fish predator, Gasterosteus aculeatus. In the absence of the higher predator, the invader consumed significantly more basal prey than the native, and consumption was additive for both mysid species - that is, group consumption was predictable from individual-level consumption. Invaders and natives were themselves equally susceptible to predation when feeding with the higher fish predator, but an MPE occurred only between the natives and higher predator, where consumption of basal prey was significantly reduced. In contrast, consumption by the invaders and higher predator remained additive. The presence of a higher predator serves to exacerbate the existing difference in individual-level consumption between invasive and native mysids. We attribute the mechanism responsible for the MPE associated with the native to a trait-mediated indirect interaction, and further suggest that the relative indifference to predator threat on the part of the invader contributes to its success and impacts within invaded communities.

  12. Extreme drought event and shrub invasion combine to reduce ecosystem functioning and resilience in water-limited climates

    NASA Astrophysics Data System (ADS)

    Caldeira, Maria; Lecomte, Xavier; David, Teresa; Pinto, Joaquim; Bugalho, Miguel; Werner, Christiane

    2016-04-01

    Extreme droughts and plant invasions are major drivers of global change that can critically affect ecosystem functioning. Shrub encroachment is increasing in many regions worldwide and extreme events are projected to increase in frequency and intensity, namely in the Mediterranean region. Nevertheless, little is known about how these drivers may interact and affect ecosystem functioning and resilience to extreme droughts. Using a manipulative shrub removal experiment and the co-occurrence of an extreme drought event (2011/2012) in a Mediterranean woodland, we show that the native shrub invasion and extreme drought combined to reduce ecosystem transpiration and the resilience of the key-stone oak tree species. We established six 25 x 25 m paired plots in a shrub (Cistus ladanifer L.) encroached Mediterranean cork-oak (Quercus suber L.) woodland. We measured sapflow and pre-dawn leaf water potential of trees and shrubs and soil water content in all plots during three years. We determined the resilience of tree transpiration to evaluate to what extent trees recovered from the extreme drought event. From February to November 2011 we conducted baseline measurements for plot comparison. In November 2011 all the shrubs from one of all the paired plots were cut and removed. Ecosystem transpiration was dominated by the water use of the invasive shrub, which further increased after the extreme drought. Simultaneously, tree transpiration in invaded plots declined much stronger (67 ± 13 %) than in plots cleared from shrubs (31 ± 11%) relative to the pre-drought year. Trees in invaded plots were not able to recover in the following wetter year showing lower resilience to the extreme drought event. Our results imply that in Mediterranean-type of climates invasion by water spending species can combine with projected recurrent extreme droughts causing critical drought tolerance thresholds of trees to be overcome increasing the probability of tree mortality (Caldeira et.al. 2015

  13. Gesturing during mental problem solving reduces eye movements, especially for individuals with lower visual working memory capacity.

    PubMed

    Pouw, Wim T J L; Mavilidi, Myrto-Foteini; van Gog, Tamara; Paas, Fred

    2016-08-01

    Non-communicative hand gestures have been found to benefit problem-solving performance. These gestures seem to compensate for limited internal cognitive capacities, such as visual working memory capacity. Yet, it is not clear how gestures might perform this cognitive function. One hypothesis is that gesturing is a means to spatially index mental simulations, thereby reducing the need for visually projecting the mental simulation onto the visual presentation of the task. If that hypothesis is correct, less eye movements should be made when participants gesture during problem solving than when they do not gesture. We therefore used mobile eye tracking to investigate the effect of co-thought gesturing and visual working memory capacity on eye movements during mental solving of the Tower of Hanoi problem. Results revealed that gesturing indeed reduced the number of eye movements (lower saccade counts), especially for participants with a relatively lower visual working memory capacity. Subsequent problem-solving performance was not affected by having (not) gestured during the mental solving phase. The current findings suggest that our understanding of gestures in problem solving could be improved by taking into account eye movements during gesturing.

  14. Psychosis as a disorder of reduced cathectic capacity: Freud's analysis of the Schreber case revisited.

    PubMed

    McGlashan, Thomas H

    2009-05-01

    Approximately 100 years ago, a prominent German public figure name Daniel Schreber wrote memoirs of his experiences in asylums. His case was diagnosed Dementia Praecox at times and Paranoia at others by his treaters. Freud analyzed Schreber's memoirs from the perspective of his "libido" theory of developmentally organized mental "cathexes" or ideational/emotional investments in self and others. Revisiting Freud's analysis of the Schreber case suggests that it may represent the first theoretical articulation that the pathophysiologic core of psychosis is one of deficit, i.e., of diminished (organic) cathectic capacity for normal mental and affective investments in life.

  15. Granulocyte, granulocyte–macrophage, and macrophage colony-stimulating factors can stimulate the invasive capacity of human lung cancer cells

    PubMed Central

    Pei, X-H; Nakanishi, Y; Takayama, K; Bai, F; Hara, N

    1999-01-01

    We and other researchers have previously found that colony-stimulating factors (CSFs), which generally include granulocyte colony-stimulating factor (G-CSF), granulocyte–macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF), promote invasion by lung cancer cells. In the present study, we studied the effects of these CSFs on gelatinase production, urokinase plasminogen activator (uPA) production and their activity in human lung cancer cells. Gelatin zymographs of conditioned media derived from human lung adenocarcinoma cell lines revealed two major bands of gelatinase activity at 68 and 92 kDa, which were characterized as matrix metalloproteinase (MMP)-2 and MMP-9 respectively. Treatment with CSFs increased the 68- and 92-kDa activity and converted some of a 92-kDa proenzyme to an 82-kDa enzyme that was consistent with an active form of the MMP-9. Plasminogen activator zymographs of the conditioned media from the cancer cells showed that CSF treatment resulted in an increase in a 48–55 kDa plasminogen-dependent gelatinolytic activity that was characterized as human uPA. The conditioned medium from the cancer cells treated with CSFs stimulated the conversion of plasminogen to plasmin, providing a direct demonstration of the ability of enhanced uPA to increase plasmin-dependent proteolysis. The enhanced invasive behaviour of the cancer cells stimulated by CSFs was well correlated with the increase in MMPs and uPA activities. These data suggest that the enhanced production of extracellular matrix-degrading proteinases by the cancer cells in response to CSF treatment may represent a biochemical mechanism which promotes the invasive behaviour of the cancer cells. © 1999 Cancer Research Campaign PMID:10408691

  16. MiR-26a enhances invasive capacity by suppressing GSK3β in human lung cancer cells.

    PubMed

    Lin, Gaoyang; Liu, Boning; Meng, Zhaowei; Liu, Yunde; Li, Xuebing; Wu, Xiang; Zhou, Qinghua; Xu, Ke

    2017-03-15

    Lung cancer is the common cause of death from cancer, and most lung cancer patients die of metastasis. MicroRNAs (miRNAs) function as either oncogenes or tumor suppressors, playing crucial role not only in tumorigenesis, but also in tumor invasion and metastasis. There are several studies showed that miR-26a is involved in carcinogenesis, however, its role in tumor metastasis need to be elucidated. In this study, we showed that ectopic expression of miR-26a enhanced migration and invasion of lung cancer cells. Glycogen synthase kinase-3β (GSK3β) was identified as a direct target of miR-26a. GSK3β expression negatively correlated with miR-26a expression in lung cancer tissues. Silencing of GSK3β achieved similar effect as miR-26a over-expression; over-expression of GSK3β reversed the enhanced effect of miR-26a on lung cancer cell migration and invasion. Further study indicated that miR-26a increased β-catenin expression and nuclear translocation. C-myc and cyclin D1, the downstream genes of β-catenin, were also up-regulated by miR-26a. Furthermore, xenograft study showed that miR-26a promoted lung cancer cell growth in vivo, and suppressed GSK3β expression. Collectively, our results demonstrated that miR-26a enhanced metastatic potential of lung cancer cells via activation of β-catenin pathway by targeting GSK3β, suggesting the potential applicability of miR-26a as a target for cancer treatment.

  17. In Vivo validation of a bioinformatics based tool to identify reduced replication capacity in HIV-1.

    PubMed

    Kitchen, Christina M R; Krogstad, Paul; Kitchen, Scott G

    2010-01-01

    Although antiretroviral drug resistance is common in treated HIV infected individuals, it is not a consistent indicator of HIV morbidity and mortality. To the contrary, HIV resistance-associated mutations may lead to changes in viral fitness that are beneficial to infected individuals. Using a bioinformatics-based model to assess the effects of numerous drug resistance mutations, we determined that the D30N mutation in HIV-1 protease had the largest decrease in replication capacity among known protease resistance mutations. To test this in silico result in an in vivo environment, we constructed several drug-resistant mutant HIV-1 strains and compared their relative fitness utilizing the SCID-hu mouse model. We found HIV-1 containing the D30N mutation had a significant defect in vivo, showing impaired replication kinetics and a decreased ability to deplete CD4+ thymocytes, compared to the wild-type or virus without the D30N mutation. In comparison, virus containing the M184V mutation in reverse transcriptase, which shows decreased replication capacity in vitro, did not have an effect on viral fitness in vivo. Thus, in this study we have verified an in silico bioinformatics result with a biological assessment to identify a unique mutation in HIV-1 that has a significant fitness defect in vivo.

  18. Search for Expectancy-Inconsistent Information Reduces Uncertainty Better: The Role of Cognitive Capacity

    PubMed Central

    Strojny, Paweł; Kossowska, Małgorzata; Strojny, Agnieszka

    2016-01-01

    Motivation and cognitive capacity are key factors in people’s everyday struggle with uncertainty. However, the exact nature of their interplay in various contexts still needs to be revealed. The presented paper reports on two experimental studies which aimed to examine the joint consequences of motivational and cognitive factors for preferences regarding incomplete information expansion. In Study 1 we demonstrate the interactional effect of motivation and cognitive capacity on information preference. High need for closure resulted in a stronger relative preference for expectancy-inconsistent information among non-depleted individuals, but the opposite among cognitively depleted ones. This effect was explained by the different informative value of questions in comparison to affirmative sentences and the potential possibility of assimilation of new information if it contradicts prior knowledge. In Study 2 we further investigated the obtained effect, showing that not only questions but also other kinds of incomplete information are subject to the same dependency. Our results support the expectation that, in face of incomplete information, motivation toward closure may be fulfilled efficiently by focusing on expectancy-inconsistent pieces of data. We discuss the obtained effect in the context of previous assumptions that high need for closure results in a simple processing style, advocating a more complex approach based on the character of the provided information. PMID:27047422

  19. Reducing the Cation Exchange Capacity of Lithium Clay to Form Better Dispersed Polymer-Clay Nanocomposites

    NASA Technical Reports Server (NTRS)

    Liang, Maggie

    2004-01-01

    Polymer-clay nanocomposites have exhibited superior strength and thermo- oxidative properties as compared to pure polymers for use in air and space craft; however, there has often been difficulty completely dispersing the clay within the matrices of the polymer. In order to improve this process, the cation exchange capacity of lithium clay is first lowered using twenty-four hour heat treatments of no heat, 130 C, 150 C, or 170 C to fixate the lithium ions within the clay layers so that they are unexchangeable. Generally, higher temperatures have generated lower cation exchange capacities. An ion exchange involving dodecylamine, octadecylamine, or dimethyl benzidine (DMBZ) is then employed to actually expand the clay galleries. X-ray diffraction and transmission electron microscopy can be used to determine whether the clay has been successfully exfoliated. Finally, resins of DMBZ with clay are then pressed into disks for characterization using dynamic mechanical analyzer and oven- aging techniques in order to evaluate their glass transition, modulus strength, and thermal-oxidative stability in comparison to neat DMBZ. In the future, they may also be tested as composites for flexural and laminar shear strength.

  20. A Hybrid Quorum Protocol for Improved Availability, Capacity, Load and Reduced Overhead

    NASA Astrophysics Data System (ADS)

    Pandey, Parul; Tripathi, Maheshwari

    2016-12-01

    Data replication is playing a vital role in the design of distributed information systems. This paper presents a novel and efficient distributed algorithm for managing replicated data and for better performance and availability. This paper presents an extension to existing wheel protocol for improved performance. Wheel protocol imposes a logical wheel structure on the set of copies of an object and gives smallest read quorum. In addition to small read quorum size for read intensive applications, it is necessary to have good write availability as well. This paper proposes two hybrid wheel protocols, which superimpose logarithmic and ring protocols on top of the wheel protocol. It shows that, both protocols help in improving write availability, read capacity, load and message overhead and also compare their performances with wheel and other protocols. Hybrid protocols expand usage of wheel protocol to different type of applications.

  1. Delayed adrenal insufficiency long after unilateral adrenalectomy: prolonged glucocorticoid therapy reduced reserved secretory capacity of cortisol.

    PubMed

    Kazama, Itsuro; Komatsu, Yasuhiro; Ohiwa, Takafumi; Sanayama, Kyo; Nagata, Mikio

    2005-06-01

    A 51-year-old woman with Cushing's syndrome underwent unilateral adrenalectomy for left adrenal adenoma. After 7 years of prednisolone treatment (with some interruptions), followed by 4 years of total withdrawal from prednisolone treatment, she presented with hypotension, weight loss, general fatigue, nausea, hyponatremia and hypoglycemia. These clinical features together with a low response in the rapid adrenocorticotropic hormone test led to the diagnosis of acute adrenal insufficiency. Relatively low serum adrenocorticotropic hormone levels in the face of increased demand for cortisol during adrenal crisis suggested a disordered hypothalamic-pituitary function, indicating secondary adrenal insufficiency. This patient demonstrated the etiology of acute adrenal insufficiency long after unilateral adrenalectomy in association with subsequent glucocorticoid therapy. A reduction in the reserved secretory capacity of cortisol after prolonged prednisolone treatment was considered to have induced secondary adrenal insufficiency, even after 4 years of total withdrawal from prednisolone.

  2. Reduced capacity but spared precision and maintenance of working memory representations in schizophrenia

    PubMed Central

    Gold, JM; Hahn, B; Zhang, W; Robinson, BM; Kappenman, ES; Beck, VM; Luck, SJ

    2010-01-01

    Context Working memory deficits are considered a core feature of schizophrenia. Several recent integrative papers have offered mechanistic computational and neurobiological models of the origins of this cognitive deficit. Objective To test predictions of these models using a new experimental paradigm from the basic science literature that makes it possible to determine whether patients with schizophrenia show: 1) deficits in working memory storage capacity, 2) deficits in the precision of working memory representations, and 3) an amplification of these deficits as the retention interval increases. Design Case control design. All subjects performed a color working memory test where they were asked to recall 3 or 4 items after a 1 or 4 second delay. All subjects also received a standard measure of intelligence and the MATRICS battery. Setting A tertiary care research outpatient clinic. Patients A total of 31 clinically stable patients with a DSM IV diagnosis of schizophrenia or schizoaffective disorder and 26 healthy volunteers participated. The two groups were similar in age, gender, and ethnicity distributions. Main Outcome measures We examined two outcome measures: 1) the number of items stored in working memory, and 2) the precision of the working memory representations. Results Patients showed a clear reduction in the number of items stored in working memory. Patients did not differ from controls in the precision of their working memory representations. There was no evidence of delay-related amplification of impairment in either capacity or precision. Conclusions Patients do not show the type of imprecision or delay-dependent amplification of impairment that are predicted on the basis of current models of the neurobiology of the illness. The models need to be revised to account for a pure reduction in the number of items that patients are able to store in working memory. PMID:20530006

  3. Mitochondrial uncoupling reduces exercise capacity despite several skeletal muscle metabolic adaptations.

    PubMed

    Schlagowski, A I; Singh, F; Charles, A L; Gali Ramamoorthy, T; Favret, F; Piquard, F; Geny, B; Zoll, J

    2014-02-15

    The effects of mitochondrial uncoupling on skeletal muscle mitochondrial adaptation and maximal exercise capacity are unknown. In this study, rats were divided into a control group (CTL, n = 8) and a group treated with 2,4-dinitrophenol, a mitochondrial uncoupler, for 28 days (DNP, 30 mg·kg(-1)·day(-1) in drinking water, n = 8). The DNP group had a significantly lower body mass (P < 0.05) and a higher resting oxygen uptake (Vo2, P < 0.005). The incremental treadmill test showed that maximal running speed and running economy (P < 0.01) were impaired but that maximal Vo2 (Vo2max) was higher in the DNP-treated rats (P < 0.05). In skinned gastrocnemius fibers, basal respiration (V0) was higher (P < 0.01) in the DNP-treated animals, whereas the acceptor control ratio (ACR, Vmax/V0) was significantly lower (P < 0.05), indicating a reduction in OXPHOS efficiency. In skeletal muscle, DNP activated the mitochondrial biogenesis pathway, as indicated by changes in the mRNA expression of PGC1-α and -β, NRF-1 and -2, and TFAM, and increased the mRNA expression of cytochrome oxidase 1 (P < 0.01). The expression of two mitochondrial proteins (prohibitin and Ndufs 3) was higher after DNP treatment. Mitochondrial fission 1 protein (Fis-1) was increased in the DNP group (P < 0.01), but mitofusin-1 and -2 were unchanged. Histochemical staining for NADH dehydrogenase and succinate dehydrogenase activity in the gastrocnemius muscle revealed an increase in the proportion of oxidative fibers after DNP treatment. Our study shows that mitochondrial uncoupling induces several skeletal muscle adaptations, highlighting the role of mitochondrial coupling as a critical factor for maximal exercise capacities. These results emphasize the importance of investigating the qualitative aspects of mitochondrial function in addition to the amount of mitochondria.

  4. Pequi leaves incorporated into the soil reduce the initial growth of cultivated, invasive and native species.

    PubMed

    Allem, Laísa N; Gomes, Anabele S; Borghetti, Fabian

    2014-12-01

    Studies have identified the phytotoxicity of many native species of the Cerrado; however, most of them were conducted either in inert substrates, or using exaggerate proportions of plant material. We investigated the phytotoxicity of pequi leaves added to substrate soil in quantities compatible with the litter produced by this species. Pequi leaves were triturated and added to red latosol in concentrations of 0.75%, 1.5% and 3%; the control was constituted of leafless soil. These mixtures were added to pots and irrigated daily to keep them moist. Germinated seeds of the cultivated sorghum and sesame, of the invasive brachiaria and of the native purple ipê, were disposed in the pots to grow for five to seven days at 30°C within a photoperiod of 12 h. Seedlings of all the species presented a reduction in their initial growth in a dose-dependent way. In general, the root growth was more affected by the treatments than the shoot growth; moreover, signs of necrosis were observed in the roots of the sorghum, sesame and brachiaria. The phytotoxic effects generated by relatively small quantities of leaves, in a reasonable range of species within a soil substrate, suggest potential allelopathy of pequi leaves under natural conditions.

  5. An environmentally friendly method for the fabrication of reduced graphene oxide foam with a super oil absorption capacity.

    PubMed

    He, Yongqiang; Liu, Yue; Wu, Tao; Ma, Junkui; Wang, Xingrui; Gong, Qiaojuan; Kong, Weina; Xing, Fubao; Liu, Yu; Gao, Jianping

    2013-09-15

    Three kinds of graphene oxide (GO) foams were fabricated using different freezing methods (unidirectional freezing drying (UDF), non-directional freezing drying, and air freezing drying), and the corresponding reduced graphene oxide (RGO) foams were prepared by their thermal reduction of those GO foams. These RGO foams were characterized by Fourier transform infrared spectroscopy, thermal gravimetric analysis, X-ray diffraction, X-ray photoelectron spectroscopy, and scanning electron microscopy. The absorption process and the factors that influence the absorption capacity were investigated. The RGO foams are hydrophobic and showed extremely high absorbing abilities for organic liquids. The absorption capacity of the RGO foams made by UDF was higher than 100 g g(-1) for all the oils tested (gasoline, diesel oil, pump oil, lubricating oil and olive oil) and had the highest value of about 122 g g(-1) for olive oil. The oil absorption capacity of the GO foams was lower than that of the RGO foams, but for olive oil, the absorption capacity was still high than 70 g g(-1), which is higher than that of most oil absorbents.

  6. Physically-based reduced-order capacity loss model for graphite anodes in Li-ion battery cells

    NASA Astrophysics Data System (ADS)

    Jin, Xing; Vora, Ashish; Hoshing, Vaidehi; Saha, Tridib; Shaver, Gregory; García, R. Edwin; Wasynczuk, Oleg; Varigonda, Subbarao

    2017-02-01

    Physically-based Li-ion electrochemical cell models have been shown capable of predicting cell performance and degradation, but are computationally expensive for optimization-oriented design applications. Faster empirical models have been developed from experimental data, but are not generalizable to operating conditions outside of the range established by the calibration data. In this paper, a reduced-order capacity-loss model for graphite anodes is derived based upon the salient physical loss mechanisms to improve computational efficiency without sacrificing model fidelity. This model captures the two primary degradation mechanisms that occur in the graphite anode of a typical lithium ion cell: a) capacity loss due to Solid Electrolyte Interface (SEI) layer growth, and b) capacity loss due to isolation of active material. The model is calibrated and validated for a commercial 2.3-Ah cell with a Lithium Iron Phosphate (LFP) cathode and graphite anode. One data set is used for calibration, another four experimental data sets are used for validation. The model matches experimental capacity degradation results within a 20% error. Moreover, the reported model is 2400× faster than currently existing more complex physically-based electrochemical models that are only slightly more accurate (in some cases).

  7. Myoblast replication is reduced in the IUGR fetus despite maintained proliferative capacity in vitro.

    PubMed

    Soto, Susan M; Blake, Amy C; Wesolowski, Stephanie R; Rozance, Paul J; Barthel, Kristen B; Gao, Bifeng; Hetrick, Byron; McCurdy, Carrie E; Garza, Natalia G; Hay, William W; Leinwand, Leslie A; Friedman, Jacob E; Brown, Laura D

    2017-03-01

    Adults who were affected by intrauterine growth restriction (IUGR) suffer from reductions in muscle mass and insulin resistance, suggesting muscle growth may be restricted by molecular events that occur during fetal development. To explore the basis of restricted fetal muscle growth, we used a sheep model of progressive placental insufficiency-induced IUGR to assess myoblast proliferation within intact skeletal muscle in vivo and isolated myoblasts stimulated with insulin in vitro Gastrocnemius and soleus muscle weights were reduced by 25% in IUGR fetuses compared to those in controls (CON). The ratio of PAX7+ nuclei (a marker of myoblasts) to total nuclei was maintained in IUGR muscle compared to CON, but the fraction of PAX7+ myoblasts that also expressed Ki-67 (a marker of cellular proliferation) was reduced by 23%. Despite reduced proliferation in vivo, fetal myoblasts isolated from IUGR biceps femoris and cultured in enriched media in vitro responded robustly to insulin in a dose- and time-dependent manner to increase proliferation. Similarly, insulin stimulation of IUGR myoblasts upregulated key cell cycle genes and DNA replication. There were no differences in the expression of myogenic regulatory transcription factors that drive commitment to muscle differentiation between CON and IUGR groups. These results demonstrate that the molecular machinery necessary for transcriptional control of proliferation remains intact in IUGR fetal myoblasts, indicating that in vivo factors such as reduced insulin and IGF1, hypoxia and/or elevated counter-regulatory hormones may be inhibiting muscle growth in IUGR fetuses.

  8. Reduced mitochondrial oxidative capacity and increased mitochondrial uncoupling impair myocardial energetics in obesity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Obesity is a risk factor for cardiovascular disease and is strongly associated with insulin resistance and type 2 diabetes. Recent studies in obese humans and animals demonstrated increased myocardial oxygen consumption (MVO2) and reduced cardiac efficiency (CE); however, the underlying mechanisms r...

  9. Anandamide (arachidonylethanolamide), a brain cannabinoid receptor agonist, reduces sperm fertilizing capacity in sea urchins by inhibiting the acrosome reaction.

    PubMed Central

    Schuel, H; Goldstein, E; Mechoulam, R; Zimmerman, A M; Zimmerman, S

    1994-01-01

    Anandamide (arachidonylethanolamide) is an endogenous cannabinoid receptor agonist in mammalian brain. Sea urchin sperm contain a high-affinity cannabinoid receptor similar to the cannabinoid receptor in mammalian brain. (-)-delta 9-Tetrahydrocannabinol (THC), the primary psychoactive cannabinoid in marihuana, reduces the fertilizing capacity of sea urchin sperm by blocking the acrosome reaction that normally is stimulated by a specific ligand in the egg's jelly coat. We now report that anandamide produces effects similar to those previously obtained with THC in Strongylocentrotus purpuratus in reducing sperm fertilizing capacity and inhibiting the egg jelly-stimulated acrosome reaction. Arachidonic acid does not inhibit the acrosome reaction under similar conditions. The adverse effects of anandamide on sperm fertilizing capacity and the acrosome reaction are reversible. The receptivity of unfertilized eggs to sperm and sperm motility are not impaired by anandamide. Under conditions where anandamide completely blocks the egg jelly-stimulated acrosome reaction, it does not inhibit the acrosome reaction artificially initiated by ionomycin, which promotes Ca2+ influx, and nigericin, which activates K+ channels in sperm. These findings provide additional evidence that the cannabinoid receptor in sperm plays a role in blocking the acrosome reaction, indicate that anandamide or a related molecule may be the natural ligand for the cannabinoid receptor in sea urchin sperm, and suggest that binding of anandamide to the cannabinoid receptor modulates stimulus-secretion-coupling in sperm by affecting an event prior to ion channel opening. PMID:8052642

  10. Reduced graphene oxide as a stable and high-capacity cathode material for Na-ion batteries

    NASA Astrophysics Data System (ADS)

    Ali, Ghulam; Mehmood, Asad; Ha, Heung Yong; Kim, Jaehoon; Chung, Kyung Yoon

    2017-01-01

    We report the feasibility of using reduced graphene oxide (RGO) as a cost-effective and high performance cathode material for sodium-ion batteries (SIBs). Graphene oxide is synthesized by a modified Hummers’ method and reduced using a solid-state microwave irradiation method. The RGO electrode delivers an exceptionally stable discharge capacity of 240 mAh g‑1 with a stable long cycling up to 1000 cycles. A discharge capacity of 134 mAh g‑1 is obtained at a high current density of 600 mA g‑1, and the electrode recovers a capacity of 230 mAh g‑1 when the current density is reset to 15 mA g‑1 after deep cycling, thus demonstrating the excellent stability of the electrode with sodium de/intercalation. The successful use of the RGO electrode demonstrated in this study is expected to facilitate the emergence of low-cost and sustainable carbon-based materials for SIB cathode applications.

  11. Reduced graphene oxide as a stable and high-capacity cathode material for Na-ion batteries

    PubMed Central

    Ali, Ghulam; Mehmood, Asad; Ha, Heung Yong; Kim, Jaehoon; Chung, Kyung Yoon

    2017-01-01

    We report the feasibility of using reduced graphene oxide (RGO) as a cost-effective and high performance cathode material for sodium-ion batteries (SIBs). Graphene oxide is synthesized by a modified Hummers’ method and reduced using a solid-state microwave irradiation method. The RGO electrode delivers an exceptionally stable discharge capacity of 240 mAh g−1 with a stable long cycling up to 1000 cycles. A discharge capacity of 134 mAh g−1 is obtained at a high current density of 600 mA g−1, and the electrode recovers a capacity of 230 mAh g−1 when the current density is reset to 15 mA g−1 after deep cycling, thus demonstrating the excellent stability of the electrode with sodium de/intercalation. The successful use of the RGO electrode demonstrated in this study is expected to facilitate the emergence of low-cost and sustainable carbon-based materials for SIB cathode applications. PMID:28098231

  12. Crif1 Deficiency Reduces Adipose OXPHOS Capacity and Triggers Inflammation and Insulin Resistance in Mice

    PubMed Central

    Ryu, Min Jeong; Kim, Soung Jung; Kim, Yong Kyung; Choi, Min Jeong; Tadi, Surendar; Lee, Min Hee; Lee, Seong Eun; Chung, Hyo Kyun; Jung, Saet Byel; Kim, Hyun-Jin; Jo, Young Suk; Kim, Koon Soon; Lee, Sang-Hee; Kim, Jin Man; Kweon, Gi Ryang; Park, Ki Cheol; Lee, Jung Uee; Kong, Young Yun; Lee, Chul-Ho; Chung, Jongkyeong; Shong, Minho

    2013-01-01

    Impaired mitochondrial oxidative phosphorylation (OXPHOS) has been proposed as an etiological mechanism underlying insulin resistance. However, the initiating organ of OXPHOS dysfunction during the development of systemic insulin resistance has yet to be identified. To determine whether adipose OXPHOS deficiency plays an etiological role in systemic insulin resistance, the metabolic phenotype of mice with OXPHOS–deficient adipose tissue was examined. Crif1 is a protein required for the intramitochondrial production of mtDNA–encoded OXPHOS subunits; therefore, Crif1 haploinsufficient deficiency in mice results in a mild, but specific, failure of OXPHOS capacity in vivo. Although adipose-specific Crif1-haploinsufficient mice showed normal growth and development, they became insulin-resistant. Crif1-silenced adipocytes showed higher expression of chemokines, the expression of which is dependent upon stress kinases and antioxidant. Accordingly, examination of adipose tissue from Crif1-haploinsufficient mice revealed increased secretion of MCP1 and TNFα, as well as marked infiltration by macrophages. These findings indicate that the OXPHOS status of adipose tissue determines its metabolic and inflammatory responses, and may cause systemic inflammation and insulin resistance. PMID:23516375

  13. The effect of the thermal reduction temperature on the structure and sorption capacity of reduced graphene oxide materials

    NASA Astrophysics Data System (ADS)

    Dolbin, Alexandr V.; Khlistyuck, Maria V.; Esel'son, Valentin B.; Gavrilko, Viktor G.; Vinnikov, Nikolay A.; Basnukaeva, Razet M.; Maluenda, Irene; Maser, Wolfgang K.; Benito, Ana M.

    2016-01-01

    The influence of reduction temperatures on the structure and the sorption capacity of thermally reduced graphene (TRGO) has been investigated systematically. A set of TRGO materials were prepared by thermal treatment of parent graphene oxide (GO) at five temperatures (T = 200, 300, 500, 700, and 900 °C). Investigations of these materials by X-ray diffraction, Raman spectroscopy and X-ray photoemission spectroscopy methods have shown that both the structure and the residual oxygen functional groups on the TRGO surface can be controlled by varying the temperature of the thermal treatment. The data on the sorption and desorption of 4He, H2, N2, Ne and Kr gases in the temperature interval T = 2-290 K clearly demonstrate that the sorption capacity of TRGO is closely related to the structural changes induced by the treatment temperatures. It is important that the sorption capacities of TRGOs treated at 300 °C and at 900 °C significantly increase for all the gases used. The prominent increase in the sorption capacity at 300 °C is attributed to the structural disorder and liberation of the pores caused by the removal of intercalated water and labile oxygen functional groups (oFGs) favored at this temperature. At 900 °C the sorption capacity increases due to the generation of new defects on the TRGO surface, which provide additional access to the internal space between the folds and sheets of the TRGO structure. By tailoring the structural properties we emphasize the potential of TRGO as a highly efficient sorbent.

  14. 40 CFR 60.1560 - Can an affected municipal waste combustion unit reduce its capacity to less than 35 tons per day...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... combustion unit reduce its capacity to less than 35 tons per day rather than comply with my State plan? 60... Small Municipal Waste Combustion Units Constructed on or Before August 30, 1999 Applicability of State Plans § 60.1560 Can an affected municipal waste combustion unit reduce its capacity to less than 35...

  15. 40 CFR 60.1560 - Can an affected municipal waste combustion unit reduce its capacity to less than 35 tons per day...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... combustion unit reduce its capacity to less than 35 tons per day rather than comply with my State plan? 60... Small Municipal Waste Combustion Units Constructed on or Before August 30, 1999 Applicability of State Plans § 60.1560 Can an affected municipal waste combustion unit reduce its capacity to less than 35...

  16. Unripe Rubus coreanus Miquel suppresses migration and invasion of human prostate cancer cells by reducing matrix metalloproteinase expression.

    PubMed

    Kim, Yesl; Lee, Seung Min; Kim, Jung-Hyun

    2014-01-01

    Rubus coreanus Miquel (RCM) is used to promote prostate health and has been shown to have anti-oxidant and anti-carcinogenic activities. However, the effects and mechanisms of RCM on prostate cancer metastasis remain unclear. PC-3 and DU 145 cells were treated with ethanol or water extract of unripe or ripe RCM and examined for cell invasion, migration, and matrix metalloproteinases (MMPs) activity and expression. Phosphoinositide 3-kinase (PI3K) and Akt activities were examined. Unripe RCM extracts exerted significant inhibitory effects on cell migration, invasion, and MMPs activities. A significant reduction in MMPs activities by unripe RCM ethanol extract treatment (UE) was associated with reduction of MMPs expression and induction of tissue inhibitors of metalloproteinases (TIMPs) expression. Furthermore, PI3K/Akt activity was diminished by UE treatment. In this study, we demonstrated that UE decreased metastatic potential of prostate cancer cells by reducing MMPs expression through the suppression of PI3K/Akt phosphorylation, thereby decreasing MMP activity and enhancing TIMPs expression.

  17. A novel high-throughput image based rapid Folin-Ciocalteau assay for assessment of reducing capacity in foods.

    PubMed

    Abderrahim, Mohamed; M Arribas, Silvia; Condezo-Hoyos, Luis

    2016-05-15

    The aim of the presented work was to develop and validate a novel high-throughput rapid Folin-Ciocalteau assay for the quantification of reducing capacity of foods based on image scanner (Image-F-C assay). The original rapid F-C assay using a 96-well plate was improved by adding a neutralization step that stabilizes the formed color, enabling image acquisition using a flatbed scanner. Although the scanner has been already used in other analytical applications, no analysis has been reported regarding the effect of the scanner model, the plate orientation or the reaction volume. In the present study, we establish that the mentioned parameters do affect the linearity and precision of image based Folin-Ciocalteau assay, and provide the optimal scanning conditions for the analyzed scanner models. Euclidean distance calculated from R (Red), G (Green) and B (Blue) values was chosen, based on linearity and sensitivity, in order to quantify the reducing capacity. An in-house program using free ImageJ macro language was written to calculate automatically the RGB values of each well. The Image-F-C assay is linear within the range of 0-20 mg L(-1) of gallic acid (R(2)≥0.9939). We compared reducing capacity values from real samples quantified by the image F-C assay and by a microplate reader and an inter-day relative standard error<8% was observed. Bland-Altman and correlation analyzes showed that there were no significant differences between the two methods.

  18. Nrdp1-mediated ErbB3 degradation inhibits glioma cell migration and invasion by reducing cytoplasmic localization of p27(Kip1).

    PubMed

    Shi, Hengliang; Gong, Hui; Cao, Kuan; Zou, Shenshan; Zhu, Bingxin; Bao, Hanmo; Wu, Yuxuan; Gao, Yong; Tang, Yuan; Yu, Rutong

    2015-09-01

    We previously reported that loss of Nrdp1 contributes to human glioma progression by reducing apoptosis. However, the role of Nrdp1 in glioma migration and invasion has not been investigated. Here, we report that ErbB3, a substrate of Nrdp1, is undetectable in normal brain tissues and grade II/III glioma tissues, but is abundant in a certain percentage of grade IV glioma tissues and is associated with the loss of Nrdp1. This suggests that Nrdp1 may be involved in glioma migration and invasion by regulating ErbB3. Thus, the role of Nrdp1/ErbB3 signaling in glioma cell migration and invasion was investigated using Nrdp1 loss- and gain-of-function. The results show that down-regulation of Nrdp1 by use of short hairpin RNA promoted glioma cell migration and invasion. In contrast, overexpression of Nrdp1 significantly inhibited glioma cell migration and invasion. Further investigation on molecular targets revealed that Nrdp1 decreased the level of ErbB3, which resulted in decreasing p-AKT thereby reducing cytoplasmic p27(Kip1). Taken together, these findings suggest that Nrdp1-mediated ErbB3 degradation suppresses glioma migration and invasion and that loss of Nrdp1 may amplify ErbB3 signaling to contribute to glioma migration and invasion. These findings suggest that Nrdp1 may be a target for glioma therapy.

  19. Lanthanum carbonate reduces urine phosphorus excretion: evidence of high-capacity phosphate binding.

    PubMed

    Pennick, Michael; Poole, Lynne; Dennis, Kerry; Smyth, Michael

    2012-01-01

    The effectiveness of phosphate binders can be assessed by evaluating urinary phosphorus excretion in healthy volunteers, which indicates the ability of the phosphate binder to reduce gastrointestinal phosphate absorption. Healthy volunteers were enrolled into one of five separate randomized trials; four were open label and one double blind. Following a screening period of ≤28 days, participants received differing tablets containing lanthanum carbonate [LC, 3000 mg/day of elemental lanthanum (in one study other doses were also used)]. Participants received a standardized phosphate diet and remained in the relevant study center throughout the duration of each treatment period. The end point in all studies was the reduction in urinary phosphorus excretion. Reductions in mean 24-h urinary phosphorus excretion in volunteers receiving a lanthanum dose of 3000 mg/day were between 236 and 468 mg/day over the five separate studies. These data in healthy volunteers can be used to estimate the amount of reduction of dietary phosphate absorption by LC. The reduction in 24-h urinary phosphorus excretion per tablet was compared with published data on other phosphate binders. Although there are limitations, evidence suggests that LC is a very effective phosphate binder in terms of binding per tablet.

  20. Tissue taurine depletion alters metabolic response to exercise and reduces running capacity in mice.

    PubMed

    Ito, Takashi; Yoshikawa, Natsumi; Schaffer, Stephen W; Azuma, Junichi

    2014-01-01

    Taurine is a sulfur-containing amino acid found in very high concentration in skeletal muscle. Taurine deficient mice engineered by knocking out the taurine transporter gene exhibit skeletal muscle wasting, structural defects, and exercise intolerance. In the present study, we investigated the mechanism underlying the development of metabolic abnormalities and exercise intolerance in muscle of the TauTKO phenotype. Running speed and endurance time of TauTKO mice were lower than those of control mice. Blood lactate level was elevated by >3-fold during treadmill running in TauTKO mice but remained largely unaltered by exercise in WT mice. Blood glucose was cleared faster during treadmill running in TauTKO mice than WT mice. AMP-activated kinase (AMPK) β-2 subunit was reduced in TauTKO muscle concomitant with a reduction in α1 and α2 subunits of AMPK. The level of PPARα and its targets, Gpx3, Cpt2, and Echs1, were also decreased in TauTKO muscle. Collectively, taurine depletion impairs metabolic adaptation to exercise in skeletal muscle, a phenomenon associated with a downregulation of AMPK and diminished NADH utilization by the mitochondrial respiratory chain. These findings suggest a crucial role of taurine in regulating energy metabolism in skeletal muscle of exercising TauTKO mice, changes that contribute to impaired exercise endurance.

  1. Tissue Taurine Depletion Alters Metabolic Response to Exercise and Reduces Running Capacity in Mice

    PubMed Central

    Yoshikawa, Natsumi; Schaffer, Stephen W.

    2014-01-01

    Taurine is a sulfur-containing amino acid found in very high concentration in skeletal muscle. Taurine deficient mice engineered by knocking out the taurine transporter gene exhibit skeletal muscle wasting, structural defects, and exercise intolerance. In the present study, we investigated the mechanism underlying the development of metabolic abnormalities and exercise intolerance in muscle of the TauTKO phenotype. Running speed and endurance time of TauTKO mice were lower than those of control mice. Blood lactate level was elevated by >3-fold during treadmill running in TauTKO mice but remained largely unaltered by exercise in WT mice. Blood glucose was cleared faster during treadmill running in TauTKO mice than WT mice. AMP-activated kinase (AMPK) β-2 subunit was reduced in TauTKO muscle concomitant with a reduction in α1 and α2 subunits of AMPK. The level of PPARα and its targets, Gpx3, Cpt2, and Echs1, were also decreased in TauTKO muscle. Collectively, taurine depletion impairs metabolic adaptation to exercise in skeletal muscle, a phenomenon associated with a downregulation of AMPK and diminished NADH utilization by the mitochondrial respiratory chain. These findings suggest a crucial role of taurine in regulating energy metabolism in skeletal muscle of exercising TauTKO mice, changes that contribute to impaired exercise endurance. PMID:25478210

  2. Diastolic function is associated with quality of life and exercise capacity in stable heart failure patients with reduced ejection fraction

    PubMed Central

    Bussoni, M.F.; Guirado, G.N.; Roscani, M.G.; Polegato, B.F.; Matsubara, L.S.; Bazan, S.G.Z.; Matsubara, B.B.

    2013-01-01

    Exercise capacity and quality of life (QOL) are important outcome predictors in patients with systolic heart failure (HF), independent of left ventricular (LV) ejection fraction (LVEF). LV diastolic function has been shown to be a better predictor of aerobic exercise capacity in patients with systolic dysfunction and a New York Heart Association (NYHA) classification ≥II. We hypothesized that the currently used index of diastolic function E/e' is associated with exercise capacity and QOL, even in optimally treated HF patients with reduced LVEF. This prospective study included 44 consecutive patients aged 55±11 years (27 men and 17 women), with LVEF<0.50 and NYHA functional class I-III, receiving optimal pharmacological treatment and in a stable clinical condition, as shown by the absence of dyspnea exacerbation for at least 3 months. All patients had conventional transthoracic echocardiography and answered the Minnesota Living with HF Questionnaire, followed by the 6-min walk test (6MWT). In a multivariable model with 6MWT as the dependent variable, age and E/e' explained 27% of the walked distance in 6MWT (P=0.002; multivariate regression analysis). No association was found between walk distance and LVEF or mitral annulus systolic velocity. Only normalized left atrium volume, a sensitive index of diastolic function, was associated with decreased QOL. Despite the small number of patients included, this study offers evidence that diastolic function is associated with physical capacity and QOL and should be considered along with ejection fraction in patients with compensated systolic HF. PMID:24036912

  3. Forest species diversity reduces disease risk in a generalist plant pathogen invasion

    USGS Publications Warehouse

    Haas, Sarah E.; Hooten, Mevin B.; Rizzo, David M.; Meentemeyer, Ross K.

    2011-01-01

    Empirical evidence suggests that biodiversity loss can increase disease transmission, yet our understanding of the 'diversity-disease hypothesis' for generalist pathogens in natural ecosystems is limited. We used a landscape epidemiological approach to examine two scenarios regarding diversity effects on the emerging plant pathogen Phytophthora ramorum across a broad, heterogeneous ecoregion: (1) an amplification effect exists where disease risk is greater in areas with higher plant diversity due to the pathogen's wide host range, or (2) a dilution effect where risk is reduced with increasing diversity due to lower competency of alternative hosts. We found evidence for pathogen dilution, whereby disease risk was lower in sites with higher species diversity, after accounting for potentially confounding effects of host density and landscape heterogeneity. Our results suggest that although nearly all plants in the ecosystem are hosts, alternative hosts may dilute disease transmission by competent hosts, thereby buffering forest health from infectious disease.

  4. Toward the physical basis of thermophilic proteins: linking of enriched polar interactions and reduced heat capacity of unfolding.

    PubMed

    Zhou, Huan-Xiang

    2002-12-01

    The enrichment of salt bridges and hydrogen bonding in thermophilic proteins has long been recognized. Another tendency, featuring lower heat capacity of unfolding (DeltaC(p)) than found in mesophilic proteins, is emerging from the recent literature. Here we present a simple electrostatic model to illustrate that formation of a salt-bridge or hydrogen-bonding network around an ionized group in the folded state leads to increased folding stability and decreased DeltaC(p). We thus suggest that the reduced DeltaC(p) of thermophilic proteins could partly be attributed to enriched polar interactions. A reduced DeltaC(p) might serve as an indicator for the contribution of polar interactions to folding stability.

  5. Antioxidant capacity reduced in scallions grown under elevated CO 2 independent of assayed light intensity

    NASA Astrophysics Data System (ADS)

    Levine, Lanfang H.; Paré, Paul W.

    2009-10-01

    Long-duration manned space missions mandate the development of a sustainable life support system and effective countermeasures against damaging space radiation. To mitigate the risk of inevitable exposure to space radiation, cultivation of fresh fruits and vegetables rich in antioxidants is an attractive alternative to pharmacological agents. However it has yet to be established whether antioxidant properties of crops can be preserved or enhanced in a space environment where environmental conditions differ from that which plants have acclimated to on earth. Scallion ( Allium fistulosum) rich in antioxidant vitamins C and A, and flavonoids was used as a model plant to study the impact of a range of CO 2 concentrations and light intensities that are likely encountered in a space habitat on food quality traits. Scallions were hydroponically grown in controlled environmental chambers under a combination of 3 CO 2 concentrations of 400, 1200 and 4000 μmol mol -1 and 3 light intensity levels of 150, 300, 450 μmol m -2 s -1. Total antioxidant activity (TAA) of scallion extracts was determined using a radical cation scavenging assay. Both elevated CO 2 and increasing light intensity enhanced biomass accumulation, but effects on TAA (based on dry weight) differed. TAA was reduced for plants grown under elevated CO 2, but remained unchanged with increases in light intensity. Elevated CO 2 stimulated greater biomass production than antioxidants, while an increase in photosynthetic photo flux promoted the synthesis of antioxidant compounds at a rate similar to that of biomass. Consequently light is a more effective stimulus than CO 2 for antioxidant production.

  6. French invasive Asian tiger mosquito populations harbor reduced bacterial microbiota and genetic diversity compared to Vietnamese autochthonous relatives

    PubMed Central

    Minard, G.; Tran, F. H.; Van, Van Tran; Goubert, C.; Bellet, C.; Lambert, G.; Kim, Khanh Ly Huynh; Thuy, Trang Huynh Thi; Mavingui, P.; Valiente Moro, C.

    2015-01-01

    The Asian tiger mosquito Aedes albopictus is one of the most significant pathogen vectors of the twenty-first century. Originating from Asia, it has invaded a wide range of eco-climatic regions worldwide. The insect-associated microbiota is now recognized to play a significant role in host biology. While genetic diversity bottlenecks are known to result from biological invasions, the resulting shifts in host-associated microbiota diversity has not been thoroughly investigated. To address this subject, we compared four autochthonous Ae. albopictus populations in Vietnam, the native area of Ae. albopictus, and three populations recently introduced to Metropolitan France, with the aim of documenting whether these populations display differences in host genotype and bacterial microbiota. Population-level genetic diversity (microsatellite markers and COI haplotype) and bacterial diversity (16S rDNA metabarcoding) were compared between field-caught mosquitoes. Bacterial microbiota from the whole insect bodies were largely dominated by Wolbachia pipientis. Targeted analysis of the gut microbiota revealed a greater bacterial diversity in which a fraction was common between French and Vietnamese populations. The genus Dysgonomonas was the most prevalent and abundant across all studied populations. Overall genetic diversities of both hosts and bacterial microbiota were significantly reduced in recently established populations of France compared to the autochthonous populations of Vietnam. These results open up many important avenues of investigation in order to link the process of geographical invasion to shifts in commensal and symbiotic microbiome communities, as such shifts may have dramatic impacts on the biology and/or vector competence of invading hematophagous insects. PMID:26441903

  7. Biodegradable interstitial release polymer loading a novel small molecule targeting Axl receptor tyrosine kinase and reducing brain tumour migration and invasion

    PubMed Central

    Yen, S-Y; Chen, S-R; Hsieh, J; Li, Y-S; Chuang, S-E; Chuang, H-M; Huang, M-H; Lin, S-Z; Harn, H-J; Chiou, T-W

    2016-01-01

    Glioblastoma multiforme (GBM) is the most common and aggressive brain tumour. The neoplasms are difficult to resect entirely because of their highly infiltration property and leading to the tumour edge is unclear. Gliadel wafer has been used as an intracerebral drug delivery system to eliminate the residual tumour. However, because of its local low concentration and short diffusion distance, patient survival improves non-significantly. Axl is an essential regulator in cancer metastasis and patient survival. In this study, we developed a controlled-release polyanhydride polymer loading a novel small molecule, n-butylidenephthalide (BP), which is not only increasing local drug concentration and extending its diffusion distance but also reducing tumour invasion, mediated by reducing Axl expression. First, we determined that BP inhibited the expression of Axl in a dose- and time-dependent manner and reduced the migratory and invasive capabilities of GBM cells. In addition, BP downregulated matrix metalloproteinase activity, which is involved in cancer cell invasion. Furthermore, we demonstrated that BP regulated Axl via the extracellular signal-regulated kinases pathway. Epithelial-to-mesenchymal transition (EMT) is related to epithelial cells in the invasive migratory mesenchymal cells that underlie cancer progression; we demonstrated that BP reduced the expression of EMT-related genes. Furthermore, we used the overexpression of Axl in GBM cells to prove that Axl is a crucial target in the inhibition of GBM EMT, migration and invasion. In an in vivo study, we demonstrated that BP inhibited tumour growth and suppressed Axl expression in a dose-dependent manner according to a subcutaneous tumour model. Most importantly, in an intracranial tumour model with BP wafer in situ treatment, we demonstrated that the BP wafer not only significantly increased the survival rate but also decreased Axl expression, and inhibited tumour invasion. These results contribute to the

  8. Forest management under climatic and social uncertainty: trade-offs between reducing climate change impacts and fostering adaptive capacity.

    PubMed

    Seidl, Rupert; Lexer, Manfred J

    2013-01-15

    The unabated continuation of anthropogenic greenhouse gas emissions and the lack of an international consensus on a stringent climate change mitigation policy underscore the importance of adaptation for coping with the all but inevitable changes in the climate system. Adaptation measures in forestry have particularly long lead times. A timely implementation is thus crucial for reducing the considerable climate vulnerability of forest ecosystems. However, since future environmental conditions as well as future societal demands on forests are inherently uncertain, a core requirement for adaptation is robustness to a wide variety of possible futures. Here we explicitly address the roles of climatic and social uncertainty in forest management, and tackle the question of robustness of adaptation measures in the context of multi-objective sustainable forest management (SFM). We used the Austrian Federal Forests (AFF) as a case study, and employed a comprehensive vulnerability assessment framework based on ecosystem modeling, multi-criteria decision analysis, and practitioner participation. We explicitly considered climate uncertainty by means of three climate change scenarios, and accounted for uncertainty in future social demands by means of three societal preference scenarios regarding SFM indicators. We found that the effects of climatic and social uncertainty on the projected performance of management were in the same order of magnitude, underlining the notion that climate change adaptation requires an integrated social-ecological perspective. Furthermore, our analysis of adaptation measures revealed considerable trade-offs between reducing adverse impacts of climate change and facilitating adaptive capacity. This finding implies that prioritization between these two general aims of adaptation is necessary in management planning, which we suggest can draw on uncertainty analysis: Where the variation induced by social-ecological uncertainty renders measures aiming to

  9. Aberrant Salience Is Related to Reduced Reinforcement Learning Signals and Elevated Dopamine Synthesis Capacity in Healthy Adults.

    PubMed

    Boehme, Rebecca; Deserno, Lorenz; Gleich, Tobias; Katthagen, Teresa; Pankow, Anne; Behr, Joachim; Buchert, Ralph; Roiser, Jonathan P; Heinz, Andreas; Schlagenhauf, Florian

    2015-07-15

    The striatum is known to play a key role in reinforcement learning, specifically in the encoding of teaching signals such as reward prediction errors (RPEs). It has been proposed that aberrant salience attribution is associated with impaired coding of RPE and heightened dopamine turnover in the striatum, and might be linked to the development of psychotic symptoms. However, the relationship of aberrant salience attribution, RPE coding, and dopamine synthesis capacity has not been directly investigated. Here we assessed the association between a behavioral measure of aberrant salience attribution, the salience attribution test, to neural correlates of RPEs measured via functional magnetic resonance imaging while healthy participants (n = 58) performed an instrumental learning task. A subset of participants (n = 27) also underwent positron emission tomography with the radiotracer [(18)F]fluoro-l-DOPA to quantify striatal presynaptic dopamine synthesis capacity. Individual variability in aberrant salience measures related negatively to ventral striatal and prefrontal RPE signals and in an exploratory analysis was found to be positively associated with ventral striatal presynaptic dopamine levels. These data provide the first evidence for a specific link between the constructs of aberrant salience attribution, reduced RPE processing, and potentially increased presynaptic dopamine function.

  10. Plasma cholesterol efflux capacity from human THP-1 macrophages is reduced in HIV-infected patients: impact of HAART[S

    PubMed Central

    El Khoury, Petra; Ghislain, Mathilde; Villard, Elise F.; Le Goff, Wilfried; Lascoux-Combe, Caroline; Yeni, Patrick; Meyer, Laurence; Vigouroux, Corinne; Goujard, Cécile; Guerin, Maryse

    2015-01-01

    The capacity of HDL to remove cholesterol from macrophages is inversely associated with the severity of angiographic coronary artery disease. The effect of human immunodeficiency virus (HIV) infection or its treatment on the ability of HDL particles to stimulate cholesterol efflux from human macrophages has never been studied. We evaluated the capacity of whole plasma and isolated HDL particles from HIV-infected subjects (n = 231) and uninfected controls (n = 200), as well as in a subset of 41 HIV subjects receiving highly active antiretroviral therapy (HAART) to mediate cholesterol efflux from human macrophages. Plasma cholesterol efflux capacity was reduced (−12%; P = 0.001) in HIV patients as compared with controls. HIV infection reduced by 27% (P < 0.05) the capacity of HDL subfractions to promote cholesterol efflux from macrophages. We observed a reduced ABCA1-dependent efflux capacity of plasma (−27%; P < 0.0001) from HIV-infected subjects as a result of a reduction in the efflux capacity of HDL3 particles. HAART administration restored the capacity of plasma from HIV patients to stimulate cholesterol efflux from human macrophages (9.4%; P = 0.04). During HIV infection, the capacity of whole plasma to remove cholesterol from macrophages is reduced, thus potentially contributing to the increased coronary heart disease in the HIV population. HAART administration restored the removal of cholesterol from macrophages by increasing HDL functionality. PMID:25573889

  11. Efficacy of plastic mesh tubes in reducing herbivory damage by the invasive nutria (Myocastor coypus) in an urban restoration site

    USGS Publications Warehouse

    Sheffels, Trevor R.; Systma, Mark D.; Carter, Jacoby; Taylor, Jimmy D.

    2014-01-01

    The restoration of stream corridors is becoming an increasingly important component of urban landscape planning, and the high cost of these projects necessitates the need to understand and address potential ecological obstacles to project success. The nutria(Myocastor coypus) is an invasive, semi-aquatic rodent native to South America that causes detrimental ecological impacts in riparian and wetland habitats throughout its introduced range, and techniques are needed to reduce nutria herbivory damage to urban stream restoration projects. We assessed the efficacy of standard Vexar® plastic mesh tubes in reducing nutria herbivory damage to newly established woody plants. The study was conducted in winter-spring 2009 at Delta Ponds, a 60-ha urban waterway in Eugene, Oregon. Woody plants protected by Vexar® tubes demonstrated 100% survival over the 3-month initial establishment period, while only 17% of unprotected plantings survived. Nutria demonstrated a preference for black cottonwood (Populus balsamifera ssp trichocarpa) over red osier dogwood (Cornussericea) and willow (Salix spp). Camera surveillance showed that nutria were more active in unprotected rather than protected treatments. Our results suggest that Vexar® plastic mesh tubing can be an effective short-term herbivory mitigation tool when habitat use by nutria is low. Additionally, planting functionally equivalent woody plant species that are less preferred by nutria, and other herbivores, may be another method for reducing herbivory and improving revegetation success. This study highlights the need to address potential wildlife damage conflicts in the planning process for stream restoration in urban landscapes.

  12. Reduced mental capacity and behavior of a rider of a bicycle simulator under alcohol stress or under dual task load

    NASA Technical Reports Server (NTRS)

    Soede, M.

    1977-01-01

    Experiments were carried out on a bicycle simulator with alcohol administration and a binary choice task in separate sessions, intending to reduce the subject's mental capacity. Before and after such sessions a visual evoked response measurement was done. The subject's performance was analyzed with describing function techniques. The results indicate that the alcohol affects the course-following task as well as the balancing task. The binary choice task is more specifically influencing the course-following task. The dual task shows a more pronounced effect on the recovery of the evoked response. The alcohol is delaying the recovery curve of the evoked response. A tentative explanation can be given which agrees with the performance data.

  13. "I Still Haven't Found What I'm Looking For": Parental Privacy Invasion Predicts Reduced Parental Knowledge

    ERIC Educational Resources Information Center

    Hawk, Skyler T.; Keijsers, Loes; Frijns, Tom; Hale, William W., III; Branje, Susan; Meeus, Wim

    2013-01-01

    This 3-year, multi-informant study examined whether youths' perceptions of parental privacy invasion predicted lower parental knowledge over time, as a function of increased adolescent secrecy. Participants were 497 Dutch adolescents (Time 1 M = 13 years, SD = 0.5; 57% boys) and both parents. Higher youth-reported invasion predicted lower…

  14. "I still haven't found what I'm looking for": parental privacy invasion predicts reduced parental knowledge.

    PubMed

    Hawk, Skyler T; Keijsers, Loes; Frijns, Tom; Hale, William W; Branje, Susan; Meeus, Wim

    2013-07-01

    This 3-year, multi-informant study examined whether youths' perceptions of parental privacy invasion predicted lower parental knowledge over time, as a function of increased adolescent secrecy. Participants were 497 Dutch adolescents (Time 1 M = 13 years, SD = 0.5; 57% boys) and both parents. Higher youth-reported invasion predicted lower father- and mother-reported knowledge 1 year later. A link between privacy invasion and youths' increased secrecy mediated the association between privacy invasion and mothers' lower knowledge. Further, mothers' perceptions of adolescent secrecy mediated the association between adolescent-reported secrecy and mothers' knowledge. No mediation existed for father-report models. The results suggest that privacy invasion is counterproductive to parents' efforts to remain knowledgeable about youths, due to increased adolescent secrecy. We discuss the implications for family communication processes and successful privacy negotiations during adolescence.

  15. MiR-128 up-regulation inhibits Reelin and DCX expression and reduces neuroblastoma cell motility and invasiveness.

    PubMed

    Evangelisti, Cristina; Florian, Maria Carolina; Massimi, Isabella; Dominici, Carlo; Giannini, Giuseppe; Galardi, Silvia; Buè, Maria Cristina; Massalini, Simone; McDowell, Heather P; Messi, Elio; Gulino, Alberto; Farace, Maria Giulia; Ciafrè, Silvia Anna

    2009-12-01

    MicroRNAs are a class of sophisticated regulators of gene expression, acting as post-transcriptional inhibitors that recognize their target mRNAs through base pairing with short regions along the 3'UTRs. Several microRNAs are tissue specific, suggesting a specialized role in tissue differentiation or maintenance, and quite a few are critically involved in tumorigenesis. We studied miR-128, a brain-enriched microRNA, in retinoic acid-differentiated neuroblastoma cells, and we found that this microRNA is up-regulated in treated cells, where it down-modulates the expression of two proteins involved in the migratory potential of neural cells: Reelin and DCX. Consistently, miR-128 ectopic overexpression suppressed Reelin and DCX, whereas the LNA antisense-mediated miR-128 knockdown caused the two proteins to increase. Ectopic miR-128 overexpression reduced neuroblastoma cell motility and invasiveness, and impaired cell growth. Finally, the analysis of a small series of primary human neuroblastomas showed an association between high levels of miR-128 expression and favorable features, such as favorable Shimada category or very young age at diagnosis. Thus, we provide evidence for a role for miR-128 in the molecular events modulating neuroblastoma progression and aggressiveness.

  16. Chlorate reduction capacity and characterisation of chlorate reducing bacteria communities in sediments of the rio Cruces wetland in southern Chile.

    PubMed

    Schwarz, Alex O; Urrutia, Homero; Vidal, José Miguel; Pérez, Norma

    2012-06-15

    This study investigated chlorate reduction kinetics in multiple samples of sediments from a longitudinal profile of a wetland located downstream of the effluent discharge of a cellulose plant, including characterisation of the bacterial communities involved. The sediments were exposed to different initial chlorate concentrations in microcosm tests, with and without the addition of acetate as an external electron donor, and in a matrix of natural water or a defined medium. At a high initial chlorate concentration of 100 mg/L, in the absence of an external electron source, the degradation curves presented first-order kinetics, influenced by electron donor availability. The first-order kinetic constant varied between 0.05 and 0.17 day(-1). Subsequently, when the initial chlorate concentration was reduced to 7 mg/L, a zero-order kinetic was obtained, with the kinetic constant presenting values between 1.1 and 1.3 mg/L-day. No correlation was observed between chlorate degradation kinetics and the location of the sampling points or the previous history of exposure to chlorate. Other factors evaluated, such as the availability of organic matter or the chlorate reducing bacteria count, also proved not to have any incidence on the results. The richness of chlorate reducing bacteria species in the different samples analysed were also similar, with the greatest similarity being found between cld genes in the samples from the upstream or downstream sampling points. Additionally, cld genes most similar to those present in PCRB like Dechlorospirillum sp., Alicycliphilus denitrificans, Dechloromonas agitata, Dechloromonas sp. LT1 and Ideonella dechloratans were detected. This study showed that the anaerobic sediments of the Cruces river wetland present a high potential for chlorate natural attenuation, regardless of the previous history of exposure to chlorate. This capacity is associated with the presence of a diverse community of chlorate reducing bacteria.

  17. Surface Defection Reduces Cytotoxicity of Zn(2-methylimidazole)2 (ZIF-8) without Compromising its Drug Delivery Capacity

    PubMed Central

    Shearier, Emily; Cheng, Peifu; Bao, Jiming

    2016-01-01

    Zn(2-methylimidazole)2 (ZIF-8), as one of the most important metal-organic framework (MOF) molecules, is a promising candidate for drug delivery due to its low-density structure, high surface area, and tunable frameworks. However, ZIF-8 exhibits a high cytotoxicity associated with its external hydrophobic surface, which significantly restricts its application in drug delivery and other biomedical applications. Commonly used chemical functionalization methods would convert the hydrophobic surface of ZIF-8 to hydrophilic, but the generated functional groups on its internal surface may reduce its pore sizes or even block its pores. Herein, a surface defection strategy was applied on the external surface of ZIF-8 to enhance its hydrophilicity without reducing or blocking the internal pores. In this approach, mechanical ball-milling was used to incur defects on the external surface of ZIF-8, leading to unsaturated Zn-sites and N-sites which subsequently bound H2O molecules in an aqueous environment. Furthermore, hydroxyurea delivery and cell cytotoxicity of ZIF-8 with and without the external surface treatment were evaluated. It was found that 5-min ball milling changed the hydrophobic–hydrophilic balance of ZIF-8, resulting in significantly higher cell viability without compromising its hydroxyurea loading and release capacity. Such a simple mechanical ball-milling followed by water-treatment provides a general technique for surface-modification of other MOF molecules, which will undoubtedly magnify their biomedical applications. PMID:26998256

  18. Reduced attentional capacity, but normal processing speed and shifting of attention in developmental dyslexia: evidence from a serial task.

    PubMed

    Romani, Cristina; Tsouknida, Effie; di Betta, Anna M; Olson, Andrew

    2011-06-01

    We report the performance of a group of adult dyslexics and matched controls in an array-matching task where two strings of either consonants or symbols are presented side by side and have to be judged to be the same or different. The arrays may differ either in the order or identity of two adjacent characters. This task does not require naming - which has been argued to be the cause of dyslexics' difficulty in processing visual arrays - but, instead, has a strong serial component as demonstrated by the fact that, in both groups, Reaction times (RTs) increase monotonically with position of a mismatch. The dyslexics are clearly impaired in all conditions and performance in the identity conditions predicts performance across orthographic tasks even after age, performance IQ and phonology are partialled out. Moreover, the shapes of serial position curves are revealing of the underlying impairment. In the dyslexics, RTs increase with position at the same rate as in the controls (lines are parallel) ruling out reduced processing speed or difficulties in shifting attention. Instead, error rates show a catastrophic increase for positions which are either searched later or more subject to interference. These results are consistent with a reduction in the attentional capacity needed in a serial task to bind together identity and positional information. This capacity is best seen as a reduction in the number of spotlights into which attention can be split to process information at different locations rather than as a more generic reduction of resources which would also affect processing the details of single objects.

  19. Selected Lactic Acid-Producing Bacterial Isolates with the Capacity to Reduce Salmonella Translocation and Virulence Gene Expression in Chickens

    PubMed Central

    Yang, Xiaojian; Brisbin, Jennifer; Yu, Hai; Wang, Qi; Yin, Fugui; Zhang, Yonggang; Sabour, Parviz; Sharif, Shayan; Gong, Joshua

    2014-01-01

    Background Probiotics have been used to control Salmonella colonization/infection in chickens. Yet the mechanisms of probiotic effects are not fully understood. This study has characterized our previously-selected lactic acid-producing bacterial (LAB) isolates for controlling Salmonella infection in chickens, particularly the mechanism underlying the control. Methodology/Principal Findings In vitro studies were conducted to characterize 14 LAB isolates for their tolerance to low pH (2.0) and high bile salt (0.3–1.5%) and susceptibility to antibiotics. Three chicken infection trials were subsequently carried out to evaluate four of the isolates for reducing the burden of Salmonella enterica serovar Typhimurium in the broiler cecum. Chicks were gavaged with LAB cultures (106–7 CFU/chick) or phosphate-buffered saline (PBS) at 1 day of age followed by Salmonella challenge (104 CFU/chick) next day. Samples of cecal digesta, spleen, and liver were examined for Salmonella counts on days 1, 3, or 4 post-challenge. Salmonella in the cecum from Trial 3 was also assessed for the expression of ten virulence genes located in its pathogenicity island-1 (SPI-1). These genes play a role in Salmonella intestinal invasion. Tested LAB isolates (individuals or mixed cultures) were unable to lower Salmonella burden in the chicken cecum, but able to attenuate Salmonella infection in the spleen and liver. The LAB treatments also reduced almost all SPI-1 virulence gene expression (9 out of 10) in the chicken cecum, particularly at the low dose. In vitro treatment with the extracellular culture fluid from a LAB culture also down-regulated most SPI-1 virulence gene expression. Conclusions/Significance The possible correlation between attenuation of Salmonella infection in the chicken spleen and liver and reduction of Salmonella SPI-1 virulence gene expression in the chicken cecum by LAB isolates is a new observation. Suppression of Salmonella virulence gene expression in vivo can be one

  20. Growth Retardation, Reduced Invasiveness, and Impaired Colistin-Mediated Cell Death Associated with Colistin Resistance Development in Acinetobacter baumannii

    PubMed Central

    Poulou, Aggeliki; Dafopoulou, Konstantina; Chabane, Yassine Nait; Kristo, Ioulia; Makris, Demosthenes; Hardouin, Julie; Cosette, Pascal; Tsakris, Athanassios; Dé, Emmanuelle

    2014-01-01

    Two colistin-susceptible/colistin-resistant (Cols/Colr) pairs of Acinetobacter baumannii strains assigned to international clone 2, which is prevalent worldwide, were sequentially recovered from two patients after prolonged colistin administration. Compared with the respective Cols isolates (Ab248 and Ab299, both having a colistin MIC of 0.5 μg/ml), both Colr isolates (Ab249 and Ab347, with colistin MICs of 128 and 32 μg/ml, respectively) significantly overexpressed pmrCAB genes, had single-amino-acid shifts in the PmrB protein, and exhibited significantly slower growth. The Colr isolate Ab347, tested by proteomic analysis in comparison with its Cols counterpart Ab299, underexpressed the proteins CsuA/B and C from the csu operon (which is necessary for biofilm formation). This isolate also underexpressed aconitase B and different enzymes involved in the oxidative stress response (KatE catalase, superoxide dismutase, and alkyl hydroperoxide reductase), suggesting a reduced response to reactive oxygen species (ROS) and, consequently, impaired colistin-mediated cell death through hydroxyl radical production. Cols isolates that were indistinguishable by macrorestriction analysis from Ab299 caused six sequential bloodstream infections, and isolates indistinguishable from Ab248 caused severe soft tissue infection, while Colr isolates indistinguishable from Ab347 and Ab249 were mainly colonizers. In particular, a Cols isolate identical to Ab299 was still invading the bloodstream 90 days after the colonization of this patient by Colr isolates. These observations indicate considerably lower invasiveness of A. baumannii clinical isolates following the development of colistin resistance. PMID:24247145

  1. High fatty acid oxidation capacity and phosphorylation control despite elevated leak and reduced respiratory capacity in northern elephant seal muscle mitochondria.

    PubMed

    Chicco, Adam J; Le, Catherine H; Schlater, Amber; Nguyen, Alex; Kaye, Spencer; Beals, Joseph W; Scalzo, Rebecca L; Bell, Christopher; Gnaiger, Erich; Costa, Daniel P; Crocker, Daniel E; Kanatous, Shane B

    2014-08-15

    Northern elephant seals (Mirounga angustirostris) are extreme, hypoxia-adapted endotherms that rely largely on aerobic metabolism during extended breath-hold dives in near-freezing water temperatures. While many aspects of their physiology have been characterized to account for these remarkable feats, the contribution of adaptations in the aerobic powerhouses of muscle cells, the mitochondria, are unknown. In the present study, the ontogeny and comparative physiology of elephant seal muscle mitochondrial respiratory function was investigated under a variety of substrate conditions and respiratory states. Intact mitochondrial networks were studied by high-resolution respirometry in saponin-permeabilized fiber bundles obtained from primary swimming muscles of pup, juvenile and adult seals, and compared with fibers from adult human vastus lateralis. Results indicate that seal muscle maintains a high capacity for fatty acid oxidation despite a progressive decrease in total respiratory capacity as animals mature from pups to adults. This is explained by a progressive increase in phosphorylation control and fatty acid utilization over pyruvate in adult seals compared with humans and seal pups. Interestingly, despite higher indices of oxidative phosphorylation efficiency, juvenile and adult seals also exhibit a ~50% greater capacity for respiratory 'leak' compared with humans and seal pups. The ontogeny of this phenotype suggests it is an adaptation of muscle to the prolonged breath-hold exercise and highly variable ambient temperatures experienced by mature elephant seals. These studies highlight the remarkable plasticity of mammalian mitochondria to meet the demands for both efficient ATP production and endothermy in a cold, oxygen-limited environment.

  2. Hydrogen-rich water enhances cadmium tolerance in Chinese cabbage by reducing cadmium uptake and increasing antioxidant capacities.

    PubMed

    Wu, Qi; Su, Nana; Cai, Jiangtao; Shen, Zhenguo; Cui, Jin

    2015-03-01

    The aim of the present paper was to understand the specific mechanism of hydrogen-rich water (HRW) in alleviating cadmium (Cd) toxicity in Chinese cabbage (Brassica campestris spp. chinensis L.). Our results showed that the addition of 50% saturation HRW significantly alleviated the Cd toxic symptoms, including the improvement of both root elongation and seedling growth inhibition. These responses were consistent with a significant decrease of Cd accumulation in roots and shoots, which was further confirmed by the histochemical staining. Molecular evidence illustrated that Cd-induced up-regulations of IRT1 and Nramp1 genes, responsible for Cd absorption, were blocked by HRW. By contrast, Cd-induced up-regulation of the HMA3 gene, which regulates Cd sequestration into the root vacuoles, was substantially strengthened by HRW. Furthermore, compared with those in Cd stress alone, the expressions of HMA2 and HMA4, which function in the transportation of Cd to xylem, were repressed by co-treatment with HRW. HRW enhanced the activities of antioxidant enzymes, including superoxide dismutase, guaiacol peroxidase, catalase and ascorbate peroxidase. These results were further confirmed by the alleviation of oxidative damage, as indicated by the decrease of thiobarbituric acid reactive substances (TBARS) and reactive oxygen species (ROS) production. Taken together, these results suggest that the improvement of Cd tolerance by HRW was associated with reduced Cd uptake and increased antioxidant defense capacities. Therefore, the application of HRW may be a promising strategy to improve Cd tolerance of Chinese cabbage.

  3. ATF3 reduces migration capacity by regulation of matrix metalloproteinases via NFκB and STAT3 inhibition in glioblastoma

    PubMed Central

    Guenzle, Jessica; Wolf, Louisa J; Garrelfs, Nicklas W C; Goeldner, Jonathan M; Osterberg, Nadja; Schindler, Cora R; Saavedra, Joseph E; Weyerbrock, Astrid

    2017-01-01

    Glioblastoma is associated with poor survival and a high recurrence rate in patients due to inevitable uncontrolled infiltrative tumor growth. The elucidation of the molecular mechanisms may offer opportunities to prevent relapses. In this study we investigated the role of the activating transcription factor 3 (ATF3) in migration of GBM cells in vitro. RNA microarray revealed that gene expression of ATF3 is induced by a variety of chemotherapeutics and experimental agents such as the nitric oxide donor JS-K (O2-(2,4-dinitrophenyl) 1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate). We found NFκB and STAT3 to be downstream targets inhibited by overexpression of ATF3. We demonstrate that ATF3 is directly involved in the regulation of matrix metalloproteinase expression and activation. Overexpression of ATF3 therefore leads to a significantly reduced migration capacity and induction of tissue inhibitors of matrix metalloproteinases. Our study for the first time identifies ATF3 as a potential novel therapeutic target in glioblastoma. PMID:28250971

  4. Downregulation of MMP1 in MDS-derived mesenchymal stromal cells reduces the capacity to restrict MDS cell proliferation.

    PubMed

    Zhao, Sida; Zhao, Youshan; Guo, Juan; Fei, Chengming; Zheng, Qingqing; Li, Xiao; Chang, Chunkang

    2017-03-06

    The role of mesenchymal stromal cells (MSCs) in the pathogenesis of myelodysplastic syndromes (MDS) has been increasingly addressed, but has yet to be clearly elucidated. In this investigation, we found that MDS cells proliferated to a greater extent on MDS-derived MSCs compared to normal MSCs. Matrix metalloproteinase 1(MMP1), which was downregulated in MDS-MSCs, was identified as an inhibitory factor of MDS cell proliferation, given that treatment with an MMP1 inhibitor or knock-down of MMP1 in normal MSCs resulted in increased MDS cell proliferation. Further investigations indicated that MMP1 induced apoptosis of MDS cells by interacting with PAR1 and further activating the p38 MAPK pathway. Inhibition of either PAR1 or p38 MAPK can reverse the apoptosis-inducing effect of MMP1. Taken together, these data indicate that downregulation of MMP1 in MSCs of MDS patients may contribute to the reduced capacity of MSCs to restrict MDS cell proliferation, which may account for the malignant proliferation of MDS cells.

  5. Downregulation of MMP1 in MDS-derived mesenchymal stromal cells reduces the capacity to restrict MDS cell proliferation

    PubMed Central

    Zhao, Sida; Zhao, Youshan; Guo, Juan; Fei, Chengming; Zheng, Qingqing; Li, Xiao; Chang, Chunkang

    2017-01-01

    The role of mesenchymal stromal cells (MSCs) in the pathogenesis of myelodysplastic syndromes (MDS) has been increasingly addressed, but has yet to be clearly elucidated. In this investigation, we found that MDS cells proliferated to a greater extent on MDS-derived MSCs compared to normal MSCs. Matrix metalloproteinase 1(MMP1), which was downregulated in MDS-MSCs, was identified as an inhibitory factor of MDS cell proliferation, given that treatment with an MMP1 inhibitor or knock-down of MMP1 in normal MSCs resulted in increased MDS cell proliferation. Further investigations indicated that MMP1 induced apoptosis of MDS cells by interacting with PAR1 and further activating the p38 MAPK pathway. Inhibition of either PAR1 or p38 MAPK can reverse the apoptosis-inducing effect of MMP1. Taken together, these data indicate that downregulation of MMP1 in MSCs of MDS patients may contribute to the reduced capacity of MSCs to restrict MDS cell proliferation, which may account for the malignant proliferation of MDS cells. PMID:28262842

  6. Reduced LPL and subcutaneous lipid storage capacity are associated with metabolic syndrome in postmenopausal women with obesity

    PubMed Central

    Ryan, A. S.; Goldberg, A. P.

    2016-01-01

    Sumary Objectives This study examines the hypothesis that lower adipose tissue lipoprotein lipase (LPL) activity and a limited capacity for subcutaneous adipocyte expansion will be associated with metabolic syndrome (MSyn) in postmenopausal women who are overweight and obese. Methods Women (N = 150; age 60 ± 1 year; BMI: 31.5 ± 0.3 kg m−2; mean ± standard errors of the means [SEM]) with and without MSyn had dual‐energy X‐ray absorptiometry scans for total body fat, CT scans for visceral and subcutaneous abdominal adipose tissue areas, lipid and glucose metabolic profiles, and abdominal and gluteal fat aspirations for subcutaneous fat cell weight (FCW; N = 150) and LPL activity (N = 100). Results Women with MSyn had similar total body fat, but 15% larger abdominal and 11% larger gluteal FCWs and more visceral fat (179 ± 7 vs. 134 ± 6 cm2) than women without MSyn (P's < 0.05). Abdominal LPL activity was 13% (P = 0.18) lower in women with than without MSyn and correlated with abdominal FCW (r = 0.49, P < 0.01) only in those without MSyn. Visceral fat and abdominal and gluteal FCWs correlated with MSyn components, and subcutaneous adipose tissue correlated with abdominal FCW (r = 0.43, P < 0.01) and LPL activity (r = 0.18, P < 0.05), independent of total body fat. Conclusions These results show that women with MSyn have lower LPL activity, limited capacity for subcutaneous adipocyte lipid storage and greater ectopic fat accumulation in viscera than women without MSyn of comparable obesity. This suggests that the development of novel therapies that would enhance adipocyte expandability might prevent the accumulation of ectopic fat and reduce the risk for MSyn in postmenopausal women with obesity.

  7. Ecological immunization: in situ training of free-ranging predatory lizards reduces their vulnerability to invasive toxic prey

    PubMed Central

    Ward-Fear, G.; Pearson, D. J.; Brown, G. P.; Rangers, Balanggarra; Shine, R.

    2016-01-01

    In Australia, large native predators are fatally poisoned when they ingest invasive cane toads (Rhinella marina). As a result, the spread of cane toads has caused catastrophic population declines in these predators. Immediately prior to the arrival of toads at a floodplain in the Kimberley region, we induced conditioned taste aversion in free-ranging varanid lizards (Varanus panoptes), by offering them small cane toads. By the end of the 18-month study, only one of 31 untrained lizards had survived longer than 110 days, compared to more than half (nine of 16) of trained lizards; the maximum known survival of a trained lizard in the presence of toads was 482 days. In situ aversion training (releasing small toads in advance of the main invasion front) offers a logistically simple and feasible way to buffer the impact of invasive toads on apex predators. PMID:26740565

  8. Ecological immunization: in situ training of free-ranging predatory lizards reduces their vulnerability to invasive toxic prey.

    PubMed

    Ward-Fear, G; Pearson, D J; Brown, G P; Rangers, Balanggarra; Shine, R

    2016-01-01

    In Australia, large native predators are fatally poisoned when they ingest invasive cane toads (Rhinella marina). As a result, the spread of cane toads has caused catastrophic population declines in these predators. Immediately prior to the arrival of toads at a floodplain in the Kimberley region, we induced conditioned taste aversion in free-ranging varanid lizards (Varanus panoptes), by offering them small cane toads. By the end of the 18-month study, only one of 31 untrained lizards had survived longer than 110 days, compared to more than half (nine of 16) of trained lizards; the maximum known survival of a trained lizard in the presence of toads was 482 days. In situ aversion training (releasing small toads in advance of the main invasion front) offers a logistically simple and feasible way to buffer the impact of invasive toads on apex predators.

  9. Non-invasive assessment of phosphate metabolism and oxidative capacity in working skeletal muscle in healthy young Chinese volunteers using (31)P Magnetic Resonance Spectroscopy.

    PubMed

    Li, Ming; Chen, Fei; Wang, Huiting; Wu, Wenbo; Zhang, Xin; Tian, Chuanshuai; Yu, Haiping; Liu, Renyuan; Zhu, Bin; Zhang, Bing; Dai, Zhenyu

    2016-01-01

    Background. Generally, males display greater strength and muscle capacity than females while performing a task. Muscle biopsy is regarded as the reference method of evaluating muscle functions; however, it is invasive and has sampling errors, and is not practical for longitudinal studies and dynamic measurement during excise. In this study, we built an in-house force control and gauge system for quantitatively applying force to quadriceps while the subjects underwent (31)P Magnetic Resonance Spectroscopy ((31)P-MRS); our aim was to investigate if there is a sex difference of phosphate metabolite change in working muscles in young heathy Chinese volunteers. Methods. Volunteers performed knee-extending excises using a force control and gauge system while lying prone in a Philips 3T Magnetic Resonance (MR) scanner. The (31)P-MRS coil was firmly placed under the middle of the quadriceps . (31)P-MRS measurements of inorganic phosphate (Pi), phosphocreatine (PCr) and adenosine triphosphate (ATP) were acquired from quadriceps while subjects were in a state of pre-, during- and post-exercise. The PCr, Pi, PCr/Pi, PCr/ATP, pH, work/energy cost ratio (WE), kPCr and oxidative capacity were compared between males and females. Results. A total of 17 volunteers underwent the study. Males: N = 10, age = 23.30 ± 1.25years; females: N = 7, age = 23.57 ± 0.79 years. In this study, males had significantly greater WE (16.33 ± 6.46 vs. 7.82 ± 2.16, p = 0.002) than females. Among PCr, Pi, PCr/Pi, PCr/ATP, pH, kPCr and oxidative capacity at different exercise status, only PCr/Pi (during-exercise, males = 5.630 ± 1.647, females = 4.014 ± 1.298, p = 0.047), PCr/ATP (during-exercise, males =1.273 ± 0.219, females = 1.523 ± 0.167, p = 0.025), and ATP (post-exercise, males = 24.469 ± 3.911 mmol/kg, females = 18.353 ± 4.818 mmol/kg, p = 0.035) had significant sex differences. Males had significantly greater PCr/Pi, but less PCr/ATP than females during exercise, suggesting males had

  10. Supine Treadmill Exercise in Lower Body Negative Pressure Combined with Resistive Exercise Counteracts Bone Loss, Reduced Aerobic Upright Exercise Capacity and Reduced Muscle Strength

    NASA Technical Reports Server (NTRS)

    Meuche, Sabine; Schneider, S. M.; Lee, S. M. C.; Macias, B. R.; Smith, S. M.; Watenpaugh, D. E.; Hargens, A. R.

    2006-01-01

    Long-term exposure to weightlessness leads to cardiovascular and musculoskeletal deconditioning. In this report, the effectiveness of combined supine treadmill exercise in a lower body negative pressure chamber (LBNPex) and flywheel resistive exercise (Rex) countermeasures was determined to prevent bone loss, reduced aerobic upright exercise capacity and reduced muscle strength. We hypothesized that exercise subjects would show less decrease in bone mineral density (BMD), peak oxygen consumption (VO2pk) and knee extensor strength (KES) than control subjects. Sixteen healthy female subjects participated in a 60-d 6(sup 0) head-down tilt bed rest (BR) study after providing written informed consent. Subjects were assigned to one of two groups: a non-exercising control group CON or an exercise group EX performing LBNPex 2-4 d/wk and Rex every 3rd-d. VO2pk was measured with a maximal, graded, upright treadmill test performed pre-BR and on 3-d after BR. BMD was assessed before and 3-d after BR. Isokinetic KES was measured before and 5-d after BR. Two-way repeated measures ANOVA were performed. Statistical significance was set at p less than 0.05. CON experienced a significant decrease in BMD in the trochanter (PRE: 0.670 plus or minus 0.045; POST: 0.646 plus or minus 0.352 g (raised dot) per square centimeter) and in the whole hip (PRE=0.894 plus or minus 0.059; POST: 0.858 plus or minus 0.057 g (raised dot) per square centimeter). BMD also decreased significantly in EX in the trochanter (PRE: 0.753 plus or minus 0.0617; POST: 0.741 plus or minus 0.061 g (raised dot) per square centimeter) and whole hip (PRE: 0.954 plus or minus 0.067; POST: 0.935 plus or minus 0.069 g (raised dot) per square centimeter). BMD losses were significantly less in EX than in CON subjects. VO2pk was significantly decreased in the CON after BR (PRE: 38.0 plus or minus 4.8; POST: 29.9 plus or minus 4.2 ml (raised dot) per kilogram per minute), but not in the EX (PRE: 39.0 plus or minus 2.0; POST

  11. Minimally invasive procedure reduces adjacent segment degeneration and disease: New benefit-based global meta-analysis

    PubMed Central

    Li, Xiao-Chuan; Huang, Chun-Ming; Zhong, Cheng-Fan; Liang, Rong-Wei; Luo, Shao-Jian

    2017-01-01

    Objective Adjacent segment pathology (ASP) is a common complication presenting in patients with axial pain and dysfunction, requiring treatment or follow-up surgery. However, whether minimally invasive surgery (MIS), including MIS transforaminal / posterior lumbar interbody fusion (MIS-TLIF/PLIF) decreases the incidence rate of ASP remains unknown. The aim of this meta-analysis was to compare the incidence rate of ASP in patients undergoing MIS versus open procedures. Methods This systematic review was undertaken by following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement. We searched electronic databases, including PubMed, EMBASE, SinoMed, and the Cochrane Library, without language restrictions, to identify clinical trials comparing MIS to open procedures. The results retrieved were last updated on June 15, 2016. Results Overall, 9 trials comprising 770 patients were included in the study; the quality of the studies included 4 moderate and 5 low-quality studies. The pooled data analysis demonstrated low heterogeneity between the trials and a significantly lower ASP incidence rate in patients who underwent MIS procedure, compared with those who underwent open procedure (p = 0.0001). Single-level lumbar interbody fusion was performed in 6 trials of 408 patients and we found a lower ASP incidence rate in MIS group, compared with those who underwent open surgery (p = 0.002). Moreover, the pooled data analysis showed a significant reduction in the incidence rate of adjacent segment disease (ASDis) (p = 0.0003) and adjacent segment degeneration (ASDeg) (p = 0.0002) for both procedures, favoring MIS procedure. Subgroup analyses showed no difference in follow-up durations between the procedures (p = 0.93). Conclusion Therefore, we conclude that MIS-TLIF/PLIF can reduce the incidence rate of ASDis and ASDeg, compared with open surgery. Although the subgroup analysis did not indicate a difference in follow-up duration between the two

  12. [Reduced waiting capacities as a possible mechanism of action of benzodiazepines. A hypothesis derived from their behavioral effects in animals].

    PubMed

    Thiébot, M H; Le Bihan, C; Soubrié, P; Simon, P

    1986-01-01

    In classical punishment procedures, suppression of responding which allows the animal to avoid electric foot-shock is attenuated by benzodiazepines (BZD). Such a release of responding is interpreted as a reflection of the anxiolytic activity of BZD. In these situations however, behavioral suppression also delays the obtention of the food-reward. Therefore, shock-mediated waiting could be as critical a target as shock-induced fear for BZD in punishment procedures. The present study was designed to investigate whether BZD are effective in reducing the capacity of animals to wait for an expected food reward. Fasted rats trained in a T-maze were allowed to choose between two magnitudes of reward: immediate but small (2 pellets) vs delayed but large (8 pellets). Diazepam (2-4 mg/kg), nitrazepam (2 mg/kg), chlordiazepoxide (16 mg/kg) or clobazam (16 mg/kg) decreased the number of times the large reward was chosen by rats subjected to a waiting period of 15 s before having access to the large reward. In conflict situations, rats trained to press a level for food reward were given both 1 pellet and 1 electric foot-shock for pressing during punished periods of fixed duration signalled by a warning stimulus. The diazepam (2 mg/kg)-induced increase in the number of punished presses (anti-punishment effect) was closely related to the percent punishment time within a session. The release of punished responding reached a statistically significant level only when the total punishment-time accounted for at least 40% of the total duration of the session.(ABSTRACT TRUNCATED AT 250 WORDS)

  13. Measurement of xanthine oxidase inhibition activity of phenolics and flavonoids with a modified cupric reducing antioxidant capacity (CUPRAC) method.

    PubMed

    Ozyürek, Mustafa; Bektaşoğlu, Burcu; Güçlü, Kubilay; Apak, Reşat

    2009-03-16

    Various dietary polyphenolics have been found to show an inhibitory effect on xanthine oxidase (XO) which mediates oxidative stress-originated diseases because of its ability to generate reactive oxygen species (ROS), including superoxide anion radical (O(2)(-)) and hydrogen peroxide. XO activity has usually been determined by following the rate of uric acid formation from xanthine-xanthine oxidase (X-XO) system using the classical XO activity assay (UV-method) at 295nm. Since some polyphenolics have strong absorption from the UV to visible region, XO-inhibitory activity of polyphenolics was alternatively determined without interference by directly measuring the formation of uric acid and hydrogen peroxide using the modified CUPRAC (cupric reducing antioxidant capacity) spectrophotometric method at 450nm. The CUPRAC absorbance of the incubation solution due to the reduction of Cu(II)-neocuproine reagent by the products of the X-XO system decreased in the presence of polyphenolics, the difference being proportional to the XO inhibition ability of the tested compound. The structure-activity relationship revealed that the flavones and flavonols with a 7-hydroxyl group such as apigenin, luteolin, kaempferol, quercetin, and myricetin inhibited XO-inhibitory activity at low concentrations (IC(50) values from 1.46 to 1.90microM), while the flavan-3-ols and naringin were less inhibitory. The findings of the developed method for quercetin and catechin in the presence of catalase were statistically alike with those of HPLC. In addition to polyphenolics, five kinds of herbs were evaluated for their XO-inhibitory activity using the developed method. The proposed spectrophotometric method was practical, low-cost, rapid, and could reliably assay uric acid and hydrogen peroxide in the presence of polyphenols (flavonoids, simple phenolic acids and hydroxycinnamic acids), and less open to interferences by UV-absorbing substances.

  14. Development of Dive Capacity in Northern Elephant Seals (Mirounga angustirostris): Reduced Body Reserves at Weaning Are Associated with Elevated Body Oxygen Stores during the Postweaning Fast.

    PubMed

    Somo, Derek A; Ensminger, David C; Sharick, Jeffrey T; Kanatous, Shane B; Crocker, Daniel E

    2015-01-01

    Developmental increases in dive capacity have been reported in numerous species of air-breathing marine vertebrates. Previous studies in juvenile phocid seals suggest that increases in physiological dive capacity during the postweaning fast (PWF) are critical to support independent aquatic foraging. Although there is a strong relationship between size at weaning and PWF duration and body reserves at weaning vary considerably, few studies have considered whether such variation in body reserve magnitude promotes phenotypic modulation of dive capacity development during the PWF. Phenotypic modulation, a form of developmental plasticity in which rates and degrees of expression of the developmental program are modulated by environmental factors, may enhance diving capacity in weanlings with reduced PWF durations due to smaller body reserves at weaning if reduced body reserves promote accelerated development of dive capacity. We longitudinally measured changes in blood and muscle oxygen stores and muscle metabolic enzymes over the first 8 wk of the PWF in northern elephant seals and determined whether rates of change in these parameters varied with body reserves at weaning. We assessed whether erythropoietin (EPO), thyroid hormones, serum nonesterified fatty acid levels, and iron status influenced blood and muscle oxygen store development or were influenced by body reserves at weaning. Although mass-specific plasma volume and blood volume were relatively stable across the fast, both were elevated in animals with reduced body reserves. Surprisingly, hemoglobin and mean corpuscular hemoglobin concentrations declined over the PWF while hematocrit remained stable, and these variables were not associated with body reserves or EPO. Swimming muscle myoglobin and serum iron levels increased rapidly early in the PWF and were not related to body reserves. Patterns in maximal activities of muscle enzymes suggested a decline in total aerobic and anaerobic metabolic capacity over the

  15. Activating Developmental Reserve Capacity Via Cognitive Training or Non-invasive Brain Stimulation: Potentials for Promoting Fronto-Parietal and Hippocampal-Striatal Network Functions in Old Age

    PubMed Central

    Passow, Susanne; Thurm, Franka; Li, Shu-Chen

    2017-01-01

    Existing neurocomputational and empirical data link deficient neuromodulation of the fronto-parietal and hippocampal-striatal circuitries with aging-related increase in processing noise and declines in various cognitive functions. Specifically, the theory of aging neuronal gain control postulates that aging-related suboptimal neuromodulation may attenuate neuronal gain control, which yields computational consequences on reducing the signal-to-noise-ratio of synaptic signal transmission and hampering information processing within and between cortical networks. Intervention methods such as cognitive training and non-invasive brain stimulation, e.g., transcranial direct current stimulation (tDCS), have been considered as means to buffer cognitive functions or delay cognitive decline in old age. However, to date the reported effect sizes of immediate training gains and maintenance effects of a variety of cognitive trainings are small to moderate at best; moreover, training-related transfer effects to non-trained but closely related (i.e., near-transfer) or other (i.e., far-transfer) cognitive functions are inconsistent or lacking. Similarly, although applying different tDCS protocols to reduce aging-related cognitive impairments by inducing temporary changes in cortical excitability seem somewhat promising, evidence of effects on short- and long-term plasticity is still equivocal. In this article, we will review and critically discuss existing findings of cognitive training- and stimulation-related behavioral and neural plasticity effects in the context of cognitive aging, focusing specifically on working memory and episodic memory functions, which are subserved by the fronto-parietal and hippocampal-striatal networks, respectively. Furthermore, in line with the theory of aging neuronal gain control we will highlight that developing age-specific brain stimulation protocols and the concurrent applications of tDCS during cognitive training may potentially facilitate

  16. Activating Developmental Reserve Capacity Via Cognitive Training or Non-invasive Brain Stimulation: Potentials for Promoting Fronto-Parietal and Hippocampal-Striatal Network Functions in Old Age.

    PubMed

    Passow, Susanne; Thurm, Franka; Li, Shu-Chen

    2017-01-01

    Existing neurocomputational and empirical data link deficient neuromodulation of the fronto-parietal and hippocampal-striatal circuitries with aging-related increase in processing noise and declines in various cognitive functions. Specifically, the theory of aging neuronal gain control postulates that aging-related suboptimal neuromodulation may attenuate neuronal gain control, which yields computational consequences on reducing the signal-to-noise-ratio of synaptic signal transmission and hampering information processing within and between cortical networks. Intervention methods such as cognitive training and non-invasive brain stimulation, e.g., transcranial direct current stimulation (tDCS), have been considered as means to buffer cognitive functions or delay cognitive decline in old age. However, to date the reported effect sizes of immediate training gains and maintenance effects of a variety of cognitive trainings are small to moderate at best; moreover, training-related transfer effects to non-trained but closely related (i.e., near-transfer) or other (i.e., far-transfer) cognitive functions are inconsistent or lacking. Similarly, although applying different tDCS protocols to reduce aging-related cognitive impairments by inducing temporary changes in cortical excitability seem somewhat promising, evidence of effects on short- and long-term plasticity is still equivocal. In this article, we will review and critically discuss existing findings of cognitive training- and stimulation-related behavioral and neural plasticity effects in the context of cognitive aging, focusing specifically on working memory and episodic memory functions, which are subserved by the fronto-parietal and hippocampal-striatal networks, respectively. Furthermore, in line with the theory of aging neuronal gain control we will highlight that developing age-specific brain stimulation protocols and the concurrent applications of tDCS during cognitive training may potentially facilitate

  17. DDR2 inhibition reduces migration and invasion of murine metastatic melanoma cells by suppressing MMP2/9 expression through ERK/NF-κB pathway.

    PubMed

    Poudel, Barun; Lee, Young-Mi; Kim, Dae-Ki

    2015-04-01

    Metastatic melanoma is one of the most deadly and evasive cancers. Collagen I in the extracellular matrix promotes the migration and invasion of tumor cells through the production of matrix metalloproteinase (MMP) 2 and 9. Discoidin domain receptor (DDR) 2 is a collagen receptor that is implicated in several cancer types including breast and prostate cancers. However, the role of DDR2 in the migration and invasion of murine melanoma cells is less studied. In the present study, we investigated the effects and underlying mechanisms of DDR2 in migration and invasion of B16BL6 melanoma cells in response to collagen I. Results demonstrated that DDR2 is expressed and is phosphorylated by collagen I in the cells. Upon down-regulation of DDR2 using small-interfering RNA (siRNA) approach, both of the cell migratory and invasive phenotypes were significantly attenuated when compared with the control cells. This effect was mediated via suppression of MMP2/9 upon DDR2 inhibition. Furthermore, inhibition of DDR2 by specific siRNA markedly reduced the activation of extracellular regulated kinase (ERK) 1 and 2 and nuclear factor of kappa B (NF-κB) in the cells when compared with the control cells. Overall, these data demonstrated that DDR2 siRNA-mediated suppression of ERK1/2 and NF-κB could down-regulate the expressions of MMP2/9 in response to collagen I to reduce the migratory and invasive phenotypes of the cells.

  18. Rhamnus cathartica (Rosales: Rhamnaceae) Invasion Reduces Ground-Dwelling Insect Abundance and Diversity in Northeast Iowa Forests.

    PubMed

    Schuh, Marissa; Larsen, Kirk J

    2015-06-01

    European buckthorn (Rhamnus cathartica L.) is an invasive woody shrub in deciduous forests of the Upper Midwest. Studies have suggested buckthorn invasion has negative effects on native plants, soil, and ecosystems, but its impacts on insects are largely unstudied. To test the impact of buckthorn invasion on ground-dwelling insects in forests of northeastern Iowa, pitfall traps were used to sample ground-dwelling insects at five sites four different periods from June to August 2013. Each site had three treatments: areas heavily infested with buckthorn, areas where buckthorn has not established, and areas where buckthorn had been removed within the past 2-10 yr. Most insects were identified to family and quantified; while ground beetles (Coleoptera: Carabidae) and ants (Hymenoptera: Formicidae) were identified to species and quantified. In total, 11,576 insects representing eight orders and 46 families were collected. Areas uninvaded by buckthorn had significantly greater insect abundance and taxonomic richness than areas invaded by buckthorn. Of the 948 ground beetles representing 40 species, abundance, species richness, and Shannon diversity indices were significantly lower in areas invaded by buckthorn compared with areas with no buckthorn. The 2,661 ants from 24 species had similar trends, but treatment differences were not significant because of high variability. These results clearly show a negative impact of buckthorn invasion on the abundance and taxonomic richness of ground-dwelling insects.

  19. A novel cantharidin analog N-Benzylcantharidinamide reduces the expression of MMP-9 and invasive potentials of Hep3B via inhibiting cytosolic translocation of HuR

    SciTech Connect

    Lee, Ji-Yeon; Chung, Tae-Wook; Choi, Hee-Jung; Lee, Chang Hyun; Eun, Jae Soon; Han, Young Taek; Choi, Jun-Yong; Kim, So-Yeon; Han, Chang-Woo; Jeong, Han-Sol; Ha, Ki-Tae

    2014-05-02

    Highlights: • We examined the inhibition of N-Benzylcantharidinamide on MMP-9-mediated invasion. • Unlike cantharidin, N-Benzylcantharidinamide has very low toxicity on Hep3B cells. • The reduced MMP-9 expression was due to HuR-mediated decrease of mRNA stability. • We suggest N-Benzylcantharidinamide as a novel inhibitor of MMP-9-related invasion. - Abstract: Invasion and metastasis are major causes of malignant tumor-associated mortality. The present study aimed to investigate the molecular events underlying inhibitory effect of N-Benzylcantharidinamide, a novel synthetic analog of cantharidin, on matrix metalloproteinase-9 (MMP-9)-mediated invasion in highly metastatic hepatocellular carcinoma Hep3B cells. In this investigation, among six analogs of cantharidin, only N-Benzylcantharidinamide has the inhibitory action on MMP-9 expression at non-toxic dose. The MMP-9 expression and invasion of Hep3B cells were significantly suppressed by treatment of N-Benzylcantharidinamide in a dose-dependent manner. On the other hand, the transcriptional activity of MMP-9 promoter and nuclear levels of NF-κB and AP-1 as the main transcriptional factors inducing MMP-9 expression were not affected by it although the level of MMP-9 mRNA was reduced by treatment of N-Benzylcantharidinamide. Interestingly, the stability of MMP-9 mRNA was significantly reduced by N-Benzylcantharidinamide-treatment. In addition, the cytosolic translocation of human antigen R (HuR), which results in the increase of MMP-9 mRNA stability through interaction of HuR with 3′-untranslated region of MMP-9 mRNA, was suppressed by treatment of N-Benzylcantharidinamide, in a dose-dependent manner. Taken together, it was demonstrated, for the first time, that N-Benzylcantharidinamide suppresses MMP-9 expression by reducing HuR-mediated MMP-9 mRNA stability for the inhibition of invasive potential in highly metastatic Hep3B cells.

  20. Environmental Consequences of Invasive Species: Greenhouse Gas Emissions of Insecticide Use and the Role of Biological Control in Reducing Emissions

    PubMed Central

    Heimpel, George E.; Yang, Yi; Hill, Jason D.; Ragsdale, David W.

    2013-01-01

    Greenhouse gas emissions associated with pesticide applications against invasive species constitute an environmental cost of species invasions that has remained largely unrecognized. Here we calculate greenhouse gas emissions associated with the invasion of an agricultural pest from Asia to North America. The soybean aphid, Aphis glycines, was first discovered in North America in 2000, and has led to a substantial increase in insecticide use in soybeans. We estimate that the manufacture, transport, and application of insecticides against soybean aphid results in approximately 10.6 kg of carbon dioxide (CO2) equivalent greenhouse gasses being emitted per hectare of soybeans treated. Given the acreage sprayed, this has led to annual emissions of between 6 and 40 million kg of CO2 equivalent greenhouse gasses in the United States since the invasion of soybean aphid, depending on pest population size. Emissions would be higher were it not for the development of a threshold aphid density below which farmers are advised not to spray. Without a threshold, farmers tend to spray preemptively and the threshold allows farmers to take advantage of naturally occurring biological control of the soybean aphid, which can be substantial. We find that adoption of the soybean aphid economic threshold can lead to emission reductions of approximately 300 million kg of CO2 equivalent greenhouse gases per year in the United States. Previous studies have documented that biological control agents such as lady beetles are capable of suppressing aphid densities below this threshold in over half of the soybean acreage in the U.S. Given the acreages involved this suggests that biological control results in annual emission reductions of over 200 million kg of CO2 equivalents. These analyses show how interactions between invasive species and organisms that suppress them can interact to affect greenhouse gas emissions. PMID:23977273

  1. Environmental consequences of invasive species: greenhouse gas emissions of insecticide use and the role of biological control in reducing emissions.

    PubMed

    Heimpel, George E; Yang, Yi; Hill, Jason D; Ragsdale, David W

    2013-01-01

    Greenhouse gas emissions associated with pesticide applications against invasive species constitute an environmental cost of species invasions that has remained largely unrecognized. Here we calculate greenhouse gas emissions associated with the invasion of an agricultural pest from Asia to North America. The soybean aphid, Aphis glycines, was first discovered in North America in 2000, and has led to a substantial increase in insecticide use in soybeans. We estimate that the manufacture, transport, and application of insecticides against soybean aphid results in approximately 10.6 kg of carbon dioxide (CO2) equivalent greenhouse gasses being emitted per hectare of soybeans treated. Given the acreage sprayed, this has led to annual emissions of between 6 and 40 million kg of CO2 equivalent greenhouse gasses in the United States since the invasion of soybean aphid, depending on pest population size. Emissions would be higher were it not for the development of a threshold aphid density below which farmers are advised not to spray. Without a threshold, farmers tend to spray preemptively and the threshold allows farmers to take advantage of naturally occurring biological control of the soybean aphid, which can be substantial. We find that adoption of the soybean aphid economic threshold can lead to emission reductions of approximately 300 million kg of CO2 equivalent greenhouse gases per year in the United States. Previous studies have documented that biological control agents such as lady beetles are capable of suppressing aphid densities below this threshold in over half of the soybean acreage in the U.S. Given the acreages involved this suggests that biological control results in annual emission reductions of over 200 million kg of CO2 equivalents. These analyses show how interactions between invasive species and organisms that suppress them can interact to affect greenhouse gas emissions.

  2. Truncated somatostatin receptor variant sst5TMD4 confers aggressive features (proliferation, invasion and reduced octreotide response) to somatotropinomas

    PubMed Central

    Luque, Raúl M.; Ibáñez-Costa, Alejandro; Neto, Leonardo Vieira; Taboada, Giselle F.; Hormaechea-Agulla, Daniel; Kasuki, Leandro; Venegas-Moreno, Eva; Moreno-Carazo, Alberto; Gálvez, María Ángeles; Soto-Moreno, Alfonso; Kineman, Rhonda D.; Culler, Michael D.; Gahete, Manuel D.; Gadelha, Mônica R.; Castaño, Justo P.

    2015-01-01

    The GH/IGF1 response of somatotropinomas to somatostatin analogues (SSA) is associated with their pattern of somatostatin receptor (sst1–sst5) expression. Recently, we demonstrated that expression of a truncated sst5-variant (sst5TMD4) can influence the secretory response of somatotropinomas to SSA-therapy; however, its potential relationship with aggressive features (e.g. invasion/proliferation) is still unknown. Here, we show that sst5TMD4 is present in 50% of non-functioning pituitary-adenomas (NFPA) (n = 30) and 89% of somatotropinomas (n = 36), its expression levels being highest in somatotropinomas > > NFPAs > > > normal pituitaries (negligible expression; n = 8). In somatotropinomas, sst5TMD4 mRNA and protein levels correlated positively, and its expression was directly associated with tumor invasiveness (cavernous/sphenoid sinus), and inversely correlated with age and GH/IGF1 reduction after 3–6 months with octreotide-LAR therapy. GNAS+ somatotropinomas expressed lower sst5TMD4 levels. ROC analysis revealed sst5TMD4 expression as the only marker, within all sst-subtypes, capable to predict tumor invasiveness in somatotropinomas. sst5TMD4 overexpression increased cell viability in cultured somatotropinoma (n = 5). Hence, presence of sst5TMD4 associates with increased aggressive features and worse prognosis in somatotropinomas, thereby providing a potentially useful tool to refine somatotropinoma diagnosis, predict outcome of clinical response to SSA-therapy and develop new therapeutic targets. PMID:25637790

  3. Landscape barriers reduce gene flow in an invasive carnivore: geographical and local genetic structure of American mink in Scotland.

    PubMed

    Zalewski, Andrzej; Piertney, Stuart B; Zalewska, Hanna; Lambin, Xavier

    2009-04-01

    To be effective, management programmes geared towards halting or reversing the spread of invasive species must focus on defined and defensible areas. This requires knowledge of the dispersal of non-native species targeted for control to better understand invasion and recolonisation scenarios. We investigated the genetic structure of invasive American mink (Neovison vison) in Scotland, and incorporated landscape genetic approaches to examine resultant patterns in relation to geographical features that may influence dispersal. Populations of mink sampled from 10 sites in two regions (Argyll and Northeast Scotland) show a distinct genetic structure. First, the majority of pairwise population comparisons yielded F(ST) values that were significantly greater than zero. Second, AMOVA revealed that most of the genetic variance was attributable to differences among regions. Assignment tests placed 89 or more of individuals into their sampled region. Bayesian clustering methods grouped samples into two clusters according to their region of origin. Wombling approach identified the Cairngorms Mountains as a major impediment to gene flow between the regions. Mantel pairwise correlations between genetic and geographical distances estimated as least-cost distance assuming a linear increase in the cost of movement with increasing elevation were higher than Euclidean distances or distance along waterways. Spatial autocorrelation analyses revealed stronger spatial structuring for females than for males. These results suggest that gene flow by American mink is restricted by landscape features (mountain ranges) and that eradication attempt should in the first instance break down the connectivity between management units separated by mountains.

  4. Effects of reducing temperatures on the hydrogen storage capacity of double-walled carbon nanotubes with Pd loading.

    PubMed

    Sheng, Qu; Wu, Huimin; Wexler, David; Liu, Huakun

    2014-06-01

    The effects of different temperatures on the hydrogen sorption characteristics of double-walled carbon nanotubes (DWCNTs) with palladium loading have been investigated. When we use different temperatures, the particle sizes and specific surface areas of the samples are different, which affects the hydrogen storage capacity of the DWCNTs. In this work, the amount of hydrogen storage capacity was determined (by AMC Gas Reactor Controller) to be 1.70, 1.85, 2.00, and 1.93 wt% for pristine DWCNTS and for 2%Pd/DWCNTs-300 degrees C, 2%Pd/DWCNTs-400 degrees C, and 2%Pd/DWCNTs-500 degrees C, respectively. We found that the hydrogen storage capacity can be enhanced by loading with 2% Pd nanoparticles and selecting a suitable temperature. Furthermore, the sorption can be attributed to the chemical reaction between atomic hydrogen and the dangling bonds of the DWCNTs.

  5. Insulin Resistance Is Associated With Reduced Mitochondrial Oxidative Capacity Measured by 31P-Magnetic Resonance Spectroscopy in Participants Without Diabetes From the Baltimore Longitudinal Study of Aging.

    PubMed

    Fabbri, Elisa; Chia, Chee W; Spencer, Richard G; Fishbein, Kenneth W; Reiter, David A; Cameron, Donnie; Zane, Ariel C; Moore, Zenobia A; Gonzalez-Freire, Marta; Zoli, Marco; Studenski, Stephanie A; Kalyani, Rita R; Egan, Josephine M; Ferrucci, Luigi

    2017-01-01

    Whether individuals with insulin resistance (IR) but without criteria for diabetes exhibit reduced mitochondrial oxidative capacity is unclear; addressing this question could guide research for new therapeutics. We investigated 248 participants without diabetes from the Baltimore Longitudinal Study of Aging (BLSA) to determine whether impaired mitochondrial capacity is associated with prediabetes, IR, and duration and severity of hyperglycemia exposure. Mitochondrial capacity was assessed as the postexercise phosphocreatine recovery time constant (τPCr) by (31)P-magnetic resonance spectroscopy, with higher τPCr values reflecting reduced capacity. Prediabetes was defined using the American Diabetes Association criteria from fasting and 2-h glucose measurements. IR and sensitivity were calculated using HOMA-IR and Matsuda indices. The duration and severity of hyperglycemia exposure were estimated as the number of years from prediabetes onset and the average oral glucose tolerance test (OGTT) 2-h glucose measurement over previous BLSA visits. Covariates included age, sex, body composition, physical activity, and other confounders. Higher likelihood of prediabetes, higher HOMA-IR, and lower Matsuda index were associated with longer τPCr. Among 205 participants with previous OGTT data, greater severity and longer duration of hyperglycemia were independently associated with longer τPC In conclusion, in individuals without diabetes a more impaired mitochondrial capacity is associated with greater IR and a higher likelihood of prediabetes.

  6. GKN2 increases apoptosis, reduces the proliferation and invasion ability of gastric cancer cells through down-regulating the JAK/STAT signaling pathway

    PubMed Central

    Ouyang, Jun; Pan, Xiaohui; Lin, Hui; Hu, Zecheng; Xiao, Ping; Hu, Haobin

    2017-01-01

    Objectives: To investigate the effect of gastric motility protein 2 (GKN2) on the proliferation, apoptosis and invasion of gastric cancer cell and on the JAK/signal transducer and activator of transcription 3 (STAT3) signaling pathway. Methods: Expression of GKN2 was qualified using Western blot analysis in four gastric cancer cell lines and immortalized human gastric mucosal epithelial cell line GES-1. The cells were then transfected with pcDNA3.1-GKN2 and control vector using Lipofectaminetm2000 and assayed for viability, apoptosis, cell cycle changes, invasion ability as well as expression of cell cycle protein D1 (Cylin D1), Bcl-2, Bax, matrix metalloproteinase 2 (MMP2), MMP9, JAK2 and p-STAT3. Results: Western blot analyses showed that the expression of GKN2 was significantly lower in 4 gastric cancer cell lines (BGC-823, SGC-7901, AGS and MKN-45) than in GES-1. Of them, SGC-7901 had the lowest expression. The line was chosen for subsequent transfection experiments. Compared with control (transfection with empty vector), pcDNA3.1-GKN2-transfected cells had significantly more GKN2 protein and mRNA, decreased cell viability, increased apoptosis, more cells arrested at G1 phase and reduced invasiveness. Expression analyses showed that expression of Cyclin D1, Bcl-2, MMP2, MMP9, JAK2 and STAT3 was significantly down-regulated, while Bax was significantly up-regulated. Conclusion: Over-expression of GKN2 can increase apoptosis, reduce proliferation and invasion ability of gastric cancer cells as a result of down-regulated JAK2/STAT3 signaling pathway. PMID:28337309

  7. Reduced Genetic Diversity and Increased Structure in American Mink on the Swedish Coast following Invasive Species Control

    PubMed Central

    Zalewska, Hanna; Lunneryd, Sven-Gunnar; André, Carl; Mikusiński, Grzegorz

    2016-01-01

    Eradication and population reductions are often used to mitigate the negative impacts of non-native invasive species on native biodiversity. However, monitoring the effectiveness of non-native species control programmes is necessary to evaluate the efficacy of these measures. Genetic monitoring could provide valuable insights into temporal changes in demographic, ecological, and evolutionary processes in invasive populations being subject to control programmes. Such programmes should cause a decrease in effective population size and/or in genetic diversity of the targeted non-native species and an increase in population genetic structuring over time. We used microsatellite DNA data from American mink (Neovison vison) to determine whether the removal of this predator on the Koster Islands archipelago and the nearby Swedish mainland affected genetic variation over six consecutive years of mink culling by trappers as part of a population control programme. We found that on Koster Islands allelic richness decreased (from on average 4.53 to 3.55), genetic structuring increased, and effective population size did not change. In contrast, the mink population from the Swedish coast showed no changes in genetic diversity or structure, suggesting the stability of this population over 6 years of culling. Effective population size did not change over time but was higher on the coast than on the islands across all years. Migration rates from the islands to the coast were almost two times higher than from the coast to the islands. Most migrants leaving the coast were localised on the southern edge of the archipelago, as expected from the direction of the sea current between the two sites. Genetic monitoring provided valuable information on temporal changes in the population of American mink suggesting that this approach can be used to evaluate and improve control programmes of invasive vertebrates. PMID:27333328

  8. Reduced Genetic Diversity and Increased Structure in American Mink on the Swedish Coast following Invasive Species Control.

    PubMed

    Zalewski, Andrzej; Zalewska, Hanna; Lunneryd, Sven-Gunnar; André, Carl; Mikusiński, Grzegorz

    2016-01-01

    Eradication and population reductions are often used to mitigate the negative impacts of non-native invasive species on native biodiversity. However, monitoring the effectiveness of non-native species control programmes is necessary to evaluate the efficacy of these measures. Genetic monitoring could provide valuable insights into temporal changes in demographic, ecological, and evolutionary processes in invasive populations being subject to control programmes. Such programmes should cause a decrease in effective population size and/or in genetic diversity of the targeted non-native species and an increase in population genetic structuring over time. We used microsatellite DNA data from American mink (Neovison vison) to determine whether the removal of this predator on the Koster Islands archipelago and the nearby Swedish mainland affected genetic variation over six consecutive years of mink culling by trappers as part of a population control programme. We found that on Koster Islands allelic richness decreased (from on average 4.53 to 3.55), genetic structuring increased, and effective population size did not change. In contrast, the mink population from the Swedish coast showed no changes in genetic diversity or structure, suggesting the stability of this population over 6 years of culling. Effective population size did not change over time but was higher on the coast than on the islands across all years. Migration rates from the islands to the coast were almost two times higher than from the coast to the islands. Most migrants leaving the coast were localised on the southern edge of the archipelago, as expected from the direction of the sea current between the two sites. Genetic monitoring provided valuable information on temporal changes in the population of American mink suggesting that this approach can be used to evaluate and improve control programmes of invasive vertebrates.

  9. Selenium exposure results in reduced reproduction in an invasive ant species and altered competitive behavior for a native ant species.

    PubMed

    De La Riva, Deborah G; Trumble, John T

    2016-06-01

    Competitive ability and numerical dominance are important factors contributing to the ability of invasive ant species to establish and expand their ranges in new habitats. However, few studies have investigated the impact of environmental contamination on competitive behavior in ants as a potential factor influencing dynamics between invasive and native ant species. Here we investigated the widespread contaminant selenium to investigate its potential influence on invasion by the exotic Argentine ant, Linepithema humile, through effects on reproduction and competitive behavior. For the fecundity experiment, treatments were provided to Argentine ant colonies via to sugar water solutions containing one of three concentrations of selenium (0, 5 and 10 μg Se mL(-1)) that fall within the range found in soil and plants growing in contaminated areas. Competition experiments included both the Argentine ant and the native Dorymyrmex bicolor to determine the impact of selenium exposure (0 or 15 μg Se mL(-1)) on exploitation- and interference-competition between ant species. The results of the fecundity experiment revealed that selenium negatively impacted queen survival and brood production of Argentine ants. Viability of the developing brood was also affected in that offspring reached adulthood only in colonies that were not given selenium, whereas those in treated colonies died in their larval stages. Selenium exposure did not alter direct competitive behaviors for either species, but selenium exposure contributed to an increased bait discovery time for D. bicolor. Our results suggest that environmental toxins may not only pose problems for native ant species, but may also serve as a potential obstacle for establishment among exotic species.

  10. Sinomenine influences capacity for invasion and migration in activated human monocytic THP-1 cells by inhibiting the expression of MMP-2, MMP-9, and CD147

    PubMed Central

    Ou, Yang-qiong; Chen, Li-hua; Li, Xue-jun; Lin, Zhi-bin; Li, Wei-dong

    2009-01-01

    Aim: The aim of this study was to investigate the mechanism of the effects of Sinomenine (SIN) on the invasion and migration ability of activated human monocytic THP-1 cells (A-THP-1). Sinomenine is a pure alkaloid extracted from the Chinese medical plant Sinomenium acutum. Methods: Human monocytic THP-1 cells were induced to differentiate into macrophages with phorbol 12-myristate 13-acetate (PMA). Cells were treated with different concentrations of SIN. The invasion and migration ability of cells was tested by in vitro transwell assays. The levels of CD147 and MMPs were evaluated by flow cytometric analysis and zymographic analysis, respectively. The mRNA expression of CD147, MMP-2, and MMP-9 was measured by RT-PCR. Results: The invasion and migration ability of A-THP-1 cells was significantly inhibited by SIN in a concentration-dependent fashion; at the same time, the levels of CD147, MMP-2, and MMP-9 were markedly down-regulated. This inhibitory effect was most notable at concentrations of 0.25 mmol/L and 1.00 mmol/L (P<0.01). Conclusion: A possible mechanism of the inhibitory effect of SIN on cell invasion and migration ability is repression of the expression of MMP-2 and MMP-9, which strongly correlates with the inhibition of CD147 activity. PMID:19305422

  11. Vitamin B-6 Supplementation Could Mediate Antioxidant Capacity by Reducing Plasma Homocysteine Concentration in Patients with Hepatocellular Carcinoma after Tumor Resection.

    PubMed

    Cheng, Shao-Bin; Lin, Ping-Ting; Liu, Hsiao-Tien; Peng, Yi-Shan; Huang, Shih-Chien; Huang, Yi-Chia

    2016-01-01

    Vitamin B-6 has a strong antioxidative effect. It would be useful to determine whether vitamin B-6 supplementation had effects on antioxidant capacities in patients with hepatocellular carcinoma (HCC) who had recently undergone tumor resection. Thirty-three HCC patients were randomly assigned to either the placebo (n = 16) group or the vitamin B-6 50 mg/d (n = 17) group for 12 weeks. Plasma pyridoxal 5'-phosphate, homocysteine, indicators of oxidative stress, and antioxidant capacities were measured. Plasma homocysteine in the vitamin B-6 group was significantly decreased at week 12, while the level of trolox equivalent antioxidant capacity (TEAC) was significantly increased at the end of the intervention period. Vitamin B-6 supplementation had a significant reducing effect on the change of plasma homocysteine (β = -2.4, p = 0.02) but not on the change of TEAC level after adjusting for potential confounders. The change of plasma homocysteine was significantly associated with the change of TEAC after adjusting for potential confounders (β = -162.0, p = 0.03). Vitamin B-6 supplementation seemed to mediate antioxidant capacity via reducing plasma homocysteine rather than having a direct antioxidative effect in HCC patients who had recently undergone tumor resection. The clinical trial number is NCT01964001, ClinicalTrials.gov.

  12. Estimates of the chromium(VI) reducing capacity in human body compartments as a mechanism for attenuating its potential toxicity and carcinogenicity.

    PubMed

    De Flora, S; Camoirano, A; Bagnasco, M; Bennicelli, C; Corbett, G E; Kerger, B D

    1997-03-01

    Estimates of the overall reducing capacity of hexavalent chromium(VI) in some human body compartments were made by relating the specific reducing activity of body fluids, cell populations or organs to their average volume, number, or weight. Although these data do not have absolute precision or universal applicability, they provide a rationale for predicting and interpreting the health effects of chromium(VI). The available evidence strongly indicates that chromium(VI) reduction in body fluids and long-lived non-target cells is expected to greatly attenuate its potential toxicity and genotoxicity, to imprint a threshold character to the carcinogenesis process, and to restrict the possible targets of its activity. For example, the chromium(VI) sequestering capacity of whole blood (187-234 mg per individual) and the reducing capacity of red blood cells (at least 93-128 mg) explain why this metal is not a systemic toxicant, except at very high doses, and also explain its lack of carcinogenicity at a distance from the portal of entry into the organism. Reduction by fluids in the digestive tract, e.g. by saliva (0.7-2.1 mg/day) and gastric juice (at least 84-88 mg/day), and sequestration by intestinal bacteria (11-24 mg eliminated daily with feces) account for the poor intestinal absorption of chromium(VI). The chromium(VI) escaping reduction in the digestive tract will be detoxified in the blood of the portal vein system and then in the liver, having an overall reducing capacity of 3300 mg. These processes give reasons for the poor oral toxicity of chromium(VI) and its lack of carcinogenicity when introduced by the oral route or swallowed following reflux from the respiratory tract. In terminal airways chromium(VI) is reduced in the epithelial lining fluid (0.9-1.8 mg) and in pulmonary alveolar macrophages (136 mg). The peripheral lung parenchyma has an overall reducing capacity of 260 mg chromium(VI), with a slightly higher specific activity as compared to the

  13. Reduced expression of the chromatin remodeling gene ARID1A enhances gastric cancer cell migration and invasion via downregulation of E-cadherin transcription.

    PubMed

    Yan, Hai-Bo; Wang, Xue-Fei; Zhang, Qian; Tang, Zhao-Qing; Jiang, Ying-Hua; Fan, Hui-Zhi; Sun, Yi-hong; Yang, Peng-Yuan; Liu, Feng

    2014-04-01

    The chromatin remodeling gene AT-rich interactive domain-containing protein 1A (ARID1A) encodes the protein BAF250a, a subunit of human SWI/SNF-related complexes. Recent studies have identified ARID1A as a tumor suppressor. Here, we show that ARID1A expression is reduced in gastric cancer (GC) tissues, which are significantly associated with local lymph node metastasis, tumor infiltration and poor patient prognosis. ARID1A silencing enforces the migration and invasion of GC cells, whereas ectopic expression of ARID1A inhibits migration. The adhesive protein E-cadherin is remarkably downregulated in response to ARID1A silencing, but it is upregulated by ARID1A overexpression. E-cadherin overexpression significantly inhibits GC cell migration and invasion, whereas CDH1 (coded E-cadherin) silencing promotes migration. Restored expression of CDH1 in ARID1A-silenced cell lines restores the inhibition of cell migration. Luciferase reporter assays and chromatin immunoprecipitation indicate that the ARID1A-associated SWI/SNF complex binds to the CDH1 promoter and modulates CDH1 transcription. ARID1A knockdown induces evident morphological changes of GC cells with increased expression of mesenchymal markers, indicating an epithelial-mesenchymal transition. ARID1A silencing does not alter the level of β-catenin but induces a subcellular redistribution of β-catenin from the plasma membrane to the cytoplasm and nucleus. Immunohistochemical studies demonstrate that reduced expression of E-cadherin is associated with local lymph node metastasis, tumor infiltration and poor clinical prognosis. ARID1A and E-cadherin expression show a strong correlation in 75.4% of the analyzed GC tissues. They are synergistically downregulated in 23.5% of analyzed GC tissues. In conclusion, ARID1A targets E-cadherin during the modulation of GC cell migration and invasion.

  14. Biological invasion by a benthivorous fish reduced the cover and species richness of aquatic plants in most lakes of a large North American ecoregion.

    PubMed

    Bajer, Przemyslaw G; Beck, Marcus W; Cross, Timothy K; Koch, Justine D; Bartodziej, William M; Sorensen, Peter W

    2016-12-01

    Biological invasions are projected to be the main driver of biodiversity and ecosystem function loss in lakes in the 21st century. However, the extent of these future losses is difficult to quantify because most invasions are recent and confounded by other stressors. In this study, we quantified the outcome of a century-old invasion, the introduction of common carp to North America, to illustrate potential consequences of introducing non-native ecosystem engineers to lakes worldwide. We used the decline in aquatic plant richness and cover as an index of ecological impact across three ecoregions: Great Plains, Eastern Temperate Forests and Northern Forests. Using whole-lake manipulations, we demonstrated that both submersed plant cover and richness declined exponentially as carp biomass increased such that plant cover was reduced to <10% and species richness was halved in lakes in which carp biomass exceeded 190 kg ha(-1) . Using catch rates amassed from 2000+ lakes, we showed that carp exceeded this biomass level in 70.6% of Great Plains lakes and 23.3% of Eastern Temperate Forests lakes, but 0% of Northern Forests lakes. Using model selection analysis, we showed that carp was a key driver of plant species richness along with Secchi depth, lake area and human development of lake watersheds. Model parameters showed that carp reduced species richness to a similar degree across lakes of various Secchi depths and surface areas. In regions dominated by carp (e.g., Great Plains), carp had a stronger impact on plant richness than human watershed development. Overall, our analysis shows that the introduction of common carp played a key role in driving a severe reduction in plant cover and richness in a majority of Great Plains lakes and a large portion of Eastern Temperate Forests lakes in North America.

  15. Reduced DNA double-strand break repair capacity and risk of squamous cell carcinoma of the head and neck--A case-control study.

    PubMed

    Liu, Zhensheng; Liu, Hongliang; Gao, Fengqin; Dahlstrom, Kristina R; Sturgis, Erich M; Wei, Qingyi

    2016-04-01

    Tobacco smoke and alcohol use play important roles in the etiology of squamous cell carcinoma of the head and neck (SCCHN). Smoking causes DNA damage, including double-strand DNA breaks (DSBs), that leads to carcinogenesis. To test the hypothesis that suboptimal DSB repair capacity is associated with risk of SCCHN, we applied a flow cytometry-based method to detect the DSB repair phenotype first in four EBV-immortalized human lymphoblastoid cell lines and then in human peripheral blood T-lymphocytes (PBTLs). With this blood-based laboratory assay, we conducted a pilot case-control study of 100 patients with newly diagnosed, previously untreated SCCHN and 124 cancer-free controls of non-Hispanic whites. We found that the mean DSB repair capacity level was significantly lower in cases (42.1%) than that in controls (54.4%) (P<0.001). When we used the median DSB repair capacity level in the controls as the cutoff value for calculating the odds ratios (ORs) with adjustment for age, sex, smoking and drinking status, the cases were more likely than the controls to have a reduced DSB repair capacity (adjusted OR=1.93; 95% confidence interval, CI=1.04-3.56, P=0.037), especially for those subjects who were ever drinkers (adjusted OR=2.73; 95% CI=1.17-6.35, P=0.020) and had oropharyngeal tumors (adjusted OR=2.17; 95% CI=1.06-4.45, P=0.035). In conclusion, these findings suggest that individuals with a reduced DSB repair capacity may be at an increased risk of developing SCCHN. Larger studies are warranted to confirm these preliminary findings.

  16. Reduced incidence of invasive pneumococcal disease after introduction of the 13-valent conjugate vaccine in Navarre, Spain, 2001-2013.

    PubMed

    Guevara, Marcela; Ezpeleta, Carmen; Gil-Setas, Alberto; Torroba, Luis; Beristain, Xabier; Aguinaga, Aitziber; García-Irure, José Javier; Navascués, Ana; García-Cenoz, Manuel; Castilla, Jesús

    2014-05-07

    Pneumococcal conjugate vaccines (PCVs) were licensed for use in children and became available for private purchase in Spain in 2001 (PCV7), 2009 (PCV10) and 2010 (PCV13). This study evaluates changes in the incidence of invasive pneumococcal disease (IPD) and the pattern of serotypes isolated in Navarre, Spain, between the period of use of PCV7 (2004-2009) and that of PCV13 (2010-2013). The percentage of children <2 years who received at least one dose of PCV in these periods ranged from 25 to 61% and 61 to 78%, respectively. Between the periods 2004-2009 and 2010-2013 IPD incidence declined by 37%, from 14.9 to 9.4 cases/100,000 inhabitants (p<0.001). In children <5 years it fell by 69% (p<0.001), in persons aged 5-64 years, by 34% (p<0.001), and in those ≥ 65, by 23% (p=0.024). The incidence of cases due to PCV13 serotypes declined by 81% (p<0.001) in children <5 years and by 52% (p<0.001) in the whole population. No significant changes were seen in the distribution of clinical presentations or in disease severity. The incidence of IPD has declined and the pattern of serotypes causing IPD has changed notably in children and moderately in adults following the replacement of PCV7 by PCV13.

  17. Fluorine-Doped Tin Oxide Nanocrystal/Reduced Graphene Oxide Composites as Lithium Ion Battery Anode Material with High Capacity and Cycling Stability.

    PubMed

    Xu, Haiping; Shi, Liyi; Wang, Zhuyi; Liu, Jia; Zhu, Jiefang; Zhao, Yin; Zhang, Meihong; Yuan, Shuai

    2015-12-16

    Tin oxide (SnO2) is a kind of anode material with high theoretical capacity. However, the volume expansion and fast capability fading during cycling have prevented its practical application in lithium ion batteries. Herein, we report that the nanocomposite of fluorine-doped tin oxide (FTO) and reduced graphene oxide (RGO) is an ideal anode material with high capacity, high rate capability, and high stability. The FTO conductive nanocrystals were successfully anchored on RGO nanosheets from an FTO nanocrystals colloid and RGO suspension by hydrothermal treatment. As the anode material, the FTO/RGO composite showed high structural stability during the lithiation and delithiation processes. The conductive FTO nanocrystals favor the formation of stable and thin solid electrolyte interface films. Significantly, the FTO/RGO composite retains a discharge capacity as high as 1439 mAhg(-1) after 200 cycles at a current density of 100 mAg(-1). Moreover, its rate capacity displays 1148 mAhg(-1) at a current density of 1000 mAg(-1).

  18. Improved sodium-storage performance of stannous sulfide@reduced graphene oxide composite as high capacity anodes for sodium-ion batteries

    NASA Astrophysics Data System (ADS)

    Wu, Lin; Lu, Haiyan; Xiao, Lifen; Ai, Xinping; Yang, Hanxi; Cao, Yuliang

    2015-10-01

    Stannous sulfide@reduced graphene oxide (SnS@RGO) composite is successfully synthesized via a facile precipitation route. The structural and morphological characterizations reveal SnS@RGO composites are composed of SnS nanoparticles of the size 5-10 nm, which are uniformly anchored on the surface of RGO. The electrochemical measurements demonstrate the reversible capacity of the SnS@RGO composite - that includes contributions from the conversion reaction of SnS to Sn and NaxS and the alloying reaction of Sn to NaxSn. The SnS@RGO electrode exhibits a reversible capacity of 457 mAh g-1 at 20 mA g-1, superior cycling stability (94% capacity retention over 100 cycles at 100 mA g-1) and adequate rate performance. Compared to the neat SnS nanoparticles, the enhanced electrochemical performance of the SnS@RGO composite is primarily due to the incorporation of RGO as a highly conductive, flexible component as well as possessing a large available surface area, which provides desirable properties such as improved electronic contact between active materials, aggregation suppression of intermediate products, and alleviation of the volume change during sodiation and desodiation. Encouraging experimental results suggest that the SnS@RGO composite is a promising material to achieve a high-capacity and stable anode for NIBs.

  19. Expression of DIAPH1 is up-regulated in colorectal cancer and its down-regulation strongly reduces the metastatic capacity of colon carcinoma cells.

    PubMed

    Lin, Yuan-Na; Izbicki, Jakob R; König, Alexandra; Habermann, Jens K; Blechner, Christine; Lange, Tobias; Schumacher, Udo; Windhorst, Sabine

    2014-04-01

    In most cases, metastatic colorectal cancer is not curable, thus new approaches are necessary to identify novel targets for colorectal cancer therapy. Actin-binding-proteins (ABPs) directly regulate motility of metastasising tumor cells, and for cortactin an association with colon cancer metastasis has been already shown. However, as its depletion only incompletely inhibits metastasis, additional, more suitable cellular targets have to be identified. Here we analyzed expression of the ABPs, DIAPH1, VASP, N-WASP, and fascin in comparison with cortactin and found that, besides cortactin, DIAPH1 was expressed with the highest frequency (63%) in colorectal cancer. As well as cortactin, DIAPH1 was not detectable in normal colon tissue and expression of both proteins was positively correlated with metastasis of colorectal cancer. To analyse the mechanistic role of DIAPH1 for metastasis of colon carcinoma cells in comparison with cortactin, expression of the proteins was stably down-regulated in the human colon carcinoma cell lines HT-29, HROC-24 and HCT-116. Analysis of metastasis of colon carcinoma cells in SCID mice revealed that depletion of DIAPH1 reduced metastasis 60-fold and depletion of cortactin 16-fold as compared with control cells. Most likely the stronger effect of DIAPH1 depletion on colon cancer metastasis is due to the fact that in vitro knock down of DIAPH1 impaired all steps of metastasis; adhesion, invasion and migration while down-regulation of cortactin only reduced adhesion and invasion. This very strong reducing effect of DIAPH1 depletion on colon carcinoma cell metastasis makes the protein a promising therapeutic target for individualized colorectal cancer therapy.

  20. Reduced densities of the invasive wasp, Vespula vulgaris (Hymenoptera: Vespidae), did not alter the invertebrate community composition of Nothofagus forests in New Zealand.

    PubMed

    Duthie, Catherine; Lester, Philip J

    2013-04-01

    Invasive common wasps (Vespula vulgaris L.) are predators of invertebrates in Nothofagus forests of New Zealand. We reduced wasp densities by poisoning in three sites over three y. We predicted an increase in the number of invertebrates and a change in the community composition in sites where wasps were poisoned (wasps removed) relative to nearby sites where wasps were not poisoned (wasps maintained). Wasp densities were significantly reduced by an average of 58.9% by poisoning. Despite this reduction in wasp densities, native bush ants (Prolasius advenus Forel) were the only taxa that was significantly influenced by wasp removal. However, contrary to our predictions there were more ants caught in pitfall traps where wasps were maintained. We believe that the higher abundance of these ants is probably because of the scarcity of honeydew in wasp-maintained sites and compensatory foraging by ants in these areas. Otherwise, our results indicated no significant effects of reduced wasp densities on the total number of invertebrates, or the number of invertebrate families, observed in pitfall or Malaise traps. An analysis of community composition (permutational multivariate analysis of variance) also indicated no significant difference between wasp-removed or wasp-maintained communities. The most parsimonious explanation for our results is that although we significantly reduced wasp numbers, we may not have reduced numbers sufficiently or for a sufficiently long period, to see a change or recovery in the community.

  1. Climate change is projected to reduce carrying capacity and redistribute species richness in North Pacific pelagic marine ecosystems.

    PubMed

    Woodworth-Jefcoats, Phoebe A; Polovina, Jeffrey J; Drazen, Jeffrey C

    2017-03-01

    Climate change is expected to impact all aspects of marine ecosystems, including fisheries. Here, we use output from a suite of 11 earth system models to examine projected changes in two ecosystem-defining variables: temperature and food availability. In particular, we examine projected changes in epipelagic temperature and, as a proxy for food availability, zooplankton density. We find that under RCP8.5, a high business-as-usual greenhouse gas scenario, increasing temperatures may alter the spatial distribution of tuna and billfish species richness across the North Pacific basin. Furthermore, warmer waters and declining zooplankton densities may act together to lower carrying capacity for commercially valuable fish by 2-5% per decade over the 21st century. These changes have the potential to significantly impact the magnitude, composition, and distribution of commercial fish catch across the pelagic North Pacific. Such changes will in turn ultimately impact commercial fisheries' economic value. Fishery managers should anticipate these climate impacts to ensure sustainable fishery yields and livelihoods.

  2. Upregulation of MHC class I in transgenic mice results in reduced force-generating capacity in slow-twitch muscle.

    PubMed

    Salomonsson, Stina; Grundtman, Cecilia; Zhang, Shi-Jin; Lanner, Johanna T; Li, Charles; Katz, Abram; Wedderburn, Lucy R; Nagaraju, Kanneboyina; Lundberg, Ingrid E; Westerblad, Håkan

    2009-05-01

    Expression of major histocompatibility complex (MHC) class I in skeletal muscle fibers is an early and consistent finding in inflammatory myopathies. To test if MHC class I has a primary role in muscle impairment, we used transgenic mice with inducible overexpression of MHC class I in their skeletal muscle cells. Contractile function was studied in isolated extensor digitorum longus (EDL, fast-twitch) and soleus (slow-twitch) muscles. We found that EDL was smaller, whereas soleus muscle was slightly larger. Both muscles generated less absolute force in myopathic compared with control mice; however, when force was expressed per cross-sectional area, only soleus muscle generated less force. Inflammation was markedly increased, but no changes were found in the activities of key mitochondrial and glycogenolytic enzymes in myopathic mice. The induction of MHC class I results in muscle atrophy and an intrinsic decrease in force-generation capacity. These observations may have important implications for our understanding of the pathophysiological processes of muscle weakness seen in inflammatory myopathies. Muscle Nerve, 2008.

  3. Reduced capacity of tumour blood vessels to produce endothelium-derived relaxing factor: significance for blood flow modification.

    PubMed Central

    Tozer, G. M.; Prise, V. E.; Bell, K. M.; Dennis, M. F.; Stratford, M. R.; Chaplin, D. J.

    1996-01-01

    The effect of nitric oxide-dependent vasodilators on vascular resistance of tumours and normal tissue was determined with the aim of modifying tumour blood flow for therapeutic benefit. Isolated preparations of the rat P22 tumour and normal rat hindlimb were perfused ex vivo. The effects on tissue vascular resistance of administration of sodium nitroprusside (SNP) and the diazeniumdiolate (or NONO-ate) NOC-7, vasodilators which act via direct release of nitric oxide (NO), were compared with the effects of acetylcholine (ACh), a vasodilator which acts primarily via receptor stimulation of endothelial cells to release NO in the form of endothelium-derived relaxing factor (EDRF). SNP and NOC-7 effectively dilated tumour blood vessels after preconstriction with phenylephrine (PE) or potassium chloride (KCl) as indicated by a decrease in vascular resistance. SNP also effectively dilated normal rat hindlimb vessels after PE/KCl constriction. Vasodilatation in the tumour preparations was accompanied by a significant rise in nitrite levels measured in the tumour effluent. ACh induced a significant vasodilation in the normal hindlimb but an anomalous vasoconstriction in the tumour. This result suggests that tumours, unlike normal tissues are incapable of releasing NO (EDRF) in response to ACh. Capacity for EDRF production may represent a difference between tumour and normal tissue blood vessels, which could be exploited for selective pharmacological manipulation of tumour blood flow. PMID:8980396

  4. Overexpression of KiSS-1 reduces colorectal cancer cell invasion by downregulating MMP-9 via blocking PI3K/Akt/NF-κB signal pathway.

    PubMed

    Chen, Shaoqin; Chen, Wei; Zhang, Xiang; Lin, Suyong; Chen, Zhihua

    2016-04-01

    Metastasis of colorectal cancer (CRC) depends critically on MMP-9. KiSS-1 is a human malignant melanoma metastasis-suppressor gene. Thus, the interaction between MMP-9 and KiSS-1 has drawn considerable attention in recent years. In the present study, it was hypothesized that KiSS-1 gene could repress the metastatic potential of colorectal cancer cells by inhibiting the expression of MMP-9. Stable transfection of KiSS-1 specific siRNA and KiSS-1 expression vector in human CRC cell line HCT-116 was achieved by lentivirus infection. Moreover, the cell proliferation, invasiveness, and apoptosis were evaluated by CCK-8 method, transwell experiment, and fluorescence activated cell sorter, respectively. We also investigated the expression of MMP-9, PI3K, Akt, pAKt, and NF-кB subunit p65 using western blotting. KiSS-1 overexpression significantly decreased the cell proliferation and invasiveness of HCT-119 cells, while apoptosis was enhanced. The result of western blotting showed that synthesis of MMP-9, PI3K, p65, and phosphorylation of Akt were significantly blocked by overexpression of KiSS-1. Concatenated treatment of KiSS-1 overexpression vector with PI3K and Akt agonists attenuated the effect of KiSS-1 on the biological activity of CRC cells and also released the expression of MMP-9, PI3K, p65, and phosphorylation of Akt from the influence of overexpression of KiSS-1. Overexpression of KiSS-1 suppressed the invasiveness of CRC cells, and the gene exerted its function by reducing the expression of MMP-9 via blocking of tge PI3K/Akt/NF-κB pathway.

  5. Sublethal exposure to crude oil during embryonic development alters cardiac morphology and reduces aerobic capacity in adult fish

    PubMed Central

    Hicken, Corinne E.; Linbo, Tiffany L.; Baldwin, David H.; Willis, Maryjean L.; Myers, Mark S.; Holland, Larry; Larsen, Marie; Stekoll, Michael S.; Rice, Stanley D.; Collier, Tracy K.; Scholz, Nathaniel L.; Incardona, John P.

    2011-01-01

    Exposure to high concentrations of crude oil produces a lethal syndrome of heart failure in fish embryos. Mortality is caused by cardiotoxic polycyclic aromatic hydrocarbons (PAHs), ubiquitous components of petroleum. Here, we show that transient embryonic exposure to very low concentrations of oil causes toxicity that is sublethal, delayed, and not counteracted by the protective effects of cytochrome P450 induction. Nearly a year after embryonic oil exposure, adult zebrafish showed subtle changes in heart shape and a significant reduction in swimming performance, indicative of reduced cardiac output. These delayed physiological impacts on cardiovascular performance at later life stages provide a potential mechanism linking reduced individual survival to population-level ecosystem responses of fish species to chronic, low-level oil pollution. PMID:21482755

  6. Comparison between standard and reduced volume radiotherapy in bladder preservation trimodality protocol for muscle-invasive bladder cancer patients

    PubMed Central

    Arafat, Waleed; Darwish, Azza; Naoum, George E; Sameh, Wael; Husseiny, Gamal El; Abd-El-Gawad, Fathy; Samir, Mostafa

    2016-01-01

    Aim Our aim is to compare the toxicity, pelvic nodal relapse, and overall survival of whole bladder irradiation only to the standard technique of whole pelvis irradiation followed by bladder boost in patients with muscle-invasive bladder carcinoma undergoing bladder preservation protocol. Material and method A total of 60 patients with transitional cell carcinoma, stage T2-3, N0, M0 bladder cancer were subjected to maximal transurethral resection bladder tumour (TURB). Then, the patients were randomised into two groups: group I (30 patients) to receive whole pelvis radiotherapy 44 Gy followed by 20 Gy bladder boost. While group II (30 patients) were randomised to receive whole bladder radiotherapy alone for a total dose of 64 Gy. In both groups, concomitant cisplatin and paclitaxel were given weekly throughout the whole course of radiotherapy where conventional 2 Gy/fraction were used. Additionally, four cycles of adjuvant cisplatin and paclitaxel were given after the end of the chemoradiotherapy induction course. Results The first assessment after the induction chemoradiotherapy showed that complete response was achieved in 73.3% of patients in group I and 76.7% of the patients in group II. After a median follow-up of 2 years, regional relapse occurred in 7.1% of patients in group I and 10.3% in group II. (p = 1). Distant metastases were detected in 17.9% of patient in group I and 13.8% in group II (p = 0.73). The 2-year disease-free survival was 60% in group I and 63.3% in group II (p = 0.79). The whole 2-year overall survival was 75% in group I and 79.3% in group II (p = 0.689). Radiation gastrointestinal (GI) acute toxicity was higher in group I than in group II (p = 0.001), while late GI radiation toxicity was comparable in both groups. Conclusion Treating the bladder only, without elective pelvic nodal irradiation, did not compromise pelvic control rate, but significantly decreased the acute radiation toxicity. PMID:27899955

  7. Combined Zoledronic Acid and Meloxicam Reduced Bone Loss and Tumor Growth in an Orthotopic Mouse Model of Bone-Invasive Oral Squamous Cell Carcinoma

    PubMed Central

    Martin, C.K.; Dirksen, W.P.; Carlton, M.M.; Lanigan, L.G.; Pillai, S.P.; Werbeck, J.L.; Simmons, J.K.; Hildreth, B.E.; London, C.A.; Toribio, R.E.; Rosol, T.J.

    2013-01-01

    Oral squamous cell carcinoma is common in cats and humans and invades oral bone. We hypothesized that the cyclooxygenase-2 inhibitor, meloxicam, with the bisphosphonate, zoledronic acid (ZOL), would inhibit tumor growth, osteolysis and invasion in feline oral squamous cell carcinoma (OSCC) xenografts in mice. Human and feline OSCC cell lines expressed cyclooxygenase (COX)-1 and 2 and the SCCF2 cells had increased COX-2 mRNA expression with bone conditioned medium. Luciferase-expressing feline SCCF2Luc cells were injected beneath the perimaxillary gingiva and mice were treated with 0.1 mg/kg ZOL twice weekly, 0.3 mg/kg meloxicam daily, combined ZOL and meloxicam, or vehicle. ZOL inhibited osteoclastic bone resorption at the tumor-bone interface. Meloxicam was more effective than ZOL at reducing xenograft growth but did not affect osteoclastic bone resorption. Although a synergistic effect of combined ZOL and meloxicam was not observed, combination therapy was well tolerated and may be useful in the clinical management of bone-invasive feline OSCC. PMID:23651067

  8. Plakoglobin Reduces the in vitro Growth, Migration and Invasion of Ovarian Cancer Cells Expressing N-Cadherin and Mutant p53

    PubMed Central

    Alaee, Mahsa; Danesh, Ghazal; Pasdar, Manijeh

    2016-01-01

    Aberrant expression of cadherins and catenins plays pivotal roles in ovarian cancer development and progression. Plakoglobin (PG, γ-catenin) is a paralog of β-catenin with dual adhesive and signaling functions. While β-catenin has known oncogenic function, PG generally acts as a tumor/metastasis suppressor. We recently showed that PG interacted with p53 and that its growth/metastasis inhibitory function may be mediated by this interaction. Very little is known about the role of PG in ovarian cancer. Here, we investigated the in vitro tumor/metastasis suppressor effects of PG in ovarian cancer cell lines with mutant p53 expression and different cadherin profiles. We showed that the N-cadherin expressing and E-cadherin and PG deficient ES-2 cells were highly migratory and invasive, whereas OV-90 cells that express E-cadherin, PG and very little/no N-cadherin were not. Exogenous expression of PG or E-cadherin or N-cadherin knockdown in ES-2 cells (ES-2-E-cad, ES-2-PG and ES-2-shN-cad) significantly reduced their migration and invasion. Also, PG expression or N-cadherin knockdown significantly decreased ES-2 cells growth. Furthermore, PG interacted with both cadherins and with wild type and mutant p53 in normal ovarian and ES-2-PG cell lines, respectively. PMID:27144941

  9. Inhibition of CD147 expression by RNA interference reduces proliferation, invasion and increases chemosensitivity in cancer stem cell-like HT-29 cells.

    PubMed

    Chen, Jie; Pan, Yuqin; He, Bangshun; Ying, Houqun; Wang, Feng; Sun, Huiling; Deng, Qiwen; Liu, Xian; Lin, Kang; Peng, Hongxin; Cho, William C; Wang, Shukui

    2015-10-01

    The association between CD147 and cancer stem cells (CSCs) provides a new angle for cancer treatments. The aim of this study was to investigate the biological roles of CD147 in colorectal CSCs. The Oct4-green fluorescent protein (GFP) vector was used to isolate CSCs and pYr-mir30-shRNA was used to generate short hairpin RNA (shRNA) specifically for CD147. After RNA interference (RNAi), CD147 was evaluated by reverse transcription‑quantitative PCR and western blot analysis, and its biological functions were assessed by MTT and invasion assays. The results showed that the differentiation of isolated CSC-like HT-29 cells was blocked and these cells were highly positive for CD44 and CD147. RNAi-mediated CD147 silencing reduced the expression of CD147 at both mRNA and protein levels. Moreover, the activities of proliferation and invasion were decreased obviously in CSCs. Knockdown of CD147 increased the chemosensitivity of CSC-like cells to gemcitabine, cisplatin, docetaxel at 0.1, 1 and 10 µM respectively, however, there was no significant difference among the three groups to paclitaxel at 10 µM. In conclusion, these results suggest that CD147 plays an important role in colorectal CSCs and might be regarded as a novel CSC-specific targeted strategy against colorectal cancer.

  10. RA-XII inhibits tumour growth and metastasis in breast tumour-bearing mice via reducing cell adhesion and invasion and promoting matrix degradation

    PubMed Central

    Leung, Hoi-Wing; Zhao, Si-Meng; Yue, Grace Gar-Lee; Lee, Julia Kin-Ming; Fung, Kwok-Pui; Leung, Ping-Chung; Tan, Ning-Hua; Lau, Clara Bik-San

    2015-01-01

    Cancer cells acquire invasive ability to degrade and adhere to extracellular matrix (ECM) and migrate to adjacent tissues. This ultimately results metastasis. Hence, the present study investigated the in vitro effects of cyclopeptide glycoside, RA-XII on cell adhesion, invasion, proliferation and matrix degradation, and its underlying mechanism in murine breast tumour cells, 4T1. The effect of RA-XII on tumour growth and metastasis in 4T1-bearing mice was also investigated. Our results showed that RA-XII inhibited tumour cell adhesion to collagen, fibronectin and laminin, RA-XII also reduced the expressions of vascular cell adhesion molecule, intracellular adhesion molecule and integrins, and integrin binding. In addition, RA-XII significantly inhibited breast tumour cell migration via interfering cofilin signaling and chemokine receptors. The activities of matrix metalloproteinase-9 and urokinase-type of plasminogen activator, and the expressions of ECM-associated proteinases were attenuated significantly by RA-XII. Furthermore, RA-XII induced G1 phase arrest and inhibited the expressions of cyclins and cyclin-dependent kinases. RA-XII inhibited the expressions of molecules in PI3K/AKT, NF-kappaB, FAK/pSRC, MAPK and EGFR signaling. RA-XII was also shown to have anti-tumour, anti-angiogenic and anti-metastatic activities in metastatic breast tumour-bearing mice. These findings strongly suggested that RA-XII is a potential anti-metastatic agent for breast cancer. PMID:26592552

  11. Reducing capacity, chlorogenic acid content and biological activity in a collection of scarlet (Solanum aethiopicum) and Gboma (S. macrocarpon) eggplants.

    PubMed

    Plazas, Mariola; Prohens, Jaime; Cuñat, Amparo Noelia; Vilanova, Santiago; Gramazio, Pietro; Herraiz, Francisco Javier; Andújar, Isabel

    2014-09-26

    Scarlet (Solanum aethiopicum) and gboma (S. macrocarpon) eggplants are important vegetables in Sub-Saharan Africa. Few studies have been made on these crops regarding the diversity of phenolic content and their biological activity. We have studied the reducing activity, the chlorogenic acid and other phenolic acid contents in a collection of 56 accessions of scarlet eggplant, including the four cultivated groups (Aculeatum, Gilo, Kumba, Shum) and the weedy intermediate S. aethiopicum-S. anguivi types, as well as in eight accessions of gboma eggplant, including the cultivated S. macrocarpon and its wild ancestor, S. dasyphyllum. A sample of the accessions evaluated in this collection has been tested for inhibition of nitric oxide (NO) using macrophage cell cultures. The results show that there is a great diversity in both crops for reducing activity, chlorogenic acid content and chlorogenic acid peak area (% of total phenolic acids). Heritability (H2) for these traits was intermediate to high in both crops. In all samples, chlorogenic acid was the major phenolic acid and accounted for more than 50% of the chromatogram peak area. Considerable differences were found among and within groups for these traits, but the greatest values for total phenolics and chlorogenic acid content were found in S. dasyphyllum. In most groups, reducing activity was positively correlated (with values of up to 0.904 in the Aculeatum group) with chlorogenic acid content. Inhibition of NO was greatest in samples having a high chlorogenic acid content. The results show that both crops are a relevant source of chlorogenic acid and other phenolic acids. The high diversity found also indicates that there are good prospects for breeding new scarlet and gboma eggplant cultivars with improved content in phenolics and bioactive properties.

  12. Lung Volume Reduction Surgery and Pulmonary Rehabilitation Improve Exercise Capacity and Reduce Dyspnea During Functional Activities in People with Emphysema

    PubMed Central

    2009-01-01

    Purpose: The purpose of this study was to examine the therapeutic effects of lung volume reduction surgery (LVRS) and pulmonary rehabilitation on levels of dyspnea during functional activities in patients with diffuse emphysema. Methods: Fifteen subjects who had undergone LVRS participated in this study. A visual analog scale (VAS) Activity Dyspnea Scales (VADS) measurement tool developed for this study was determined reliable in 10 subjects. The VADS was used to assess changes in dyspnea with functional activity in 10 subjects prior to and following the interventions of LVRS and pulmonary rehabilitation. Results: Results of this study indicate that LVRS followed by pulmonary rehabilitation significantly reduces levels of dyspnea during functional activities. Conclusion: The VADS developed for this study is a valid and reliable method of assessing changes in levels of dyspnea during functional activities in the LVRS population. PMID:20467532

  13. Evaluation of in vitro antioxidant capacity and reducing potential of polyherbal drug- Bhāraṅgyādi

    PubMed Central

    Kajaria, Divya Kumari; Gangwar, Mayank; Sharma, Amit Kumar; Tripathi, Yamini Bhusan; Tripathi, Jyoti Shankar; Tiwari, Shrikant

    2012-01-01

    Background: Present work was designed to investigate antioxidant activity of polyherbal formulation in search for new, safe and inexpensive antioxidant. Clerodendrum serratum, Hedychium spicatum and Inula racemosa, were extensively used in ayurvedic medicine and were investigated together in the form of polyherbal compound (Bhāraṅgyādi) for their antioxidant potential. Materials and Methods: Hydroalcoholic extract was prepared from the above samples and was tested for total reducing power and in vitro antioxidant activity by ABTS+ assay, Superoxide anion scavenging activity assay and lipid per-oxidation assay. Result: Reducing power shows dose depended increase in concentration maximum absorption of 0.677 ± 0.017 at 1000 μg/ml compared with standard Quercetin 0.856±0.020. ABTS+ assay shows maximum inhibition of 64.2 ± 0.86 with EC50 675.31 ± 4.24. Superoxide free radical shows maximum scavenging activity of 62.45 ± 1.86 with EC50 774.70 ± 5.45. Anti-lipidperoxidation free radicals scavenge maximum absorption of 67.25± 1.89 with EC50 is 700.08 ± 6.81. Ascorbic acid was used as standard with IC50 value is 4.6 μg/ml. The result suggests polyherbal formulation to be a good potential for antioxidant activity. Oxidative stress results from imbalance between free radical-generation and radical scavenging systems. This will lead to tissue damage and oxidative stress. Conclusion: In conclusion, we strongly suggest that Polyherbal compounds are source of potential antioxidant for radical scavenging. The highly positive correlation of antiradical scavenging activity and total polyphenolic content in Polyherbal compounds indicates that polyphenols are important components which could be used for the free radical scavenging activity. Further study is needed for isolation and characterization of the active moiety responsible for biological activity and to treat in various stress condition. PMID:23929990

  14. A reduced core to skin temperature gradient, not a critical core temperature, affects aerobic capacity in the heat.

    PubMed

    Cuddy, John S; Hailes, Walter S; Ruby, Brent C

    2014-07-01

    in beginning and ending core temperatures or baseline 3-mile run time. This capacity difference appears to result from a magnified core to skin gradient via an environmental temperature advantageous to convective heat loss, and in part from an increased sweat rate.

  15. Reduced graphene oxide/carbon nanotubes sponge: A new high capacity and long life anode material for sodium-ion batteries

    NASA Astrophysics Data System (ADS)

    Yan, Dong; Xu, Xingtao; Lu, Ting; Hu, Bingwen; Chua, Daniel H. C.; Pan, Likun

    2016-06-01

    Reduced graphene oxide/carbon nanotubes (CNTs) sponge (GCNTS) is fabricated via a simple freeze drying of graphene oxide/CNTs mixed solution and subsequent thermal treatment in nitrogen atmosphere, and used as anodes for sodium-ion batteries (SIBs) for the first time. The morphology, structure and electrochemical performance of GCNTS are characterized by field emission scanning electron microscopy, transmission electron microscopy, X-ray diffraction, X-ray photoelectron spectroscopy, Raman spectroscopy, nitrogen adsorption-desorption isotherms, galvanostatic charge/discharge tests, cyclic voltammetry and electrochemical impedance spectroscopy, respectively. The results show that GCNTS with 20 wt % CNTs has a highest charge capacity of 436 mA h g-1 after 100 cycles at a current density of 50 mA g-1 and even at a high current density of 10 A g-1, a capacity of 195 mA h g-1 is maintained after 7440 cycles. The high capacity, excellent rate performance and long life cycling enable the GCNTS to be a promising candidate for practical SIBs.

  16. Overexpression of diacylglycerol acyltransferase-1 reduces phospholipid synthesis, proliferation, and invasiveness in simian virus 40-transformed human lung fibroblasts.

    PubMed

    Bagnato, Carolina; Igal, R Ariel

    2003-12-26

    Diacylglycerol (DAG) is a versatile molecule that participates as substrate in the synthesis of structural and energetic lipids, and acts as the physiological signal that activates protein kinase C. Diacylglycerol acyltransferase (DGAT), the last committed enzyme in triacylglycerol synthesis, could potentially regulate the content and use of both signaling and glycerolipid substrate DAG by converting it into triacylglycerol. To test this hypothesis, we stably overexpressed the DGAT1 mouse gene in human lung SV40-transformed fibroblasts (DGAT cells), which contains high levels of DAG. DGAT cells exhibited a 3.9-fold higher DGAT activity and a 3.2-fold increase in triacylglycerol content, whereas DAG and phosphatidylcholine decreased by 70 and 20%, respectively, compared with empty vector-transfected SV40 cells (Control cells). Both acylation and de novo synthesis of phosphatidylcholine, phosphatidylethanolamine, and sphingomyelin were reduced by 30-40% in DGAT cells compared with controls, suggesting that DGAT used substrates for triacylglycerol synthesis that had originally been destined to produce phospholipids. The incorporation of [14C]DAG and [14C]fatty acids released from plasma membrane by additions of either phospholipase C or phospholipase A2 into triacylglycerol was increased by 6.2- and 2.8-fold, respectively, in DGAT cells compared with control cells, indicating that DGAT can attenuate signaling lipids. Finally, DGAT overexpression reversed the neoplastic phenotype because it dramatically reduced the cell growth rate and suppressed the anchorage-independent growth of the SV40 cells. These results strongly support the view that DGAT participates in the regulation of membrane lipid synthesis and lipid signaling, thereby playing an important role in modulating cell growth properties.

  17. The metabolic costs of improving ethanol yield by reducing glycerol formation capacity under anaerobic conditions in Saccharomyces cerevisiae

    PubMed Central

    2013-01-01

    Background Finely regulating the carbon flux through the glycerol pathway by regulating the expression of the rate controlling enzyme, glycerol-3-phosphate dehydrogenase (GPDH), has been a promising approach to redirect carbon from glycerol to ethanol and thereby increasing the ethanol yield in ethanol production. Here, strains engineered in the promoter of GPD1 and deleted in GPD2 were used to investigate the possibility of reducing glycerol production of Saccharomyces cerevisiae without jeopardising its ability to cope with process stress during ethanol production. For this purpose, the mutant strains TEFmut7 and TEFmut2 with different GPD1 residual expression were studied in Very High Ethanol Performance (VHEP) fed-batch process under anaerobic conditions. Results Both strains showed a drastic reduction of the glycerol yield by 44 and 61% while the ethanol yield improved by 2 and 7% respectively. TEFmut2 strain showing the highest ethanol yield was accompanied by a 28% reduction of the biomass yield. The modulation of the glycerol formation led to profound redox and energetic changes resulting in a reduction of the ATP yield (YATP) and a modulation of the production of organic acids (acetate, pyruvate and succinate). Those metabolic rearrangements resulted in a loss of ethanol and stress tolerance of the mutants, contrarily to what was previously observed under aerobiosis. Conclusions This work demonstrates the potential of fine-tuned pathway engineering, particularly when a compromise has to be found between high product yield on one hand and acceptable growth, productivity and stress resistance on the other hand. Previous study showed that, contrarily to anaerobiosis, the resulting gain in ethanol yield was accompanied with no loss of ethanol tolerance under aerobiosis. Moreover those mutants were still able to produce up to 90 gl-1 ethanol in an anaerobic SSF process. Fine tuning metabolic strategy may then open encouraging possibilities for further

  18. Superiority of Minimally Invasive Oesophagectomy in Reducing In-Hospital Mortality of Patients with Resectable Oesophageal Cancer: A Meta-Analysis

    PubMed Central

    Zhou, Can; Zhang, Li; Wang, Hua; Ma, Xiaoxia; Shi, Bohui; Chen, Wuke; He, Jianjun; Wang, Ke; Liu, Peijun; Ren, Yu

    2015-01-01

    Background Compared with open oesophagectomy (OE), minimally invasive oesophagectomy (MIO) proves to have benefits in reducing the risk of pulmonary complications for patients with resectable oesophageal cancer. However, it is unknown whether MIO has superiority in reducing the occurrence of in-hospital mortality (IHM). Objective The objective of this meta-analysis was to explore the effect of MIO vs. OE on the occurrence of in-hospital mortality (IHM). Data Sources Sources such as Medline (through December 31, 2014), Embase (through December 31, 2014), Wiley Online Library (through December 31, 2014), and the Cochrane Library (through December 31, 2014) were searched. Study Selection Data of randomized and non-randomized clinical trials related to MIO versus OE were included. Interventions Eligible studies were those that reported patients who underwent MIO procedure. The control group included patients undergoing conventional OE. Study Appraisal and Synthesis Methods Fixed or random -effects models were used to calculate summary odds ratios (ORs) or relative risks (RRs) for quantification of associations. Heterogeneity among studies was evaluated by using Cochran’s Q and I2 statistics. Results A total of 48 studies involving 14,311 cases of resectable oesophageal cancer were included in the meta-analysis. Compared to patients undergoing OE, patients undergoing MIO had statistically reduced occurrence of IHM (OR=0.69, 95%CI =0.55 -0.86). Patients undergoing MIO also had significantly reduced incidence of pulmonary complications (PCs) (RR=0.73, 95%CI = 0.63-0.86), pulmonary embolism (PE) (OR=0.71, 95%CI= 0.51-0.99) and arrhythmia (OR=0.79, 95%CI = 0.68-0.92). Non-significant reductions were observed among the included studies in the occurrence of anastomotic leak (AL) (OR=0.93, 95%CI =0.78-1.11), or Gastric Tip Necrosis (GTN) (OR=0.89, 95%CI =0.54-1.49). Limitation Most of the included studies were non-randomized case-control studies, with a diversity of study

  19. Combined VEGFR and CTLA-4 blockade increases the antigen-presenting function of intratumoral DCs and reduces the suppressive capacity of intratumoral MDSCs

    PubMed Central

    Du Four, Stephanie; Maenhout, Sarah K; Niclou, Simone P; Thielemans, Kris; Neyns, Bart; Aerts, Joeri L

    2016-01-01

    Melanoma brain metastases (MBM) occur in 10% to 50% of melanoma patients. They are often associated with a high morbidity and despite the improvements in the treatment of advanced melanoma, including immunotherapy, patients with MBM still have a poor prognosis. Antiangiogenic treatment was shown to reduce the immunosuppressive tumor microenvironment. Therefore we investigated the effect of the combination of VEGFR- and CTLA-4 blockade on the immune cells within the tumor microenvironment. In this study we investigated the effect of the combination of axitinib, a TKI against VEGFR-1, -2 and -3, with therapeutic inhibition of CTLA-4 in subcutaneous and intracranial mouse melanoma models. The combination of axitinib with αCTLA-4 reduced tumor growth and increased survival in both intracranial and subcutaneous models. Investigation of the splenic immune cells showed an increased number of CD4+ and CD8+ T cells after combination treatment. Moreover, combination treatment increased the number of intratumoral dendritic cells (DCs) and monocytic myeloid-derived suppressor cells (moMDSCs). When these immune cell populations were sorted from the subcutaneous and intracranial tumors of mice treated with axitinib+αCTLA-4, we observed an increased antigen-presenting function of DCs and a reduced suppressive capacity of moMDSCs on a per cell basis. Our results suggest that the combination of antiangiogenesis and checkpoint inhibition can lead to an enhanced antitumor effect leading to increased survival. We found that this effect is in part due to an enhanced antitumor immune response generated by an increased antigen-presenting function of intratumoral DCs in combination with a reduced suppressive capacity of intratumoral moMDSCs. PMID:27904768

  20. Combined VEGFR and CTLA-4 blockade increases the antigen-presenting function of intratumoral DCs and reduces the suppressive capacity of intratumoral MDSCs.

    PubMed

    Du Four, Stephanie; Maenhout, Sarah K; Niclou, Simone P; Thielemans, Kris; Neyns, Bart; Aerts, Joeri L

    2016-01-01

    Melanoma brain metastases (MBM) occur in 10% to 50% of melanoma patients. They are often associated with a high morbidity and despite the improvements in the treatment of advanced melanoma, including immunotherapy, patients with MBM still have a poor prognosis. Antiangiogenic treatment was shown to reduce the immunosuppressive tumor microenvironment. Therefore we investigated the effect of the combination of VEGFR- and CTLA-4 blockade on the immune cells within the tumor microenvironment. In this study we investigated the effect of the combination of axitinib, a TKI against VEGFR-1, -2 and -3, with therapeutic inhibition of CTLA-4 in subcutaneous and intracranial mouse melanoma models. The combination of axitinib with αCTLA-4 reduced tumor growth and increased survival in both intracranial and subcutaneous models. Investigation of the splenic immune cells showed an increased number of CD4(+) and CD8(+) T cells after combination treatment. Moreover, combination treatment increased the number of intratumoral dendritic cells (DCs) and monocytic myeloid-derived suppressor cells (moMDSCs). When these immune cell populations were sorted from the subcutaneous and intracranial tumors of mice treated with axitinib+αCTLA-4, we observed an increased antigen-presenting function of DCs and a reduced suppressive capacity of moMDSCs on a per cell basis. Our results suggest that the combination of antiangiogenesis and checkpoint inhibition can lead to an enhanced antitumor effect leading to increased survival. We found that this effect is in part due to an enhanced antitumor immune response generated by an increased antigen-presenting function of intratumoral DCs in combination with a reduced suppressive capacity of intratumoral moMDSCs.

  1. Adverse effects of reduced oxygen tension on the proliferative capacity of rat kidney and insulin-secreting cell lines involve DNA damage and stress responses

    SciTech Connect

    Chen Jianhua Jones, R. Huw; Tarry-Adkins, Jane; Smith, Noel H.; Ozanne, Susan E.

    2008-10-01

    Standard cell culture conditions do not reflect the physiological environment in terms of oxygen tension (20% vs 3%). The effects of lowering oxygen tension on cell proliferation in culture can be beneficial as well as detrimental depending on the cell line studied, but the molecular mechanism underlying such effects is not fully understood. We observed that the proliferative capacity of the rat cell lines NRK and INS-1 was inhibited when cultured under 3% oxygen as compared to 20% oxygen. Suppression of proliferation in NRK cells was accompanied by induction of DNA double strand breaks whereas in INS-1 cells it was accompanied by up-regulation of p53 and p27. Although Sirt1 was up-regulated in both cell lines by 3% oxygen the effects on antioxidant enzymes (MnSOD, CuZnSOD and catalase) were cell line specific. Marked up-regulation of heme oxygenase-1 (HO-1) was detected in both NRK and INS-1 cells when cultured in 3% oxygen. HO-1 expression can be readily induced by exposure to hydrogen peroxide in culture. These results suggest that reduced oxygen tension suppresses the proliferative capacity of these two cell lines through a stress response that is similar to an oxidative stress response but the molecular events that lead to the reduced cell proliferation are cell line specific.

  2. Characterization of phenolics, in vitro reducing capacity and anti-glycation activity of red grape skins recovered from winemaking by-products.

    PubMed

    Sri Harsha, P S C; Gardana, Claudio; Simonetti, Paolo; Spigno, Giorgia; Lavelli, Vera

    2013-07-01

    Red grape skins recovered from ten winemaking processes were analyzed for total phenolic content (Folin Ciocalteu assay), proanthocyanidins (n-butanol/HCl assay), individual phenolics (UPLC-DAD-MS), in vitro ferric ion reducing capacity and anti-glycation activity by bovine serum albumin/fructose and bovine serum albumin/methylglyoxal model systems. The aim was to assess if these by-products have potential as dietary anti-glycation agents, to prevent the glyco-oxidative stress associated with type-2 diabetes. Variability was observed in total phenolics (12.1-53.6g gallic acid Eq/kg), proanthocyanidins (7.2-51.1g/kg), anthocyanins (2.5-13.8 g malvidin 3-O glucoside Eq/kg), flavonols (0.3-2.6g quercetin 3-O glucoside Eq/kg) and reducing capacity (103-511 mmol Fe(II) Eq/kg). For all samples, the anti-glycation effectiveness was higher than that of commercial nutraceutical preparations. Hence, in spite of differences in cultivar, location of the vineyard and winemaking procedures, these by-products could be used as a source of cost-effective anti-glycation agent either as a food ingredient or as a nutraceutical preparation.

  3. Resistant ticks inhibit Metarhizium infection prior to haemocoel invasion by reducing fungal viability on the cuticle surface.

    PubMed

    Ment, Dana; Churchill, Alice C L; Gindin, Galina; Belausov, Eduard; Glazer, Itamar; Rehner, Stephen A; Rot, Asael; Donzelli, Bruno G G; Samish, Michael

    2012-06-01

    We studied disease progression of, and host responses to, four species in the Metarhizium anisopliae complex expressing green fluorescent protein (GFP). We compared development and determined their relative levels of virulence against two susceptible arthropods, the cattle tick Rhipicephalus annulatus and the lepidopteran Galleria mellonella, and two resistant ticks, Hyalomma excavatum and Rhipicephalus sanguineus. Metarhizium brunneum Ma7 caused the greatest mortality of R. annulatus, Metarhizium robertsii ARSEF 2575 and Metarhizium pingshaense PPRC51 exhibited intermediate levels of virulence, and Metarhizium majus PPRC27 caused low mortality of cattle ticks. Conidia of all four species germinated on all hosts examined, but on resistant hosts, sustained hyphal growth was inhibited and GFP emission steadily and significantly decreased over time, suggesting a loss of fungal viability. Cuticle penetration was observed only for the three most virulent species infecting susceptible hosts. Cuticles of resistant and susceptible engorged female ticks showed significant increases in red autofluorescence at sites immediately under fungal hyphae. This is the first report (i) of tick mortality occurring after cuticle penetration but prior to haemocoel colonization and (ii) that resistant ticks do not support development of Metarhizium germlings on the outer surface of the cuticle. Whether reduced Metarhizium viability on resistant tick cuticles is due to antibiosis or limited nutrient availability is unknown.

  4. Ionizing radiation modulates human macrophages towards a pro-inflammatory phenotype preserving their pro-invasive and pro-angiogenic capacities

    PubMed Central

    Teresa Pinto, Ana; Laranjeiro Pinto, Marta; Patrícia Cardoso, Ana; Monteiro, Cátia; Teixeira Pinto, Marta; Filipe Maia, André; Castro, Patrícia; Figueira, Rita; Monteiro, Armanda; Marques, Margarida; Mareel, Marc; dos Santos, Susana Gomes; Seruca, Raquel; Adolfo Barbosa, Mário; Rocha, Sónia; José Oliveira, Maria

    2016-01-01

    In order to improve the efficacy of conventional radiotherapy, attention has been paid to immune cells, which not only modulate cancer cell response to therapy but are also highly recruited to tumours after irradiation. Particularly, the effect of ionizing radiation on macrophages, using therapeutically relevant doses, is not well understood. To evaluate how radiotherapy affects macrophage behaviour and macrophage-mediated cancer cell activity, human monocyte derived-macrophages were subjected, for a week, to cumulative ionizing radiation doses, as used during cancer treatment (2 Gy/fraction/day). Irradiated macrophages remained viable and metabolically active, despite DNA damage. NF-kappaB transcription activation and increased Bcl-xL expression evidenced the promotion of pro-survival activity. A significant increase of pro-inflammatory macrophage markers CD80, CD86 and HLA-DR, but not CCR7, TNF and IL1B was observed after 10 Gy cumulative doses, while anti-inflammatory markers CD163, MRC1, VCAN and IL-10 expression decreased, suggesting the modulation towards a more pro-inflammatory phenotype. Moreover, ionizing radiation induced macrophage morphological alterations and increased their phagocytic rate, without affecting matrix metalloproteases (MMP)2 and MMP9 activity. Importantly, irradiated macrophages promoted cancer cell-invasion and cancer cell-induced angiogenesis. Our work highlights macrophage ability to sustain cancer cell activities as a major concern that needs to be addressed to improve radiotherapy efficacy. PMID:26735768

  5. Oral administration of a combination of select lactic acid bacteria strains to reduce the Salmonella invasion and inflammation of broiler chicks.

    PubMed

    Chen, C-Y; Tsen, H-Y; Lin, C-L; Yu, B; Chen, C-S

    2012-09-01

    One-day-old chicks are susceptible to infection by strains of Salmonella enterica subspecies. Because multistrain probiotics are suggested to be more effective than monostrain probiotics due to the additive and synergistic effects, in this study, we prepared a multistrain formula A (MFA) consisting of 4 lactic acid bacteria (LAB) strains selected by enhancing the TNF-α production for mouse macrophage 264.7 cells. The antagonistic effect of this MFA against the cecal colonization, viscera invasiveness, as well as the inflammation of 1-d-old chicks challenged with Salmonella Typhimurium were then assayed. One-day-old chicks were fed with MFA from d 1 to d 3, and on d 4, chicks were challenged with Salmonella Typhimurium (200 μL, 10(6) cfu/mL). The livers, spleens, and cecal tonsils of chicks were then removed on d 3 and 6 postinfection. Compared with the multistrain formula B (MFB) which consisted of LAB strains selected at random, the efficacy of MFA to reduce the Salmonella counts recovered from the cecal tonsils, spleens, and livers of chicks were significantly higher. Moreover, when the levels of proinflammatory cytokines, such as IL-1β, IL-6, interferon (IFN)-γ, and anti-inflmmatory cytokine, that is, IL-10, in cecal tonsils were measured by reverse-transcription real-time quantitative PCR; it was found that chicks fed with MFA for 3 d had lower levels of IL-1β, IL-6, IFN-γ and a higher level of IL-10 in the cecal tonsils of chicks as compared with those of the chicks fed with MFB or without LAB. These results suggest that multistrain probiotics consisting of LAB strains selected by immunomodulatory activity and adherence are more effective than those consisting of strains selected at random in antagonistic effect against Salmonella colonization, invasion, and the induced inflammation.

  6. PEGylation of the peptide Bac7(1-35) reduces renal clearance while retaining antibacterial activity and bacterial cell penetration capacity.

    PubMed

    Benincasa, Monica; Zahariev, Sotir; Pelillo, Chiara; Milan, Annalisa; Gennaro, Renato; Scocchi, Marco

    2015-05-05

    The proline-rich antibacterial peptide Bac7(1-35) protects mice against Salmonella typhimurium infection, despite its rapid clearance. To overcome this problem the peptide was linked to a polyethylene glycol (PEG) molecule either via a cleavable ester bond or via a non-hydrolysable amide bond. Both the PEGylated conjugates retained most of the in vitro activity against S. typhimurium. In addition, the ester bond was cleaved in human serum or plasma, releasing a carboxymethyl derivative of Bac7(1-35) which accounts for a higher activity of this peptide with relative to the other, non-hydrolysable form. Both PEGylated peptides maintained the capacity of the unconjugated form to kill bacteria without permeabilizing the bacterial membranes, by penetrating into cells. They exploited the same transporter as unmodified Bac7(1-35), suggesting it has the capacity to internalize quite sizeable cargo if this is linked to Bac7 fragment. PEGylation allows the peptide to have a wide distribution in mice, and a slow renal clearance, indicating that this strategy would improve the bioavailability of Bac7, and in principle of other antimicrobial peptides. This can be an equally important issue to reducing cytotoxicity for therapeutic use of these antibacterials.

  7. Regeneration Capacity of Small Clonal Fragments of the Invasive Mikania micrantha H.B.K.: Effects of Burial Depth and Stolon Internode Length

    PubMed Central

    Li, Xiaoxia; Shen, Yide; Huang, Qiaoqiao; Fan, Zhiwei; Huang, Dongdong

    2013-01-01

    The perennial stoloniferous herbaceous vine Mikania micrantha H.B.K. is among the most noxious exotic invaders in China and the world. Disturbance can fragment stolons of M. micrantha and disperse these fragments over long distances or bury them in soils at different depths. To test their regeneration capacity, single-node stolon fragments with stolon internode lengths of 0, 3, 6 and 12 cm were buried in soil at 0, 2, 5 and 8 cm depths, respectively. The fragments were growing for nine weeks, and their emergence status, growth and morphological traits were measured. The results indicated that increasing burial depth significantly decreased survival rate and increased the emergence time of the M. micrantha plants. At an 8-cm burial depth, very few fragments (2.19%) emerged and survived. Burial did not affect the total biomass and root to shoot ratio of the surviving M. micrantha plants that emerged from the 0- and 2-cm burial depths. Increasing internode length significantly increased survival rate and growth measures, but there was no interaction effect with burial depth for any traits measured. These results suggest that M. micrantha can regenerate from buried stolon fragments, and thus, disturbance may contribute to the spread of this exotic invader. Any human activities producing stolon fragments or facilitating dispersal should be avoided. PMID:24367686

  8. Regeneration capacity of small clonal fragments of the invasive Mikania micrantha H.B.K.: effects of burial depth and stolon internode length.

    PubMed

    Li, Xiaoxia; Shen, Yide; Huang, Qiaoqiao; Fan, Zhiwei; Huang, Dongdong

    2013-01-01

    The perennial stoloniferous herbaceous vine Mikania micrantha H.B.K. is among the most noxious exotic invaders in China and the world. Disturbance can fragment stolons of M. micrantha and disperse these fragments over long distances or bury them in soils at different depths. To test their regeneration capacity, single-node stolon fragments with stolon internode lengths of 0, 3, 6 and 12 cm were buried in soil at 0, 2, 5 and 8 cm depths, respectively. The fragments were growing for nine weeks, and their emergence status, growth and morphological traits were measured. The results indicated that increasing burial depth significantly decreased survival rate and increased the emergence time of the M. micrantha plants. At an 8-cm burial depth, very few fragments (2.19%) emerged and survived. Burial did not affect the total biomass and root to shoot ratio of the surviving M. micrantha plants that emerged from the 0- and 2-cm burial depths. Increasing internode length significantly increased survival rate and growth measures, but there was no interaction effect with burial depth for any traits measured. These results suggest that M. micrantha can regenerate from buried stolon fragments, and thus, disturbance may contribute to the spread of this exotic invader. Any human activities producing stolon fragments or facilitating dispersal should be avoided.

  9. Ciguatoxin reduces regenerative capacity of axotomized peripheral neurons and delays functional recovery in pre-exposed mice after peripheral nerve injury

    PubMed Central

    Au, Ngan Pan Bennett; Kumar, Gajendra; Asthana, Pallavi; Tin, Chung; Mak, Yim Ling; Chan, Leo Lai; Lam, Paul Kwan Sing; Ma, Chi Him Eddie

    2016-01-01

    Ciguatera fish poisoning (CFP) results from consumption of tropical reef fish containing ciguatoxins (CTXs). Pacific (P)-CTX-1 is among the most potent known CTXs and the predominant source of CFP in the endemic region responsible for the majority of neurological symptoms in patients. Chronic and persistent neurological symptoms occur in some CFP patients, which often result in incomplete functional recovery for years. However, the direct effects of exposure to CTXs remain largely unknown. In present study, we exposed mice to CTX purified from ciguatera fish sourced from the Pacific region. P-CTX-1 was detected in peripheral nerves within hours and persisted for two months after exposure. P-CTX-1 inhibited axonal regrowth from axotomized peripheral neurons in culture. P-CTX-1 exposure reduced motor function in mice within the first two weeks of exposure before returning to baseline levels. These pre-exposed animals exhibited delayed sensory and motor functional recovery, and irreversible motor deficits after peripheral nerve injury in which formation of functional synapses was impaired. These findings are consistent with reduced muscle function, as assessed by electromyography recordings. Our study provides strong evidence that the persistence of P-CTX-1 in peripheral nerves reduces the intrinsic growth capacity of peripheral neurons, resulting in delayed functional recovery after injury. PMID:27229176

  10. Ciguatoxin reduces regenerative capacity of axotomized peripheral neurons and delays functional recovery in pre-exposed mice after peripheral nerve injury.

    PubMed

    Au, Ngan Pan Bennett; Kumar, Gajendra; Asthana, Pallavi; Tin, Chung; Mak, Yim Ling; Chan, Leo Lai; Lam, Paul Kwan Sing; Ma, Chi Him Eddie

    2016-05-27

    Ciguatera fish poisoning (CFP) results from consumption of tropical reef fish containing ciguatoxins (CTXs). Pacific (P)-CTX-1 is among the most potent known CTXs and the predominant source of CFP in the endemic region responsible for the majority of neurological symptoms in patients. Chronic and persistent neurological symptoms occur in some CFP patients, which often result in incomplete functional recovery for years. However, the direct effects of exposure to CTXs remain largely unknown. In present study, we exposed mice to CTX purified from ciguatera fish sourced from the Pacific region. P-CTX-1 was detected in peripheral nerves within hours and persisted for two months after exposure. P-CTX-1 inhibited axonal regrowth from axotomized peripheral neurons in culture. P-CTX-1 exposure reduced motor function in mice within the first two weeks of exposure before returning to baseline levels. These pre-exposed animals exhibited delayed sensory and motor functional recovery, and irreversible motor deficits after peripheral nerve injury in which formation of functional synapses was impaired. These findings are consistent with reduced muscle function, as assessed by electromyography recordings. Our study provides strong evidence that the persistence of P-CTX-1 in peripheral nerves reduces the intrinsic growth capacity of peripheral neurons, resulting in delayed functional recovery after injury.

  11. Mutants of the major ryegrass pollen allergen, Lol p 5, with reduced IgE-binding capacity: candidates for grass pollen-specific immunotherapy.

    PubMed

    Swoboda, Ines; De Weerd, Nicole; Bhalla, Prem L; Niederberger, Verena; Sperr, W R; Valent, Peter; Kahlert, Helga; Fiebig, Helmut; Verdino, Petra; Keller, Walter; Ebner, Christof; Spitzauer, Susanne; Valenta, Rudolf; Singh, Mohan B

    2002-01-01

    More than 400 million individuals are sensitized to grass pollen allergens. Group 5 allergens represent the most potent grass pollen allergens recognized by more than 80 % of grass pollen allergic patients. The aim of our study was to reduce the allergenic activity of group 5 allergens for specific immunotherapy of grass pollen allergy. Based on B- and T-cell epitope mapping studies and on sequence comparison of group 5 allergens from different grasses, point mutations were introduced by site-directed mutagenesis in highly conserved sequence domains of Lol p 5, the group 5 allergen from ryegrass. We obtained Lol p 5 mutants with low IgE-binding capacity and reduced allergenic activity as determined by basophil histamine release and by skin prick testing in allergic patients. Circular dichroism analysis showed that these mutants exhibited an overall structural fold similar to the recombinant Lol p 5 wild-type allergen. In addition, Lol p 5 mutants retained the ability to induce proliferation of group 5 allergen-specific T cell lines and clones. Our results demonstrate that a few point mutations in the Lol p 5 sequence yield mutants with reduced allergenic activity that represent potential vaccine candidates for immunotherapy of grass pollen allergy.

  12. Novel total antioxidant capacity index for dietary polyphenols and vitamins C and E, using their cupric ion reducing capability in the presence of neocuproine: CUPRAC method.

    PubMed

    Apak, Resat; Güçlü, Kubilay; Ozyürek, Mustafa; Karademir, Saliha Esin

    2004-12-29

    The chemical diversity of antioxidants makes it difficult to separate and quantify antioxidants from the vegetable matrix. Therefore, it is desirable to establish a method that can measure the total antioxidant activity level directly from vegetable extracts. The current literature clearly states that there is no "total antioxidant" as a nutritional index available for food labeling because of the lack of standard quantitation methods. Thus, this work reports the development of a simple, widely applicable antioxidant capacity index for dietary polyphenols and vitamins C and E, utilizing the copper(II)-neocuproine [Cu(II)-Nc] reagent as the chromogenic oxidizing agent. Because the copper(II) (or cupric) ion reducing ability of polyphenols is measured, the method is named by our research group "cupric reducing antioxidant capacity" abbreviated as the CUPRAC method. This method should be advantageous over the ferric reducing antioxidant power (FRAP) method because the redox chemistry of copper(II)-as opposed to that of ferric ion-involves faster kinetics. The method comprises mixing of the antioxidant solution (directly or after acid hydrolysis) with a copper(II) chloride solution, a neocuproine alcoholic solution, and an ammonium acetate aqueous buffer at pH 7 and subsequent measurement of the developed absorbance at 450 nm after 30 min. Because the color development is fast for compounds such as ascorbic acid, gallic acid, and quercetin but slow for naringin and naringenin, the latter compounds were assayed after incubation at 50 degrees C on a water bath for 20 min [after Cu(II)-Nc reagent addition] so as to force the oxidation reaction to reach completion. The flavonoid glycosides were hydrolyzed to their corresponding aglycons by refluxing in 1.2 M HCl-containing 50% MeOH so as to exert maximal reducing power toward Cu(II)-Nc. Certain compounds also needed incubation after acid hydrolysis to fully exhibit their reducing capability. The CUPRAC antioxidant

  13. Drug-tolerant cancer cells show reduced tumor-initiating capacity: depletion of CD44 cells and evidence for epigenetic mechanisms.

    PubMed

    Yan, Hong; Chen, Xin; Zhang, Qiuping; Qin, Jichao; Li, Hangwen; Liu, Can; Calhoun-Davis, Tammy; Coletta, Luis Della; Klostergaard, Jim; Fokt, Izabela; Skora, Stanislaw; Priebe, Waldemar; Bi, Yongyi; Tang, Dean G

    2011-01-01

    Cancer stem cells (CSCs) possess high tumor-initiating capacity and have been reported to be resistant to therapeutics. Vice versa, therapy-resistant cancer cells seem to manifest CSC phenotypes and properties. It has been generally assumed that drug-resistant cancer cells may all be CSCs although the generality of this assumption is unknown. Here, we chronically treated Du145 prostate cancer cells with etoposide, paclitaxel and some experimental drugs (i.e., staurosporine and 2 paclitaxel analogs), which led to populations of drug-tolerant cells (DTCs). Surprisingly, these DTCs, when implanted either subcutaneously or orthotopically into NOD/SCID mice, exhibited much reduced tumorigenicity or were even non-tumorigenic. Drug-tolerant DLD1 colon cancer cells selected by a similar chronic selection protocol also displayed reduced tumorigenicity whereas drug-tolerant UC14 bladder cancer cells demonstrated either increased or decreased tumor-regenerating capacity. Drug-tolerant Du145 cells demonstrated low proliferative and clonogenic potential and were virtually devoid of CD44(+) cells. Prospective knockdown of CD44 in Du145 cells inhibited cell proliferation and tumor regeneration, whereas restoration of CD44 expression in drug-tolerant Du145 cells increased cell proliferation and partially increased tumorigenicity. Interestingly, drug-tolerant Du145 cells showed both increases and decreases in many "stemness" genes. Finally, evidence was provided that chronic drug exposure generated DTCs via epigenetic mechanisms involving molecules such as CD44 and KDM5A. Our results thus reveal that 1) not all DTCs are necessarily CSCs; 2) conventional chemotherapeutic drugs such as taxol and etoposide may directly target CD44(+) tumor-initiating cells; and 3) DTCs generated via chronic drug selection involve epigenetic mechanisms.

  14. Combining Natural Attenuation Capacity and use of Targeted Technological Mitigation Measures for Reducing Diffuse Nutrient Emissions to Surface Waters: The Danish Way

    NASA Astrophysics Data System (ADS)

    Kronvang, B.; Højberg, A. L.; Hoffmann, C. C.; Windolf, J.; Blicher-Mathiesen, G.

    2015-12-01

    Excess nitrogen (N) and phosphorus (P) emissions to surface waters are a high priority environmental problem worldwide for protection of water resources in times of population growth and climate change. As clean water is a scarce resource the struggle for reducing nutrient emissions are an ongoing issue for many countries and regions. Since the mid1980s a wide range of national regulatory general measures have been implemented to reduce land based nitrogen (N) and phosphorus (P) loadings of the Danish aquatic environment. These measures have addressed both point source emissions and emissions from diffuse sources especially from agricultural production. Following nearly 4 decades of combating nutrient pollution our surface waters such as lakes and estuaries are only slowly responding on the 50% reduction in N and 56% reduction in P. Therefore, the implementation of the EU Water Framework Directive in Danish surface waters still call for further reductions of N and P loadings. Therefore, a new era of targeted implemented measures was the outcome of a Commission on Nature and Agriculture established by the Danish Government in 2013. Their White Book points to the need of increased growth and better environment through more targeted and efficient regulation using advanced technological mitigation methods that are implemented intelligently according to the local natural attenuation capacity for nutrients in the landscape. As a follow up a national consensus model for N was established chaining existing leaching, 3D groundwater and surface water models that enable a calculation of the N dynamics and attenuation capacity within a scale of 15 km2. Moreover, several research projects have been conducted to investigate the effect of a suite of targeted mitigation measures such as restored natural wetlands, constructed wetlands, controlled drainage, buffer strips and constructed buffer strips. The results of these studies will be shared in this presentation.

  15. Resource competition in plant invasions: emerging patterns and research needs

    PubMed Central

    Gioria, Margherita; Osborne, Bruce A.

    2014-01-01

    Invasions by alien plants provide a unique opportunity to examine competitive interactions among plants. While resource competition has long been regarded as a major mechanism responsible for successful invasions, given a well-known capacity for many invaders to become dominant and reduce plant diversity in the invaded communities, few studies have measured resource competition directly or have assessed its importance relative to that of other mechanisms, at different stages of an invasion process. Here, we review evidence comparing the competitive ability of invasive species vs. that of co-occurring native plants, along a range of environmental gradients, showing that many invasive species have a superior competitive ability over native species, although invasive congeners are not necessarily competitively superior over native congeners, nor are alien dominants are better competitors than native dominants. We discuss how the outcomes of competition depend on a number of factors, such as the heterogeneous distribution of resources, the stage of the invasion process, as well as phenotypic plasticity and evolutionary adaptation, which may result in increased or decreased competitive ability in both invasive and native species. Competitive advantages of invasive species over natives are often transient and only important at the early stages of an invasion process. It remains unclear how important resource competition is relative to other mechanisms (competition avoidance via phenological differences, niche differentiation in space associated with phylogenetic distance, recruitment and dispersal limitation, indirect competition, and allelopathy). Finally, we identify the conceptual and methodological issues characterizing competition studies in plant invasions, and we discuss future research needs, including examination of resource competition dynamics and the impact of global environmental change on competitive interactions between invasive and native species. PMID

  16. Resource competition in plant invasions: emerging patterns and research needs.

    PubMed

    Gioria, Margherita; Osborne, Bruce A

    2014-01-01

    Invasions by alien plants provide a unique opportunity to examine competitive interactions among plants. While resource competition has long been regarded as a major mechanism responsible for successful invasions, given a well-known capacity for many invaders to become dominant and reduce plant diversity in the invaded communities, few studies have measured resource competition directly or have assessed its importance relative to that of other mechanisms, at different stages of an invasion process. Here, we review evidence comparing the competitive ability of invasive species vs. that of co-occurring native plants, along a range of environmental gradients, showing that many invasive species have a superior competitive ability over native species, although invasive congeners are not necessarily competitively superior over native congeners, nor are alien dominants are better competitors than native dominants. We discuss how the outcomes of competition depend on a number of factors, such as the heterogeneous distribution of resources, the stage of the invasion process, as well as phenotypic plasticity and evolutionary adaptation, which may result in increased or decreased competitive ability in both invasive and native species. Competitive advantages of invasive species over natives are often transient and only important at the early stages of an invasion process. It remains unclear how important resource competition is relative to other mechanisms (competition avoidance via phenological differences, niche differentiation in space associated with phylogenetic distance, recruitment and dispersal limitation, indirect competition, and allelopathy). Finally, we identify the conceptual and methodological issues characterizing competition studies in plant invasions, and we discuss future research needs, including examination of resource competition dynamics and the impact of global environmental change on competitive interactions between invasive and native species.

  17. Investigating Invasives

    ERIC Educational Resources Information Center

    Lightbody, Mary

    2008-01-01

    Invasive species, commonly known as "invasives," are nonnative plants, animals, and microbes that completely take over and change an established ecosystem. The consequences of invasives' spread are significant. In fact, many of the species that appear on the Endangered Species list are threatened by invasives. Therefore, the topic of invasive…

  18. Developing Functional Parameters for a Science-Based Vehicle Cleaning Program to Reduce Transport of Non-Indigenous Invasive Plant Species

    DTIC Science & Technology

    2011-06-01

    and DoD focus in managing the spread of invasive species. American Society of Agronomy , 1-5 November, 2009, Pittsburgh, PA. Howard, H, Balbach H, Rew...LJ, Ayers P and Anderson AB (2009) Tracking Military vehicles to better understand invasive species spread. American Society of Agronomy , Pittsburgh

  19. Knockdown of BC200 RNA expression reduces cell migration and invasion by destabilizing mRNA for calcium-binding protein S100A11.

    PubMed

    Shin, Heegwon; Lee, Jungmin; Kim, Youngmi; Jang, Seonghui; Lee, Yunhee; Kim, Semi; Lee, Younghoon

    2017-03-01

    Although BC200 RNA is best known as a neuron-specific non-coding RNA, it is overexpressed in various cancer cells. BC200 RNA was recently shown to contribute to metastasis in several cancer cell lines, but the underlying mechanism was not understood in detail. To examine this mechanism, we knocked down BC200 RNA in cancer cells, which overexpress the RNA, and examined cell motility, profiling of ribosome footprints, and the correlation between cell motility changes and genes exhibiting altered ribosome profiles. We found that BC200 RNA knockdown reduced cell migration and invasion, suggesting that BC200 RNA promotes cell motility. Our ribosome profiling analysis identified 29 genes whose ribosomal occupations were altered more than 2-fold by BC200 RNA knockdown. Many (> 30%) of them were directly or indirectly related to cancer progression. Among them, we focused on S100A11 (which showed a reduced ribosome footprint) because its expression was previously shown to increase cellular motility. S100A11 was decreased at both the mRNA and protein levels following knockdown of BC200 RNA. An actinomycin-chase experiment showed that BC200 RNA knockdown significantly decreased the stability of the S100A11 mRNA without changing its transcription rate, suggesting that the down-regulation of S100A11 was mainly caused by destabilization of its mRNA. Finally, we showed that the BC200 RNA-knockdown-induced decrease in cell motility was mainly mediated by S100A11. Together, our results show that BC200 RNA promotes cell motility by stabilizing S100A11 transcripts.

  20. MicroRNA-125a Reduces Proliferation and Invasion of Oral Squamous Cell Carcinoma Cells by Targeting Estrogen-related Receptor α

    PubMed Central

    Tiwari, Ankana; Shivananda, Swamy; Gopinath, Kodaganur S.; Kumar, Arun

    2014-01-01

    Estrogen-related receptor α (ESRRA) functions as a transcription factor and regulates the expression of several genes, such as WNT11 and OPN. Up-regulation of ESRRA has been reported in several cancers. However, the mechanism underlying its up-regulation is unclear. Furthermore, the reports regarding the role and regulation of ESRRA in oral squamous cell carcinoma (OSCC) are completely lacking. Here, we show that tumor suppressor miR-125a directly binds to the 3′UTR of ESRRA and represses its expression. Overexpression of miR-125a in OSCC cells drastically reduced the level of ESRRA, decreased cell proliferation, and increased apoptosis. Conversely, the delivery of an miR-125a inhibitor to these cells drastically increased the level of ESRRA, increased cell proliferation, and decreased apoptosis. miR-125a-mediated down-regulation of ESRRA impaired anchorage-independent colony formation and invasion of OSCC cells. Reduced cell proliferation and increased apoptosis of OSCC cells were dependent on the presence of the 3′UTR in ESRRA. The delivery of an miR-125a mimic to OSCC cells resulted in marked regression of xenografts in nude mice, whereas the delivery of an miR-125a inhibitor to OSCC cells resulted in a significant increase of xenografts and abrogated the tumor suppressor function of miR-125a. We observed an inverse correlation between the expression levels of miR-125a and ESRRA in OSCC samples. In summary, up-regulation of ESRRA due to down-regulation of miR-125a is not only a novel mechanism for its up-regulation in OSCC, but decreasing the level of ESRRA by using a synthetic miR-125a mimic may have an important role in therapeutic intervention of OSCC and other cancers. PMID:25266720

  1. MicroRNA-125a reduces proliferation and invasion of oral squamous cell carcinoma cells by targeting estrogen-related receptor α: implications for cancer therapeutics.

    PubMed

    Tiwari, Ankana; Shivananda, Swamy; Gopinath, Kodaganur S; Kumar, Arun

    2014-11-14

    Estrogen-related receptor α (ESRRA) functions as a transcription factor and regulates the expression of several genes, such as WNT11 and OPN. Up-regulation of ESRRA has been reported in several cancers. However, the mechanism underlying its up-regulation is unclear. Furthermore, the reports regarding the role and regulation of ESRRA in oral squamous cell carcinoma (OSCC) are completely lacking. Here, we show that tumor suppressor miR-125a directly binds to the 3'UTR of ESRRA and represses its expression. Overexpression of miR-125a in OSCC cells drastically reduced the level of ESRRA, decreased cell proliferation, and increased apoptosis. Conversely, the delivery of an miR-125a inhibitor to these cells drastically increased the level of ESRRA, increased cell proliferation, and decreased apoptosis. miR-125a-mediated down-regulation of ESRRA impaired anchorage-independent colony formation and invasion of OSCC cells. Reduced cell proliferation and increased apoptosis of OSCC cells were dependent on the presence of the 3'UTR in ESRRA. The delivery of an miR-125a mimic to OSCC cells resulted in marked regression of xenografts in nude mice, whereas the delivery of an miR-125a inhibitor to OSCC cells resulted in a significant increase of xenografts and abrogated the tumor suppressor function of miR-125a. We observed an inverse correlation between the expression levels of miR-125a and ESRRA in OSCC samples. In summary, up-regulation of ESRRA due to down-regulation of miR-125a is not only a novel mechanism for its up-regulation in OSCC, but decreasing the level of ESRRA by using a synthetic miR-125a mimic may have an important role in therapeutic intervention of OSCC and other cancers.

  2. A reduced fraction of plant N derived from atmospheric N (%Ndfa) and reduced rhizobial nifH gene numbers indicate a lower capacity for nitrogen fixation in nodules of white clover exposed to long-term CO2 enrichment

    NASA Astrophysics Data System (ADS)

    Watanabe, T.; Bowatte, S.; Newton, P. C. D.

    2013-06-01

    Using the δ15N natural abundance method, we found that the fraction of nitrogen derived from atmospheric N (%Ndfa) in field grown white clover (Trifolium repens L.) plants was significantly lower (72.0% vs. 89.5%, p = 0.047 in a grassland exposed to elevated CO2 for 13 yr using Free Air Carbon Dioxide Enrichment (FACE). Twelve months later we conducted an experiment to investigate the reasons behind the reduced N fixation. We took cuttings from white clover plants growing in the FACE and established individual plants in a glasshouse using soil from the appropriate ambient or elevated CO2 treatments. The established plants were then transplanted back into their "rings of origin" and sampled over a 6 week period. We used molecular ecological analyses targeting nifH genes and transcripts of rhizobia in symbiosis with white clover (Trifolium repens L.) to understand the potential mechanisms. Shoot biomass was significantly lower in eCO2 but there was no difference in nodule number or mass per plant. The numbers of nifH genes and gene transcripts per nodule were significantly reduced under eCO2 but the ratio of gene to transcript number and the strains of rhizobia present were the same in both treatments. We conclude that the capacity for biological nitrogen fixation was reduced by eCO2 in white clover and was related to the reduced rhizobia numbers in nodules. We discuss the finding of reduced gene number in relation to factors controlling bacteroid DNA amount which may imply an influence of nitrogen as well as phosphorus.

  3. A reduced fraction of plant N derived from atmospheric N (%Ndfa) and reduced rhizobial nifH gene numbers indicate a lower capacity for nitrogen fixation in nodules of white clover exposed to long-term CO2 enrichment

    NASA Astrophysics Data System (ADS)

    Watanabe, T.; Bowatte, S.; Newton, P. C. D.

    2013-12-01

    Using the δ15N natural abundance method, we found that the fraction of nitrogen derived from atmospheric N (%Ndfa) in field-grown white clover (Trifolium repens L.) plants was significantly lower (72.0% vs. 89.8%, p = 0.047 in a grassland exposed to elevated CO2 for 13 yr using free air carbon dioxide enrichment (FACE). Twelve months later we conducted an experiment to investigate the reasons behind the reduced N fixation. We took cuttings from white clover plants growing in the FACE and established individual plants in a glasshouse using soil from the appropriate ambient or elevated CO2 treatments. The established plants were then transplanted back into their "rings of origin" and sampled over a 6-week period. We used molecular ecological analyses targeting nifH genes and transcripts of rhizobia in symbiosis with white clover (Trifolium repens L.) to understand the potential mechanisms. Shoot biomass was significantly lower in eCO2, but there was no difference in nodule number or mass per plant. The numbers of nifH genes and gene transcripts per nodule were significantly reduced under eCO2, but the ratio of gene to transcript number and the strains of rhizobia present were the same in both treatments. We conclude that the capacity for biological nitrogen fixation was reduced by eCO2 in white clover and was related to the reduced rhizobia numbers in nodules. We discuss the finding of reduced gene number in relation to factors controlling bacteroid DNA amount, which may imply an influence of nitrogen as well as phosphorus.

  4. Do low oxygen environments facilitate marine invasions? Relative tolerance of native and invasive species to low oxygen conditions.

    PubMed

    Lagos, Marcelo E; Barneche, Diego R; White, Craig R; Marshall, Dustin J

    2017-02-17

    Biological invasions are one of the biggest threats to global biodiversity. Marine artificial structures are proliferating worldwide and provide a haven for marine invasive species. Such structures disrupt local hydrodynamics, which can lead to the formation of oxygen-depleted microsites. The extent to which native fauna can cope with such low oxygen conditions, and whether invasive species, long associated with artificial structures in flow-restricted habitats, have adapted to these conditions remains unclear. We measured water flow and oxygen availability in marinas and piers at the scales relevant to sessile marine invertebrates (mm). We then measured the capacity of invasive and native marine invertebrates to maintain metabolic rates under decreasing levels of oxygen using standard laboratory assays. We found that marinas reduce water flow relative to piers, and that local oxygen levels can be zero in low flow conditions. We also found that for species with erect growth forms, invasive species can tolerate much lower levels of oxygen relative to native species. Integrating the field and laboratory data showed that up to 30% of available microhabitats within low flow environments are physiologically stressful for native species, while only 18% of the same habitat is physiologically stressful for invasive species. These results suggest that invasive species have adapted to low oxygen habitats associated with manmade habitats, and artificial structures may be creating niche opportunities for invasive species.

  5. Four weeks of speed endurance training reduces energy expenditure during exercise and maintains muscle oxidative capacity despite a reduction in training volume.

    PubMed

    Iaia, F Marcello; Hellsten, Ylva; Nielsen, Jens Jung; Fernström, Maria; Sahlin, Kent; Bangsbo, Jens

    2009-01-01

    We studied the effect of an alteration from regular endurance to speed endurance training on muscle oxidative capacity, capillarization, as well as energy expenditure during submaximal exercise and its relationship to mitochondrial uncoupling protein 3 (UCP3) in humans. Seventeen endurance-trained runners were assigned to either a speed endurance training (SET; n = 9) or a control (Con; n = 8) group. For a 4-wk intervention (IT) period, SET replaced the ordinary training ( approximately 45 km/wk) with frequent high-intensity sessions each consisting of 8-12 30-s sprint runs separated by 3 min of rest (5.7 +/- 0.1 km/wk) with additional 9.9 +/- 0.3 km/wk at low running speed, whereas Con continued the endurance training. After the IT period, oxygen uptake was 6.6, 7.6, 5.7, and 6.4% lower (P < 0.05) at running speeds of 11, 13, 14.5, and 16 km/h, respectively, in SET, whereas remained the same in Con. No changes in blood lactate during submaximal running were observed. After the IT period, the protein expression of skeletal muscle UCP3 tended to be higher in SET (34 +/- 6 vs. 47 +/- 7 arbitrary units; P = 0.06). Activity of muscle citrate synthase and 3-hydroxyacyl-CoA dehydrogenase, as well as maximal oxygen uptake and 10-km performance time, remained unaltered in both groups. In SET, the capillary-to-fiber ratio was the same before and after the IT period. The present study showed that speed endurance training reduces energy expenditure during submaximal exercise, which is not mediated by lowered mitochondrial UCP3 expression. Furthermore, speed endurance training can maintain muscle oxidative capacity, capillarization, and endurance performance in already trained individuals despite significant reduction in the amount of training.

  6. The p.R1819_C1948delinsS mutation makes von Willebrand factor ADAMTS13-resistant and reduces its collagen-binding capacity.

    PubMed

    Daidone, Viviana; Saga, Giorgia; Barbon, Giovanni; Pontara, Elena; Cattini, Maria G; Morpurgo, Margherita; Zanotti, Giuseppe; Casonato, Alessandra

    2015-08-01

    This report concerns abnormal ADAMTS13 (a disintegrin and metalloprotease with a thrombospondin type 1 motif, member 13) and collagen interactions coinciding with the p.R1819_C1948delinsS von Willebrand factor (VWF) mutation associated with the deletion of the C-terminus of the A3 domain (amino acids 1819-1947) in a patient with a history of bleeding. The von Willebrand disease (VWD) phenotype of the patient featured low plasma and platelet VWF, multimers with smears extending over the highest normal oligomers in plasma, but not platelets, and an impaired collagen-binding capacity. In vitro full-length p.R1819_C1948delinsS VWF expression showed impaired VWF release, increased cellular content with normally-multimerized VWF and impaired collagen binding. The recombinant p.R1819_C1948delinsS VWF fragment, extending from domains A2 to B3 (p.R1819_C1948delinsS A2-B3 VWF), was completely resistant to proteolysis by ADAMTS13 in the presence of 1·5 mol/l urea, unlike its normal counterpart. The defect stems from impaired ADAMTS13 binding to p.R1819_C1948delinsS A2-B3, analysed under static conditions. Partial deletion of the C-terminus of the A3 domain thus makes VWF resistant to ADAMTS13, interfering with ADAMTS13 binding to VWF, and impairing the collagen-binding capacity of VWF. The p.R1819_C1948delinsS mutation has both haemorrhagic features (defective collagen binding, reduced VWF levels) and prothrombotic (ADAMTS13 resistance) features, and the latter probably mitigate the patient's bleeding symptoms.

  7. Axitinib increases the infiltration of immune cells and reduces the suppressive capacity of monocytic MDSCs in an intracranial mouse melanoma model.

    PubMed

    Du Four, Stephanie; Maenhout, Sarah K; De Pierre, Kari; Renmans, Dries; Niclou, Simone P; Thielemans, Kris; Neyns, Bart; Aerts, Joeri L

    2015-04-01

    Melanoma patients are at a high risk of developing brain metastases, which are strongly vascularized and therefore have a significant risk of spontaneous bleeding. VEGF not only plays a role in neo-angiogenesis but also in the antitumor immune response. VEGFR-targeted therapy might not only have an impact on the tumor vascularization but also on tumor-infiltrating immune cells. In this study, we investigated the effect of axitinib, a small molecule TKI of VEGFR-1, -2, and -3, on tumor growth and on the composition of tumor-infiltrating immune cells in subcutaneous and intracranial mouse melanoma models. In vivo treatment with axitinib induced a strong inhibition of tumor growth and significantly improved survival in both tumor models. Characterization of the immune cells within the spleen and tumor of tumor-bearing mice respectively showed a significant increase in the number of CD3(+)CD8(+) T cells and CD11b(+) cells of axitinib-treated mice. More specifically, we observed a significant increase of intratumoral monocytic myeloid-derived suppressor cells (moMDSCs; CD11b(+)Ly6C(high)Ly6G(-)). Interestingly, in vitro proliferation assays showed that moMDSCs isolated from spleen or tumor of axitinib-treated mice had a reduced suppressive capacity on a per cell basis as compared to those isolated from vehicle-treated mice. Moreover, MDSCs from axitinib-treated animals displayed the capacity to stimulate allogeneic T cells. Thus, treatment with axitinib induces differentiation of moMDSC toward an antigen-presenting phenotype. Based on these observations, we conclude that the impact of axitinib on tumor growth and survival is most likely not restricted to direct anti-angiogenic effects but also involves important effects on tumor immunity.

  8. Reduced volume and increased training intensity elevate muscle Na+-K+ pump alpha2-subunit expression as well as short- and long-term work capacity in humans.

    PubMed

    Bangsbo, Jens; Gunnarsson, Thomas P; Wendell, Jesper; Nybo, Lars; Thomassen, Martin

    2009-12-01

    The present study examined muscle adaptations and alterations in work capacity in endurance-trained runners as a result of a reduced amount of training combined with speed endurance training. For a 6- to 9-wk period, 17 runners were assigned to either a speed endurance group with a 25% reduction in the amount of training but including speed endurance training consisting of six to twelve 30-s sprint runs 3-4 times/wk (SET group n = 12) or a control group (n = 5), which continued the endurance training ( approximately 55 km/wk). For the SET group, the expression of the muscle Na(+)-K(+) pump alpha(2)-subunit was 68% higher (P < 0.05) and the plasma K(+) level was reduced (P < 0.05) during repeated intense running after 9 wk. Performance in a 30-s sprint test and the first of the supramaximal exhaustive runs was improved (P < 0.05) by 7% and 36%, respectively, after the speed endurance training period. In the SET group, maximal O(2) uptake was unaltered, but the 3-km (3,000-m) time was reduced (P < 0.05) from 10.4 +/- 0.1 to 10.1 +/- 0.1 min and the 10-km (10,000-m) time was improved from 37.3 +/- 0.4 to 36.3 +/- 0.4 min (means +/- SE). Muscle protein expression and performance remained unaltered in the control group. The present data suggest that both short- and long-term exercise performances can be improved with a reduction in training volume if speed endurance training is performed and that the Na(+)-K(+) pump plays a role in the control of K(+) homeostasis and in the development of fatigue during repeated high-intensity exercise.

  9. Reduced parasite motility and micronemal protein secretion by a p38 MAPK inhibitor leads to a severe impairment of cell invasion by the apicomplexan parasite Eimeria tenella.

    PubMed

    Bussière, Françoise I; Brossier, Fabien; Le Vern, Yves; Niepceron, Alisson; Silvestre, Anne; de Sablet, Thibaut; Lacroix-Lamandé, Sonia; Laurent, Fabrice

    2015-01-01

    E. tenella infection is associated with a severe intestinal disease leading to high economic losses in poultry industry. Mitogen activated protein kinases (MAPKs) are implicated in early response to infection and are divided in three pathways: p38, extracellular signal-regulated protein kinase (ERK) and c-Jun N-terminal kinase (JNK). Our objective was to determine the importance of these kinases on cell invasion by E. tenella. We evaluated the effect of specific inhibitors (ERK: PD98059, JNKII: SP600125, p38 MAPK: SB203580) on the invasion of epithelial cells. Incubation of SP600125 and SB203580 with epithelial cells and parasites significantly inhibited cell invasion with the highest degree of inhibition (90%) for SB203580. Silencing of the host p38α MAPK expression by siRNA led to only 20% decrease in cell invasion. In addition, when mammalian epithelial cells were pre-treated with SB203580, and washed prior infection, a 30% decrease in cell invasion was observed. This decrease was overcome when a p38 MAPK activator, anisomycin was added during infection. This suggests an active but limited role of the host p38 MAPK in this process. We next determined whether SB203580 has a direct effect on the parasite. Indeed, parasite motility and secretion of micronemal proteins (EtMIC1, 2, 3 and 5) that are involved in cell invasion were both decreased in the presence of the inhibitor. After chasing the inhibitor, parasite motility and secretion of micronemal proteins were restored and subsequently cell invasion. SB203580 inhibits cell invasion by acting partly on the host cell and mainly on the parasite.

  10. Reduced Parasite Motility and Micronemal Protein Secretion by a p38 MAPK Inhibitor Leads to a Severe Impairment of Cell Invasion by the Apicomplexan Parasite Eimeria tenella

    PubMed Central

    Bussière, Françoise I.; Le Vern, Yves; Niepceron, Alisson; Silvestre, Anne; de Sablet, Thibaut; Lacroix-Lamandé, Sonia; Laurent, Fabrice

    2015-01-01

    E. tenella infection is associated with a severe intestinal disease leading to high economic losses in poultry industry. Mitogen activated protein kinases (MAPKs) are implicated in early response to infection and are divided in three pathways: p38, extracellular signal-regulated protein kinase (ERK) and c-Jun N-terminal kinase (JNK). Our objective was to determine the importance of these kinases on cell invasion by E. tenella. We evaluated the effect of specific inhibitors (ERK: PD98059, JNKII: SP600125, p38 MAPK: SB203580) on the invasion of epithelial cells. Incubation of SP600125 and SB203580 with epithelial cells and parasites significantly inhibited cell invasion with the highest degree of inhibition (90%) for SB203580. Silencing of the host p38α MAPK expression by siRNA led to only 20% decrease in cell invasion. In addition, when mammalian epithelial cells were pre-treated with SB203580, and washed prior infection, a 30% decrease in cell invasion was observed. This decrease was overcome when a p38 MAPK activator, anisomycin was added during infection. This suggests an active but limited role of the host p38 MAPK in this process. We next determined whether SB203580 has a direct effect on the parasite. Indeed, parasite motility and secretion of micronemal proteins (EtMIC1, 2, 3 and 5) that are involved in cell invasion were both decreased in the presence of the inhibitor. After chasing the inhibitor, parasite motility and secretion of micronemal proteins were restored and subsequently cell invasion. SB203580 inhibits cell invasion by acting partly on the host cell and mainly on the parasite. PMID:25689363

  11. Invasive Species

    EPA Pesticide Factsheets

    Invasive species have significantly changed the Great Lakes ecosystem. An invasive species is a plant or animal that is not native to an ecosystem, and whose introduction is likely to cause economic, human health, or environmental damage.

  12. Invasive Candidiasis

    MedlinePlus

    ... Invasive candidiasis is an infection caused by a yeast (a type of fungus) called Candida . Unlike Candida ... mouth and throat (also called “thrush”) or vaginal “yeast infections,” invasive candidiasis is a serious infection that ...

  13. Will inundation and salinity levels associated with projected sea level rise reduce the survival, growth, and reproductive capacity of Sarcocornia pacifica (pickleweed)?

    USGS Publications Warehouse

    Woo, I.; Takekawa, J.Y.

    2012-01-01

    In the San Francisco Bay Estuary, CA, USA, sea level rise (SLR) is projected to increase by 1.4 m during the next 90 years resulting in increased inundation and salt water intrusion up-estuary. Since inundation and salinity are critical factors that drive vegetation structure and composition in coastal wetlands, we asked whether inundation and salinity levels associated with SLR would reduce the survival, growth, and reproductive capacity of a dominant halophyte, Sarcocornia pacifica (pickleweed). We conducted a 4 × 4 factorial greenhouse experiment to examine the effects of a range of inundation periods (25, 50, 75, and 100%) and water salinities (0, 10, 20, 30 psu) on individual S. pacifica adults and seedlings. We found that inundation and salinity treatments affected the height of adults and seedlings combined. When examined separately, adult height was negatively affected by inundation ≥75%, while seedling height was affected by the interaction of both inundation and salinity. Adult belowground biomass was negatively affected by complete inundation. Seedling aboveground biomass decreased 46% at the highest salinity (30 psu) and belowground biomass decreased at salinities ≥20 psu. Adult flower production was not affected by treatments but was reduced by 38% at 30 psu salinity for seedlings. While adult survival was 99%, seedling survival was 56% with greatest mortality at low (25%) inundation, possibly because their roots were more susceptible to desiccation. Vegetation structure of the marsh platform comprised of S. pacifica adults will be susceptible to greater inundation rates associated with SLR. Our results suggest that adults may grow less tall, thus altering the vegetation structure and likely the tidal marsh wildlife that rely on these habitats.

  14. An electrochemical sensor for gallic acid based on Fe₂O₃/electro-reduced graphene oxide composite: Estimation for the antioxidant capacity index of wines.

    PubMed

    Gao, Feng; Zheng, Delun; Tanaka, Hidekazu; Zhan, Fengping; Yuan, Xiaoning; Gao, Fei; Wang, Qingxiang

    2015-12-01

    A highly sensitive electrochemical sensor for gallic acid (GA), an important polyphenolic compound, was fabricated using the hybrid material of chitosan (CS), fishbone-shaped Fe2O3 (fFe2O3), and electrochemically reduced graphene oxide (ERGO) as the sensing matrix. The electrochemical characterization experiments showed that the CS-fFe2O3-ERGO modified glassy carbon electrode (CS-fFe2O3-ERGO/GCE) had large surface area, excellent electronic conductivity and high stability. The GA presented a superior electrochemical response on CS-fFe2O3-ERGO/GCE in comparison with the single-component modified electrode. The electrochemical mechanism and optimal test conditions of GA on the electrode surface were carefully investigated. Under the optimal conditions, the oxidation peak currents in differential pulse voltammetry (DPV) experiments exhibited a good linear relationship with the logarithmic values of GA concentration over the range from 1.0×10(-6)M to 1.0×10(-4)M. Based on signal-to-noise (S/N) characteristic of 3, the detection limit was estimated to be 1.5×10(-7)M. The proposed sensor has also been applied for estimating the antioxidant capacity index of real samples of red and white wines.

  15. Effects of chitosan nanoparticle-mediated BRAF siRNA interference on invasion and metastasis of gastric cancer cells.

    PubMed

    Huo, Jian

    2016-08-01

    To observe the changes in invasion capacity of gastric cancer BGC823 cells after being treated with chitosan-encapsulated BRAF siRNA nanoparticles, and to evaluate the effects of the nanoparticle-mediated BRAF siRNA interference on cell invasion and metastasis, BRAF siRNA was encapsulated with chitosan into nanoparticles sized 350 nm to treat gastric cancer cells. Silencing of BRAF was detected by Western blot and PCR, and cell invasion was observed by the Transwell assay. The nanoparticles significantly downregulated BRAF expression in BGC823 cells (P < 0.01) and inhibited their invasion (P < 0.001). Chitosan nanoparticle-mediated BRAF siRNA interference evidently reduced the invasion capacity of gastric cancers.

  16. Induction of Wnt-inducible signaling protein-1 correlates with invasive breast cancer oncogenesis and reduced type 1 cell-mediated cytotoxic immunity: a retrospective study.

    PubMed

    Klinke, David J

    2014-01-01

    Innate and type 1 cell-mediated cytotoxic immunity function as important extracellular control mechanisms that maintain cellular homeostasis. Interleukin-12 (IL12) is an important cytokine that links innate immunity with type 1 cell-mediated cytotoxic immunity. We recently observed in vitro that tumor-derived Wnt-inducible signaling protein-1 (WISP1) exerts paracrine action to suppress IL12 signaling. The objective of this retrospective study was three fold: 1) to determine whether a gene signature associated with type 1 cell-mediated cytotoxic immunity was correlated with overall survival, 2) to determine whether WISP1 expression is increased in invasive breast cancer, and 3) to determine whether a gene signature consistent with inhibition of IL12 signaling correlates with WISP1 expression. Clinical information and mRNA expression for genes associated with anti-tumor immunity were obtained from the invasive breast cancer arm of the Cancer Genome Atlas study. Patient cohorts were identified using hierarchical clustering. The immune signatures associated with the patient cohorts were interpreted using model-based inference of immune polarization. Reverse phase protein array, tissue microarray, and quantitative flow cytometry in breast cancer cell lines were used to validate observed differences in gene expression. We found that type 1 cell-mediated cytotoxic immunity was correlated with increased survival in patients with invasive breast cancer, especially in patients with invasive triple negative breast cancer. Oncogenic transformation in invasive breast cancer was associated with an increase in WISP1. The gene expression signature in invasive breast cancer was consistent with WISP1 as a paracrine inhibitor of type 1 cell-mediated immunity through inhibiting IL12 signaling and promoting type 2 immunity. Moreover, model-based inference helped identify appropriate immune signatures that can be used as design constraints in genetically engineering better pre

  17. Hydroxyl radical scavenging assay of phenolics and flavonoids with a modified cupric reducing antioxidant capacity (CUPRAC) method using catalase for hydrogen peroxide degradation.

    PubMed

    Ozyürek, Mustafa; Bektaşoğlu, Burcu; Güçlü, Kubilay; Apak, Reşat

    2008-06-02

    Hydroxyl radicals (OH) generated in the human body may play an important role in tissue injury at sites of inflammation in oxidative stress-originated diseases. As a more convenient, efficient, and less costly alternative to HPLC/electrochemical detection techniques and to the nonspecific, low-yield deoxyribose (TBARS) test, we used a salicylate probe for detecting OH generated by the reaction of iron(II)-EDTA complex with H(2)O(2). The produced hydroxyl radicals attack both the salicylate probe and the hydroxyl radical scavengers that are incubated in solution for 10 min. Added radical scavengers compete with salicylate for the OH produced, and diminish chromophore formation from Cu(II)-neocuproine. At the end of the incubation period, the reaction was stopped by adding catalase. With the aid of this reaction, a kinetic approach was adopted to assess the hydroxyl radical scavenging properties of polyphenolics, flavonoids and other compounds (e.g., ascorbic acid, glucose, mannitol). A second-order rate constant for the reaction of the scavenger with OH could be deduced from the inhibition of colour formation due to the salicylate probe. In addition to phenolics and flavonoids, five kinds of herbs were evaluated for their OH scavenging activity using the developed method. The modified CUPRAC (cupric ion reducing antioxidant capacity) assay proved to be efficient for ascorbic acid, gallic acid and chlorogenic acid, for which the deoxyribose assay test is basically nonresponsive. An important contribution of this developed assay is the inhibition of the Fenton reaction with catalase degradation of hydrogen peroxide so that the remaining H(2)O(2) would neither give a CUPRAC absorbance nor involve in redox cycling of phenolic antioxidants, enabling the rapid assay of polyphenolics.

  18. Cognitive Control Links Alcohol Use, Trait Disinhibition, and Reduced Cognitive Capacity: Evidence for Medial Prefrontal Cortex Dysregulation during Reward-Seeking Behavior*

    PubMed Central

    Bogg, Tim; Fukunaga, Rena; Finn, Peter R.; Brown, Joshua W.

    2011-01-01

    Background Guided by the prediction of response-outcome theory of cognitive control (Alexander and Brown, 2010a), the present study examined reward-seeking medial prefrontal cortex (mPFC) activity as a common neuro-functional marker of excessive alcohol consumption, trait disinhibition, and reduced cognitive capacity; all of which have shown consistent patterns of covariation in previous psychometric research (e.g., Bogg and Finn, 2010). Methods A sample of 18-to-23-year-old university students with a heterogeneous prevalence of alcohol dependence was assessed with functional magnetic resonance imaging (fMRI) while completing a version of the Balloon Analogue Risk Task (Lejuez et al., 2002). A follow-back typical weekly alcohol consumption interview, self-report measures of trait disinhibition and IQ, and a complex span working memory task also were administered. Results Correlational region-of-interest analyses showed greater typical weekly alcohol consumption, greater trait disinhibition, and lower IQ were associated with greater reductions in mPFC activity during reward-seeking behaviors (successive inflation choices). The results also showed greater typical weekly alcohol consumption, greater trait disinhibition, and lower IQ were associated with greater increases in mPFC activity during reward-seeking outcomes (successive successful inflation outcomes). No significant relations with the measure of working memory were found. Conclusions The findings suggest mPFC activity during risk/reward appraisal and performance monitoring is a common neuro-functional feature of co-varying expressions of excessive alcohol consumption, trait disinhibition, and lower IQ. PMID:21992873

  19. Pharmacokinetics of perfluorobutane following intravenous bolus injection and continuous infusion of sonazoid in healthy volunteers and in patients with reduced pulmonary diffusing capacity.

    PubMed

    Landmark, Kristin Eitrem; Johansen, Per Wiik; Johnson, Judith A; Johansen, Bjørn; Uran, Steinar; Skotland, Tore

    2008-03-01

    The ultrasound contrast agent Sonazoidtrade mark was administered as an i.v. bolus injection of 0.6 microL microbubbles/kg body weight or as a continuous infusion over 30 min at a rate of 1.2 microL microbubbles/kg body weight to healthy volunteers and patients with reduced pulmonary diffusing capacity. Expired air and blood samples were collected from 32 subjects and perfluorobutane (PFB) gas was analyzed using validated gas chromatography mass spectrometry methods. Blood concentrations of PFB declined biphasicly with a distribution half-life (t(0.5 to 15)) of 2 to 3 min and an elimination half-life (t(15 to 120)) of 30 to 45 min. Area under the curve (AUC) values in patients with impaired gas diffusion were significantly larger than those in healthy volunteers. The exhalation kinetics were somewhat variable with a PFB elimination half-life (t(15 to 120)) of 28 to 111 min. Clearance of PFB was independent of study population and mode of administration. There were no deaths and no serious adverse events that resulted in the withdrawal of a subject from the study. With the exception that arthralgia predominated in healthy volunteers, healthy volunteers and diseased subjects did not show a different adverse event profile whether Sonazoid was administered as a bolus injection or as an infusion. Assessment of laboratory parameters (serum biochemistry, haematology and urinalysis), vital signs, oxygen saturation and electrocardiograms (ECGs) showed no changes which caused safety concern. (E-mail: Kristin.Landmark@ge.com).

  20. Increasing Working Memory Load Reduces Processing of Cross-Modal Task-Irrelevant Stimuli Even after Controlling for Task Difficulty and Executive Capacity

    PubMed Central

    Simon, Sharon S.; Tusch, Erich S.; Holcomb, Phillip J.; Daffner, Kirk R.

    2016-01-01

    The classic account of the load theory (LT) of attention suggests that increasing cognitive load leads to greater processing of task-irrelevant stimuli due to competition for limited executive resource that reduces the ability to actively maintain current processing priorities. Studies testing this hypothesis have yielded widely divergent outcomes. The inconsistent results may, in part, be related to variability in executive capacity (EC) and task difficulty across subjects in different studies. Here, we used a cross-modal paradigm to investigate whether augmented working memory (WM) load leads to increased early distracter processing, and controlled for the potential confounders of EC and task difficulty. Twenty-three young subjects were engaged in a primary visual WM task, under high and low load conditions, while instructed to ignore irrelevant auditory stimuli. Demands of the high load condition were individually titrated to make task difficulty comparable across subjects with differing EC. Event-related potentials (ERPs) were used to measure neural activity in response to stimuli presented in both the task relevant modality (visual) and task-irrelevant modality (auditory). Behavioral results indicate that the load manipulation and titration procedure of the primary visual task were successful. ERPs demonstrated that in response to visual target stimuli, there was a load-related increase in the posterior slow wave, an index of sustained attention and effort. Importantly, under high load, there was a decrease of the auditory N1 in response to distracters, a marker of early auditory processing. These results suggest that increased WM load is associated with enhanced attentional engagement and protection from distraction in a cross-modal setting, even after controlling for task difficulty and EC. Our findings challenge the classic LT and offer support for alternative models. PMID:27536226

  1. Increasing Working Memory Load Reduces Processing of Cross-Modal Task-Irrelevant Stimuli Even after Controlling for Task Difficulty and Executive Capacity.

    PubMed

    Simon, Sharon S; Tusch, Erich S; Holcomb, Phillip J; Daffner, Kirk R

    2016-01-01

    The classic account of the load theory (LT) of attention suggests that increasing cognitive load leads to greater processing of task-irrelevant stimuli due to competition for limited executive resource that reduces the ability to actively maintain current processing priorities. Studies testing this hypothesis have yielded widely divergent outcomes. The inconsistent results may, in part, be related to variability in executive capacity (EC) and task difficulty across subjects in different studies. Here, we used a cross-modal paradigm to investigate whether augmented working memory (WM) load leads to increased early distracter processing, and controlled for the potential confounders of EC and task difficulty. Twenty-three young subjects were engaged in a primary visual WM task, under high and low load conditions, while instructed to ignore irrelevant auditory stimuli. Demands of the high load condition were individually titrated to make task difficulty comparable across subjects with differing EC. Event-related potentials (ERPs) were used to measure neural activity in response to stimuli presented in both the task relevant modality (visual) and task-irrelevant modality (auditory). Behavioral results indicate that the load manipulation and titration procedure of the primary visual task were successful. ERPs demonstrated that in response to visual target stimuli, there was a load-related increase in the posterior slow wave, an index of sustained attention and effort. Importantly, under high load, there was a decrease of the auditory N1 in response to distracters, a marker of early auditory processing. These results suggest that increased WM load is associated with enhanced attentional engagement and protection from distraction in a cross-modal setting, even after controlling for task difficulty and EC. Our findings challenge the classic LT and offer support for alternative models.

  2. Membrane Vesicles Released by a hypervesiculating Escherichia coli Nissle 1917 tolR Mutant Are Highly Heterogeneous and Show Reduced Capacity for Epithelial Cell Interaction and Entry

    PubMed Central

    Pérez-Cruz, Carla; Cañas, María-Alexandra; Giménez, Rosa; Badia, Josefa; Mercade, Elena; Aguilera, Laura

    2016-01-01

    Membrane vesicles (MVs) produced by Gram-negative bacteria are being explored for novel clinical applications due to their ability to deliver active molecules to distant host cells, where they can exert immunomodulatory properties. MVs released by the probiotic Escherichia coli Nissle 1917 (EcN) are good candidates for testing such applications. However, a drawback for such studies is the low level of MV isolation from in vitro culture supernatants, which may be overcome by the use of mutants in cell envelope proteins that yield a hypervesiculation phenotype. Here, we confirm that a tolR mutation in EcN increases MV production, as determined by protein, LPS and fluorescent lipid measurements. Transmission electron microscopy (TEM) of negatively stained MVs did not reveal significant differences with wild type EcN MVs. Conversely, TEM observation after high-pressure freezing followed by freeze substitution of bacterial samples, together with cryo-TEM observation of plunge-frozen hydrated isolated MVs showed considerable structural heterogeneity in the EcN tolR samples. In addition to common one-bilayer vesicles (OMVs) and the recently described double-bilayer vesicles (O-IMVs), other types of MVs were observed. Time-course experiments of MV uptake in Caco-2 cells using rhodamine- and DiO-labelled MVs evidenced that EcN tolR MVs displayed reduced internalization levels compared to the wild-type MVs. The low number of intracellular MVs was due to a lower cell binding capacity of the tolR-derived MVs, rather than a different entry pathway or mechanism. These findings indicate that heterogeneity of MVs from tolR mutants may have a major impact on vesicle functionality, and point to the need for conducting a detailed structural analysis when MVs from hypervesiculating mutants are to be used for biotechnological applications. PMID:28036403

  3. Effect of pH buffering capacity and sources of dietary sulfur on rumen fermentation, sulfide production, methane production, sulfate reducing bacteria, and total Archaea in in vitro rumen cultures.

    PubMed

    Wu, Hao; Meng, Qingxiang; Yu, Zhongtang

    2015-06-01

    The effects of three types of dietary sulfur on in vitro fermentation characteristics, sulfide production, methane production, and microbial populations at two different buffer capacities were examined using in vitro rumen cultures. Addition of dry distilled grain with soluble (DDGS) generally decreased total gas production, degradation of dry matter and neutral detergent fiber, and concentration of total volatile fatty acids, while increasing ammonia concentration. High buffering capacity alleviated these adverse effects on fermentation. Increased sulfur content resulted in decreased methane emission, but total Archaea population was not changed significantly. The population of sulfate reducing bacteria was increased in a sulfur type-dependent manner. These results suggest that types of dietary sulfur and buffering capacity can affect rumen fermentation and sulfide production. Diet buffering capacity, and probably alkalinity, may be increased to alleviate some of the adverse effects associated with feeding DDGS at high levels.

  4. Therapeutic potential for phenytoin: targeting Na(v)1.5 sodium channels to reduce migration and invasion in metastatic breast cancer.

    PubMed

    Yang, Ming; Kozminski, David J; Wold, Lindsey A; Modak, Rohan; Calhoun, Jeffrey D; Isom, Lori L; Brackenbury, William J

    2012-07-01

    Voltage-gated Na(+) channels (VGSCs) are heteromeric membrane protein complexes containing pore-forming α subunits and smaller, non-pore-forming β subunits. VGSCs are classically expressed in excitable cells, including neurons and muscle cells, where they mediate action potential firing, neurite outgrowth, pathfinding, and migration. VGSCs are also expressed in metastatic cells from a number of cancers. The Na(v)1.5 α subunit (encoded by SCN5A) is expressed in breast cancer (BCa) cell lines, where it enhances migration and invasion. We studied the expression of SCN5A in BCa array data, and tested the effect of the VGSC-blocking anticonvulsant phenytoin (5,5-diphenylhydantoin) on Na(+) current, migration, and invasion in BCa cells. SCN5A was up-regulated in BCa samples in several datasets, and was more highly expressed in samples from patients who had a recurrence, metastasis, or died within 5 years. SCN5A was also overexpressed as an outlier in a subset of samples, and associated with increased odds of developing metastasis. Phenytoin inhibited transient and persistent Na(+) current recorded from strongly metastatic MDA-MB-231 cells, and this effect was more potent at depolarized holding voltages. It may thus be an effective VGSC-blocking drug in cancer cells, which typically have depolarized membrane potentials. At a concentration within the therapeutic range used to treat epilepsy, phenytoin significantly inhibited the migration and invasion of MDA-MB-231 cells, but had no effect on weakly metastatic MCF-7 cells, which do not express Na(+) currents. We conclude that phenytoin suppresses Na(+) current in VGSC-expressing metastatic BCa cells, thus inhibiting VGSC-dependent migration and invasion. Together, our data support the hypothesis that SCN5A is up-regulated in BCa, favoring an invasive/metastatic phenotype. We therefore propose that repurposing existing VGSC-blocking therapeutic drugs should be further investigated as a potential new strategy to improve

  5. Successful approaches for battling invasive species in developed countries

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Biological invasions increasingly threaten natural resources and reduce biological diversity worldwide. To curtail biological invasions, developed countries have adopted multitire approaches that systematically address the process of invasion, encompassing introduction, establishment, spread and nat...

  6. Inhibition of ADP-ribosylation factor-like 6 interacting protein 1 suppresses proliferation and reduces tumor cell invasion in CaSki human cervical cancer cells.

    PubMed

    Guo, Fengjie; Liu, Yan; Li, Yalin; Li, Guancheng

    2010-12-01

    ADP-ribosylation factor-like 6 interacting protein 1 (ARL6IP1) is an apoptotic regulator. To investigate the role of ARL6IP1 in human cervical cancer progression, we designed and used short hairpin RNA (shRNA) to inhibit ARL6IP1 expression in CaSki cells and validated its effect on cell proliferation and invasion. Changes in gene expression were analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR) or western blot. Down-regulation of ARL6IP1 expression by infection with ARL6IP1-specific RNAi-expressing vector inhibited CaSki cell proliferation and colony formation. In addition, down-regulation of ARL6IP1 expression arrested CaSki cell cycling at the G0/G1 phase and mitigated CaSki cell migration, determined by wound healing assays. ARL6IP1 was involved in cervical cancer cell growth, cell cycle progression, and invasion through regulation of gene expression, such as Caspase-3, Caspase-9, p53, TAp63, NF-κB, MAPK, Bcl-2, and Bcl-xL, suggesting that ARL6IP1 could have important implications in cervical cancer biology. Our findings illustrate the biological significance of ARL6IP1 in cervical cancer progression, and provide novel evidence that ARL6IP1 may serve as a therapeutic target in the prevention of human cervical cancer.

  7. Reduced Need for Rescue Antiemetics and Improved Capacity to Eat in Patients Receiving Acupuncture Compared to Patients Receiving Sham Acupuncture or Standard Care during Radiotherapy

    PubMed Central

    Steineck, Gunnar; Börjeson, Sussanne

    2017-01-01

    Objective. To evaluate if consumption of emesis-related care and eating capacity differed between patients receiving verum acupuncture, sham acupuncture, or standard care only during radiotherapy. Methods. Patients were randomized to verum (n = 100) or sham (n = 100) acupuncture (telescopic blunt sham needle) (median 12 sessions) and registered daily their consumption of antiemetics and eating capacity. A standard care group (n = 62) received standard care only and delivered these data once. Results. More patients in the verum (n = 73 of 89 patients still undergoing radiotherapy; 82%, Relative Risk (RR) 1.23, 95% Confidence Interval (CI) 1.01–1.50) and the sham acupuncture group (n = 79 of 95; 83%, RR 1.24, CI 1.03–1.52) did not need any antiemetic medications, as compared to the standard care group (n = 42 out of 63; 67%) after receiving 27 Gray dose of radiotherapy. More patients in the verum (n = 50 of 89; 56%, RR 1.78, CI 1.31–2.42) and the sham acupuncture group (n = 58 of 94 answering patients; 62%, RR 1.83, CI 1.20–2.80) were capable of eating as usual, compared to the standard care group (n = 20 of 63; 39%). Conclusion. Patients receiving acupuncture had lower consumption of antiemetics and better eating capacity than patients receiving standard antiemetic care, plausible by nonspecific effects of the extra care during acupuncture. PMID:28270851

  8. Dual Role of Signaling Pathways Leading to Ca2+ and Cyclic AMP Elevation in Host Cell Invasion by Trypanosoma cruzi

    PubMed Central

    Caler, Elisabet V.; Morty, Rory E.; Burleigh, Barbara A.; Andrews, Norma W.

    2000-01-01

    Cell invasion by the protozoan parasite Trypanosoma cruzi involves activation of host signaling pathways and the recruitment and fusion of lysosomes at the parasite entry site. A major signaling pathway regulating invasion of fibroblasts, epithelial cells, and myoblasts involves mobilization of Ca2+ from intracellular stores and requires the activity of a T. cruzi serine peptidase, oligopeptidase B (OPB). Deletion of the OPB gene results in a marked defect in trypomastigote virulence, consistent with a greatly reduced cell invasion capacity. Here we show that uptake by macrophages, on the other hand, is largely independent of OPB expression and sensitive to inhibition of by cytochalasin D. The residual invasion capacity of OPBnull trypomastigotes in fibroblasts still involves lysosome recruitment, although in a significantly delayed fashion. Transient elevations in intracellular Ca2+ concentrations were observed in host cells exposed to both wild-type and OPBnull trypomastigotes, but the signals triggered by the mutant parasites were less vigorous and delayed. The capacity of triggering elevation in host cell cyclic AMP (cAMP), however, was unaltered in OPBnull trypomastigotes. Modulation in cAMP levels preferentially affected the residual cell invasion capacity of OPBnull parasites, suggesting that this signaling pathway can play a dominant role in promoting cell invasion in the absence of the major OPB-dependent pathway. PMID:11083771

  9. Randomized Noninferiority Trial of Reduced High-Dose Volume Versus Standard Volume Radiation Therapy for Muscle-Invasive Bladder Cancer: Results of the BC2001 Trial (CRUK/01/004)

    SciTech Connect

    Huddart, Robert A.; Hall, Emma; Hussain, Syed A.; Jenkins, Peter; Rawlings, Christine; Tremlett, Jean; Crundwell, Malcolm; Adab, Fawzi A.; Sheehan, Denise; Syndikus, Isabel; Hendron, Carey; Lewis, Rebecca; Waters, Rachel; James, Nicholas D.

    2013-10-01

    Purpose: To test whether reducing radiation dose to uninvolved bladder while maintaining dose to the tumor would reduce side effects without impairing local control in the treatment of muscle-invasive bladder cancer. Methods and Materials: In this phase III multicenter trial, 219 patients were randomized to standard whole-bladder radiation therapy (sRT) or reduced high-dose volume radiation therapy (RHDVRT) that aimed to deliver full radiation dose to the tumor and 80% of maximum dose to the uninvolved bladder. Participants were also randomly assigned to receive radiation therapy alone or radiation therapy plus chemotherapy in a partial 2 × 2 factorial design. The primary endpoints for the radiation therapy volume comparison were late toxicity and time to locoregional recurrence (with a noninferiority margin of 10% at 2 years). Results: Overall incidence of late toxicity was less than predicted, with a cumulative 2-year Radiation Therapy Oncology Group grade 3/4 toxicity rate of 13% (95% confidence interval 8%, 20%) and no statistically significant differences between groups. The difference in 2-year locoregional recurrence free rate (RHDVRT − sRT) was 6.4% (95% confidence interval −7.3%, 16.8%) under an intention to treat analysis and 2.6% (−12.8%, 14.6%) in the “per-protocol” population. Conclusions: In this study RHDVRT did not result in a statistically significant reduction in late side effects compared with sRT, and noninferiority of locoregional control could not be concluded formally. However, overall low rates of clinically significant toxicity combined with low rates of invasive bladder cancer relapse confirm that (chemo)radiation therapy is a valid option for the treatment of muscle-invasive bladder cancer.

  10. GeOx/Reduced Graphene Oxide Composite as an Anode for Li-ion Batteries: Enhanced Capacity via Reversible Utilization of Li2O along with Improved Rate Performance

    SciTech Connect

    Lv, Dongping; Gordin, Mikhail; Yi, Ran; Xu, Terrence; Song, Jiangxuan; Jiang, Yingbing; Choi, Daiwon; Wang, Donghai

    2014-09-01

    A self-assembled GeOx/reduced graphene oxide (GeOx/RGO) composite, where GeOx nanoparticles were grown directly on reduced graphene oxide sheets, was synthesized via a facile one-step reduction approach and studied by X-ray diffraction, transmission electron microscopy, energy dispersive X-ray spectroscopy, electron energy loss spectroscopy elemental mapping, and other techniques. Electrochemical evaluation indicates that incorporation of reduced graphene oxide enhances both the rate capability and reversible capacity of GeOx, with the latter being due to the RGO enabling reversible utilization of Li2O. The composite delivers a high reversible capacity of 1600 mAhg-1 at a current density of 100 mAg-1, and still maintains a capacity of 410 mAhg-1 at a high current density of 20 Ag-1. Owing to the flexible reduced graphene oxide sheets enwrapping the GeOx particles, the cycling stability of the composite was also improved significantly. To further demonstrate its feasibility in practical applications, the synthesized GeOx/RGO composite anode was successfully paired with a high voltage LiNi0.5Mn1.5O4 cathode to form a full cell, which showed good cycling and rate performance.

  11. High concentrations of polycyclic aromatic hydrocarbons (naphthalene, phenanthrene and pyrene) failed to explain biochar's capacity to reduce soil nitrous oxide emissions.

    PubMed

    Alburquerque, J A; Sánchez-Monedero, M A; Roig, A; Cayuela, M L

    2015-01-01

    The presence of polycyclic aromatic hydrocarbons (PAHs) has been postulated as a mechanism by which biochar might mitigate N(2)O emissions. We studied whether and to what extent N(2)O emissions were influenced by the three most abundant PAHs in biochar: naphthalene, phenanthrene and pyrene. We hypothesised that biochars contaminated with PAHs would show a larger N(2)O mitigation capacity and that increasing PAH concentrations in biochar would lead to higher mitigation potentials. Our results demonstrate that the high-temperature biochar (550 °C) had a higher capacity to mitigate soil N(2)O emissions than the low-temperature biochar (350 °C). At low PAH concentrations, PAHs do not significantly contribute to the reductions in soil N(2)O emissions; while biochar stimulated soil N(2)O emissions when it was spiked with high concentrations of PAHs. This study suggests that the impact of biochar on soil N(2)O emissions is due to other compositional and/or structural properties of biochar rather than to PAH concentration.

  12. Germination and extrusion as combined processes for reducing phytates and increasing phenolics content and antioxidant capacity of Oryza sativa L. whole grain flours.

    PubMed

    Albarracín, M; De Greef, D M; González, R J; Drago, S R

    2015-01-01

    Whole rice (WR) products with low phytic acid (PA) content and enhanced bio-functional components were obtained by the combination of germination and extrusion processes. Germination conditions (24 h - 35 °C), with a previous soaking process (24 h - 20 °C), were chosen according to the remnant PA content and germination rate. Specific mechanical energy consumption, expansion, sensorial and mechanical hardness, specific volume, solubility, water absorption, free phenolic content (FPC) and antioxidant capacity were evaluated. Results indicated that 175 °C and 14 g 100 g(-1) of moisture were the most appropriate conditions to obtain expanded products and precooked flours based on germinated WR. Selected extruded product presented less PA content (821.6 9 ± 10.3 versus 695.2 0 ± 1.6 mg 100 g(-1)) and higher Fe bio-accessibility, FPC (45.2 9 ± 1.61 versus 66.3 5 ± 3.35 mg GAE g(-1)) and antioxidant capacity compared with WR (34.9 5 ± 0.8 versus 54.6 3 ± 1.6 µmol trolox g(-1)). Combining germination-extrusion processes could be a strategy to obtain expanded products or precooked flours based on WR with enhanced health benefits.

  13. Sequential elution liquid chromatography can significantly increase the probability of a successful separation by simultaneously increasing the peak capacity and reducing the separation disorder.

    PubMed

    Socia, Adam; Foley, Joe P

    2014-01-10

    This paper demonstrates that sequential elution liquid chromatography (SE-LC), an approach in which two or more elution modes are employed in series for the separation of two or more groups of compounds, can be used to separate not only weak acids (or weak bases) from neutral compounds, but weak acids and weak bases from neutral compounds (and each other) by the sequential application of either of two types of an extended pH gradient prior to a solvent gradient. It also details a comparison, based on peak capacity and separation disorder, of the probability of success of this approach with the unimodal elution approach taken by conventional column liquid chromatography. For an HPLC peak capacity of 120 and samples of moderate complexity (e.g., 12 components), the probability of success (Rs≥1) increases from 37.9% (HPLC) to 85.8% (SE-LC). Different columns were evaluated for their utility for SE-LC using the following criteria: (1) the prediction of the elution order of the groups based on the degree of ionization of the compounds; and (2) the closeness of the peak shape to the ideal Gaussian distribution. The best columns overall were the Zorbax SB-AQ and Waters XBridge Shield columns, as they provided both between-class and within-class separations of all compounds, as well as the lowest degree of tailing of 4-ethylaniline using the pH 2 to pH 8 gradient.

  14. An impaired health related muscular fitness contributes to a reduced walking capacity in patients with schizophrenia: a cross-sectional study

    PubMed Central

    2013-01-01

    Background Patients with schizophrenia report muscle weakness. The relation of this muscle weakness with performing daily life activities such as walking is however not yet studied. The aim of this study was to quantify walking capacity and health related muscular fitness in patients with schizophrenia compared with age-, gender and body mass index (BMI)-matched healthy controls. Secondly, we identified variables that could explain the variability in walking capacity and in health related muscular fitness in patients with schizophrenia. Methods A total of 100 patients with schizophrenia and 40 healthy volunteers were initially screened. Eighty patients with schizophrenia (36.8±10.0 years) and the 40 age-, gender- and body mass index (BMI)-matched healthy volunteers (37.1±10.3 years) were finally included. All participants performed a standing broad jump test (SBJ) and a six-minute walk test (6MWT) and filled out the International Physical Activity Questionnaire. Patients additionally had a fasting metabolic laboratory screening and were assessed for psychiatric symptoms. Results Patients with schizophrenia did have lower 6MWT (17.9%, p<0.001) [effect size (ES)=−1.01] and SBJ (14.1%, p<0.001) (ES=−0.57) scores. Patients were also less physically active (1291.0±1201.8 metabolic equivalent-minutes/week versus 2463.1±1365.3, p<0.001) (ES=−0.91) than controls. Schizophrenia patients with metabolic syndrome (MetS) (35%) had a 23.9% lower (p<0.001) SBJ-score and 22.4% (p<0.001) lower 6MWT-score than those without MetS. In multiple regression analysis, 71.8% of the variance in 6MWT was explained by muscular fitness, BMI, presence of MetS and physical activity participation, while 53.9% of the variance in SBJ-score was explained by age, illness duration, BMI and physical activity participation. Conclusions The walking capacity and health-related muscular fitness are impaired in patients with schizophrenia and both should be a major focus in daily clinical practice

  15. Invasive Candidiasis.

    PubMed

    McCarty, Todd P; Pappas, Peter G

    2016-03-01

    Invasive candidiasis is a collective term that refers to a group of infectious syndromes caused by a variety of species of Candida, 5 of which cause most cases. Candidemia is the most commonly recognized syndrome associated with invasive candidiasis. Certain conditions may influence the likelihood for one species versus another in a specific clinical scenario, and this can have important implications for selection of antifungal therapy and the duration of treatment. Molecular diagnostic technology plays an ever-increasing role as an adjunct to traditional culture-based diagnostics, offering significant potential toward improvement in patient care.

  16. CONSERVATION PROGRAMS THAT PROMOTE INVASIVE SPECIES

    EPA Science Inventory

    Invasive plant species are degrading the structure and function of ecosystems throughout the world. Although most state and federal conservation agencies in the U.S. attempt to reduce the impact of invasive species, some agency activities can contribute to the spread of invasive...

  17. Degradative capacities and 16S rRNA-targeted whole-cell hybridization of sulfate-reducing bacteria in an anaerobic enrichment culture utilizing alkylbenzenes from crude oil

    SciTech Connect

    Rabus, R.; Widdel, F.; Fukui, Manabu

    1996-10-01

    Production of sulfide in oil field waters, a process which is referred to as souring, has been of concern. Hydrogen sulfide may lead to poisoning, contamination of oil and gas, corrosion of pipelines, conversion of iron mineral to ferrous sulfide. This study used a previously established sulfate-reducing enrichment culture on crude oil as a model system of bacterial habitats in which crude oil is the only potential source of organic substrates, and the enrichment culture was studied in detail including substrate preferences and major nutritional types of sulfate-reducing bacteria in the enrichment culture. 74 refs., 2 figs., 2 tabs.

  18. Minimally invasive procedures

    PubMed Central

    Baltayiannis, Nikolaos; Michail, Chandrinos; Lazaridis, George; Anagnostopoulos, Dimitrios; Baka, Sofia; Mpoukovinas, Ioannis; Karavasilis, Vasilis; Lampaki, Sofia; Papaiwannou, Antonis; Karavergou, Anastasia; Kioumis, Ioannis; Pitsiou, Georgia; Katsikogiannis, Nikolaos; Tsakiridis, Kosmas; Rapti, Aggeliki; Trakada, Georgia; Zissimopoulos, Athanasios; Zarogoulidis, Konstantinos

    2015-01-01

    Minimally invasive procedures, which include laparoscopic surgery, use state-of-the-art technology to reduce the damage to human tissue when performing surgery. Minimally invasive procedures require small “ports” from which the surgeon inserts thin tubes called trocars. Carbon dioxide gas may be used to inflate the area, creating a space between the internal organs and the skin. Then a miniature camera (usually a laparoscope or endoscope) is placed through one of the trocars so the surgical team can view the procedure as a magnified image on video monitors in the operating room. Specialized equipment is inserted through the trocars based on the type of surgery. There are some advanced minimally invasive surgical procedures that can be performed almost exclusively through a single point of entry—meaning only one small incision, like the “uniport” video-assisted thoracoscopic surgery (VATS). Not only do these procedures usually provide equivalent outcomes to traditional “open” surgery (which sometimes require a large incision), but minimally invasive procedures (using small incisions) may offer significant benefits as well: (I) faster recovery; (II) the patient remains for less days hospitalized; (III) less scarring and (IV) less pain. In our current mini review we will present the minimally invasive procedures for thoracic surgery. PMID:25861610

  19. Nanofluid heat capacities

    NASA Astrophysics Data System (ADS)

    Starace, Anne K.; Gomez, Judith C.; Wang, Jun; Pradhan, Sulolit; Glatzmaier, Greg C.

    2011-12-01

    Significant increases in the heat capacity of heat transfer fluids are needed not only to reduce the costs of liquid heating and cooling processes, but also to bring clean energy producing technologies like concentrating solar power (CSP) to price parity with conventional energy generation. It has been postulated that nanofluids could have higher heat capacities than conventional fluids. In this work, nano- and micron-sized particles were added to five base fluids (poly-α olefin, mineral oil, ethylene glycol, a mixture of water and ethylene glycol, and calcium nitrate tetrahydrate), and the resulting heat capacities were measured and compared with those of the neat base fluids and the weighted average of the heat capacities of the components. The particles used were inert metals and metal oxides that did not undergo any phase transitions over the temperature range studied. In the nanofluids studied here, we found no increase in heat capacity upon the addition of the particles larger than the experimental error.

  20. Patients with knee osteoarthritis demonstrate improved gait pattern and reduced pain following a non-invasive biomechanical therapy: a prospective multi-centre study on Singaporean population

    PubMed Central

    2014-01-01

    Background Previous studies have shown the effect of a unique therapy with a non-invasive biomechanical foot-worn device (AposTherapy) on Caucasian western population suffering from knee osteoarthritis. The purpose of the current study was to evaluate the effect of this therapy on the level of symptoms and gait patterns in a multi-ethnic Singaporean population suffering from knee osteoarthritis. Methods Fifty-eight patients with bilateral medial compartment knee osteoarthritis participated in the study. All patients underwent a computerized gait test and completed two self-assessment questionnaires (WOMAC and SF-36). The biomechanical device was calibrated to each patient, and therapy commenced. Changes in gait patterns and self-assessment questionnaires were reassessed after 3 and 6 months of therapy. Results A significant improvement was seen in all of the gait parameters following 6 months of therapy. Specifically, gait velocity increased by 15.9%, step length increased by 10.3%, stance phase decreased by 5.9% and single limb support phase increased by 2.7%. In addition, pain, stiffness and functional limitation significantly decreased by 68.3%, 66.7% and 75.6%, respectively. SF-36 physical score and mental score also increased significantly following 6 months of therapy (46.1% and 22.4%, respectively) (P < 0.05 for all parameters). Conclusions Singaporean population with medial compartment knee osteoarthritis demonstrated improved gait patterns, reported alleviation in symptoms and improved function and quality of life following 6 months of therapy with a unique biomechanical device. Trial registration Registration number NCT01562652. PMID:24383821

  1. Discriminating the drivers of edge effects on nest predation: forest edges reduce capture rates of ship rats (Rattus rattus), a globally invasive nest predator, by altering vegetation structure.

    PubMed

    Ruffell, Jay; Didham, Raphael K; Barrett, Paul; Gorman, Nic; Pike, Rhonda; Hickey-Elliott, Andrée; Sievwright, Karin; Armstrong, Doug P

    2014-01-01

    Forest edges can strongly affect avian nest success by altering nest predation rates, but this relationship is inconsistent and context dependent. There is a need for researchers to improve the predictability of edge effects on nest predation rates by examining the mechanisms driving their occurrence and variability. In this study, we examined how the capture rates of ship rats, an invasive nest predator responsible for avian declines globally, varied with distance from the forest edge within forest fragments in a pastoral landscape in New Zealand. We hypothesised that forest edges would affect capture rates by altering vegetation structure within fragments, and that the strength of edge effects would depend on whether fragments were grazed by livestock. We measured vegetation structure and rat capture rates at 488 locations ranging from 0-212 m from the forest edge in 15 forest fragments, seven of which were grazed. Contrary to the vast majority of previous studies of edge effects on nest predation, ship rat capture rates increased with increasing distance from the forest edge. For grazed fragments, capture rates were estimated to be 78% lower at the forest edge than 118 m into the forest interior (the farthest distance for grazed fragments). This relationship was similar for ungrazed fragments, with capture rates estimated to be 51% lower at the forest edge than 118 m into the forest interior. A subsequent path analysis suggested that these 'reverse' edge effects were largely or entirely mediated by changes in vegetation structure, implying that edge effects on ship rats can be predicted from the response of vegetation structure to forest edges. We suggest the occurrence, strength, and direction of edge effects on nest predation rates may depend on edge-driven changes in local habitat when the dominant predator is primarily restricted to forest patches.

  2. Fusicoccin A, a Phytotoxic Carbotricyclic Diterpene Glucoside of Fungal Origin, Reduces Proliferation and Invasion of Glioblastoma Cells by Targeting Multiple Tyrosine Kinases1

    PubMed Central

    Bury, Marina; Andolfi, Anna; Rogister, Bernard; Cimmino, Alessio; Mégalizzi, Véronique; Mathieu, Véronique; Feron, Olivier; Evidente, Antonio; Kiss, Robert

    2013-01-01

    Glioblastoma multiforme (GBM) is a deadly cancer that possesses an intrinsic resistance to pro-apoptotic insults, such as conventional chemotherapy and radiotherapy, and diffusely invades the brain parenchyma, which renders it elusive to total surgical resection. We found that fusicoccin A, a fungal metabolite from Fusicoccum amygdali, decreased the proliferation and migration of human GBM cell lines in vitro, including several cell lines that exhibit varying degrees of resistance to pro-apoptotic stimuli. The data demonstrate that fusicoccin A inhibits GBM cell proliferation by decreasing growth rates and increasing the duration of cell division and also decreases two-dimensional (measured by quantitative video microscopy) and three-dimensional (measured by Boyden chamber assays) migration. These effects of fusicoccin A treatment translated into structural changes in actin cytoskeletal organization and a loss of GBM cell adhesion. Therefore, fusicoccin A exerts cytostatic effects but low cytotoxic effects (as demonstrated by flow cytometry). These cytostatic effects can partly be explained by the fact that fusicoccin inhibits the activities of a dozen kinases, including focal adhesion kinase (FAK), that have been implicated in cell proliferation and migration. Overexpression of FAK, a nonreceptor protein tyrosine kinase, directly correlates with the invasive phenotype of aggressive human gliomas because FAK promotes cell proliferation and migration. Fusicoccin A led to the down-regulation of FAK tyrosine phosphorylation, which occurred in both normoxic and hypoxic GBM cell culture conditions. In conclusion, the current study identifies a novel compound that could be used as a chemical template for generating cytostatic compounds designed to combat GBM. PMID:23544164

  3. Fusicoccin a, a phytotoxic carbotricyclic diterpene glucoside of fungal origin, reduces proliferation and invasion of glioblastoma cells by targeting multiple tyrosine kinases.

    PubMed

    Bury, Marina; Andolfi, Anna; Rogister, Bernard; Cimmino, Alessio; Mégalizzi, Véronique; Mathieu, Véronique; Feron, Olivier; Evidente, Antonio; Kiss, Robert

    2013-04-01

    Glioblastoma multiforme (GBM) is a deadly cancer that possesses an intrinsic resistance to pro-apoptotic insults, such as conventional chemotherapy and radiotherapy, and diffusely invades the brain parenchyma, which renders it elusive to total surgical resection. We found that fusicoccin A, a fungal metabolite from Fusicoccum amygdali, decreased the proliferation and migration of human GBM cell lines in vitro, including several cell lines that exhibit varying degrees of resistance to pro-apoptotic stimuli. The data demonstrate that fusicoccin A inhibits GBM cell proliferation by decreasing growth rates and increasing the duration of cell division and also decreases two-dimensional (measured by quantitative video microscopy) and three-dimensional (measured by Boyden chamber assays) migration. These effects of fusicoccin A treatment translated into structural changes in actin cytoskeletal organization and a loss of GBM cell adhesion. Therefore, fusicoccin A exerts cytostatic effects but low cytotoxic effects (as demonstrated by flow cytometry). These cytostatic effects can partly be explained by the fact that fusicoccin inhibits the activities of a dozen kinases, including focal adhesion kinase (FAK), that have been implicated in cell proliferation and migration. Overexpression of FAK, a nonreceptor protein tyrosine kinase, directly correlates with the invasive phenotype of aggressive human gliomas because FAK promotes cell proliferation and migration. Fusicoccin A led to the down-regulation of FAK tyrosine phosphorylation, which occurred in both normoxic and hypoxic GBM cell culture conditions. In conclusion, the current study identifies a novel compound that could be used as a chemical template for generating cytostatic compounds designed to combat GBM.

  4. Reduced replication capacity of influenza A(H1N1)pdm09 virus during the 2010-2011 winter season in Tottori, Japan.

    PubMed

    Tsuneki, Akeno; Itagaki, Asao; Tsuchie, Hideaki; Tokuhara, Misato; Okada, Takayoshi; Narai, Sakae; Kasagi, Masaaki; Tanaka, Kiyoshi; Kageyama, Seiji

    2013-11-01

    A novel swine-origin influenza A(H1N1)pdm09 virus has been circulating in humans since March-April, 2009. The 2009-2010 epidemic involved predominantly a single subtype of A(H1N1)pdm09 (at 96%, 46/48) in the sentinel sites of this study. However, A(H1N1)pdm09 started to circulate together with other type/subtype (49%, 33/68) at the first peak in the next epidemic season in 2010-2011: A(H1N1)pdm09/A(H3N2) (9%, 6/68), A(H1N1)pdm09/B (35%, 24/68), and A(H1N1)pdm09/A(H3N2)/B (4%, 3/68). Single infection of A(H1N1)pdm09 became a rare event (8%, 5/65) at the second peak of the same season in 2010-2011 compared with that at the first peak (50%, 34/68). Concurrently with this decline, single infections of others, A(H3N2) or B, became evident (6%, 4/65; 14%, 9/65, respectively). Triple infections were more common (29%, 19/65) at the second peak than at the first peak (4%). The A(H1N1)pdm09 detected in 2010-2011 produced less virus upon 72 hr of incubation in vitro after the inoculations at 10(4) and 3,300 copies/ml (2.3 × 10(9) and 2.3 × 10(9) copies/ml on average) than that in 2009-2010 (3.7 × 10(9) and 1.3 × 10(10) copies/ml on average; P<0.05 by ANOVA test), respectively. As described above, the replication capacity of A(H1N1)pdm09 seems to have deteriorated in the 2010-2011 season presumably due to substantial herd immunity and allowed the existence of other type/subtype. These results suggest that assessment of replication capacity is indispensable for analysis of influenza epidemics.

  5. Ultradispersed Nanoarchitecture of LiV3O8 Nanoparticle/Reduced Graphene Oxide with High-Capacity and Long-Life Lithium-Ion Battery Cathodes

    PubMed Central

    Mo, Runwei; Du, Ying; Rooney, David; Ding, Guqiao; Sun, Kening

    2016-01-01

    Lack of high-performance cathode materials has become the major barriers to lithium-ion battery applications in advanced communication equipment and electric vehicles. In this paper, we report a versatile interfacial reaction strategy, which is based on the idea of space confinement, for the synthesis of ultradispersed LiV3O8 nanoparticles (~10 nm) on graphene (denoted as LVO NPs-GNs) with an unprecedented degree of control on the separation and manipulation of the nucleation, growth, anchoring, and crystallization of nanoparticles in a water-in-oil emulsion system over free growth in solution. The prepared LVO NPs-GNs composites displayed high performance as an cathode material for lithium-ion battery, including high reversible lithium storage capacity (237 mA h g−1 after 200 cycles), high Coulombic efficiency (about 98%), excellent cycling stability and high rate capability (as high as 176 mA h g−1 at 0.9 A g−1, 128 mA h g−1 at 1.5 A g−1, 91 mA h g−1 at 3 A g−1 and 59 mA h g−1 at 6 A g−1, respectively). Very significantly, the preparation method employed can be easily adapted and may opens the door to complex hybrid materials design and engineering with graphene for advanced energy storage. PMID:26817818

  6. Ultradispersed Nanoarchitecture of LiV3O8 Nanoparticle/Reduced Graphene Oxide with High-Capacity and Long-Life Lithium-Ion Battery Cathodes

    NASA Astrophysics Data System (ADS)

    Mo, Runwei; Du, Ying; Rooney, David; Ding, Guqiao; Sun, Kening

    2016-01-01

    Lack of high-performance cathode materials has become the major barriers to lithium-ion battery applications in advanced communication equipment and electric vehicles. In this paper, we report a versatile interfacial reaction strategy, which is based on the idea of space confinement, for the synthesis of ultradispersed LiV3O8 nanoparticles (~10 nm) on graphene (denoted as LVO NPs-GNs) with an unprecedented degree of control on the separation and manipulation of the nucleation, growth, anchoring, and crystallization of nanoparticles in a water-in-oil emulsion system over free growth in solution. The prepared LVO NPs-GNs composites displayed high performance as an cathode material for lithium-ion battery, including high reversible lithium storage capacity (237 mA h g-1 after 200 cycles), high Coulombic efficiency (about 98%), excellent cycling stability and high rate capability (as high as 176 mA h g-1 at 0.9 A g-1, 128 mA h g-1 at 1.5 A g-1, 91 mA h g-1 at 3 A g-1 and 59 mA h g-1 at 6 A g-1, respectively). Very significantly, the preparation method employed can be easily adapted and may opens the door to complex hybrid materials design and engineering with graphene for advanced energy storage.

  7. Tissue-specific and SRSF1-dependent splicing of fibronectin, a matrix protein that controls host cell invasion

    PubMed Central

    Lopez-Mejia, Isabel Cristina; De Toledo, Marion; Della Seta, Flavio; Fafet, Patrick; Rebouissou, Cosette; Deleuze, Virginie; Blanchard, Jean Marie; Jorgensen, Christian; Tazi, Jamal; Vignais, Marie-Luce

    2013-01-01

    Cell invasion targets specific tissues in physiological placental implantation and pathological metastasis, which raises questions about how this process is controlled. We compare dermis and endometrium capacities to support trophoblast invasion, using matching sets of human primary fibroblasts in a coculture assay with human placental explants. Substituting endometrium, the natural trophoblast target, with dermis dramatically reduces trophoblast interstitial invasion. Our data reveal that endometrium expresses a higher rate of the fibronectin (FN) extra type III domain A+ (EDA+) splicing isoform, which displays stronger matrix incorporation capacity. We demonstrate that the high FN content of the endometrium matrix, and not specifically the EDA domain, supports trophoblast invasion by showing that forced incorporation of plasma FN (EDA–) promotes efficient trophoblast invasion. We further show that the serine/arginine-rich protein serine/arginine-rich splicing factor 1 (SRSF1) is more highly expressed in endometrium and, using RNA interference, that it is involved in the higher EDA exon inclusion rate in endometrium. Our data therefore show a mechanism by which tissues can be distinguished, for their capacity to support invasion, by their different rates of EDA inclusion, linked to their SRSF1 protein levels. In the broader context of cancer pathology, the results suggest that SRSF1 might play a central role not only in the tumor cells, but also in the surrounding stroma. PMID:23966470

  8. Degradative capacities and 16S rRNA-targeted whole-cell hybridization of sulfate-reducing bacteria in an anaerobic enrichment culture utilizing alkylbenzenes from crude oil.

    PubMed Central

    Rabus, R; Fukui, M; Wilkes, H; Widdle, F

    1996-01-01

    A mesophilic sulfate-reducing enrichment culture growing anaerobically on crude oil was used as a model system to study which nutritional types of sulfate-reducing bacteria may develop on original petroleum constituents in oil wells, tanks, and pipelines. Chemical analysis of oil hydrocarbons during growth revealed depletion of toluene and o-xylene within 1 month and of m-xylene, o-ethyltoluene, m-ethyltoluene, m-propyltoluene, and m-isopropyltoluene within approximately 2 months. In anaerobic counting series, the highest numbers of CFU (6 x 10(6) to 8 x 10(6) CFU ml-1) were obtained with toluene and benzoate. Almost the same numbers were obtained with lactate, a substrate often used for detection of the vibrio-shaped, incompletely oxidizing Desulfovibrio sp. In the present study, however, lactate yielded mostly colonies of oval to rod-shaped, completely oxidizing, sulfate-reducing bacteria which were able to grow slowly on toluene or crude oil. Desulfovibrio species were detected only at low numbers (3 x 10(5) CFU ml-1). In agreement with this finding, a fluorescently labeled, 16S rRNA-targeted oligonucleotide probe described in the literature as specific for members of the Desulfovibrionaceae (suggested family) hybridized only with a small portion (< 5%) of the cells in the enrichment culture. These results are consistent with the observation that known Desulfovibrio species do not utilize aromatic hydrocarbons, the predominant substrates in the enrichment culture. All known sulfate-reducing bacteria which utilize aromatic compounds belong to a separate branch, the Desulfobacteriaceae (suggested family). Most members of this family are complete oxidizers. For specific hybridization with members of this branch, the probe had to be modified by a nucleotide exchange. Indeed, this modified probe hybridized with more than 95% of the cells in the enrichment culture. The results show that completely oxidizing, alkylbenzene-utilizing sulfate-reducing bacteria rather than

  9. Dioxin exposure reduces the steroidogenic capacity of mouse antral follicles mainly at the level of HSD17B1 without altering atresia.

    PubMed

    Karman, Bethany N; Basavarajappa, Mallikarjuna S; Hannon, Patrick; Flaws, Jodi A

    2012-10-01

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a potent ovarian toxicant. Previously, we demonstrated that in vitro TCDD (1nM) exposure decreases production/secretion of the sex steroid hormones progesterone (P4), androstenedione (A4), testosterone (T), and 17β-estradiol (E2) in mouse antral follicles. The purpose of this study was to determine the mechanism by which TCDD inhibits steroidogenesis. Specifically, we examined the effects of TCDD on the steroidogenic enzymes, atresia, and the aryl hydrocarbon receptor (AHR) protein. TCDD exposure for 48h increased levels of A4, without changing HSD3B1 protein, HSD17B1 protein, estrone (E1), T or E2 levels. Further, TCDD did not alter atresia ratings compared to vehicle at 48h. TCDD, however, did down regulate the AHR protein at 48h. TCDD exposure for 96h decreased transcript levels for Cyp11a1, Cyp17a1, Hsd17b1, and Cyp19a1, but increased Hsd3b1 transcript. TCDD exposure particularly lowered both Hsd17b1 transcript and HSD17B1 protein. However, TCDD exposure did not affect levels of E1 in the media nor atresia ratings at 96h. TCDD, however, decreased levels of the proapoptotic factor Bax. Collectively, these data suggest that TCDD exposure causes a major block in the steroidogenic enzyme conversion of A4 to T and E1 to E2 and that it regulates apoptotic pathways, favoring survival over death in antral follicles. Finally, the down-regulation of the AHR protein in TCDD exposed follicles persisted at 96h, indicating that the activation and proteasomal degradation of this receptor likely plays a central role in the impaired steroidogenic capacity and altered apoptotic pathway of exposed antral follicles.

  10. Suppression of the PI3K pathway in vivo reduces cystitis-induced bladder hypertrophy and restores bladder capacity examined by magnetic resonance imaging.

    PubMed

    Qiao, Zhongwei; Xia, Chunmei; Shen, Shanwei; Corwin, Frank D; Liu, Miao; Guan, Ruijuan; Grider, John R; Qiao, Li-Ya

    2014-01-01

    This study utilized magnetic resonance imaging (MRI) to monitor the real-time status of the urinary bladder in normal and diseased states following cyclophosphamide (CYP)-induced cystitis, and also examined the role of the phosphoinositide 3-kinase (PI3K) pathway in the regulation of urinary bladder hypertrophy in vivo. Our results showed that under MRI visualization the urinary bladder wall was significantly thickened at 8 h and 48 h post CYP injection. The intravesical volume of the urinary bladder was also markedly reduced. Treatment of the cystitis animals with a specific PI3K inhibitor LY294002 reduced cystitis-induced bladder wall thickening and enlarged the intravesical volumes. To confirm the MRI results, we performed H&E stain postmortem and examined the levels of type I collagen by real-time PCR and western blot. Inhibition of the PI3K in vivo reduced the levels of type I collagen mRNA and protein in the urinary bladder ultimately attenuating cystitis-induced bladder hypertrophy. The bladder mass calculated according to MRI data was consistent to the bladder weight measured ex vivo under each drug treatment. MRI results also showed that the urinary bladder from animals with cystitis demonstrated high magnetic signal intensity indicating considerable inflammation of the urinary bladder when compared to normal animals. This was confirmed by examination of the pro-inflammatory factors showing that interleukin (IL)-1α, IL-6 and tumor necrosis factor (TNF)α levels in the urinary bladder were increased with cystitis. Our results suggest that MRI can be a useful technique in tracing bladder anatomy and examining bladder hypertrophy in vivo during disease development and the PI3K pathway has a critical role in regulating bladder hypertrophy during cystitis.

  11. In vitro digestion testing of lipid-based delivery systems: calcium ions combine with fatty acids liberated from triglyceride rich lipid solutions to form soaps and reduce the solubilization capacity of colloidal digestion products.

    PubMed

    Devraj, Ravi; Williams, Hywel D; Warren, Dallas B; Mullertz, Anette; Porter, Christopher J H; Pouton, Colin W

    2013-01-30

    In vitro digestion testing is of practical importance to predict the fate of drugs administered in lipid-based delivery systems. Calcium ions are often added to digestion media to increase the extent of digestion of long-chain triglycerides (LCTs), but the effects they have on phase behaviour of the products of digestion, and consequent drug solubilization, are not well understood. This study investigates the effect of calcium and bile salt concentrations on the rate and extent of in vitro digestion of soybean oil, as well as the solubilizing capacity of the digestion products for two poorly water-soluble drugs, fenofibrate and danazol. In the presence of higher concentrations of calcium ions, the solubilization capacities of the digests were reduced for both drugs. This effect is attributed to the formation of insoluble calcium soaps, visible as precipitates during the digestions. This reduces the availability of liberated fatty acids to form mixed micelles and vesicles, thereby reducing drug solubilization. The use of high calcium concentrations does indeed force in vitro digestion of LCTs but may overestimate the extent of drug precipitation that occurs within the intestinal lumen.

  12. Dioxin exposure reduces the steroidogenic capacity of mouse antral follicles mainly at the level of HSD17B1 without altering atresia

    SciTech Connect

    Karman, Bethany N. Basavarajappa, Mallikarjuna S. Hannon, Patrick Flaws, Jodi A.

    2012-10-01

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a potent ovarian toxicant. Previously, we demonstrated that in vitro TCDD (1 nM) exposure decreases production/secretion of the sex steroid hormones progesterone (P4), androstenedione (A4), testosterone (T), and 17β-estradiol (E2) in mouse antral follicles. The purpose of this study was to determine the mechanism by which TCDD inhibits steroidogenesis. Specifically, we examined the effects of TCDD on the steroidogenic enzymes, atresia, and the aryl hydrocarbon receptor (AHR) protein. TCDD exposure for 48 h increased levels of A4, without changing HSD3B1 protein, HSD17B1 protein, estrone (E1), T or E2 levels. Further, TCDD did not alter atresia ratings compared to vehicle at 48 h. TCDD, however, did down regulate the AHR protein at 48 h. TCDD exposure for 96 h decreased transcript levels for Cyp11a1, Cyp17a1, Hsd17b1, and Cyp19a1, but increased Hsd3b1 transcript. TCDD exposure particularly lowered both Hsd17b1 transcript and HSD17B1 protein. However, TCDD exposure did not affect levels of E1 in the media nor atresia ratings at 96 h. TCDD, however, decreased levels of the proapoptotic factor Bax. Collectively, these data suggest that TCDD exposure causes a major block in the steroidogenic enzyme conversion of A4 to T and E1 to E2 and that it regulates apoptotic pathways, favoring survival over death in antral follicles. Finally, the down‐regulation of the AHR protein in TCDD exposed follicles persisted at 96 h, indicating that the activation and proteasomal degradation of this receptor likely plays a central role in the impaired steroidogenic capacity and altered apoptotic pathway of exposed antral follicles. -- Highlights: ► TCDD disrupts steroidogenic enzymes in mouse antral follicles. ► TCDD particularly affects the HSD17B1 enzyme in mouse antral follicles. ► TCDD does not affect atresia ratings in mouse antral follicles. ► TCDD decreases levels of the proapoptitic factor Bax in mouse antral follicles.

  13. The use of pruned chipped branches to increase the soil infiltration capacity and reduce the soil losses on citrus orchards in Eastern Spain

    NASA Astrophysics Data System (ADS)

    González-Pelayo, Óscar; Llovet, Joan; Giménez-Morera, Antonio; Jordán, Antonio; Pereira, Paulo; Novara, Agata; García-Orenes, Fuensanta; Cerdà, Artemi

    2015-04-01

    Soil water erosion is causing problems on the agriculture land of the world. The high erosion rates registered in the agriculture land are due to the lack of a vegetation cover that protects the soil. High erosion rates in agriculture lands are found in Africa, Europe, Asia, and any other continent. Soil erosion on citrus orchards has been researched recently and shown huge erosion rates in the Mediterranean and in China. All this research findings allow us to confirm that the soil erosion rates on citrus orchards are not sustainable and strategies to control the soil erosion should be applied. The increasing erosion rates are due to the bare soils, but also are due to the soil structure degradation and soil organic matter exhaustion. Some authors applied cover on crops to avoid the raindrop impact and the surfaces wash but there is a need to develop new strategies to reduce soil losses and keep sustainable the citrus productions. The agriculture production also results in a large amount of residues than can be a resource to improve the soil cover. This has been done in road embankments, in forest land affected by wildfires and on afforestation. As a consequence of the mechanization of the agriculture, and the reduction of the draft animals (mainly horses, mules, donkeys and oxen), the straw and the pruned branches are being a residue instead of a resource in many developed countries. Straw was used as a forage and the pruned branches as a source of heat and energy but both can be used as a mulch to control the soil erosion. The pruned branches can contribute with a valuable source of nutrients and a good soil protection. The leaves of the trees, and some parts of the plants, once harvest can contribute to reduce the soil losses. Our goal is to test if a residue such as the chipped pruned branches can be transformed as a resource that will help to control the soil erosion rates. Straw has been seen as a very efficient to reduce the water losses in agriculture land

  14. Reduced miR-3127-5p expression promotes NSCLC proliferation/invasion and contributes to dasatinib sensitivity via the c-Abl/Ras/ERK pathway

    PubMed Central

    Sun, Yifeng; Chen, Chang; Zhang, Peng; Xie, Huikang; Hou, Likun; Hui, Zheng; Xu, Yongjie; Du, Qiaoling; Zhou, Xiao; Su, Bo; Gao, Wen

    2014-01-01

    miR-3127-5p is a primate-specific miRNA which is down-regulated in recurrent NSCLC tissue vs. matched primary tumor tissue (N = 15) and in tumor tissue vs. normal lung tissue (N = 177). Reduced miR-3127-5p expression is associated with a higher Ki-67 proliferation index and unfavorable prognosis in NSCLC. Overexpression of miR-3127-5p significantly reduced NSCLC cells proliferation, migration, and motility in vitro and in vivo. The oncogene ABL1 was a direct miR-3127-5p target, and miR-3127-5p regulated the activation of the Abl/Ras/ERK pathway and transactivated downstream proliferation/metastasis-associated molecules. Overexpression of miR-3127-5p in A549 or H292 cells resulted in enhanced resistance to dasatinib, an Abl/src tyrosine kinase inhibitor. miR-3127-5p expression levels were correlated with dasatinib sensitivity in NSCLC cell lines without K-Ras G12 mutation. In conclusion, miR-3127-5p acts as a tumor suppressor gene and is a potential biomarker for dasatinib sensitivity in the non-mutated Ras subset of NSCLC. PMID:25284075

  15. In Situ Synthesis of MnS Hollow Microspheres on Reduced Graphene Oxide Sheets as High-Capacity and Long-Life Anodes for Li- and Na-Ion Batteries.

    PubMed

    Xu, Xijun; Ji, Shaomin; Gu, Mingzhe; Liu, Jun

    2015-09-23

    Uniform MnS hollow microspheres in situ crystallized on reduced graphene oxide (RGO) nanosheets via a facile hydrothermal method. The MnS/RGO composite material was used as the anode for Na-ion batteries for the first time and exhibited excellent cycling performance, superior specific capacity, and great cycle stability and rate capability for both Li- and Na-ion batteries. Compared with nonencapsulated pure MnS hollow microspheres, these MnS/RGO nanocomposites demonstrated excellent charge-discharge stability and long cycle life. Li-ion storage testing revealed that these MnS/RGO nanocomposites deliver high discharge-charge capacities of 640 mAh g(-1) at 1.0 A g(-1) after 400 cycles and 830 mAh g(-1) at 0.5 A g(-1) after 100 cycles. The MnS/RGO nanocomposites even retained a specific capacity of 308 mAh g(-1) at a current density of 0.1 A g(-1) after 125 cycles as the anode for Na-ion batteries. The outstanding electrochemical performance of the MnS/RGO composite attributed to the RGO nanosheets greatly improved the electronic conductivity and efficiently mitigated the stupendous volume expansion during the progress of charge and discharge.

  16. Nucleotides with altered hydrogen bonding capacities impede human DNA polymerase η by reducing synthesis in the presence of the major cisplatin DNA adduct.

    PubMed

    Nilforoushan, Arman; Furrer, Antonia; Wyss, Laura A; van Loon, Barbara; Sturla, Shana J

    2015-04-15

    Human DNA polymerase η (hPol η) contributes to anticancer drug resistance by catalyzing the replicative bypass of DNA adducts formed by the widely used chemotherapeutic agent cis-diamminedichloroplatinum (cisplatin). A chemical basis for overcoming bypass-associated resistance requires greater knowledge of how small molecules influence the hPol η-catalyzed bypass of DNA adducts. In this study, we demonstrated how synthetic nucleoside triphosphates act as hPol η substrates and characterized their influence on hPol η-mediated DNA synthesis over unmodified and platinated DNA. The single nucleotide incorporation efficiency of the altered nucleotides varied by more than 10-fold and the higher incorporation rates appeared to be attributable to the presence of an additional hydrogen bond between incoming dNTP and templating base. Finally, full-length DNA synthesis in the presence of increasing concentrations of synthetic nucleotides reduced the amount of DNA product independent of the template, representing the first example of hPol η inhibition in the presence of a platinated DNA template.

  17. Natural nitration of CXCL12 reduces its signaling capacity and chemotactic activity in vitro and abrogates intra-articular lymphocyte recruitment in vivo

    PubMed Central

    Janssens, Rik; Mortier, Anneleen; Boff, Daiane; Vanheule, Vincent; Gouwy, Mieke; Franck, Charlotte; Larsen, Olav; Rosenkilde, Mette M.; Van Damme, Jo; Amaral, Flávio A.; Teixeira, Mauro M.; Struyf, Sofie; Proost, Paul

    2016-01-01

    The chemokine CXCL12/stromal cell-derived factor-1 is important for leukocyte migration to lymphoid organs and inflamed tissues and stimulates tumor development. In vitro, CXCL12 activity through CXCR4 is abolished by proteolytic processing. However, limited information is available on in vivo effects of posttranslationally modified CXCL12. Natural CXCL12 was purified from the coculture supernatant of stromal cells stimulated with leukocytes and inflammatory agents. In this conditioned medium, CXCL12 with a nitration on Tyr7, designated [3-NT7]CXCL12, was discovered via Edman degradation. CXCL12 and [3-NT7]CXCL12 were chemically synthesized to evaluate the biological effects of this modification. [3-NT7]CXCL12 recruited β-arrestin 2 and phosphorylated the Akt kinase similar to CXCL12 in receptor-transfected cells. Also the affinity of CXCL12 and [3-NT7]CXCL12 for glycosaminoglycans, the G protein-coupled chemokine receptor CXCR4 and the atypical chemokine receptor ACKR3 were comparable. However, [3-NT7]CXCL12 showed a reduced ability to enhance intracellular calcium concentrations, to generate inositol triphosphate, to phosphorylate ERK1/2 and to induce monocyte and lymphocyte chemotaxis in vitro. Moreover, nitrated CXCL12 failed to induce in vivo extravasation of lymphocytes to the joint. In summary, nitration on Tyr7 under inflammatory conditions is a novel natural posttranslational regulatory mechanism of CXCL12 which may downregulate the CXCR4-mediated inflammatory and tumor-promoting activities of CXCL12. PMID:27566567

  18. The NOX2-mediated ROS producing capacity of recipient cells is associated with reduced T cell infiltrate in an experimental model of chronic renal allograft inflammation.

    PubMed

    Kraaij, Marina D; Koekkoek, Karin M; Gelderman, Kyra A; van Kooten, Cees

    2014-03-01

    We previously showed that anti-inflammatory Mph (Mph2) can both in vitro and in vivo induce regulatory T cells (Tregs) in a reactive oxygen species (ROS)-dependent fashion. As influx of Mph is an important characteristic of chronic inflammatory responses, we investigated the impact of NOX2-mediated ROS production by recipient cells in an experimental model of chronic allograft inflammation. We used a kidney transplantation (Tx) model with Lewis (Lew) rats as donor and congenic DA.Ncf1(DA/DA) (low ROS) and DA.Ncf1(E3/E3) (normal ROS) rats as recipients. At day 7 the contralateral kidney was removed, and the animals were sacrificed four weeks after Tx. Renal function and injury were monitored in serum and urine and the composition of the infiltrate was analyzed by immunohistochemistry. Four weeks after Tx, large leukocyte clusters were observed in the allograft, in which signs of ROS production could be demonstrated. These clusters showed no difference regarding composition of myeloid cells or the number of FoxP3 positive cells. However, T cell infiltrate was significantly reduced in the DA.Ncf1(E3/E3) recipients having normal ROS production. Therefore, this study suggests a regulatory effect of ROS on T cell infiltration, but no effect on other inflammatory cells in the allograft.

  19. Invasion percolation with memory

    SciTech Connect

    Kharabaf, H.; Yortsos, Y.C.

    1997-06-01

    Motivated by the problem of finding the minimum threshold path (MTP) in a lattice of elements with random thresholds {tau}{sub i}, we propose a new class of invasion processes, in which the front advances by minimizing or maximizing the measure S{sub n}={summation}{sub i}{tau}{sub i}{sup n} for real n. This rule assigns long-time memory to the invasion process. If the rule minimizes S{sub n} (case of minimum penalty), the fronts are stable and connected to invasion percolation in a gradient [J. P. Hulin, E. Clement, C. Baudet, J. F. Gouyet, and M. Rosso, Phys. Rev. Lett. {bold 61}, 333 (1988)] but in a correlated lattice, with invasion percolation [D. Wilkinson and J. F. Willemsen, J. Phys. A {bold 16}, 3365 (1983)] recovered in the limit {vert_bar}n{vert_bar}={infinity}. For small n, the MTP is shown to be related to the optimal path of the directed polymer in random media (DPRM) problem [T. Halpin-Healy and Y.-C. Zhang, Phys. Rep. {bold 254}, 215 (1995)]. In the large n limit, however, it reduces to the backbone of a mixed site-bond percolation cluster. The algorithm allows for various properties of the MTP and the DPRM to be studied. In the unstable case (case of maximum gain), the front is a self-avoiding random walk. {copyright} {ital 1997} {ital The American Physical Society}

  20. Long-chain acyl-CoA synthetase 2 knockdown leads to decreased fatty acid oxidation in fat body and reduced reproductive capacity in the insect Rhodnius prolixus.

    PubMed

    Alves-Bezerra, Michele; Klett, Eric L; De Paula, Iron F; Ramos, Isabela B; Coleman, Rosalind A; Gondim, Katia C

    2016-07-01

    Long-chain acyl-CoA esters are important intermediates in lipid metabolism and are synthesized from fatty acids by long-chain acyl-CoA synthetases (ACSL). The hematophagous insect Rhodnius prolixus, a vector of Chagas' disease, produces glycerolipids in the midgut after a blood meal, which are stored as triacylglycerol in the fat body and eggs. We identified twenty acyl-CoA synthetase genes in R. prolixus, two encoding ACSL isoforms (RhoprAcsl1 and RhoprAcsl2). RhoprAcsl1 transcripts increased in posterior midgut on the second day after feeding, and RhoprAcsl2 was highly transcribed on the tenth day. Both enzymes were expressed in Escherichia coli. Recombinant RhoprACSL1 and RhoprACSL2 had broad pH optima (7.5-9.5 and 6.5-9.5, respectively), were inhibited by triacsin C, and were rosiglitazone-insensitive. Both showed similar apparent Km for palmitic and oleic acid (2-6 μM), but different Km for arachidonic acid (0.5 and 6 μM for RhoprACSL1-Flag and RhoprACSL2-Flag, respectively). The knockdown of RhoprAcsl1 did not result in noticeable phenotypes. However, RhoprACSL2 deficient insects exhibited a 2.5-fold increase in triacylglycerol content in the fat body, and 90% decrease in fatty acid β-oxidation. RhoprAcsl2 knockdown also resulted in 20% increase in lifespan, delayed digestion, 30% reduced oviposition, and 50% reduction in egg hatching. Laid eggs and hatched nymphs showed remarkable alterations in morphology. In summary, R. prolixus ACSL isoforms have distinct roles on lipid metabolism. Although RhoprACSL1 functions remain unclear, we propose that RhoprACSL2 is the main contributor for the formation of the intracellular acyl-CoA pool channeled for β-oxidation in the fat body, and is also required for normal reproduction.

  1. Feeding soybean meal increases the blood level of isoflavones and reduces the steroidogenic capacity in bovine corpora lutea, without affecting peripheral progesterone concentrations.

    PubMed

    Cools, S; Van den Broeck, W; Vanhaecke, L; Heyerick, A; Bossaert, P; Hostens, M; Opsomer, G

    2014-01-30

    Thirty-three Holstein-Friesian cows were followed from 14 days pre partum until the fourth ovulation post partum. Housing conditions and basic ration were identical for all animals. Concentrates were individually supplemented according to the daily milk production level, using two different types of protein rich concentrates: soybean meal and rapeseed meal. Soybean and rapeseed meal are known to be respectively high and low in isoflavones. Cows were randomly divided into three groups and blocked for parity. Group I (n=11) was supplemented with soybean meal and acted as control group. Groups II (n=11) and III (n=11) were respectively supplemented with soybean and rapeseed meal and were subjected to a biopsy sampling of the corpus luteum at day 9 of the first three postpartal estrous cycles. Soybean meal supplementation to lactating dairy cows (1.72 kg on average) induced an increase in the blood concentration of equol, dihydrodaidzein, o-desmethylangolensin in both soy groups and resulted in a reduced area occupied by steroidogenic (P=0.012) and endothelial cells (P=0.0007) in the luteal biopsies. Blood concentrations of equol and glycitein were negatively correlated with the areas occupied by steroidogenic (r=-0.410 with P=0.0002, respectively r=-0.351 with P=0.008) and endothelial cells (r=-0.337 with P=0.01, respectively r=-0.233 with P=0.085) in the 3 first estrous cycles. The latter however did not affect the diestrous peripheral blood progesterone concentration.

  2. Influence of nitric oxide on the intracellular reduced glutathione pool: different cellular capacities and strategies to encounter nitric oxide-mediated stress.

    PubMed

    Berendji, D; Kolb-Bachofen, V; Meyer, K L; Kröncke, K D

    1999-10-01

    Different cell types exhibit huge differences towards the cytotoxic action of NO. In search for an explanation, we used subtoxic concentrations of the NO-donors S-nitrosocysteine (SNOC) for short-term challenge and of (Z)-1-[N-(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1- ium-1,2-diolate (DETA/NO) for longer periods of exposure, respectively, and subtoxic concentrations of the oxidant H2O2 to determine the impact on intracellular reduced glutathione (GSH) concentrations. We find that GSH concentrations are always decreased, but that different cell types show different responses. Incubation of the relatively NO-sensitive murine lymphocytes with both NO-donors, but not with H2O2, resulted in a nearly complete loss of intracellular GSH. Short-term NO-treatment of P815 mastocytoma cells, also sensitive to NO-mediated cell death, decreased GSH to a similar extent only if either glutathione reductase (GSHR) activity or y-glutamylcysteine synthetase (gammaGCS) activity were inhibited concomitantly by specific inhibitors. Long-term NO-treatment of P815 cells, however, resulted in a significant decrease of GSH that could be further enhanced by inhibiting gammaGCS activity. In contrast, neither short-term nor long-term NO-exposure nor H2O2-treatment affected intracellular GSH levels of L929 fibroblasts, which were previously shown to be extremely resistant towards NO, whereas concomitant gammaGCS inhibition, but not GSHR inhibition, completely decreased GSH concentrations. These results show that different cell types use different pathways trying to maintain glutathione concentrations to cope with nitrosative stress, and the overall capability to maintain a critical amount of GSH correlates with susceptibility to NO-induced cell death.

  3. In vitro adaptation of SAV3 in cell culture correlates with reduced in vivo replication capacity and virulence to Atlantic salmon (Salmo salar L.) parr.

    PubMed

    Petterson, Elin; Guo, Tz-Chun; Evensen, Øystein; Haugland, Øyvind; Mikalsen, Aase B

    2015-10-01

    Salmonid alphavirus (SAV) is the causative agent of pancreas disease affecting Atlantic salmon and rainbow trout and causes a major burden to the aquaculture industry. This study describes a Norwegian subtype SAV3 virus isolate (SAV3-H10) subjected to serial passages in Chinook salmon embryo cells (CHSE-214) followed by Asian Grouper skin cells (AGK). Two passages from CHSE and one after transfer to AGK cells were chosen for further investigation, based on variation in degree and development of cytopathic effect (CPE). After plaque purification, several in vitro studies were performed. Cell viability after infection, viral replication and ability to cause morphological changes in CHSE and AGK cells was studied for the three isolates. The AGK-transferred isolate was identified with the strongest abilities to reduce cell viability, replicate more and cause more CPE in cell culture when compared with the early and late CHSE-grown isolates. Subsequently, the isolates were tested in an experimental fish challenge, showing higher viral load and higher pathological score for the least cell-cultured isolate. Full-length sequencing of the viral genome of the three isolates revealed divergence in four amino acid positions and the AGK-grown isolate also had a 3 nt deletion in the 3'UTR. In conclusion, we show that cell culture of SAV3-H10 selects for strains inducing earlier CPE in vitro with increased viral replication. In vivo, the effect is reversed, with lower replication levels and lower pathology scores in target organs. This study outlines a path to identify potential virulence motifs of SAV3.

  4. The altered tumoricidal capacity of macrophages isolated from tumor- bearing mice is related to reduce expression of the inducible nitric oxide synthase gene

    PubMed Central

    1996-01-01

    Nitric oxide (NO) is a major effector molecule in the destruction of tumor cells by activated macrophages. However, in many cases, developing neoplasms appear to be capable of impairing steps in the complex process leading to NO production as a means of avoiding immune destruction. After activation with lipopolysaccharide (LPS), peritoneal- elicited macrophages (PEM) from mice bearing mammary tumors display alterations in their ability to lyse tumor cells due to reduced production of NO. In contrast, when these same cells are stimulated with LPS in combination with interferon gamma (IFN-gamma), they are able to produce NO and lyse targets at normal levels. Since tumor- associated macrophages are intimately associated with the cells of the developing tumor, their ability to produce NO and lyse tumor targets is likely to be more relevant to controlling tumor growth. This population of macrophages exhibited a more profound inability to produce NO and lyse targets and, unlike the PEM, was not able to upregulate these functions even when treated with combinations of LPS and IFN-gamma. Northern and Western blots revealed that inducible nitric oxide synthase (iNOS) mRNA and protein levels correlated directly with the ability of each macrophage population to produce NO, and the levels of these macromolecules were altered sufficiently in tumor bearers' macrophages to account for the diminished NO production described. These results indicate that a spatial gradient of suppression of macrophage cytolytic activity and iNOS expression exists in mammary tumor-bearing mice, whereby macrophages from within the tumor exhibit a more pronounced suppression than the more distally located PEM. This suppression may be due to proximity of the macrophages to the developing tumor, macrophage maturational state, or both. PMID:8666890

  5. A Comprehensive Study of the Use of Cu(I)/4,4'-Dicarboxy-2,2'-biquinoline Complexes to Measure the Total Reducing Capacity: Application in Herbal Extracts.

    PubMed

    Manoel, Hariane R; Moya, Horacio D

    2015-12-14

    A method for the determination of total reducing capacity (TRC) based on the reduction of Cu(II) to Cu(I) by antioxidants in a buffered solution (pH 7.0) containing 4,4'-dicarboxy-2,2'-biquinoline acid (BCA) was developed. Absorbance values at 558 nm characteristic of the Cu(I)/BCA complexes formed were used to determine the TRC of aqueous extracts of twelve Brazilian plants. The TRC values obtained with the suggested method correlated well with values obtained using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) method (r² = 0.959). They were also compared with the total polyphenol content (using the Folin-Ciocalteu reagent) and the good agreement (r² = 0.919) indicates that the polyphenols should be responsible for this reducing capacity. The method proposed here (and successfully applied in plant extracts) can be used to measure the TRC of aqueous samples derived from other plants (e.g., teas, juices, beers and wines) and even in biological samples (e.g., serum, urine and follicular fluid). To achieve a structure-activity relationship of the proposed reaction, the reduction capability of 25 standard antioxidants (phenolic derivatives, flavonoids, stilbenoids, vitamins, etc.) was individually evaluated and the apparent molar absorptivity values (at 558 nm) obtained were compared and discussed.

  6. Efficacy of Intralipid infusion in reducing amphotericin-B-associated nephrotoxicity in head and neck invasive fungal infection: A randomized, controlled trial.

    PubMed

    Hasibi, Mehrdad; Jafari, Sirous; Manshadi, Seyyed Ali; Asadollahi, Marjan; Salehi, Mohammadreza; Zarch, Varasteh Vakili; Kouhi, Ali

    2017-02-01

    Amphotericin B deoxycholate (ABD) is the best therapeutic agent available for the treatment of most systemic fungal infections. However, some untoward adverse effects such as nephrotoxicity may limit its appropriate therapeutic use. We conducted a randomized, controlled trial ofthe infusion of fat emulsion (Intralipid) shortly after the infusion of ABD to evaluate its effects on reducing ABD-associated nephrotoxicity. Our patient population was made up of 31 patients who were randomized into two groups: an intervention group (n = 16) and a control group (15 patients). There were no statistically significant differences between the two groups in demographic or clinical variables. All patients received 1mg/kg/day of ABD in dextrose 5%. In addition, the patients in the intervention arm received Intralipid 10%, which was started as soon as possible within 1 hour after the infusion of ABD. ABD-associated nephrotoxicity was defined as a minimum 50% increase in baseline serum creatinine to a minimum of 2mg/dl. We also measured daily serum creatinine changes during the first 2 weeks of treatment, and we compared some other relevant indices of renal function, as well as ABD-related hypokalemia. We found no statistically significant differences between the two treatments in terms of ABD-associated nephrotoxicity or any of the other indices. We conclude that the administration of Intralipid 10% early after infusion of ABD in dextrose 5% does not have any effect in decreasing ABD-associated nephrotoxicity or hypokalemia.

  7. CSF1R blockade slows the progression of amyotrophic lateral sclerosis by reducing microgliosis and invasion of macrophages into peripheral nerves

    PubMed Central

    Martínez-Muriana, Anna; Mancuso, Renzo; Francos-Quijorna, Isaac; Olmos-Alonso, Adrian; Osta, Rosario; Perry, V. Hugh; Navarro, Xavier; Gomez-Nicola, Diego; López-Vales, Ruben

    2016-01-01

    Inflammation is a common neuropathological feature in several neurological disorders, including amyotrophic lateral sclerosis (ALS). We have studied the contribution of CSF1R signalling to inflammation in ALS, as a pathway previously reported to control the expansion and activation of microglial cells. We found that microglial cell proliferation in the spinal cord of SOD1G93A transgenic mice correlates with the expression of CSF1R and its ligand CSF1. Administration of GW2580, a selective CSF1R inhibitor, reduced microglial cell proliferation in SOD1G93A mice, indicating the importance of CSF1-CSF1R signalling in microgliosis in ALS. Moreover, GW2580 treatment slowed disease progression, attenuated motoneuron cell death and extended survival of SOD1G93A mice. Electrophysiological assessment revealed that GW2580 treatment protected skeletal muscle from denervation prior to its effects on microglial cells. We found that macrophages invaded the peripheral nerve of ALS mice before CSF1R-induced microgliosis occurred. Interestingly, treatment with GW2580 attenuated the influx of macrophages into the nerve, which was partly caused by the monocytopenia induced by CSF1R inhibition. Overall, our findings provide evidence that CSF1R signalling regulates inflammation in the central and peripheral nervous system in ALS, supporting therapeutic targeting of CSF1R in this disease. PMID:27174644

  8. Shifts in dynamic regime of an invasive lady beetle are linked to the invasion and insecticidal management of its prey.

    PubMed

    Bahlai, Christine A; van der Werf, Wopke; vander Werf, Wopke; O'Neal, Matthew; Hemerik, Lia; Landis, Douglas A

    2015-10-01

    The spread and impact of invasive species may vary over time in relation to changes in the species itself, the biological community of which it is part, or external controls on the system. We investigate whether there have been changes in dynamic regimes over the last 20 years of two invasive species in the midwestern United States, the multicolored Asian lady beetle Harmonia axyridis and the soybean aphid Aphis glycines. We show by model selection that after its 1993 invasion into the American Midwest, the year-to-year population dynamics of H. axyridis were initially governed by a logistic rule supporting gradual rise to a stable carrying capacity. After invasion of the soybean aphid in 2000, food resources at the landscape level became abundant, supporting a higher year-to-year growth rate and a higher but unstable carrying capacity, with two-year cycles in both aphid and lady beetle abundance as a consequence. During 2005-2007, farmers in the Midwest progressively increased their use of insecticides for managing A. glycines, combining prophylactic seed treatment with curative spraying based on thresholds. This human intervention dramatically reduced the soybean aphid as a major food resource for H. axyridis at landscape level and corresponded to a reverse shift towards the original logistic rule for year-to-year dynamics. Thus, we document a short episode of major predator-prey fluctuations in an important agricultural system resulting from two biological invasions that were apparently damped by widespread insecticide use. Recent advances in development of plant resistance to A. glycines in soybeans may mitigate the need for pesticidal control and achieve the same stabilization of pest and predator populations at lower cost and environmental burden.

  9. The ghost of a recent invasion in the reduced feeding rates of spitting cobras during the dry season in a rainforest region of tropical Africa?

    NASA Astrophysics Data System (ADS)

    Luiselli, Luca

    2001-12-01

    Two species of cobras ( Naja melanoleuca and Naja nigricollis) are known to occur in south eastern Nigeria, where much of the pristine rainforest surface has been felled in the last thirty years, and where the actual landscape is generally constituted by a mosaic of farmlands, plantations, suburban areas, with a few remnant forest fragments. In this region, Naja nigricollis is currently extending its range, especially by exploiting recently deforested areas. Based on the known general distribution range of this species and on the available literature data, it appears that Naja nigricollis has been colonizing the forested region of south eastern Nigeria, starting from the relatively arid savannas of central Nigeria, where this species aestivates during the driest months. In the forest region, however, snakes do not need to aestivate during the dry season. Nevertheless, whereas Naja melanoleuca has a foraging activity extended all-the-year round, Naja nigricollis reduces feeding rates during the dry months, although it does not suspend above-ground activity in these months. I suggest that rainforest spitting cobras suspend feeding during the dry months because their behaviour is just a 'ghost' of their recent past, when they were 'normal' spitting cobras of dry savana regions, which were thus constrained to aestivate during the dry season as it is the rule in this species in central and northern Nigeria. The 'gost-of-the-past hypothesis' seems to fit well with the 'invading' presence of Naja nigricollis in Nigerian areas where they were reported as rare or, even, absent, up to a few decades ago. Other hypotheses are discussed, and rejected.

  10. Contemporary Pharyngeal and Invasive emm1 and Invasive emm12 Group A Streptococcus Isolates Exhibit Similar In Vivo Selection for CovRS Mutants in Mice

    PubMed Central

    Feng, Wenchao; Liu, Mengyao; Chen, Daniel G.; Yiu, Rossana; Fang, Ferric C.; Lei, Benfang

    2016-01-01

    Group A Streptococcus (GAS) causes diverse infections ranging from common pharyngitis to rare severe invasive infections. Invasive GAS isolates can have natural mutations in the virulence regulator CovRS, which result in enhanced expression of multiple virulence genes, suppressed the expression of the protease SpeB, and increased virulence. It is believed that CovRS mutations arise during human infections with GAS carrying wild-type CovRS and are not transmissible. CovRS mutants of invasive GAS of the emm1 genotype arise readily during experimental infection in mice. It is possible that invasive GAS arises from pharyngeal GAS through rare genetic mutations that confer the capacity of mutated GAS to acquire covRS mutations during infection. The objective of this study was to determine whether contemporary pharyngeal emm1 GAS isolates have a reduced propensity to acquire CovRS mutations in vivo compared with invasive emm1 GAS and whether emm3, emm12, and emm28 GAS acquire CovRS mutants in mouse infection. The propensity of invasive and pharyngeal emm1 and invasive emm3, emm12, and emm28 SpeBA+ isolates to acquire variants with the SpeBA- phenotype was determined during subcutaneous infection of mice. The majority of both invasive and pharyngeal emm1 SpeBA+ isolates and two of three emm12 isolates, but not emm3 and emm28 isolates, were found to acquire SpeBA- variants during skin infection in mice. All analyzed SpeBA- variants of emm1 and emm12 GAS from the mouse infection acquired covRS mutations and produced more platelet-activating factor acetylhydrolase SsE. Thus, contemporary invasive and pharyngeal emm1 GAS isolates and emm12 GAS have a similar capacity to acquire covRS mutations in vivo. The rarity of severe invasive infections caused by GAS does not appear to be attributable to a reduced ability of pharyngeal isolates to acquire CovRS mutations. PMID:27611332

  11. Parasite-mediated predation between native and invasive amphipods.

    PubMed Central

    MacNeil, Calum; Dick, Jaimie T A; Hatcher, Melanie J; Terry, Rebecca S; Smith, Judith E; Dunn, Alison M

    2003-01-01

    Parasites can structure biological communities directly through population regulation and indirectly by processes such as apparent competition. However, the role of parasites in the process of biological invasion is less well understood and mechanisms of parasite mediation of predation among hosts are unclear. Mutual predation between native and invading species is an important factor in determining the outcome of invasions in freshwater amphipod communities. Here, we show that parasites mediate mutual intraguild predation among native and invading species and may thereby facilitate the invasion process. We find that the native amphipod Gammarus duebeni celticus is host to a microsporidian parasite, Pleistophora sp. (new species), with a frequency of infection of 0-90%. However, the parasite does not infect three invading species, G. tigrinus, G. pulex and Crangonyx pseudogracilis. In field and laboratory manipulations, we show that the parasite exhibits cryptic virulence: the parasite does not affect host fitness in single-species populations, but virulence becomes apparent when the native and invading species interact. That is, infection has no direct effect on G. d. celticus survivorship, size or fecundity; however, in mixed-species experiments, parasitized natives show a reduced capacity to prey on the smaller invading species and are more likely to be preyed upon by the largest invading species. Thus, by altering dominance relationships and hierarchies of mutual predation, parasitism strongly influences, and has the potential to change, the outcome of biological invasions. PMID:12816645

  12. Giant invasive prolactinomas

    SciTech Connect

    Murphy, F.Y.; Vesely, D.L.; Jordan, R.M.; Flanigan, S.; Kohler, P.O.

    1987-11-01

    Two of the largest prolactinomas ever documented that have been followed for nine and 10 years, respectively, demonstrate how aggressive prolactinomas may become and how difficult invasive prolactinomas are to treat. One of these prolactinomas invaded both internal auditory canals and simultaneously grew inferiorly, reducing the bony support of the skull and necessitating the patient to utilize both hands to hold his head up. The second patient's prolactinoma invaded the sphenoidal, ethmoidal, and cavernous sinuses. Both of these patients had neurosurgical debulking of their tumors followed by radiation therapy. Neither patient's prolactin levels decreased significantly during their first five years post-surgically, at which time bromocriptine was added. Since then, there has been a gradual lowering of serum prolactin levels and a decrease in the size of these tumors. These cases demonstrate that prolonged treatment and very large doses of bromocriptine may be necessary for tumor reduction in patients with invasive prolactinomas.

  13. Mental capacity.

    PubMed

    Williams, Ruth

    2010-02-03

    Three short videos exploring some of the different principles in the Mental Capacity Act 2009 are available on Social Care TV, an online channel intended mainly for the social care sector, although the films are relevant to any professionals whose work is affected by the act. The dramas, which are set in a residential home, a person's own home and a residential school for young people with learning difficulties, concern thedecision-making process and can be viewed at www.scie.org.uk/socialcaretv/topic.asp?guid=377dbe1b-de0c-4d66-bb87-22a243542db2.

  14. Cadherin-11 Promotes Invasive Behavior of Fibroblast-like Synoviocytes

    PubMed Central

    Kiener, Hans P.; Niederreiter, Birgit; Lee, David M.; Jimenez-Boj, Esther; Smolen, Josef S.; Brenner, Michael B.

    2009-01-01

    Objective To define the expression pattern of cadherin-11 in destructive pannus tissue of patients with rheumatoid arthritis and to determine if cadherin-11 expression in fibroblast-like synoviocytes controls their invasive capacity. Methods Cadherin-11 expression in rheumatoid synovial tissue was evaluated using immunohistochemistry. To examine the role of cadherin-11 in regulating the invasive behavior of fibroblast-like synoviocytes, we generated L-cell clones expressing wild-type cadherin-11, mutant cadherin-11, and empty vector transfected controls. The invasive capacity of L-cell transfectants and cultured fibroblast-like synoviocytes treated with a blocking cadherin-11-Fc protein or control immunoglobulin was determined in Matrigel invasion assays. Results Immunohistochemistry revealed that cadherin-11 is abundantly expressed in cells at the cartilage-pannus junction in rheumatoid synovitis. Invasion assays demonstrate a twofold increased invasive capacity of cadherin-11 transfected L-cells compared to L-cells transfected with E-cadherin or control vector. The invasive behavior of the L-cells stably transfected with a cadherin-11 construct that lacked the juxta-membrane cytoplasmic domain (cadherin-11 ΔJMD) was diminished to the level of vector control L-cells. Further, treatment with the cadherin-11-Fc fusion protein diminished the invasive capacity of fibroblast-like synoviocytes. Conclusion These in vitro studies implicate a role for cadherin-11 in promoting cell invasion and contribute insight into the invasive nature of fibroblast-like synoviocytes in chronic synovitis and rheumatoid arthritis. PMID:19404963

  15. New pasture plants intensify invasive species risk.

    PubMed

    Driscoll, Don A; Catford, Jane A; Barney, Jacob N; Hulme, Philip E; Inderjit; Martin, Tara G; Pauchard, Aníbal; Pyšek, Petr; Richardson, David M; Riley, Sophie; Visser, Vernon

    2014-11-18

    Agricultural intensification is critical to meet global food demand, but intensification threatens native species and degrades ecosystems. Sustainable intensification (SI) is heralded as a new approach for enabling growth in agriculture while minimizing environmental impacts. However, the SI literature has overlooked a major environmental risk. Using data from eight countries on six continents, we show that few governments regulate conventionally bred pasture taxa to limit threats to natural areas, even though most agribusinesses promote taxa with substantial weed risk. New pasture taxa (including species, subspecies, varieties, cultivars, and plant-endophyte combinations) are bred with characteristics typical of invasive species and environmental weeds. By introducing novel genetic and endophyte variation, pasture taxa are imbued with additional capacity for invasion and environmental impact. New strategies to prevent future problems are urgently needed. We highlight opportunities for researchers, agribusiness, and consumers to reduce environmental risks associated with new pasture taxa. We also emphasize four main approaches that governments could consider as they build new policies to limit weed risks, including (i) national lists of taxa that are prohibited based on environmental risk; (ii) a weed risk assessment for all new taxa; (iii) a program to rapidly detect and control new taxa that invade natural areas; and (iv) the polluter-pays principle, so that if a taxon becomes an environmental weed, industry pays for its management. There is mounting pressure to increase livestock production. With foresight and planning, growth in agriculture can be achieved sustainably provided that the scope of SI expands to encompass environmental weed risks.

  16. Plant invasions and extinction debts.

    PubMed

    Gilbert, Benjamin; Levine, Jonathan M

    2013-01-29

    Whether introduced species invasions pose a major threat to biodiversity is hotly debated. Much of this debate is fueled by recent findings that competition from introduced organisms has driven remarkably few plant species to extinction. Instead, native plant species in invaded ecosystems are often found in refugia: patchy, marginal habitats unsuitable to their nonnative competitors. However, whether the colonization and extinction dynamics of these refugia allow long-term native persistence is uncertain. Of particular concern is the possibility that invasive plants may induce an extinction debt in the native flora, where persistence over the short term masks deterministic extinction trajectories. We examined how invader impacts on landscape structure influence native plant persistence by combining recently developed quantitative techniques for evaluating metapopulation persistence with field measurements of an invaded plant community. We found that European grass invasion of an edaphically heterogeneous California landscape has greatly decreased the likelihood of the persistence of native metapopulations. It does so via two main pathways: (i) decreasing the size of native refugia, which reduces seed production and increases local extinction, and (ii) eroding the dispersal permeability of the matrix between refugia, which reduces their connectivity. Even when native plant extinction is the deterministic outcome of invasion, the time to extinction can be on the order of hundreds of years. We conclude that the relatively short time since invasion in many parts of the world is insufficient to observe the full impact of plant invasions on native biodiversity.

  17. Invasive mycoses: diagnostic challenges.

    PubMed

    Ostrosky-Zeichner, Luis

    2012-01-01

    Despite the availability of newer antifungal drugs, outcomes for patients with invasive fungal infections (IFIs) continue to be poor, in large part due to delayed diagnosis and initiation of appropriate antifungal therapy. Standard histopathologic diagnostic techniques are often untenable in at-risk patients, and culture-based diagnostics typically are too insensitive or nonspecific, or provide results after too long a delay for optimal IFI management. Newer surrogate markers of IFIs with improved sensitivity and specificity are needed to enable earlier diagnosis and, ideally, to provide prognostic information and/or permit therapeutic monitoring. Surrogate assays should also be accessible and easy to implement in the hospital. Several nonculture-based assays of newer surrogates are making their way into the medical setting or are currently under investigation. These new or up-and-coming surrogates include antigens/antibodies (mannan and antimannan antibodies) or fungal metabolites (d-arabinitol) for detection of invasive candidiasis, the Aspergillus cell wall component galactomannan used to detect invasive aspergillosis, or the fungal cell wall component and panfungal marker β-glucan. In addition, progress continues with use of polymerase chain reaction- or other nucleic acid- or molecular-based assays for diagnosis of either specific or generic IFIs, although the various methods must be better standardized before any of these approaches can be more fully implemented into the medical setting. Investigators are also beginning to explore the possibility of combining newer surrogate markers with each other or with more standard diagnostic approaches to improve sensitivity, specificity, and capacity for earlier diagnosis, at a time when fungal burden is still relatively low and more responsive to antifungal therapy.

  18. Esophagectomy - minimally invasive

    MedlinePlus

    Minimally invasive esophagectomy; Robotic esophagectomy; Removal of the esophagus - minimally invasive; Achalasia - esophagectomy; Barrett esophagus - esophagectomy; Esophageal cancer - esophagectomy - laparoscopic; Cancer of the ...

  19. CRP2, a new invadopodia actin bundling factor critically promotes breast cancer cell invasion and metastasis

    PubMed Central

    Dieterle, Monika; Moreau, Flora; Al Absi, Antoun; Steinmetz, André; Oudin, Anaïs; Berchem, Guy; Janji, Bassam; Thomas, Clément

    2016-01-01

    A critical process underlying cancer metastasis is the acquisition by tumor cells of an invasive phenotype. At the subcellular level, invasion is facilitated by actin-rich protrusions termed invadopodia, which direct extracellular matrix (ECM) degradation. Here, we report the identification of a new cytoskeletal component of breast cancer cell invadopodia, namely cysteine-rich protein 2 (CRP2). We found that CRP2 was not or only weakly expressed in epithelial breast cancer cells whereas it was up-regulated in mesenchymal/invasive breast cancer cells. In addition, high expression of the CRP2 encoding gene CSRP2 was associated with significantly increased risk of metastasis in basal-like breast cancer patients. CRP2 knockdown significantly reduced the invasive potential of aggressive breast cancer cells, whereas it did not impair 2D cell migration. In keeping with this, CRP2-depleted breast cancer cells exhibited a reduced capacity to promote ECM degradation, and to secrete and express MMP-9, a matrix metalloproteinase repeatedly associated with cancer progression and metastasis. In turn, ectopic expression of CRP2 in weakly invasive cells was sufficient to stimulate cell invasion. Both GFP-fused and endogenous CRP2 localized to the extended actin core of invadopodia, a structure primarily made of actin bundles. Purified recombinant CRP2 autonomously crosslinked actin filaments into thick bundles, suggesting that CRP2 contributes to the formation/maintenance of the actin core. Finally, CRP2 depletion significantly reduced the incidence of lung metastatic lesions in two xenograft mouse models of breast cancer. Collectively, our data identify CRP2 as a new cytoskeletal component of invadopodia that critically promotes breast cancer cell invasion and metastasis. PMID:26883198

  20. Biological invasions, ecological resilience and adaptive governance.

    PubMed

    Chaffin, Brian C; Garmestani, Ahjond S; Angeler, David G; Herrmann, Dustin L; Stow, Craig A; Nyström, Magnus; Sendzimir, Jan; Hopton, Matthew E; Kolasa, Jurek; Allen, Craig R

    2016-12-01

    In a world of increasing interconnections in global trade as well as rapid change in climate and land cover, the accelerating introduction and spread of invasive species is a critical concern due to associated negative social and ecological impacts, both real and perceived. Much of the societal response to invasive species to date has been associated with negative economic consequences of invasions. This response has shaped a war-like approach to addressing invasions, one with an agenda of eradications and intense ecological restoration efforts towards prior or more desirable ecological regimes. This trajectory often ignores the concept of ecological resilience and associated approaches of resilience-based governance. We argue that the relationship between ecological resilience and invasive species has been understudied to the detriment of attempts to govern invasions, and that most management actions fail, primarily because they do not incorporate adaptive, learning-based approaches. Invasive species can decrease resilience by reducing the biodiversity that underpins ecological functions and processes, making ecosystems more prone to regime shifts. However, invasions do not always result in a shift to an alternative regime; invasions can also increase resilience by introducing novelty, replacing lost ecological functions or adding redundancy that strengthens already existing structures and processes in an ecosystem. This paper examines the potential impacts of species invasions on the resilience of ecosystems and suggests that resilience-based approaches can inform policy by linking the governance of biological invasions to the negotiation of tradeoffs between ecosystem services.

  1. Biological invasions, ecological resilience and adaptive governance

    USGS Publications Warehouse

    Chaffin, Brian C.; Garmestani, Ahjond S.; Angeler, David G.; Herrmann, Dustin L.; Stow, Craig A.; Nystrom, Magnus; Sendzimir, Jan; Hopton, Matthew E.; Kolasa, Jurek; Allen, Craig R.

    2016-01-01

    In a world of increasing interconnections in global trade as well as rapid change in climate and land cover, the accelerating introduction and spread of invasive species is a critical concern due to associated negative social and ecological impacts, both real and perceived. Much of the societal response to invasive species to date has been associated with negative economic consequences of invasions. This response has shaped a war-like approach to addressing invasions, one with an agenda of eradications and intense ecological restoration efforts towards prior or more desirable ecological regimes. This trajectory often ignores the concept of ecological resilience and associated approaches of resilience-based governance. We argue that the relationship between ecological resilience and invasive species has been understudied to the detriment of attempts to govern invasions, and that most management actions fail, primarily because they do not incorporate adaptive, learning-based approaches. Invasive species can decrease resilience by reducing the biodiversity that underpins ecological functions and processes, making ecosystems more prone to regime shifts. However, invasions do not always result in a shift to an alternative regime; invasions can also increase resilience by introducing novelty, replacing lost ecological functions or adding redundancy that strengthens already existing structures and processes in an ecosystem. This paper examines the potential impacts of species invasions on the resilience of ecosystems and suggests that resilience-based approaches can inform policy by linking the governance of biological invasions to the negotiation of tradeoffs between ecosystem services.

  2. VARIATION IN RESOURCE ACQISITION AND UTILIZATION TRAITS BETWEEN NATIVE AND INVASIVE PERENNIAL FORBS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Understanding the factors influencing ecosystem invasibility is a vital, yet elusive, ecological goal. Although some research suggests functional group similarity between native and invasive plants reduces invasibility, other studies indicate only a weak correlation between functional group composi...

  3. Fibronectin Binding Proteins SpsD and SpsL Both Support Invasion of Canine Epithelial Cells by Staphylococcus pseudintermedius

    PubMed Central

    Pietrocola, Giampiero; Gianotti, Valentina; Richards, Amy; Nobile, Giulia; Geoghegan, Joan A.; Rindi, Simonetta; Monk, Ian R.; Bordt, Andrea S.; Foster, Timothy J.; Fitzgerald, J. Ross

    2015-01-01

    In this study, we investigated the cell wall-anchored fibronectin-binding proteins SpsD and SpsL from the canine commensal and pathogen Staphylococcus pseudintermedius for their role in promoting bacterial invasion of canine progenitor epidermal keratinocytes (CPEK). Invasion was examined by the gentamicin protection assay and fluorescence microscopy. An ΔspsD ΔspsL mutant of strain ED99 had a dramatically reduced capacity to invade CPEK monolayers, while no difference in the invasion level was observed with single mutants. Lactococcus lactis transformed with plasmids expressing SpsD and SpsL promoted invasion, showing that both proteins are important. Soluble fibronectin was required for invasion, and an RGD-containing peptide or antibodies recognizing the integrin α5β1 markedly reduced invasion, suggesting an important role for the integrin in this process. Src kinase inhibitors effectively blocked internalization, suggesting a functional role for the kinase in invasion. In order to identify the minimal fibronectin-binding region of SpsD and SpsL involved in the internalization process, recombinant fragments of both proteins were produced. The SpsD520–846 and SpsL538–823 regions harboring the major fibronectin-binding sites inhibited S. pseudintermedius internalization. Finally, the effects of staphylococcal invasion on the integrity of different cell lines were examined. Because SpsD and SpsL are critical factors for adhesion and invasion, blocking these processes could provide a strategy for future approaches to treating infections. PMID:26238710

  4. Fibronectin Binding Proteins SpsD and SpsL Both Support Invasion of Canine Epithelial Cells by Staphylococcus pseudintermedius.

    PubMed

    Pietrocola, Giampiero; Gianotti, Valentina; Richards, Amy; Nobile, Giulia; Geoghegan, Joan A; Rindi, Simonetta; Monk, Ian R; Bordt, Andrea S; Foster, Timothy J; Fitzgerald, J Ross; Speziale, Pietro

    2015-10-01

    In this study, we investigated the cell wall-anchored fibronectin-binding proteins SpsD and SpsL from the canine commensal and pathogen Staphylococcus pseudintermedius for their role in promoting bacterial invasion of canine progenitor epidermal keratinocytes (CPEK). Invasion was examined by the gentamicin protection assay and fluorescence microscopy. An ΔspsD ΔspsL mutant of strain ED99 had a dramatically reduced capacity to invade CPEK monolayers, while no difference in the invasion level was observed with single mutants. Lactococcus lactis transformed with plasmids expressing SpsD and SpsL promoted invasion, showing that both proteins are important. Soluble fibronectin was required for invasion, and an RGD-containing peptide or antibodies recognizing the integrin α5β1 markedly reduced invasion, suggesting an important role for the integrin in this process. Src kinase inhibitors effectively blocked internalization, suggesting a functional role for the kinase in invasion. In order to identify the minimal fibronectin-binding region of SpsD and SpsL involved in the internalization process, recombinant fragments of both proteins were produced. The SpsD520-846 and SpsL538-823 regions harboring the major fibronectin-binding sites inhibited S. pseudintermedius internalization. Finally, the effects of staphylococcal invasion on the integrity of different cell lines were examined. Because SpsD and SpsL are critical factors for adhesion and invasion, blocking these processes could provide a strategy for future approaches to treating infections.

  5. Evolutionary origins of invasive populations

    PubMed Central

    Lee, Carol Eunmi; Gelembiuk, Gregory William

    2008-01-01

    What factors shape the evolution of invasive populations? Recent theoretical and empirical studies suggest that an evolutionary history of disturbance might be an important factor. This perspective presents hypotheses regarding the impact of disturbance on the evolution of invasive populations, based on a synthesis of the existing literature. Disturbance might select for life-history traits that are favorable for colonizing novel habitats, such as rapid population growth and persistence. Theoretical results suggest that disturbance in the form of fluctuating environments might select for organismal flexibility, or alternatively, the evolution of evolvability. Rapidly fluctuating environments might favor organismal flexibility, such as broad tolerance or plasticity. Alternatively, longer fluctuations or environmental stress might lead to the evolution of evolvability by acting on features of the mutation matrix. Once genetic variance is generated via mutations, temporally fluctuating selection across generations might promote the accumulation and maintenance of genetic variation. Deeper insights into how disturbance in native habitats affects evolutionary and physiological responses of populations would give us greater capacity to predict the populations that are most likely to tolerate or adapt to novel environments during habitat invasions. Moreover, we would gain fundamental insights into the evolutionary origins of invasive populations. PMID:25567726

  6. Invasive plants may promote predator-mediated feedback that inhibits further invasion

    PubMed Central

    Smith, Lauren M; Schmitz, Oswald J

    2015-01-01

    Understanding the impacts of invasive species requires placing invasion within a full community context. Plant invaders are often considered in the context of herbivores that may drive invasion by avoiding invaders while consuming natives (enemy escape), or inhibit invasion by consuming invaders (biotic resistance). However, predators that attack those herbivores are rarely considered as major players in invasion. Invasive plants often promote predators, generally by providing improved habitat. Here, we show that predator-promoting invaders may initiate a negative feedback loop that inhibits invasion. By enabling top-down control of herbivores, predator-promoting invaders lose any advantage gained through enemy escape, indirectly favoring natives. In cases where palatable invaders encounter biotic resistance, predator promotion may allow an invader to persist, but not dominate. Overall, results indicate that placing invaders in a full community context may reveal reduced impacts of invaders compared to expectations based on simple plant–plant or plant–herbivore subsystems. PMID:26120430

  7. Reduced volume but increased training intensity elevates muscle Na+-K+ pump alpha1-subunit and NHE1 expression as well as short-term work capacity in humans.

    PubMed

    Iaia, F Marcello; Thomassen, Martin; Kolding, Helle; Gunnarsson, Thomas; Wendell, Jesper; Rostgaard, Thomas; Nordsborg, Nikolai; Krustrup, Peter; Nybo, Lars; Hellsten, Ylva; Bangsbo, Jens

    2008-03-01

    The present study examined muscle adaptations and alterations in work capacity in endurance-trained runners after a change from endurance to sprint training. Fifteen runners were assigned to either a sprint training (ST, n = 8) or a control (CON, n = 7) group. ST replaced their normal training by 30-s sprint runs three to four times a week, whereas CON continued the endurance training (approximately 45 km/wk). After the 4-wk sprint period, the expression of the muscle Na+-K+ pump alpha1-subunit and Na+/H+-exchanger isoform 1 was 29 and 30% higher (P < 0.05), respectively. Furthermore, plasma K+ concentration was reduced (P < 0.05) during repeated intense running. In ST, performance in a 30-s sprint test, Yo-Yo intermittent recovery test, and two supramaximal exhaustive runs was improved (P < 0.05) by 7, 19, 27, and 19%, respectively, after the sprint training period, whereas pulmonary maximum oxygen uptake and 10-k time were unchanged. No changes in CON were observed. The present data suggest a role of the Na+-K+ pump in the control of K+ homeostasis and in the development of fatigue during repeated high-intensity exercise. Furthermore, performance during intense exercise can be improved and endurance performance maintained even with a reduction in training volume if the intensity of training is very high.

  8. Invasive and non-invasive assessment of portal hypertension.

    PubMed

    Leung, Jonathan Chung-Fai; Loong, Thomson Chi-Wang; Pang, James; Wei, Jeremy Lok; Wong, Vincent Wai-Sun

    2017-03-30

    Portal hypertension is the central driver of complications in patients with chronic liver diseases and cirrhosis. The diagnosis of portal hypertension has important prognostic and clinical implications. In particular, screening for varices in patients with portal hypertension can effectively reduce the morbidity and mortality of variceal bleeding. In this article, we review the invasive and non-invasive methods to assess portal hypertension. Hepatic venous pressure gradient remains the gold standard to measure portal pressure but is invasive and seldom performed outside expert centers and research settings. In recent years, a number of non-invasive tests of fibrosis have shown good correlation with liver histology. They also show promise in identifying patients with portal hypertension and large varices. As a result, the latest Baveno VI consensus guidelines endorse the use of liver stiffness measurement by transient elastography and platelet count as initial assessment to select patients for varices screening. On the other hand, the performance of non-invasive tests in assessing the response to non-selective beta-blockers or transjugular intrahepatic portosystemic shunting is either suboptimal or unclear.

  9. SOST Inhibits Prostate Cancer Invasion

    SciTech Connect

    Hudson, Bryan D.; Hum, Nicholas R.; Thomas, Cynthia B.; Kohlgruber, Ayano; Sebastian, Aimy; Collette, Nicole M.; Coleman, Matthew A.; Christiansen, Blaine A.; Loots, Gabriela G.

    2015-11-06

    Inhibitors of Wnt signaling have been shown to be involved in prostate cancer (PC) metastasis; however the role of Sclerostin (Sost) has not yet been explored. Here we show that elevated Wnt signaling derived from Sost deficient osteoblasts promotes PC invasion, while rhSOST has an inhibitory effect. In contrast, rhDKK1 promotes PC elongation and filopodia formation, morphological changes characteristic of an invasive phenotype. Furthermore, rhDKK1 was found to activate canonical Wnt signaling in PC3 cells, suggesting that SOST and DKK1 have opposing roles on Wnt signaling in this context. Gene expression analysis of PC3 cells co-cultured with OBs exhibiting varying amounts of Wnt signaling identified CRIM1 as one of the transcripts upregulated under highly invasive conditions. We found CRIM1 overexpression to also promote cell-invasion. These findings suggest that bone-derived Wnt signaling may enhance PC tropism by promoting CRIM1 expression and facilitating cancer cell invasion and adhesion to bone. We concluded that SOST and DKK1 have opposing effects on PC3 cell invasion and that bone-derived Wnt signaling positively contributes to the invasive phenotypes of PC3 cells by activating CRIM1 expression and facilitating PC-OB physical interaction. As such, we investigated the effects of high concentrations of SOST in vivo. In conclusion, we found that PC3-cells overexpressing SOST injected via the tail vein in NSG mice did not readily metastasize, and those injected intrafemorally had significantly reduced osteolysis, suggesting that targeting the molecular bone environment may influence bone metastatic prognosis in clinical settings.

  10. SOST Inhibits Prostate Cancer Invasion

    DOE PAGES

    Hudson, Bryan D.; Hum, Nicholas R.; Thomas, Cynthia B.; ...

    2015-11-06

    Inhibitors of Wnt signaling have been shown to be involved in prostate cancer (PC) metastasis; however the role of Sclerostin (Sost) has not yet been explored. Here we show that elevated Wnt signaling derived from Sost deficient osteoblasts promotes PC invasion, while rhSOST has an inhibitory effect. In contrast, rhDKK1 promotes PC elongation and filopodia formation, morphological changes characteristic of an invasive phenotype. Furthermore, rhDKK1 was found to activate canonical Wnt signaling in PC3 cells, suggesting that SOST and DKK1 have opposing roles on Wnt signaling in this context. Gene expression analysis of PC3 cells co-cultured with OBs exhibiting varyingmore » amounts of Wnt signaling identified CRIM1 as one of the transcripts upregulated under highly invasive conditions. We found CRIM1 overexpression to also promote cell-invasion. These findings suggest that bone-derived Wnt signaling may enhance PC tropism by promoting CRIM1 expression and facilitating cancer cell invasion and adhesion to bone. We concluded that SOST and DKK1 have opposing effects on PC3 cell invasion and that bone-derived Wnt signaling positively contributes to the invasive phenotypes of PC3 cells by activating CRIM1 expression and facilitating PC-OB physical interaction. As such, we investigated the effects of high concentrations of SOST in vivo. In conclusion, we found that PC3-cells overexpressing SOST injected via the tail vein in NSG mice did not readily metastasize, and those injected intrafemorally had significantly reduced osteolysis, suggesting that targeting the molecular bone environment may influence bone metastatic prognosis in clinical settings.« less

  11. The invasive stoloniferous clonal plant Alternanthera philoxeroides outperforms its co-occurring non-invasive functional counterparts in heterogeneous soil environments – invasion implications

    PubMed Central

    Wang, Tong; Hu, Jiangtao; Miao, Linlin; Yu, Dan; Liu, Chunhua

    2016-01-01

    Environmental heterogeneity is considered to play a defining role in promoting invasion success, and it favours clonal plants. Although clonality has been demonstrated to be correlated with the invasion success of several species of clonal invasive plants in heterogeneous environments, little is known about how the spatial scale of heterogeneity affects their performance. In addition, the factors that distinguish invasive from non-invasive clonal species and that enhance the invasive potential of clonal exotic invaders in heterogeneous environments remain unclear. In this study, we compared several traits of a noxious clonal invasive species, Alternanthera philoxeroides, with its co-occurring non-invasive functional counterparts, the native congener Alternanthera sessilis, the exotic Myriophyllum aquaticum and the native Jussiaea repens, in three manipulative substrates with different soil distribution patterns. We found that the invasive performance of A. philoxeroides was not enhanced by heterogeneity and that it was generally scale independent. However, A. philoxeroides showed some advantages over the three non-invasives with respect to trait values and phenotypic variation. These advantages may enhance the competitive capacity of A. philoxeroides and thus promote its invasion success in heterogeneous environments. PMID:27897247

  12. The invasion mode of GH(3) cells is conditioned by collagen subtype, and its efficiency depends on cell-cell adhesion.

    PubMed

    Azorín, Erika; Solano-Agama, Carmen; Mendoza-Garrido, M Eugenia

    2012-12-15

    The adaptation of GH(3) cells to different microenvironments is a consequence of a partial compromise with the tumor phenotype. A collagen type IV enriched microenvironment favors an invasive phenotype and increases the substrate adhesion capacity, whereas it decreases the phosphorylation of the regulatory myosin light chain and the aggregation capacity. In contrast, the higher internal tension and increased aggregation capacity induced by collagen type I/III are factors that reduce the invasion rate. Our results show, for the first time, the importance of collagen subtypes in determining the migratory strategy: collagen I/III favors mesenchymal-like motility, whereas collagen type IV induces an ameboid-type displacement. The reciprocal modulation of the myosin light chain kinase and the Rho-kinase determines the invasive capacity through changes in tissue cohesion, extracellular matrix affinity, regulatory myosin light chain phosphorylation and spatial distribution. The collagen subtype determines which of the mechano-transduction signaling pathways will regulate the tensional homeostasis and affect the invasion ability as well as the preferred migration strategy of the cells.

  13. Attacking invasive grasses

    USGS Publications Warehouse

    Keeley, Jon E.

    2015-01-01

    In grasslands fire may play a role in the plant invasion process, both by creating disturbances that potentially favour non-native invasions and as a possible tool for controlling alien invasions. Havill et al. (Applied Vegetation Science, 18, 2015, this issue) determine how native and non-native species respond to different fire regimes as a first step in understanding the potential control of invasive grasses.

  14. Diet, physical exercise and cognitive behavioral training as a combined workplace based intervention to reduce body weight and increase physical capacity in health care workers - a randomized controlled trial

    PubMed Central

    2011-01-01

    Background Health care workers comprise a high-risk workgroup with respect to deterioration and early retirement. There is high prevalence of obesity and many of the workers are overweight. Together, these factors play a significant role in the health-related problems within this sector. The present study evaluates the effects of the first 3-months of a cluster randomized controlled lifestyle intervention among health care workers. The intervention addresses body weight, general health variables, physical capacity and musculoskeletal pain. Methods 98 female, overweight health care workers were cluster-randomized to an intervention group or a reference group. The intervention consisted of an individually dietary plan with an energy deficit of 1200 kcal/day (15 min/hour), strengthening exercises (15 min/hour) and cognitive behavioral training (30 min/hour) during working hours 1 hour/week. Leisure time aerobic fitness was planned for 2 hour/week. The reference group was offered monthly oral presentations. Body weight, BMI, body fat percentage (bioimpedance), waist circumference, blood pressure, musculoskeletal pain, maximal oxygen uptake (maximal bicycle test), and isometric maximal muscle strength of 3 body regions were measured before and after the intervention period. Results In an intention-to-treat analysis from pre to post tests, the intervention group significantly reduced body weight with 3.6 kg (p < 0.001), BMI from 30.5 to 29.2 (p < 0.001), body fat percentage from 40.9 to 39.3 (p < 0.001), waist circumference from 99.7 to 95.5 cm (p < 0.001) and blood pressure from 134/85 to 127/80 mmHg (p < 0.001), with significant difference between the intervention and control group (p < 0.001) on all measures. No effect of intervention was found in musculoskeletal pain, maximal oxygen uptake and muscle strength, but on aerobic fitness. Conclusion The significantly reduced body weight, body fat, waist circumference and blood pressure as well as increased aerobic fitness

  15. The Oncogenic Lung Cancer Fusion Kinase CD74-ROS Activates a Novel Invasiveness Pathway Through E-Syt1 Phosphorylation

    PubMed Central

    Jun, Hyun Jung; Johnson, Hannah; Bronson, Roderick T.; de Feraudy, Sebastien; White, Forest; Charest, Alain

    2013-01-01

    Patients with lung cancer often present with metastatic disease and therefore have a very poor prognosis. The recent discovery of several novel ROS receptor tyrosine kinase molecular alterations in non-small-cell lung cancer (NSCLC) presents a therapeutic opportunity for the development of new targeted treatment strategies. Here, we report that the NSCLC-derived fusion CD74-ROS, which accounts for 30% of all ROS fusion kinases in NSCLC, is an active and oncogenic tyrosine kinase. We found that CD74-ROS expressing cells were highly invasive in vitro and metastatic in vivo. Pharmacological inhibition of CD74-ROS kinase activity reversed its transforming capacity by attenuating downstrream signaling networks. Using quantitative phosphoproteomics, we uncovered a mechanism by which CD74-ROS activates a novel pathway driving cell invasion. Expression of CD74-ROS resulted in the phosphorylation of the extended synaptotagmin-like protein E-Syt1. Elimination of E-Syt1 expression drastically reduced invasiveness both in vitro and in vivo without modifying the oncogenic activity of CD74-ROS. Furthermore, expression of CD74-ROS in non-invasive NSCLC cell lines readily confered invasive properties that paralleled the acquisition of E-Syt1 phosphorylation. Taken together, our findings indicate that E-Syt1 is a mediator of cancer cell invasion and molecularly define ROS fusion kinases as therapeutic targets in the treatment of NSCLC. PMID:22659450

  16. Using resistance and resilience concepts to reduce impacts of invasive annual grasses and altered fire regimes on the sagebrush ecosystem and greater sage-grouse: a strategic multi-scale approach

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This Report provides a strategic approach for conservation of sagebrush ecosystems and Greater Sage-Grouse (sage-grouse) that focuses specifically on habitat threats caused by invasive annual grasses and altered fire regimes. It uses information on (1) factors that influence sagebrush ecosystem resi...

  17. Invasive species in agriculture

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Agricultural production of food, feed, fiber or fuel is a local human activity with global ecological impacts, including the potential to foster invasions. Agriculture plays an unusual role in biological invasions, in that it is both a source of non-indigenous invasive species (NIS) and especially s...

  18. New pasture plants intensify invasive species risk

    PubMed Central

    Driscoll, Don A.; Catford, Jane A.; Barney, Jacob N.; Hulme, Philip E.; Inderjit; Martin, Tara G.; Pauchard, Aníbal; Pyšek, Petr; Richardson, David M.; Riley, Sophie; Visser, Vernon

    2014-01-01

    Agricultural intensification is critical to meet global food demand, but intensification threatens native species and degrades ecosystems. Sustainable intensification (SI) is heralded as a new approach for enabling growth in agriculture while minimizing environmental impacts. However, the SI literature has overlooked a major environmental risk. Using data from eight countries on six continents, we show that few governments regulate conventionally bred pasture taxa to limit threats to natural areas, even though most agribusinesses promote taxa with substantial weed risk. New pasture taxa (including species, subspecies, varieties, cultivars, and plant-endophyte combinations) are bred with characteristics typical of invasive species and environmental weeds. By introducing novel genetic and endophyte variation, pasture taxa are imbued with additional capacity for invasion and environmental impact. New strategies to prevent future problems are urgently needed. We highlight opportunities for researchers, agribusiness, and consumers to reduce environmental risks associated with new pasture taxa. We also emphasize four main approaches that governments could consider as they build new policies to limit weed risks, including (i) national lists of taxa that are prohibited based on environmental risk; (ii) a weed risk assessment for all new taxa; (iii) a program to rapidly detect and control new taxa that invade natural areas; and (iv) the polluter-pays principle, so that if a taxon becomes an environmental weed, industry pays for its management. There is mounting pressure to increase livestock production. With foresight and planning, growth in agriculture can be achieved sustainably provided that the scope of SI expands to encompass environmental weed risks. PMID:25368175

  19. Rubus idaeus L Inhibits Invasion Potential of Human A549 Lung Cancer Cells by Suppression Epithelial-to-Mesenchymal Transition and Akt Pathway In Vitro and Reduces Tumor Growth In Vivo.

    PubMed

    Chu, Shu-Chen; Hsieh, Yih-Shou; Hsu, Li-Sung; Chen, Kuo-Shuen; Chiang, Chien-Cheng; Chen, Pei-Ni

    2014-05-01

    The metastasis of lung cancer is the most prevalent cause of patient death. Various treatment strategies have targeted the prevention of the occurrence of metastasis. The epithelial-mesenchymal transition (EMT) in lung cancer cells is considered a prerequisite to acquire the invasive/migratory phenotype and to subsequently achieve metastasis. However, the effects ofRubus idaeuson cancer invasion and the EMT of the human lung carcinoma remain unclear. In this article, we test the hypothesis thatR idaeusethyl acetate (RIAE) possesses an antimetastatic effect and reverses the EMT potential of human lung A549 cells. We extract the raspberryR idaeuswith methanol (RIME), chloroform (RICE), ethyl acetate (RIAE),n-butanol (RIBE), and water (RIWE). The RIAE treatment obviously inhibits the invasive (P< .001), motility (P< .001), spreading, and migratory potential (P< .001) of highly metastatic human lung cancer A549 cells. The zymography and promoter luciferase analysis reveals that RIAE decreases the proteinase and transcription activities of MMP-2 and u-PA. Molecular analyses show that RIAE increases the E-cadherin level that is mainly localized at the cellular membrane. This result was also verified through confocal analyses. RIAE also induces the upregulation of an epithelial marker, such as α-catenin, and decreases mesenchymal markers, such as snail-1 and N-cadherin, that promote cell invasion and metastasis. RIAE inhibits MMP-2 and u-PA by attenuating the NF-κB and p-Akt expression. The inhibition of RIAE on the growth of A549 cells in vivo was also verified using a cancer cell xenograft nude mice model. Our results show the anti-invasive/antitumor effects of RIAE and associated mechanisms, which suggest that RIAE should be further tested in clinically relevant models to exploit its potential benefits against metastatic lung cancer cells.

  20. Cyclic mechanical stretching promotes migration but inhibits invasion of rat bone marrow stromal cells.

    PubMed

    Zhang, Bingyu; Luo, Qing; Chen, Zhe; Sun, Jinghui; Xu, Baiyao; Ju, Yang; Song, Guanbin

    2015-03-01

    Bone marrow stromal cells (BMSCs, also broadly known as bone marrow-derived mesenchymal stem cells) are multipotent stem cells that have a self-renewal capacity and multilineage differentiation potential. Mechanical stretching plays a vital role in regulating the proliferation and differentiation of BMSCs. However, little is known about the effects of cyclic stretching on BMSC migration and invasion. In this study, using a custom-made cell-stretching device, we studied the effects of cyclic mechanical stretching on rat BMSC migration and invasion using a Transwell Boyden Chamber. The protein secretion of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) was detected by gelatin zymography, and the activation of focal adhesion kinase (FAK) and extracellular signal regulated kinase1/2 (ERK1/2) was measured by western blot. We found that cyclic mechanical stretching with 10% amplitude at 1Hz frequency for 8h promotes BMSC migration, but reduces BMSC invasion. FAK and ERK1/2 signals were activated in BMSCs after exposure to cyclic stretching. In the presence of the FAK phosphorylation blocker PF573228 or the ERK1/2 phosphorylation blocker PD98059, the cyclic-stretch-promoted migration of BMSCs was completely suppressed. On the other hand, cyclic mechanical stretching reduced the secretion of MMP-2 and MMP-9 in BMSCs, and PF573228 suppressed the cyclic-stretch-reduced secretion of MMP-2 and MMP-9. The decrease of BMSC invasion induced by mechanical stretching is partially restored by PF573228 but remained unaffected by PD98059. Taken together, these data show that cyclic mechanical stretching promotes BMSC migration via the FAK-ERK1/2 signalling pathway, but reduces BMSC invasion by decreasing secretion of MMP-2 and MMP-9 via FAK, independent of the ERK1/2 signal.

  1. Patterns of woody plant invasion in an Argentinean coastal grassland

    NASA Astrophysics Data System (ADS)

    Alberio, Constanza; Comparatore, Viviana

    2014-01-01

    Coastal dune grasslands are fragile ecosystems that have historically been subjected to various types of uses and human activities. In Buenos Aires Province (Argentina), these areas are frequently afforested for urban and touristic development. The introduction and subsequent spread of exotic tree species is one of the main threats to conservation of natural grasslands as invasive trees strongly transform their structure and composition. The aim of this study was to identify patterns of woody plant invasion comparing plant communities and environmental variables between invaded and non-invaded areas surrounding the coastal village of Mar Azul, Argentina. Coastal grasslands in this area are being invaded by Populus alba (white poplar) and Acacia longifolia (coast wattle). The height of the saplings and the richness of the accompanying vegetation were evaluated in relation to the distance from the edge of the mature tree patches. Also, the cover, richness and diversity of all species in the invaded and non-invaded areas were measured, as well as soil pH, temperature and particle size. Negative correlations were found between the height of the saplings and distance to mature tree patches in all areas. The richness of the accompanying vegetation was negatively and positively correlated with the distance from the poplar and acacia area, respectively. The most abundant native species was Cortaderia selloana. Less cover, richness and diversity of native plant species and greater soil particle size were found in invaded areas, where the proportion of bare soil was higher. Also, a higher proportion of leaf litter in the invaded areas was registered. The results emphasize the invasive capacity of P. alba and A. longifolia advancing on the native communities and reducing their richness. Knowledge of the impact of invasive woody plants in coastal grasslands is important to design active management strategies for conservation purposes.

  2. Lack of belowground mutualisms hinders Pinaceae invasions.

    PubMed

    Nuñez, Martin A; Horton, Thomas R; Simberloff, Daniel

    2009-09-01

    Why particular invasions succeed and others fail is not well understood. The role of soil biota has been proposed as important. However, the role of mutualists has received much less attention than that of pathogens. Here we report that lack of adequate ectomycorrhizal fungi hinders invasion by exotic Pinaceae on Isla Victoria, Argentina, by reducing both the probability of establishment and growth of invading individuals. More than one hundred exotic tree species were introduced to this island ca. 80 years ago, but invasive trees are found in high densities only in areas adjacent to plantations. With a series of greenhouse and field experiments we found lower mycorrhizal colonization levels and few fungal species far from original plantings, and key fungal mutualists are confined to areas near plantations, probably owing to dispersal limitations. Low inoculum levels far from the plantations are retarding the invasion. Our experiments indicate that positive interactions belowground can play a key but underappreciated role in invasion dynamics.

  3. Contemporary review of minimally invasive pancreaticoduodenectomy

    PubMed Central

    Dai, Rui; Turley, Ryan S; Blazer, Dan G

    2016-01-01

    AIM To assess the current literature describing various minimally invasive techniques for and to review short-term outcomes after minimally invasive pancreaticoduodenectomy (PD). METHODS PD remains the only potentially curative treatment for periampullary malignancies, including, most commonly, pancreatic adenocarcinoma. Minimally invasive approaches to this complex operation have begun to be increasingly reported in the literature and are purported by some to reduce the historically high morbidity of PD associated with the open technique. In this systematic review, we have searched the literature for high-quality publications describing minimally invasive techniques for PD-including laparoscopic, robotic, and laparoscopic-assisted robotic approaches (hybrid approach). We have identified publications with the largest operative experiences from well-known centers of excellence for this complex procedure. We report primarily short term operative and perioperative results and some short term oncologic endpoints. RESULTS Minimally invasive techniques include laparoscopic, robotic and hybrid approaches and each of these techniques has strong advocates. Consistently, across all minimally invasive modalities, these techniques are associated less intraoperative blood loss than traditional open PD (OPD), but in exchange for longer operating times. These techniques are relatively equivalent in terms of perioperative morbidity and short term oncologic outcomes. Importantly, pancreatic fistula rate appears to be comparable in most minimally invasive series compared to open technique. Impact of minimally invasive technique on length of stay is mixed compared to some traditional open series. A few series have suggested that initiation of and time to adjuvant therapy may be improved with minimally invasive techniques, however this assertion remains controversial. In terms of short-terms costs, minimally invasive PD is significantly higher than that of OPD. CONCLUSION Minimally

  4. Hybridization increases invasive knotweed success

    PubMed Central

    Parepa, Madalin; Fischer, Markus; Krebs, Christine; Bossdorf, Oliver

    2014-01-01

    Hybridization is one of the fundamental mechanisms by which rapid evolution can occur in exotic species. If hybrids show increased vigour, this could significantly contribute to invasion success. Here, we compared the success of the two invasive knotweeds, Fallopia japonica and F. sachalinensis, and their hybrid, F. × bohemica, in competing against experimental communities of native plants. Using plant material from multiple clones of each taxon collected across a latitudinal gradient in Central Europe, we found that knotweed hybrids performed significantly better in competition with a native community and that they more strongly reduced the growth of the native plants. One of the parental species, F. sachalinensis, regenerated significantly less well from rhizomes, and this difference disappeared if activated carbon was added to the substrate, which suggests allelopathic inhibition of F. sachalinensis regeneration by native plants. We found substantial within-taxon variation in competitive success in all knotweed taxa, but variation was generally greatest in the hybrid. Interestingly, there was also significant variation within the genetically uniform F. japonica, possibly reflecting epigenetic differences. Our study shows that invasive knotweed hybrids are indeed more competitive than their parents and that hybridization increased the invasiveness of the exotic knotweed complex. PMID:24665343

  5. Minimally invasive aortic valve surgery

    PubMed Central

    Castrovinci, Sebastiano; Emmanuel, Sam; Moscarelli, Marco; Murana, Giacomo; Caccamo, Giuseppa; Bertolino, Emanuela Clara; Nasso, Giuseppe; Speziale, Giuseppe; Fattouch, Khalil

    2016-01-01

    Aortic valve disease is a prevalent disorder that affects approximately 2% of the general adult population. Surgical aortic valve replacement is the gold standard treatment for symptomatic patients. This treatment has demonstrably proven to be both safe and effective. Over the last few decades, in an attempt to reduce surgical trauma, different minimally invasive approaches for aortic valve replacement have been developed and are now being increasingly utilized. A narrative review of the literature was carried out to describe the surgical techniques for minimally invasive aortic valve surgery and report the results from different experienced centers. Minimally invasive aortic valve replacement is associated with low perioperative morbidity, mortality and a low conversion rate to full sternotomy. Long-term survival appears to be at least comparable to that reported for conventional full sternotomy. Minimally invasive aortic valve surgery, either with a partial upper sternotomy or a right anterior minithoracotomy provides early- and long-term benefits. Given these benefits, it may be considered the standard of care for isolated aortic valve disease. PMID:27582764

  6. PIK3R1 targeting by miR-21 suppresses tumor cell migration and invasion by reducing PI3K/AKT signaling and reversing EMT, and predicts clinical outcome of breast cancer.

    PubMed

    Yan, Li-Xu; Liu, Yan-Hui; Xiang, Jian-Wen; Wu, Qi-Nian; Xu, Lei-Bo; Luo, Xin-Lan; Zhu, Xiao-Lan; Liu, Chao; Xu, Fang-Ping; Luo, Dong-Lan; Mei, Ping; Xu, Jie; Zhang, Ke-Ping; Chen, Jie

    2016-02-01

    We have previously shown that dysregulation of miR-21 functioned as an oncomiR in breast cancer. The aim of the present study was to elucidate the mechanisms by which miR-21 regulate breast tumor migration and invasion. We applied pathway analysis on genome microarray data and target-predicting algorithms for miR-21 target screening, and used luciferase reporting assay to confirm the direct target. Thereafter, we investigated the function of the target gene phosphoinositide-3-kinase, regulatory subunit 1 (α) (PIK3R1), and detected PIK3R1 coding protein (p85α) by immunohistochemistry and miR-21 by RT-qPCR on 320 archival paraffin-embedded tissues of breast cancer to evaluate the correlation of their expression with prognosis. First, we found that PIK3R1 suppressed growth, invasiveness, and metastatic properties of breast cancer cells. Next, we identified the PIK3R1 as a direct target of miR-21 and showed that it was negatively regulated by miR-21. Furthermore, we demonstrated that p85α overexpression phenocopied the suppression effects of antimiR-21 on breast cancer cell growth, migration and invasion, indicating its tumor suppressor role in breast cancer. On the contrary, PIK3R1 knockdown abrogated antimiR‑21-induced effect on breast cancer cells. Notably, antimiR-21 induction increased p85α, accompanied by decreased p-AKT level. Besides, antimiR-21/PIK3R1-induced suppression of invasiveness in breast cancer cells was mediated by reversing epithelial-mesenchymal transition (EMT). p85α downregulation was found in 25 (7.8%) of the 320 breast cancer patients, and was associated with inferior 5-year disease-free survival (DFS) and overall survival (OS). Taken together, we provide novel evidence that miR-21 knockdown suppresses cell growth, migration and invasion partly by inhibiting PI3K/AKT activation via direct targeting PIK3R1 and reversing EMT in breast cancer. p85α downregulation defined a specific subgroup of breast cancer with shorter 5-year DFS and OS

  7. Evolution Arrests Invasions of Cooperative Populations

    NASA Astrophysics Data System (ADS)

    Korolev, Kirill S.

    2015-11-01

    Population expansions trigger many biomedical and ecological transitions, from tumor growth to invasions of non-native species. Although population spreading often selects for more invasive phenotypes, we show that this outcome is far from inevitable. In cooperative populations, mutations reducing dispersal have a competitive advantage. Such mutations then steadily accumulate at the expansion front, bringing invasion to a halt. Our findings are a rare example of evolution driving the population into an unfavorable state, and they could lead to new strategies to combat unwelcome invaders.

  8. Invasion of Porphyromonas gingivalis strains into vascular cells and tissue

    PubMed Central

    Olsen, Ingar; Progulske-Fox, Ann

    2015-01-01

    Porphyromonas gingivalis is considered a major pathogen in adult periodontitis and is also associated with multiple systemic diseases, for example, cardiovascular diseases. One of its most important virulence factors is invasion of host cells. The invasion process includes attachment, entry/internalization, trafficking, persistence, and exit. The present review discusses these processes related to P. gingivalis in cardiovascular cells and tissue. Although most P. gingivalis strains invade, the invasion capacity of strains and the mechanisms of invasion including intracellular trafficking among them differ. This is consistent with the fact that there are significant differences in the pathogenicity of P. gingivalis strains. P. gingivalis invasion mechanisms are also dependent on types of host cells. Although much is known about the invasion process of P. gingivalis, we still have little knowledge of its exit mechanisms. Nevertheless, it is intriguing that P. gingivalis can remain viable in human cardiovascular cells and atherosclerotic plaque and later exit and re-enter previously uninfected host cells. PMID:26329158

  9. Minimally invasive osteosynthesis technique for articular fractures.

    PubMed

    Beale, Brian S; Cole, Grayson

    2012-09-01

    Articular fractures require accurate reduction and rigid stabilization to decrease the chance of osteoarthritis and joint dysfunction. Articular fractures have been traditionally repaired by arthrotomy and internal fixation. Recently, minimally invasive techniques have been introduced to treat articular fractures, reducing patient morbidity and improving the accuracy of reduction. A variety of techniques, including distraction, radiographic imaging, and arthroscopy, are used with the minimally invasive osteosynthesis technique of articular fractures to achieve a successful repair and outcome.

  10. Contrasting phenotypic plasticity in the photoprotective strategies of the invasive species Carpobrotus edulis and the coexisting native species Crithmum maritimum.

    PubMed

    Fenollosa, Erola; Munné-Bosch, Sergi; Pintó-Marijuan, Marta

    2017-01-05

    Photoprotective strategies vary greatly within the plant kingdom and reflect a plant's physiological status and capacity to cope with environment variations. The plasticity and intensity of these responses may determine plant success. Invasive species are reported to show increased vigor to displace native species. Describing the mechanisms that confer such vigor is essential to understanding the success of invasive species. We performed an experiment whereby two species were monitored: Carpobrotus edulis, an aggressive invasive species in the Mediterranean basin, and Crithmum maritimum, a coexisting native species in the Cap de Creus Natural Park (NE Spain). We analyzed their photoprotective responses to seasonal environmental dynamics by comparing the capacity of the invader to respond to the local environmental stresses throughout the year. Our study analyses ecophysiological markers and photoprotective strategies to gain an insight into the success of invaders. We found that both species showed completely different but effective photoprotective strategies: in summer, C. edulis took special advantage of the xanthophyll cycle, whereas the success of C. maritimum in summer stemmed from morphological changes and alterations on β-carotene content. Winter also presented differences between the species, as the native showed reduced Fv /Fm ratios. Our experimental design allowed us to introduce a new approach to compare phenotypic plasticity: the integrated phenotypic plasticity index (PPint ), defined as the maximum Euclidian distance between phenotypes, using a combination of different variables to describe them. This index revealed significantly greater phenotypic plasticity in the invasive species compared to the native species.

  11. Coevolution between native and invasive plant competitors: implications for invasive species management.

    PubMed

    Leger, Elizabeth A; Espeland, Erin K

    2010-03-01

    Invasive species may establish in communities because they are better competitors than natives, but in order to remain community dominants, the competitive advantage of invasive species must be persistent. Native species that are not extirpated when highly invasive species are introduced are likely to compete with invaders. When population sizes and genetic diversity of native species are large enough, natives may be able to evolve traits that allow them to co-occur with invasive species. Native species may also evolve to become significant competitors with invasive species, and thus affect the fitness of invaders. Invasive species may respond in turn, creating either transient or continuing coevolution between competing species. In addition to demographic factors such as population size and growth rates, a number of factors including gene flow, genetic drift, the number of selection agents, encounter rates, and genetic diversity may affect the ability of native and invasive species to evolve competitive ability against one another. We discuss how these factors may differ between populations of native and invasive plants, and how this might affect their ability to respond to selection. Management actions that maintain genetic diversity in native species while reducing population sizes and genetic diversity in invasive species could promote the ability of natives to evolve improved competitive ability.

  12. Coevolution between native and invasive plant competitors: implications for invasive species management

    PubMed Central

    Leger, Elizabeth A; Espeland, Erin K

    2010-01-01

    Invasive species may establish in communities because they are better competitors than natives, but in order to remain community dominants, the competitive advantage of invasive species must be persistent. Native species that are not extirpated when highly invasive species are introduced are likely to compete with invaders. When population sizes and genetic diversity of native species are large enough, natives may be able to evolve traits that allow them to co-occur with invasive species. Native species may also evolve to become significant competitors with invasive species, and thus affect the fitness of invaders. Invasive species may respond in turn, creating either transient or continuing coevolution between competing species. In addition to demographic factors such as population size and growth rates, a number of factors including gene flow, genetic drift, the number of selection agents, encounter rates, and genetic diversity may affect the ability of native and invasive species to evolve competitive ability against one another. We discuss how these factors may differ between populations of native and invasive plants, and how this might affect their ability to respond to selection. Management actions that maintain genetic diversity in native species while reducing population sizes and genetic diversity in invasive species could promote the ability of natives to evolve improved competitive ability. PMID:25567917

  13. [Invasive and minimally invasive hemodynamic monitoring].

    PubMed

    Hansen, Matthias

    2016-10-01

    Advanced hemodynamic monitoring is necessary for adequate management of high-risk patients or patients with derangement of circulation. Studies demonstrate a benefit of early goal directed therapy in unstable cardiopulmonary situations. In these days we have different possibilities of minimally invasive or invasive hemodynamic monitoring. Minimally invasive measurements like pulse conture analysis or pulse wave analysis being less accurate under some circumstances, however only an artery catheter is needed for cardiac output monitoring. Pulmonary artery, transpulmonary thermodilution and lithium dilution technology have acceptable accuracy in cardiac output measurement. For therapy of unstable circulation there are additionally parameters to obtain. The pulmonary artery catheter is the device with the largest rate of complications, used by a trained crew and with a correct indication, his use is unchained justified.

  14. MicroRNA-92b represses invasion-metastasis cascade of esophageal squamous cell carcinoma

    PubMed Central

    Ma, Gang; Jing, Chao; Li, Lin; Huang, Furong; Ding, Fang; Wang, Baona; Lin, Dongmei; Luo, Aiping; Liu, Zhihua

    2016-01-01

    Invasion and metastasis are major contributors to cancer-caused death in patients suffered from esophageal squamous cell carcinoma (ESCC). To explore the microRNAs involved in regulating invasion-metastasis cascade of ESCC, we established two pairs of sublines (30-U/D and 180-U/D) with distinct motility capacity from two ESCC cell lines (KYSE30 and KYSE180). Screening of the differentially expressed microRNAs identified that microRNA-92b-3p (miR-92b) could dramatically inhibit invasion and metastasis of ESCC cells in vitro and in vivo. Subsequent studies showed that miR-92b exerted its inhibitory function through suppressing the expression of integrin αV (ITGAV), which further reduced phosphrylated FAK and impaired Rac1 activation. Moreover, higher expression of miR-92b in ESCC tissues correlated inversely with lymph node metastasis and indicated better prognosis. Together, these results for the first time describe how miR-92b suppresses the motility of ESCC cells and provide a promise for diagnosis or therapy of ESCC invasion and metastasis. PMID:26934001

  15. ESM1 mediates NGFR-induced invasion and metastasis in murine oral squamous cell carcinoma

    PubMed Central

    Chen, Chen; Shin, June Ho; Eggold, Joshua T.; Chung, Man Ki; Zhang, Luhua H.; Lee, Jeremy; Sunwoo, John B.

    2016-01-01

    Oral squamous cell carcinoma (OSCC) is a highly invasive and metastatic malignancy. The nerve growth factor receptor (NGFR) has been observed to be expressed on a subset of cells in OSCC, and NGFR+ cells have greater tumor-initiating capacity in vivo. Further, inhibition of NGFR reduces tumor growth, indicating a functional role of this receptor; however, the mechanisms by which NGFR confers enhanced tumor formation are not known. Here, we used an established murine model of OSCC and gene expression array analysis to identify ESM1 as a downstream target gene of NGFR, critical for tumor invasion and metastasis. ESM1 encodes a protein called endocan, which has the property of regulating proliferation, differentiation, migration, and adhesion of different cell types. Incubation of NGFR+ murine OSCC cells with nerve growth factor resulted in increased expression of ESM1. Importantly, ESM1 overexpression conferred an enhanced migratory, invasive, and metastatic phenotype, similar to what has been correlated with NGFR expression. Conversely, shRNA knockdown of ESM1 in NGFR overexpressing OSCC cells abrogated the tumor growth kinetics and the invasive and metastatic properties associated with NGFR. Together, our data indicate that NGFR plays an important role in the pathogenesis and progression of OSCC via regulation of ESM1. PMID:27683113

  16. Gallium(III), cobalt(III) and copper(II) protoporphyrin IX exhibit antimicrobial activity against Porphyromonas gingivalis by reducing planktonic and biofilm growth and invasion of host epithelial cells.

    PubMed

    Olczak, Teresa; Maszczak-Seneczko, Dorota; Smalley, John W; Olczak, Mariusz

    2012-08-01

    Porphyromonas gingivalis acquires heme for growth, and initiation and progression of periodontal diseases. One of its heme acquisition systems consists of the HmuR and HmuY proteins. This study analyzed the antimicrobial activity of non-iron metalloporphyrins against P. gingivalis during planktonic growth, biofilm formation, epithelial cell adhesion and invasion, and employed hmuY, hmuR and hmuY-hmuR mutants to assess the involvement of HmuY and HmuR proteins in the acquisition of metalloporphyrins. Iron(III) mesoporphyrin IX (mesoheme) and iron(III) deuteroporphyrin IX (deuteroheme) supported planktonic growth of P. gingivalis cells, biofilm accumulation, as well as survival, adhesion and invasion of HeLa cells in a way analogous to protoheme. In contrast, cobalt(III), gallium(III) and copper(II) protoporphyrin IX exhibited antimicrobial activity against P. gingivalis, and thus represent potentially useful antibacterial compounds with which to target P. gingivalis. P. gingivalis hmuY, hmuR and hmuY-hmuR mutants showed decreased growth and infection of epithelial cells in the presence of all metalloporphyrins examined. In conclusion, the HmuY protein may not be directly involved in transport of free metalloporphyrins into the bacterial cell, but it may also play a protective role against metalloporphyrin toxicity by binding an excess of these compounds.

  17. Invasive predators and global biodiversity loss

    PubMed Central

    Glen, Alistair S.; Nimmo, Dale G.; Ritchie, Euan G.; Dickman, Chris R.

    2016-01-01

    Invasive species threaten biodiversity globally, and invasive mammalian predators are particularly damaging, having contributed to considerable species decline and extinction. We provide a global metaanalysis of these impacts and reveal their full extent. Invasive predators are implicated in 87 bird, 45 mammal, and 10 reptile species extinctions—58% of these groups’ contemporary extinctions worldwide. These figures are likely underestimated because 23 critically endangered species that we assessed are classed as “possibly extinct.” Invasive mammalian predators endanger a further 596 species at risk of extinction, with cats, rodents, dogs, and pigs threatening the most species overall. Species most at risk from predators have high evolutionary distinctiveness and inhabit insular environments. Invasive mammalian predators are therefore important drivers of irreversible loss of phylogenetic diversity worldwide. That most impacted species are insular indicates that management of invasive predators on islands should be a global conservation priority. Understanding and mitigating the impact of invasive mammalian predators is essential for reducing the rate of global biodiversity loss. PMID:27638204

  18. Fort Collins Science Center: Invasive Species Science

    USGS Publications Warehouse

    Stohlgren, Tom

    2004-01-01

    FORT is also the administrative home of the National Institute of Invasive Species Science, a growing consortium of partnerships between government and private organizations established by the U.S. Geological Survey (USGS) and its many cooperators. The Institute was formed to develop cooperative approaches for invasive species science that meet the urgent needs of land managers and the public. Its mission is to work with others to coordinate data and research from many sources to predict and reduce the effects of harmful nonnative plants, animals, and diseases in natural areas and throughout the United States, with a strategic approach to information management, research, modeling, technical assistance, and outreach. The Institute research team will develop local-, regional-, and national- scale maps of invasive species and identify priority invasive species, vulnerable habitats, and pathways of invasion. County-level and point data on occurrence will be linked to plot-level and site-level information on species abundance and spread. FORT scientists and Institute partners are working to integrate remote sensing data and GIS-based predictive models to track the spread of invasive species across the country. This information will be linked to control and restoration efforts to evaluate their cost-effectiveness. Understanding both successes and failures will advance the science of invasive species containment and control as well as restoration of habitats and native biodiversity.

  19. Economic impact of minimally invasive lumbar surgery

    PubMed Central

    Hofstetter, Christoph P; Hofer, Anna S; Wang, Michael Y

    2015-01-01

    Cost effectiveness has been demonstrated for traditional lumbar discectomy, lumbar laminectomy as well as for instrumented and noninstrumented arthrodesis. While emerging evidence suggests that minimally invasive spine surgery reduces morbidity, duration of hospitalization, and accelerates return to activites of daily living, data regarding cost effectiveness of these novel techniques is limited. The current study analyzes all available data on minimally invasive techniques for lumbar discectomy, decompression, short-segment fusion and deformity surgery. In general, minimally invasive spine procedures appear to hold promise in quicker patient recovery times and earlier return to work. Thus, minimally invasive lumbar spine surgery appears to have the potential to be a cost-effective intervention. Moreover, novel less invasive procedures are less destabilizing and may therefore be utilized in certain indications that traditionally required arthrodesis procedures. However, there is a lack of studies analyzing the economic impact of minimally invasive spine surgery. Future studies are necessary to confirm the durability and further define indications for minimally invasive lumbar spine procedures. PMID:25793159

  20. GnRH regulates trophoblast invasion via RUNX2-mediated MMP2/9 expression

    PubMed Central

    Peng, Bo; Zhu, Hua; Klausen, Christian; Ma, Liyang; Wang, Yan-ling; Leung, Peter C.K.

    2016-01-01

    STUDY HYPOTHESIS We hypothesized that Runt-related transcription factor 2 (RUNX2), matrix metalloproteinase (MMP)2 and MMP9 are involved in basal and gonadotrophin-releasing hormone (GnRH)-induced human extravillous trophoblast (EVT) cell invasion. STUDY FINDING Our finding indicates that GnRH-induced RUNX2 expression enhances the invasive capacity of EVT cells by modulating the expression of MMP2 and MMP9. WHAT IS KNOWN ALREADY GnRH is expressed in first-trimester placenta and exerts pro-invasive effects on EVT cells in vitro. RUNX2 regulates MMP2 and MMP9 expression and is often associated with invasive phenotypes. STUDY DESIGN, SAMPLES/MATERIALS, METHODS First-trimester human placenta (n = 9) was obtained from women undergoing elective termination of pregnancy. The localization of RUNX2, MMP2 and MMP9 in first-trimester human placenta was examined by immunohistochemistry. Primary or immortalized (HTR-8/SVneo) EVT cells were treated alone or in combination with GnRH, GnRH antagonist Antide, MAPK kinase inhibitor PD98095, phosphatidylinositol 3-kinase inhibitor LY294002, MMP2/9 inhibitor or small interfering RNAs (siRNAs) targeting RUNX2, MMP2 and/or MMP9. Protein and mRNA levels were measured by western blot and RT–PCR, respectively. Cell invasiveness was evaluated by transwell Matrigel or collagen I invasion assays. MAIN RESULTS AND THE ROLE OF CHANCE RUNX2, MMP2 and MMP9 were detected in the cell column regions of human first-trimester placental villi. GnRH treatment increased RUNX2 mRNA and protein levels in HTR-8/SVneo cells and primary EVTs, and these effects were attenuated by co-treatment with Antide, PD98095 or LY294002. Down-regulation of RUNX2 by siRNA reduced basal and GnRH-induced MMP2/9 expression and cell invasion. Moreover, pharmacological inhibition or siRNA-mediated knockdown of MMP2/9 reduced basal and GnRH-induced cell invasion. LIMITATIONS, REASONS FOR CAUTION The lack of an in vivo model is the major limitation of our in vitro study. WIDER

  1. Neonatal invasive candidiasis.

    PubMed

    Stronati, M; Decembrino, L

    2006-12-01

    Over the last two decades, systemic fungal infections have emerged to play a primary role in hospital-acquired infections. C. albicans is involved in 75% of neonatal candidiasis; however, the incidence of infection from C. parapsilosis is also increasing significantly. The higher incidence observed in the high-risk group of very low birth weight (VLBW) infants is linked to their special physical characteristics and the diagnostic and therapeutic invasive procedures they undergo. Colonization is a relevant risk factor depending on the colonized site , the fungal species and the type of colonization. Serological tests have a low specificity and sensitivity; in many cases, they do not distinguish between colonization and infection. Blood culture, although the best diagnostic test for determining systemic infection, can result negative, even in cases of deep organ involvement. In addition, fungi grow more slowly than bacteria in cultures. So, the difficulty in diagnosing systemic candidiasis and its aspecific clinical features may make empirical therapy appropriate. Amphotericin B (AmB) alone or combined with 5-fluorocytosine remains the drug of choice. Fluconazole represents a valid alternative. Recently developed new formulations of amphotericin incapsulated in liposomes can avoid possible adverse effects. Prognosis depends on the specific micro-organism involved; mortality is higher in the presence of C. albicans. As prognosis is associated with high mortality, prevention measures to reduce risk factors are of critical importance.

  2. The invasion of non-native grasses into California grasslands has caused a shift in energy partitioning between latent and sensible heat flux, reduced albedo and higher surface temperatures

    NASA Astrophysics Data System (ADS)

    Koteen, L. E.; Harte, J.; Baldocchi, D. D.

    2012-12-01

    In California, native grasses have been largely displaced across millions of acres of grassland habitat by the invasion of non-native grasses from Mediterranean Europe. Although seemingly subtle, this shift in grass species composition has altered the water and energy cycles in these ecosystems due to a shift in life cycle strategy. Native California grasses are perennial and long-lived. To survive California's long summer drought, they possess deep roots to harvest moisture along the full depth of the soil profile. Aboveground, most California perennial grasses are bunchy and dense, covering the ground and restricting soil evaporation. Their growing season extends over most of the year, thus maintaining an unbroken interaction along the soil-plant-atmosphere continuum, and enabling the plants to draw water from deep soil layers well into the dry summer. In contrast, the now-dominant non-native grasses are annuals. They grow from seed each year when Autumn rains begin, and die with the onset of summer drought. Aboveground, non-native annuals are sparse relative to native perennials, and possess a shallow root system with the large majority of root biomass above 20 cm depth. To determine the impact of this land cover shift on ecosystem water and energy cycles, we measured the components of the surface energy balance at a grassland site in northern coastal California where remnant perennial grasses are found growing alongside regions that have undergone non-native invasion. Specifically, in locations dominated by each grass type, we measured net radiation and ground and canopy heat flux through the surface renewal method. We also measured midday PAR albedo to determine the impact of grassland invasion on energy capture. In three years of measurements, corresponding to average, wet and dry years, we found that energy partitioning during the growing season is similar between grass types. However, once non-native annual grasses senesce in mid to late spring, the ratio

  3. How to manage biological invasions under globalization.

    PubMed

    Perrings, Charles; Dehnen-Schmutz, Katharina; Touza, Julia; Williamson, Mark

    2005-05-01

    Protecting national borders against biological invasions is becoming increasingly difficult because those whose actions result in invasions seldom bear legal responsibility for those actions. Invasion costs are often an externality (an unintended side effect) of international trade. Externalities are best dealt with by internalizing them; that is, by getting those who harm society to meet the cost. This is the 'polluter pays principle', which, under current trade rules, is difficult to implement. Tariffs could, however, be used to confront exporters with the costs of their actions, and the right to do this should be embedded in trade agreements. At the same time, international aid could be used to protect donor societies against the inability of some other countries to take appropriate biosecurity measures. The impact of invasions can thus be reduced by tackling their economic externalities.

  4. In vitro cell migration and invasion assays.

    PubMed

    Kramer, Nina; Walzl, Angelika; Unger, Christine; Rosner, Margit; Krupitza, Georg; Hengstschläger, Markus; Dolznig, Helmut

    2013-01-01

    Determining the migratory and invasive capacity of tumor and stromal cells and clarifying the underlying mechanisms is most relevant for novel strategies in cancer diagnosis, prognosis, drug development and treatment. Here we shortly summarize the different modes of cell travelling and review in vitro methods, which can be used to evaluate migration and invasion. We provide a concise summary of established migration/invasion assays described in the literature, list advantages, limitations and drawbacks, give a tabular overview for convenience and depict the basic principles of the assays graphically. In many cases particular research problems and specific cell types do not leave a choice for a broad variety of usable assays. However, for most standard applications using adherent cells, based on our experience we suggest to use exclusion zone assays to evaluate migration/invasion. We substantiate our choice by demonstrating that the advantages outbalance the drawbacks e.g. the simple setup, the easy readout, the kinetic analysis, the evaluation of cell morphology and the feasibility to perform the assay with standard laboratory equipment. Finally, innovative 3D migration and invasion models including heterotypic cell interactions are discussed. These methods recapitulate the in vivo situation most closely. Results obtained with these assays have already shed new light on cancer cell spreading and potentially will uncover unknown mechanisms.

  5. Positive feedback between mycorrhizal fungi and plants influences plant invasion success and resistance to invasion.

    PubMed

    Zhang, Qian; Yang, Ruyi; Tang, Jianjun; Yang, Haishui; Hu, Shuijin; Chen, Xin

    2010-08-24

    Negative or positive feedback between arbuscular mycorrhizal fungi (AMF) and host plants can contribute to plant species interactions, but how this feedback affects plant invasion or resistance to invasion is not well known. Here we tested how alterations in AMF community induced by an invasive plant species generate feedback to the invasive plant itself and affect subsequent interactions between the invasive species and its native neighbors. We first examined the effects of the invasive forb Solidago canadensis L. on AMF communities comprising five different AMF species. We then examined the effects of the altered AMF community on mutualisms formed with the native legume forb species Kummerowia striata (Thunb.) Schindl. and on the interaction between the invasive and native plants. The host preferences of the five AMF were also assessed to test whether the AMF form preferred mutualistic relations with the invasive and/or the native species. We found that S. canadensis altered AMF spore composition by increasing one AMF species (Glomus geosporum) while reducing Glomus mosseae, which is the dominant species in the field. The host preference test showed that S. canadensis had promoted the abundance of AMF species (G. geosporum) that most promoted its own growth. As a consequence, the altered AMF community enhanced the competitiveness of invasive S. canadensis at the expense of K. striata. Our results demonstrate that the invasive S. canadensis alters soil AMF community composition because of fungal-host preference. This change in the composition of the AMF community generates positive feedback to the invasive S. canadensis itself and decreases AM associations with native K. striata, thereby making the native K. striata less dominant.

  6. Allergic Lung Inflammation Reduces Tissue Invasion and Enhances Survival from Pulmonary Pneumococcal Infection in Mice, Which Correlates with Increased Expression of Transforming Growth Factor β1 and SiglecF(low) Alveolar Macrophages.

    PubMed

    Sanfilippo, Alan M; Furuya, Yoichi; Roberts, Sean; Salmon, Sharon L; Metzger, Dennis W

    2015-07-01

    Asthma is generally thought to confer an increased risk for invasive pneumococcal disease (IPD) in humans. However, recent reports suggest that mortality rates from IPD are unaffected in patients with asthma and that chronic obstructive pulmonary disease (COPD), a condition similar to asthma, protects against the development of complicated pneumonia. To clarify the effects of asthma on the subsequent susceptibility to pneumococcal infection, ovalbumin (OVA)-induced allergic lung inflammation (ALI) was induced in mice followed by intranasal infection with A66.1 serotype 3 Streptococcus pneumoniae. Surprisingly, mice with ALI were significantly more resistant to lethal infection than non-ALI mice. The heightened resistance observed following ALI correlated with enhanced early clearance of pneumococci from the lung, decreased bacterial invasion from the airway into the lung tissue, a blunted inflammatory cytokine and neutrophil response to infection, and enhanced expression of transforming growth factor β1 (TGF-β1). Neutrophil depletion prior to infection had no effect on enhanced early bacterial clearance or resistance to IPD in mice with ALI. Although eosinophils recruited into the lung during ALI appeared to be capable of phagocytizing bacteria, neutralization of interleukin-5 (IL-5) to inhibit eosinophil recruitment likewise had no effect on early clearance or survival following infection. However, enhanced resistance was associated with an increase in levels of clodronate-sensitive, phagocytic SiglecF(low) alveolar macrophages within the airways following ALI. These findings suggest that, while the risk of developing IPD may actually be decreased in patients with acute asthma, additional clinical data are needed to better understand the risk of IPD in patients with different asthma phenotypes.

  7. An epigenetically distinct breast cancer cell subpopulation promotes collective invasion

    PubMed Central

    Westcott, Jill M.; Prechtl, Amanda M.; Maine, Erin A.; Dang, Tuyen T.; Esparza, Matthew A.; Sun, Han; Zhou, Yunyun; Xie, Yang; Pearson, Gray W.

    2015-01-01

    Tumor cells can engage in a process called collective invasion, in which cohesive groups of cells invade through interstitial tissue. Here, we identified an epigenetically distinct subpopulation of breast tumor cells that have an enhanced capacity to collectively invade. Analysis of spheroid invasion in an organotypic culture system revealed that these “trailblazer” cells are capable of initiating collective invasion and promote non-trailblazer cell invasion, indicating a commensal relationship among subpopulations within heterogenous tumors. Canonical mesenchymal markers were not sufficient to distinguish trailblazer cells from non-trailblazer cells, suggesting that defining the molecular underpinnings of the trailblazer phenotype could reveal collective invasion-specific mechanisms. Functional analysis determined that DOCK10, ITGA11, DAB2, PDFGRA, VASN, PPAP2B, and LPAR1 are highly expressed in trailblazer cells and required to initiate collective invasion, with DOCK10 essential for metastasis. In patients with triple-negative breast cancer, expression of these 7 genes correlated with poor outcome. Together, our results indicate that spontaneous conversion of the epigenetic state in a subpopulation of cells can promote a transition from in situ to invasive growth through induction of a cooperative form of collective invasion and suggest that therapeutic inhibition of trailblazer cell invasion may help prevent metastasis. PMID:25844900

  8. Parasites and invasions: changes in gastrointestinal helminth assemblages in invasive and native rodents in Senegal.

    PubMed

    Diagne, Christophe; Ribas, Alexis; Charbonnel, Nathalie; Dalecky, Ambroise; Tatard, Caroline; Gauthier, Philippe; Haukisalmi, Voitto; Fossati-Gaschignard, Odile; Bâ, Khalilou; Kane, Mamadou; Niang, Youssoupha; Diallo, Mamoudou; Sow, Aliou; Piry, Sylvain; Sembène, Mbacké; Brouat, Carine

    2016-12-01

    Understanding why some exotic species become widespread and abundant in their colonised range is a fundamental issue that still needs to be addressed. Among many hypotheses, newly established host populations may benefit from a parasite loss ("enemy release" hypothesis) through impoverishment of their original parasite communities or reduced infection levels. Moreover, the fitness of competing native hosts may be negatively affected by the acquisition of exotic taxa from invaders ("parasite spillover") and/or by an increased transmission risk of native parasites due to their amplification by invaders ("parasite spillback"). We focused on gastrointestinal helminth communities to determine whether these predictions could explain the ongoing invasion success of the commensal house mouse (Mus musculus domesticus) and black rat (Rattus rattus), as well as the associated decrease in native Mastomys spp., in Senegal. For both invasive species, our results were consistent with the predictions of the enemy release hypothesis. A decrease in overall gastrointestinal helminth prevalence and infracommunity species richness was observed along the invasion gradients as well as lower specific prevalence/abundance (Aspiculuris tetraptera in Mus musculus domesticus, Hymenolepis diminuta in Rattus rattus) on the invasion fronts. Conversely, we did not find strong evidence of GIH spillover or spillback in invasion fronts, where native and invasive rodents co-occurred. Further experimental research is needed to determine whether and how the loss of gastrointestinal helminths and reduced infection levels along invasion routes may result in any advantageous effects on invader fitness and competitive advantage.

  9. Requirements for invasion of epithelial cells by Actinobacillus actinomycetemcomitans.

    PubMed Central

    Sreenivasan, P K; Meyer, D H; Fives-Taylor, P M

    1993-01-01

    Actinobacillus actinomycetemcomitans, an oral bacterium implicated in human periodontal disease, was recently demonstrated to invade cultured epithelial cells (D. H. Meyer, P. K. Sreenivasan, and P. M. Fives-Taylor, Infect. Immun. 59:2719-2726, 1991). This report characterizes the requirements for invasion of KB cells by A. actinomycetemcomitans. The roles of bacterial and host factors were investigated by using selective agents that influence specific bacterial or host cell functions. Inhibition of bacterial protein synthesis decreased invasion, suggesting the absence of a preformed pool of proteins involved in A. actinomycetemcomitans invasion. Inhibition of bacterial and eukaryotic energy synthesis also decreased invasion, confirming that A. actinomycetemcomitans invasion is an active process. Bacterial adherence to KB cells was indicated by scanning electron microscopy of infected KB cells. Further, the addition of A. actinomycetemcomitans-specific serum to the bacterial inoculum reduced invasion substantially, suggesting a role for bacterial attachment in invasion. Many of the adherent bacteria invaded the epithelial cells under optimal conditions. Inhibitors of receptor-mediated endocytosis inhibited invasion by A. actinomycetemcomitans. Like that of many facultatively intracellular bacteria, A. actinomycetemcomitans invasion was not affected by eukaryotic endosomal acidification. These are the first published observations describing the requirements for epithelial cell invasion by a periodontopathogen. They demonstrate that A. actinomycetemcomitans utilizes a mechanism similar to those used by many but not all invasive bacteria to gain entry into eukaryotic cells. Images PMID:8454326

  10. Outcomes After Minimally Invasive Esophagectomy

    PubMed Central

    Luketich, James D.; Pennathur, Arjun; Awais, Omar; Levy, Ryan M.; Keeley, Samuel; Shende, Manisha; Christie, Neil A.; Weksler, Benny; Landreneau, Rodney J.; Abbas, Ghulam; Schuchert, Matthew J.; Nason, Katie S.

    2014-01-01

    Background Esophagectomy is a complex operation and is associated with significant morbidity and mortality. In an attempt to lower morbidity, we have adopted a minimally invasive approach to esophagectomy. Objectives Our primary objective was to evaluate the outcomes of minimally invasive esophagectomy (MIE) in a large group of patients. Our secondary objective was to compare the modified McKeown minimally invasive approach (videothoracoscopic surgery, laparoscopy, neck anastomosis [MIE-neck]) with our current approach, a modified Ivor Lewis approach (laparoscopy, videothoracoscopic surgery, chest anastomosis [MIE-chest]). Methods We reviewed 1033 consecutive patients undergoing MIE. Elective operation was performed on 1011 patients; 22 patients with nonelective operations were excluded. Patients were stratified by surgical approach and perioperative outcomes analyzed. The primary endpoint studied was 30-day mortality. Results The MIE-neck was performed in 481 (48%) and MIE-Ivor Lewis in 530 (52%). Patients undergoing MIE-Ivor Lewis were operated in the current era. The median number of lymph nodes resected was 21. The operative mortality was 1.68%. Median length of stay (8 days) and ICU stay (2 days) were similar between the 2 approaches. Mortality rate was 0.9%, and recurrent nerve injury was less frequent in the Ivor Lewis MIE group (P < 0.001). Conclusions MIE in our center resulted in acceptable lymph node resection, postoperative outcomes, and low mortality using either an MIE-neck or an MIE-chest approach. The MIE Ivor Lewis approach was associated with reduced recurrent laryngeal nerve injury and mortality of 0.9% and is now our preferred approach. Minimally invasive esophagectomy can be performed safely, with good results in an experienced center. PMID:22668811

  11. Assessing urban adaptive capacity to climate change.

    PubMed

    Araya-Muñoz, Dahyann; Metzger, Marc J; Stuart, Neil; Wilson, A Meriwether W; Alvarez, Luis

    2016-12-01

    Despite the growing number of studies focusing on urban vulnerability to climate change, adaptive capacity, which is a key component of the IPCC definition of vulnerability, is rarely assessed quantitatively. We examine the capacity of adaptation in the Concepción Metropolitan Area, Chile. A flexible methodology based on spatial fuzzy modelling was developed to standardise and aggregate, through a stepwise approach, seventeen indicators derived from widely available census statistical data into an adaptive capacity index. The results indicate that all the municipalities in the CMA increased their level of adaptive capacity between 1992 and 2002. However, the relative differences between municipalities did not change significantly over the studied timeframe. Fuzzy overlay allowed us to standardise and to effectively aggregate indicators with differing ranges and granularities of attribute values into an overall index. It also provided a conceptually sound and reproducible means of exploring the interplay of many indicators that individually influence adaptive capacity. Furthermore, it captured the complex, aggregated and continued nature of the adaptive capacity, favouring to deal with gaps of data and knowledge associated with the concept of adaptive capacity. The resulting maps can help identify municipalities where adaptive capacity is weak and identify which components of adaptive capacity need strengthening. Identification of these capacity conditions can stimulate dialogue amongst policymakers and stakeholders regarding how to manage urban areas and how to prioritise resources for urban development in ways that can also improve adaptive capacity and thus reduce vulnerability to climate change.

  12. The Human Release Hypothesis for biological invasions: human activity as a determinant of the abundance of invasive plant species.

    PubMed

    Zimmermann, Heike; Brandt, Patric; Fischer, Joern; Welk, Erik; von Wehrden, Henrik

    2014-01-01

    Research on biological invasions has increased rapidly over the past 30 years, generating numerous explanations of how species become invasive. While the mechanisms of invasive species establishment are well studied, the mechanisms driving abundance patterns (i.e. patterns of population density and population size) remain poorly understood. It is assumed that invasive species typically have higher abundances in their new environments than in their native ranges, and patterns of invasive species abundance differ between invaded regions. To explain differences in invasive species abundance, we propose the Human Release Hypothesis. In parallel to the established Enemy Release Hypothesis, this hypothesis states that the differences in abundance of invasive species are found between regions because population expansion is reduced in some regions through continuous land management and associated cutting of the invasive species. The Human Release Hypothesis does not negate other important drivers of species invasions, but rather should be considered as a potentially important complementary mechanism. We illustrate the hypothesis via a case study on an invasive rose species, and hypothesize which locations globally may be most likely to support high abundances of invasive species. We propose that more extensive empirical work on the Human Release Hypothesis could be useful to test its general applicability.

  13. Prostate resection - minimally invasive

    MedlinePlus

    ... invasive - discharge Transurethral resection of the prostate - discharge Review Date 6/29/2015 Updated by: Jennifer Sobol, ... the Michigan Institute of Urology, West Bloomfield, MI. Review provided by VeriMed Healthcare Network. Also reviewed by ...

  14. Minimally invasive stomas.

    PubMed

    Hellinger, Michael D; Al Haddad, Abdullah

    2008-02-01

    Traditionally, stoma creation and end stoma reversal have been performed via a laparotomy incision. However, in many situations, stoma construction may be safely performed in a minimally invasive nature. This may include a trephine, laparoscopic, or combined approach. Furthermore, Hartmann's colostomy reversal, a procedure traditionally associated with substantial morbidity, may also be performed laparoscopically. The authors briefly review patient selection, preparation, and indications, and focus primarily on surgical techniques and results of minimally invasive stoma creation and Hartmann's reversal.

  15. Minimally invasive lumbar foraminotomy.

    PubMed

    Deutsch, Harel

    2013-07-01

    Lumbar radiculopathy is a common problem. Nerve root compression can occur at different places along a nerve root's course including in the foramina. Minimal invasive approaches allow easier exposure of the lateral foramina and decompression of the nerve root in the foramina. This video demonstrates a minimally invasive approach to decompress the lumbar nerve root in the foramina with a lateral to medial decompression. The video can be found here: http://youtu.be/jqa61HSpzIA.

  16. Parasites and marine invasions

    USGS Publications Warehouse

    Torchin, M.E.; Lafferty, K.D.; Kuris, A.M.

    2002-01-01

    Introduced marine species are a major environmental and economic problem. The rate of these biological invasions has substantially increased in recent years due to the globalization of the world's economies. The damage caused by invasive species is often a result of the higher densities and larger sizes they attain compared to where they are native. A prominent hypothesis explaining the success of introduced species is that they are relatively free of the effects of natural enemies. Most notably, they may encounter fewer parasites in their introduced range compared to their native range. Parasites are ubiquitous and pervasive in marine systems, yet their role in marine invasions is relatively unexplored. Although data on parasites of marine organisms exist, the extent to which parasites can mediate marine invasions, or the extent to which invasive parasites and pathogens are responsible for infecting or potentially decimating native marine species have not been examined. In this review, we present a theoretical framework to model invasion success and examine the evidence for a relationship between parasite presence and the success of introduced marine species. For this, we compare the prevalence and species richness of parasites in several introduced populations of marine species with populations where they are native. We also discuss the potential impacts of introduced marine parasites on native ecosystems.

  17. Invasive crayfish in the Pacific Northwest

    USGS Publications Warehouse

    Pearl, Christopher A.; McCreary, Brome; Adams, Michael

    2011-01-01

    Invasive species directly threaten freshwater biodiversity, particularly in regions of high aquatic richness like the Pacific Northwest (PNW). Crayfish are among the most impactful of aquatic invasive species. Invasive crayfish are considered ecosystem engineers due to their ability to alter basic wetland properties, such as reducing vegetation and bank integrity and increasing turbidity. In areas where invasion is advanced, crayfish pose major economic and ecological problems. Crayfish have been widely introduced for aquaculture and can become established in a wide range of habitat conditions. They also may be spread by anglers who use them as bait. Several non-native crayfish are established in the PNW, but the extent of their invasion is not well known. At least two groups are known from scattered sites in the PNW, and both have proven problematic for native species in other parts of the world: Red swamp crayfish (Procambarus clarkii) and several members of the genus Orconectes. Both groups are native to areas of the eastern United States. Both are identified globally as invasives of high concern and appear on the Oregon Department of Fish and Wildlife's "10 Most Unwanted" and the U.S. Forest Service's "Primary Species of Concern" lists for stream systems in the PNW. Despite the presence of introduced crayfish in the PNW and their high potential for negative effects, the scope of their invasion and effects on aquatic systems are not well known. The U.S. Geological Survey (USGS), along with local groups and state agencies, is working to clarify crayfish distribution and to outline which basins may not yet be invaded. Other goals are to improve understanding of habitat associations of invasive crayfish and their potential effects on native crayfish.

  18. Long non-coding RNA HOTAIR promotes carcinogenesis and invasion of gastric adenocarcinoma

    SciTech Connect

    Lee, Na Keum; Lee, Jung Hwa; Park, Chan Hyuk; Yu, Dayeon; Lee, Yong Chan; Cheong, Jae-Ho; Noh, Sung Hoon; Lee, Sang Kil

    2014-08-22

    Highlights: • HOTAIR expression was tested in fifty patients with gastric cancer. • Cell proliferation was measured after HOTAIR silencing in gastric cancer cell line. • siRNA–HOTAIR suppresses cell invasiveness and capacity of migration. • Knock down of HOTAR leads to decreased expression of EMT markers. • Inhibition of HOTAIR induces apoptosis and cell cycle arrest. - Abstract: Gastric cancer is one of the major causes of cancer death worldwide; however, the mechanism of carcinogenesis is complex and poorly understood. Long non-coding RNA HOTAIR (HOX transcript antisense RNA) recently emerged as a promoter of metastasis in various cancers including gastric cancer. Here we investigated the impact of HOTAIR on apoptosis, cell proliferation and cell cycle to dissect the carcinogenesis of gastric cancer. We examined the mechanism of invasion and metastasis and analyzed the clinical significance of HOTAIR. Downregulation of HOTAIR was confirmed by two different siRNAs. The expression of HOTAIR was significantly elevated in various gastric cancer cell lines and tissues compared to normal control. si-HOTAIR significantly reduced viability in MKN 28, MKN 74, and KATO III cells but not in AGS cells. si-HOTAIR induced apoptosis in KATO III cells. Lymphovascular invasion and lymph node metastasis were more common in the high level of HOTAIR group. si-HOTAIR significantly decreased invasiveness and migration. si-HOTAIR led to differential expression of epithelial to mesenchymal transition markers. We found that HOTAIR was involved in inhibition of apoptosis and promoted invasiveness, supporting a role for HOTAIR in carcinogenesis and progression of gastric cancer.

  19. Androgen receptor and prostate cancer invasion.

    PubMed

    Bonaccorsi, Lorella; Muratori, Monica; Carloni, Vinicio; Zecchi, Sandra; Formigli, Lucia; Forti, Gianni; Baldi, Elisabetta

    2003-02-01

    Evidence indicates that androgen-sensitive prostate cancer cells have a lower malignant potential. We previously demonstrated that expression of androgen receptor (AR) by transfection of the androgen-independent prostate cancer cell line PC3 decreases invasion and adhesion of these cells through modulation of alpha6beta4 expression. Treatment with the androgen further reduced adhesion and invasion of the cells without, however, modifying alpha6beta4. Here we investigated whether the androgen has a direct effect on alpha6beta4-EGF receptor (EGFR) interaction and signalling leading to invasion of these cells. Immunoconfocal microscopy demonstrated that in control cells (PC3-Neo), alpha6beta4 and EGFR colocalize and redistribute in response to epidermal growth factor (EGF). In PC3-AR cells colocalization and redistribution between the two molecules was reduced and abolished by pre-treatment with R1881. Co-immunoprecipitation studies demonstrated that tyrosine phosphorylation of beta4 in response to EGF was reduced in PC3-AR cells compared to PC3-Neo. Immunoconfocal and co-immunoprecipitation studies demonstrated colocalization at membrane level and co-immunoprecipitation of EGFR and AR, indicating an interaction between the two proteins. PI3K activity, a key signalling pathway for invasion of these cells, was decreased in PC3-AR cells in response to EGF and further reduced by treatment with R1881. EGFR internalization was strongly reduced in PC3-AR compared with PC3-Neo cells and was reduced by treatment with R1881. In conclusion, the expression of AR by transfection in PC3 cells confers a less malignant phenotype by interfering with EGFR--alpha6beta4 interaction and signalling leading to invasion through a mechanism involving an interaction between the classic AR and EGFR.

  20. On Gaussian feedback capacity

    NASA Technical Reports Server (NTRS)

    Dembo, Amir

    1989-01-01

    Pinsker and Ebert (1970) proved that in channels with additive Gaussian noise, feedback at most doubles the capacity. Cover and Pombra (1989) proved that feedback at most adds half a bit per transmission. Following their approach, the author proves that in the limit as signal power approaches either zero (very low SNR) or infinity (very high SNR), feedback does not increase the finite block-length capacity (which for nonstationary Gaussian channels replaces the standard notion of capacity that may not exist). Tighter upper bounds on the capacity are obtained in the process. Specializing these results to stationary channels, the author recovers some of the bounds recently obtained by Ozarow.

  1. Severe plant invasions can increase mycorrhizal fungal abundance and diversity.

    PubMed

    Lekberg, Ylva; Gibbons, Sean M; Rosendahl, Søren; Ramsey, Philip W

    2013-07-01

    Invasions by non-native plants can alter ecosystem functions and reduce native plant diversity, but relatively little is known about their effect on belowground microbial communities. We show that invasions by knapweed (Centaurea stoebe) and leafy spurge (Euphorbia esula, hereafter spurge)--but not cheatgrass (Bromus tectorum)--support a higher abundance and diversity of symbiotic arbuscular mycorrhizal fungi (AMF) than multi-species native plant communities. The higher AMF richness associated with knapweed and spurge is unlikely due to a co-invasion by AMF, because a separate sampling showed that individual native forbs hosted a similar AMF abundance and richness as exotic forbs. Native grasses associated with fewer AMF taxa, which could explain the reduced AMF richness in native, grass-dominated communities. The three invasive plant species harbored distinct AMF communities, and analyses of co-occurring native and invasive plants indicate that differences were partly driven by the invasive plants and were not the result of pre-invasion conditions. Our results suggest that invasions by mycotrophic plants that replace poorer hosts can increase AMF abundance and richness. The high AMF richness in monodominant plant invasions also indicates that the proposed positive relationship between above and belowground diversity is not always strong. Finally, the disparate responses among exotic plants and consistent results between grasses and forbs suggest that AMF respond more to plant functional group than plant provenance.

  2. Severe plant invasions can increase mycorrhizal fungal abundance and diversity

    PubMed Central

    Lekberg, Ylva; Gibbons, Sean M; Rosendahl, Søren; Ramsey, Philip W

    2013-01-01

    Invasions by non-native plants can alter ecosystem functions and reduce native plant diversity, but relatively little is known about their effect on belowground microbial communities. We show that invasions by knapweed (Centaurea stoebe) and leafy spurge (Euphorbia esula, hereafter spurge)—but not cheatgrass (Bromus tectorum)—support a higher abundance and diversity of symbiotic arbuscular mycorrhizal fungi (AMF) than multi-species native plant communities. The higher AMF richness associated with knapweed and spurge is unlikely due to a co-invasion by AMF, because a separate sampling showed that individual native forbs hosted a similar AMF abundance and richness as exotic forbs. Native grasses associated with fewer AMF taxa, which could explain the reduced AMF richness in native, grass-dominated communities. The three invasive plant species harbored distinct AMF communities, and analyses of co-occurring native and invasive plants indicate that differences were partly driven by the invasive plants and were not the result of pre-invasion conditions. Our results suggest that invasions by mycotrophic plants that replace poorer hosts can increase AMF abundance and richness. The high AMF richness in monodominant plant invasions also indicates that the proposed positive relationship between above and belowground diversity is not always strong. Finally, the disparate responses among exotic plants and consistent results between grasses and forbs suggest that AMF respond more to plant functional group than plant provenance. PMID:23486251

  3. Heat Capacity Analysis Report

    SciTech Connect

    A. Findikakis

    2004-11-01

    The purpose of this report is to provide heat capacity values for the host and surrounding rock layers for the waste repository at Yucca Mountain. The heat capacity representations provided by this analysis are used in unsaturated zone (UZ) flow, transport, and coupled processes numerical modeling activities, and in thermal analyses as part of the design of the repository to support the license application. Among the reports that use the heat capacity values estimated in this report are the ''Multiscale Thermohydrologic Model'' report, the ''Drift Degradation Analysis'' report, the ''Ventilation Model and Analysis Report, the Igneous Intrusion Impacts on Waste Packages and Waste Forms'' report, the ''Dike/Drift Interactions report, the Drift-Scale Coupled Processes (DST and TH Seepage) Models'' report, and the ''In-Drift Natural Convection and Condensation'' report. The specific objective of this study is to determine the rock-grain and rock-mass heat capacities for the geologic stratigraphy identified in the ''Mineralogic Model (MM3.0) Report'' (BSC 2004 [DIRS 170031], Table 1-1). This report provides estimates of the heat capacity for all stratigraphic layers except the Paleozoic, for which the mineralogic abundance data required to estimate the heat capacity are not available. The temperature range of interest in this analysis is 25 C to 325 C. This interval is broken into three separate temperature sub-intervals: 25 C to 95 C, 95 C to 114 C, and 114 C to 325 C, which correspond to the preboiling, trans-boiling, and postboiling regimes. Heat capacity is defined as the amount of energy required to raise the temperature of a unit mass of material by one degree (Nimick and Connolly 1991 [DIRS 100690], p. 5). The rock-grain heat capacity is defined as the heat capacity of the rock solids (minerals), and does not include the effect of water that exists in the rock pores. By comparison, the rock-mass heat capacity considers the heat capacity of both solids and pore

  4. Simulating effects of cheatgrass invasion on native bunchgrass productivity under different precipitation scenarios

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Preventing the spread of cheatgrass is a high priority for natural resource managers in the western United States. Cheatgrass invasion is deleterious in numerous ways, including diminishing local biodiversity, increasing fire risks, and lowering carrying capacity. Because management is expensive, ...

  5. [Fasting and physical endurance capacity].

    PubMed

    Schürch, P M

    1993-03-01

    Fasting, or zero calorie diets are used not only by overweight people as a means of losing weight, but by athletes too. Their use is then explained on philosophical grounds, with the aim of even enhancing sports performance. The purpose of this investigation consisted of quantifying the effects of a 10-day fast on maximum performance capacity and endurance (as measured on a bicycle ergometer) of 12 female students of physical education of normal weight. The measurements included resting and exercise metabolism determinants, as well as weight and lean body mass. The main results show that after the diet period the maximum ergometric performance was lower in absolute terms as well as in relation to weight or lean body mass. Performance capacity for submaximal exercise was also reduced. Fat combustion was enhanced both at rest and during exercise. The reduction of maximum performance and endurance capacity may be explained by an enhanced muscle breakdown, an efficiency drop of muscular work, and an inadequate glycogen content of the acting muscles. Shorter fasting periods of 24-36 hours also lead to a lower performance level for exercise bouts extending from several minutes to 1-3 hours. An enhancement of fat combustion was always conspicuous. One may conclude that optimal physical performance is dependent on full hepatic and muscle glycogen stores. Glycogen concentration in the liver decreases sharply as a matter of fact after merely one day of carbohydrate shortage. Zero calorie or low carbohydrate diets are thus at variance with an optimal physical work capacity.

  6. [Minimally invasive spine surgery: past and present].

    PubMed

    Corniola, M V; Stienen, M N; Tessitore, E; Schaller, K; Gautschi, O P

    2015-11-18

    In the early twentieth century, the understanding of spine biomechanics and the advent of surgical techniques of the lumbar spine, led to the currently emerging concept of minimal invasive spine surgery, By reducing surgical access, blood loss, infection rate and general morbidity, functional prognosis of patients is improved. This is a real challenge for the spine surgeon, who has to maintain a good operative result by significantly reducing surgical collateral damages due to the relatively traumatic conventional access.

  7. Problems of Excess Capacity

    NASA Technical Reports Server (NTRS)

    Douglas, G.

    1972-01-01

    The problems of excess capacity in the airline industry are discussed with focus on the following topics: load factors; fair rate of return on investment; service-quality rivalry among airlines; pricing (fare) policies; aircraft production; and the impacts of excess capacity on operating costs. Also included is a discussion of the interrelationships among these topics.

  8. Liquid heat capacity lasers

    DOEpatents

    Comaskey, Brian J.; Scheibner, Karl F.; Ault, Earl R.

    2007-05-01

    The heat capacity laser concept is extended to systems in which the heat capacity lasing media is a liquid. The laser active liquid is circulated from a reservoir (where the bulk of the media and hence waste heat resides) through a channel so configured for both optical pumping of the media for gain and for light amplification from the resulting gain.

  9. Temperature-Specific Competition between Invasive Mosquitofish and an Endangered Cyprinodontid Fish

    PubMed Central

    Carmona-Catot, Gerard; Magellan, Kit; García-Berthou, Emili

    2013-01-01

    Condition-specific competition is widespread in nature. Species inhabiting heterogeneous environments tend to differ in competitive abilities depending on environmental stressors. Interactions between these factors can allow coexistence of competing species, which may be particularly important between invasive and native species. Here, we examine the effects of temperature on competitive interactions between invasive mosquitofish, Gambusia holbrooki, and an endemic Iberian toothcarp, Aphanius iberus. We compare the tendency to approach heterospecifics and food capture rates between these two species, and examine differences between sexes and species in aggressive interactions, at three different temperatures (19, 24 and 29°C) in three laboratory experiments. Mosquitofish exhibit much more aggression than toothcarp. We show that mosquitofish have the capacity to competitively displace toothcarp through interference competition and this outcome is more likely at higher temperatures. We also show a reversal in the competitive hierarchy through reduced food capture rate by mosquitofish at lower temperatures and suggest that these two types of competition may act synergistically to deprive toothcarp of food at higher temperatures. Males of both species carry out more overtly aggressive acts than females, which is probably related to the marked sexual dimorphism and associated mating systems of these two species. Mosquitofish may thus impact heavily on toothcarp, and competition from mosquitofish, especially in warmer summer months, may lead to changes in abundance of the native species and displacement to non-preferred habitats. Globally increasing temperatures mean that highly invasive, warm-water mosquitofish may be able to colonize environments from which they are currently excluded through reduced physiological tolerance to low temperatures. Research into the effects of temperature on interactions between native and invasive species is thus of fundamental

  10. Temperature-specific competition between invasive mosquitofish and an endangered cyprinodontid fish.

    PubMed

    Carmona-Catot, Gerard; Magellan, Kit; García-Berthou, Emili

    2013-01-01

    Condition-specific competition is widespread in nature. Species inhabiting heterogeneous environments tend to differ in competitive abilities depending on environmental stressors. Interactions between these factors can allow coexistence of competing species, which may be particularly important between invasive and native species. Here, we examine the effects of temperature on competitive interactions between invasive mosquitofish, Gambusia holbrooki, and an endemic Iberian toothcarp, Aphanius iberus. We compare the tendency to approach heterospecifics and food capture rates between these two species, and examine differences between sexes and species in aggressive interactions, at three different temperatures (19, 24 and 29°C) in three laboratory experiments. Mosquitofish exhibit much more aggression than toothcarp. We show that mosquitofish have the capacity to competitively displace toothcarp through interference competition and this outcome is more likely at higher temperatures. We also show a reversal in the competitive hierarchy through reduced food capture rate by mosquitofish at lower temperatures and suggest that these two types of competition may act synergistically to deprive toothcarp of food at higher temperatures. Males of both species carry out more overtly aggressive acts than females, which is probably related to the marked sexual dimorphism and associated mating systems of these two species. Mosquitofish may thus impact heavily on toothcarp, and competition from mosquitofish, especially in warmer summer months, may lead to changes in abundance of the native species and displacement to non-preferred habitats. Globally increasing temperatures mean that highly invasive, warm-water mosquitofish may be able to colonize environments from which they are currently excluded through reduced physiological tolerance to low temperatures. Research into the effects of temperature on interactions between native and invasive species is thus of fundamental

  11. Ca2+-activated K+ channel (KCa) stimulation improves relaxant capacity of PDE5 inhibitors in human penile arteries and recovers the reduced efficacy of PDE5 inhibition in diabetic erectile dysfunction

    PubMed Central

    González-Corrochano, R; La Fuente, JM; Cuevas, P; Fernández, A; Chen, MX; Sáenz de Tejada, I; Angulo, J

    2013-01-01

    Background and Purpose We have evaluated the influence of calcium-activated potassium channels (KCa) activation on cGMP-mediated relaxation in human penile tissues from non-diabetic and diabetic patients, and on the effects of PDE5 inhibitors on erectile responses in control and diabetic rats. Experimental Approach Cavernosal tissues were collected from organ donors and from patients with erectile dysfunction (ED). Relaxations of corpus cavernosum strips (HCC) and penile resistance arteries (HPRA) obtained from these specimens were evaluated. Intracavernosal pressure (ICP) increases to cavernosal nerve electrical stimulation were determined in anaesthetized diabetic and non-diabetic rats. Key Results Concentration-dependent vasodilation to the PDE5 inhibitor, sildenafil, in HPRA was sensitive to endothelium removal, NO/cGMP pathway inhibition and KCa blockade. Accordingly, activation of KCa with NS-8 (10 μM) significantly potentiated sildenafil-induced relaxations in HPRA (EC50 0.49 ± 0.22 vs. 5.21 ± 0.63 μM). In HCC, sildenafil-induced relaxation was unaffected by KCa blockade or activation. Potentiating effects in HPRA were reproduced with an alternative PDE5 inhibitor (tadalafil) and KCa activator (NS1619) and prevented by removing the endothelium. Large-conductance KCa (BK) and intermediate-conductance KCa (IK) contribute to NS-8-induced effects and were immunodetected in human and rat penile arteries. NS-8 potentiated sildenafil-induced enhancement of erectile responses in rats. Activation of KCa recovered the impaired relaxation to sildenafil in diabetic HPRA while sildenafil completely reversed diabetes-induced ED in rats only when combined with KCa activation. Conclusions and Implications Activation of KCa improves vasodilatory capacity of PDE5 inhibitors in diabetic and non-diabetic HPRA, resulting in the recovery of erectile function in diabetic rats. These results suggest a therapeutic potential for KCa activation in diabetic ED. PMID:23441682

  12. Who needs capacity?

    PubMed

    Buchanan, Alec

    2015-01-01

    The UK Law Commission's Discussion Paper, Criminal Liability: Insanity and Automatism, recommends introducing the concept of capacity to the insanity defence. The concept of capacity has an established role in those parts of the law that concern the validity of the decisions that people make, for instance in composing a will or entering into a contract. Making mental capacity a criterion for criminal responsibility in a mentally disordered defendant, however, is potentially problematic. First, the term capacity already has several different meanings in the literature on the jurisprudence of mental abnormality. Second, using the concept of capacity in the way that the Law Commission proposes poses difficulties that relate to the provision of testimony by expert witnesses.

  13. Biological invasions: recommendations for U.S. policy and management.

    PubMed

    Lodge, David M; Williams, Susan; MacIsaac, Hugh J; Hayes, Keith R; Leung, Brian; Reichard, Sarah; Mack, Richard N; Moyle, Peter B; Smith, Maggie; Andow, David A; Carlton, James T; McMichael, Anthony

    2006-12-01

    The Ecological Society of America has evaluated current U.S. national policies and practices on biological invasions in light of current scientific knowledge. Invasions by harmful nonnative species are increasing in number and area affected; the damages to ecosystems, economic activity, and human welfare are accumulating. Without improved strategies based on recent scientific advances and increased investments to counter invasions, harm from invasive species is likely to accelerate. Federal leadership, with the cooperation of state and local governments, is required to increase the effectiveness of prevention of invasions, detect and respond quickly to new potentially harmful invasions, control and slow the spread of existing invasions, and provide a national center to ensure that these efforts are coordinated and cost effective. Specifically, the Ecological Society of America recommends that the federal government take the following six actions: (1) Use new information and practices to better manage commercial and other pathways to reduce the transport and release of potentially harmful species; (2) Adopt more quantitative procedures for risk analysis and apply them to every species proposed for importation into the country; (3) Use new cost-effective diagnostic technologies to increase active surveillance and sharing of information about invasive species so that responses to new invasions can be more rapid and effective; (4) Create new legal authority and provide emergency funding to support rapid responses to emerging invasions; (5) Provide funding and incentives for cost-effective programs to slow the spread of existing invasive species in order to protect still uninvaded ecosystems, social and industrial infrastructure, and human welfare; and (6) Establish a National Center for Invasive Species Management (under the existing National Invasive Species Council) to coordinate and lead improvements in federal, state, and international policies on invasive species

  14. Refrigerator with variable capacity compressor and cycle priming action through capacity control and associated methods

    DOEpatents

    Gomes, Alberto Regio; Litch, Andrew D.; Wu, Guolian

    2016-03-15

    A refrigerator appliance (and associated method) that includes a condenser, evaporator and a multi-capacity compressor. The appliance also includes a pressure reducing device arranged within an evaporator-condenser refrigerant circuit, and a valve system for directing or restricting refrigerant flow through the device. The appliance further includes a controller for operating the compressor upon the initiation of a compressor ON-cycle at a priming capacity above a nominal capacity for a predetermined or calculated duration.

  15. miR-135a Inhibits the Invasion of Cancer Cells via Suppression of ERRα

    PubMed Central

    Tribollet, Violaine; Barenton, Bruno; Kroiss, Auriane; Vincent, Séverine; Zhang, Ling; Forcet, Christelle; Cerutti, Catherine; Périan, Séverine; Allioli, Nathalie; Samarut, Jacques; Vanacker, Jean-Marc

    2016-01-01

    MicroRNA-135a (miR-135a) down-modulates parameters of cancer progression and its expression is decreased in metastatic breast cancers (as compared to non-metastatic tumors) as well as in prostate tumors relative to normal tissue. These expression and activity patterns are opposite to those of the Estrogen-Related Receptor α (ERRα), an orphan member of the nuclear receptor family. Indeed high expression of ERRα correlates with poor prognosis in breast and prostate cancers, and the receptor promotes various traits of cancer aggressiveness including cell invasion. Here we show that miR-135a down-regulates the expression of ERRα through specific sequences of its 3’UTR. As a consequence miR-135a also reduces the expression of downstream targets of ERRα. miR-135a also decreases cell invasive potential in an ERRα-dependent manner. Our results suggest that the decreased expression of miR-135a in metastatic tumors leads to elevated ERRα expression, resulting in increased cell invasion capacities. PMID:27227989

  16. 5′-Inositol phosphatase SHIP2 recruits Mena to stabilize invadopodia for cancer cell invasion

    PubMed Central

    Zaoui, Kossay; Huang, Bruce H.; Sangwan, Veena; Gertler, Frank B.

    2016-01-01

    Invadopodia are specialized membrane protrusions that support degradation of extracellular matrix (ECM) by cancer cells, allowing invasion and metastatic spread. Although early stages of invadopodia assembly have been elucidated, little is known about maturation of invadopodia into structures competent for ECM proteolysis. The localized conversion of phosphatidylinositol(3,4,5)-triphosphate and accumulation of phosphatidylinositol(3,4)-bisphosphate at invadopodia is a key determinant for invadopodia maturation. Here we investigate the role of the 5′-inositol phosphatase, SHIP2, and reveal an unexpected scaffold function of SHIP2 as a prerequisite for invadopodia-mediated ECM degradation. Through biochemical and structure-function analyses, we identify specific interactions between SHIP2 and Mena, an Ena/VASP-family actin regulatory protein. We demonstrate that SHIP2 recruits Mena, but not VASP, to invadopodia and that disruption of SHIP2–Mena interaction in cancer cells leads to attenuated capacity for ECM degradation and invasion in vitro, as well as reduced metastasis in vivo. Together, these findings identify SHIP2 as a key modulator of carcinoma invasiveness and a target for metastatic disease. PMID:27597754

  17. 5'-Inositol phosphatase SHIP2 recruits Mena to stabilize invadopodia for cancer cell invasion.

    PubMed

    Rajadurai, Charles V; Havrylov, Serhiy; Coelho, Paula P; Ratcliffe, Colin D H; Zaoui, Kossay; Huang, Bruce H; Monast, Anie; Chughtai, Naila; Sangwan, Veena; Gertler, Frank B; Siegel, Peter M; Park, Morag

    2016-09-12

    Invadopodia are specialized membrane protrusions that support degradation of extracellular matrix (ECM) by cancer cells, allowing invasion and metastatic spread. Although early stages of invadopodia assembly have been elucidated, little is known about maturation of invadopodia into structures competent for ECM proteolysis. The localized conversion of phosphatidylinositol(3,4,5)-triphosphate and accumulation of phosphatidylinositol(3,4)-bisphosphate at invadopodia is a key determinant for invadopodia maturation. Here we investigate the role of the 5'-inositol phosphatase, SHIP2, and reveal an unexpected scaffold function of SHIP2 as a prerequisite for invadopodia-mediated ECM degradation. Through biochemical and structure-function analyses, we identify specific interactions between SHIP2 and Mena, an Ena/VASP-family actin regulatory protein. We demonstrate that SHIP2 recruits Mena, but not VASP, to invadopodia and that disruption of SHIP2-Mena interaction in cancer cells leads to attenuated capacity for ECM degradation and invasion in vitro, as well as reduced metastasis in vivo. Together, these findings identify SHIP2 as a key modulator of carcinoma invasiveness and a target for metastatic disease.

  18. The Plasmodium falciparum rhoptry protein RhopH3 plays essential roles in host cell invasion and nutrient uptake

    PubMed Central

    Sherling, Emma S; Knuepfer, Ellen; Brzostowski, Joseph A; Miller, Louis H; Blackman, Michael J; van Ooij, Christiaan

    2017-01-01

    Merozoites of the protozoan parasite responsible for the most virulent form of malaria, Plasmodium falciparum, invade erythrocytes. Invasion involves discharge of rhoptries, specialized secretory organelles. Once intracellular, parasites induce increased nutrient uptake by generating new permeability pathways (NPP) including a Plasmodium surface anion channel (PSAC). RhopH1/Clag3, one member of the three-protein RhopH complex, is important for PSAC/NPP activity. However, the roles of the other members of the RhopH complex in PSAC/NPP establishment are unknown and it is unclear whether any of the RhopH proteins play a role in invasion. Here we demonstrate that RhopH3, the smallest component of the complex, is essential for parasite survival. Conditional truncation of RhopH3 substantially reduces invasive capacity. Those mutant parasites that do invade are defective in nutrient import and die. Our results identify a dual role for RhopH3 that links erythrocyte invasion to formation of the PSAC/NPP essential for parasite survival within host erythrocytes. DOI: http://dx.doi.org/10.7554/eLife.23239.001 PMID:28252384

  19. Invasive Bordetella holmesii infections.

    PubMed

    Fishbain, Joel T; Riederer, Kathleen; Sawaf, Hadi; Mody, Rupal

    2015-02-01

    Bordetella holmesii is a rare cause of invasive human disease. The fastidious and unusual nature of this organism makes routine isolation and identification challenging. We report two cases of B. holmesii bacteremia that were rapidly identified by matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (MALDI-TOF MS) when standard techniques failed to provide speciation. There are no current standards for susceptibility testing or treatment recommendations. The rare occurrence and challenges in identifying this pathogen led us to perform a comprehensive review of the epidemiology, clinical presentations, and treatment options for this potentially invasive pathogen.

  20. Intracellular Parasite Invasion Strategies

    NASA Astrophysics Data System (ADS)

    Sibley, L. D.

    2004-04-01

    Intracellular parasites use various strategies to invade cells and to subvert cellular signaling pathways and, thus, to gain a foothold against host defenses. Efficient cell entry, ability to exploit intracellular niches, and persistence make these parasites treacherous pathogens. Most intracellular parasites gain entry via host-mediated processes, but apicomplexans use a system of adhesion-based motility called ``gliding'' to actively penetrate host cells. Actin polymerization-dependent motility facilitates parasite migration across cellular barriers, enables dissemination within tissues, and powers invasion of host cells. Efficient invasion has brought widespread success to this group, which includes Toxoplasma, Plasmodium, and Cryptosporidium.

  1. Over-invasion by functionally equivalent invasive species.

    PubMed

    Russell, James C; Sataruddin, Nurul S; Heard, Allison D

    2014-08-01

    Multiple invasive species have now established at most locations around the world, and the rate of new species invasions and records of new invasive species continue to grow. Multiple invasive species interact in complex and unpredictable ways, altering their invasion success and impacts on biodiversity. Incumbent invasive species can be replaced by functionally similar invading species through competitive processes; however the generalized circumstances leading to such competitive displacement have not been well investigated. The likelihood of competitive displacement is a function of the incumbent advantage of the resident invasive species and the propagule pressure of the colonizing invasive species. We modeled interactions between populations of two functionally similar invasive species and indicated the circumstances under which dominance can be through propagule pressure and incumbent advantage. Under certain circumstances, a normally subordinate species can be incumbent and reject a colonizing dominant species, or successfully colonize in competition with a dominant species during simultaneous invasion. Our theoretical results are supported by empirical studies of the invasion of islands by three invasive Rattus species. Competitive displacement is prominent in invasive rats and explains the replacement of R. exulans on islands subsequently invaded by European populations of R. rattus and R. norvegicus. These competition outcomes between invasive species can be found in a broad range of taxa and biomes, and are likely to become more common. Conservation management must consider that removing an incumbent invasive species may facilitate invasion by another invasive species. Under very restricted circumstances of dominant competitive ability but lesser impact, competitive displacement may provide a novel method of biological control.

  2. Invasion triangle: an organizational framework for species invasion

    PubMed Central

    Perkins, Lora B; Leger, Elizabeth A; Nowak, Robert S

    2011-01-01

    Species invasion is a complex, multifactor process. To encapsulate this complexity into an intuitively appealing, simple, and straightforward manner, we present an organizational framework in the form of an invasion triangle. The invasion triangle is an adaptation of the disease triangle used by plant pathologists to help envision and evaluate interactions among a host, a pathogen, and an environment. Our modification of this framework for invasive species incorporates the major processes that result in invasion as the three sides of the triangle: (1) attributes of the potential invader; (2) biotic characteristics of a potentially invaded site; and (3) environmental conditions of the site. The invasion triangle also includes the impact of external influences on each side of the triangle, such as climate and land use change. This paper introduces the invasion triangle, discusses how accepted invasion hypotheses are integrated in this framework, describes how the invasion triangle can be used to focus research and management, and provides examples of application. The framework provided by the invasion triangle is easy to use by both researchers and managers and also applicable at any level of data intensity, from expert opinion to highly controlled experiments. The organizational framework provided by the invasion triangle is beneficial for understanding and predicting why species are invasive in specific environments, for identifying knowledge gaps, for facilitating communication, and for directing management in regard to invasive species. PMID:22393528

  3. Pharmacokinetics of triclopyr (3,5,6-trichloro-2-pyridinyloxyacetic acid) in the beagle dog and rhesus monkey: perspective on the reduced capacity of dogs to excrete this organic acid relative to the rat, monkey, and human.

    PubMed

    Timchalk, C; Nolan, R J

    1997-06-01

    The pharmacokinetics of triclopyr (3,5,6-trichloro-2-pyridinyloxyacetic acid) were measured in the beagle dog and rhesus monkey and compared with the kinetics observed in rats and humans. In addition, studies were conducted in anesthetized dogs to better understand the mechanism by which [14C]triclopyr is eliminated in this species. Triclopyr was dissolved in distilled water, and administered as a single oral dose of 0.5, 5, or 20 mg/kg to three male dogs. A single male rhesus monkey was given an intravenous dose of 30 mg [14C]triclopyr/kg body wt on two occasions separated by 10 days. Anesthetized male dogs, were implanted with venous, arterial, and urethral catheters and given increasing amounts of triclopyr to produce plasma triclopyr levels ranging from 0.3 to 27 microg eq/mL. In the monkey, triclopyr was rapidly eliminated from the plasma (t1/2 = 6.3 hr) with >95% of the urinary 14C activity excreted within 24 hr postdosing. In the dog, orally administered triclopyr was rapidly and effectively absorbed at every dose level with virtually all of it excreted in the urine by 72 hr postdosing. However, the kinetics were slightly nonlinear, and the fraction of the dose excreted in the urine decreased with increasing dose. Several nonlinear processes may collectively contribute to the modest nonlinear pharmacokinetics in the dog. Plasma protein binding of triclopyr in the dog ranged from 94 to 99%, was nonlinear, and was an important determinant in the renal clearance of triclopyr. The nonlinear plasma protein binding indicates that glomerular filtration became disproportionately more important as plasma triclopyr concentration increased. There was good evidence for a high-affinity low-capacity active-secretory process that was saturated by low plasma triclopyr concentrations. As plasma triclopyr concentrations increased, tubular reabsorption begins to exceed secretion, resulting in decreased renal clearance. The volume of distribution, normalized for body weight

  4. [Minimally invasive operations in vascular surgery].

    PubMed

    Stádler, Petr; Sedivý, Petr; Dvorácek, Libor; Slais, Marek; Vitásek, Petr; El Samman, Khaled; Matous, Pavel

    2011-01-01

    Minimally invasive surgery provides an attractive alternative compared with conventional surgical approaches and is popular with patients, particularly because of its favourable cosmetic results. Vascular surgery has taken its inspiration from general surgery and, over the past few years, has also been reducing the invasiveness of its operating methods. In addition to traditional laparoscopic techniques, we most frequently encounter the endovascular treatment of aneurysms of the thoracic and abdominal aorta and, most recently, robot-assisted surgery in the area of the abdominal aorta and pelvic arteries. Minimally invasive surgical interventions also have other advantages, including less operative trauma, a reduction in post-operative pain, shorter periods spent in the intensive care unit and overall hospitalization times, an earlier return to normal life and, finally, a reduction in total treatment costs.

  5. The oxidation capacity of Mn3O4 nanoparticles is significantly enhanced by anchoring them onto reduced graphene oxide to facilitate regeneration of surface-associated Mn(III).

    PubMed

    Duan, Lin; Wang, Zhongyuan; Hou, Yan; Wang, Zepeng; Gao, Guandao; Chen, Wei; Alvarez, Pedro J J

    2016-10-15

    Metal oxides are often anchored to graphene materials to achieve greater contaminant removal efficiency. To date, the enhanced performance has mainly been attributed to the role of graphene materials as a conductor for electron transfer. Herein, we report a new mechanism via which graphene materials enhance oxidation of organic contaminants by metal oxides. Specifically, Mn3O4-rGO nanocomposites (Mn3O4 nanoparticles anchored to reduced graphene oxide (rGO) nanosheets) enhanced oxidation of 1-naphthylamine (used here as a reaction probe) compared to bare Mn3O4. Spectroscopic analyses (X-ray photoelectron spectroscopy and Fourier transform infrared spectroscopy) show that the rGO component of Mn3O4-rGO was further reduced during the oxidation of 1-naphthylamine, although rGO reduction was not the result of direct interaction with 1-naphthylamine. We postulate that rGO improved the oxidation efficiency of anchored Mn3O4 by re-oxidizing Mn(II) formed from the reaction between Mn3O4 and 1-naphthylamine, thereby regenerating the surface-associated oxidant Mn(III). The proposed role of rGO was verified by separate experiments demonstrating its ability to oxidize dissolved Mn(II) to Mn(III), which subsequently can oxidize 1-naphthylamine. The role of dissolved oxygen in re-oxidizing Mn(II) was ruled out by anoxic (N2-purged) control experiments showing similar results as O2-sparged tests. Opposite pH effects on the oxidation efficiency of Mn3O4-rGO versus bare Mn3O4 were also observed, corroborating the proposed mechanism because higher pH facilitates oxidation of surface-associated Mn(II) even though it lowers the oxidation potential of Mn3O4. Overall, these findings may guide the development of novel metal oxide-graphene nanocomposites for contaminant removal.

  6. A novel uPAg-KPI fusion protein inhibits the growth and invasion of human ovarian cancer cells in vitro.

    PubMed

    Zhao, Li-Ping; Xu, Tian-Min; Kan, Mu-Jie; Xiao, Ye-Chen; Cui, Man-Hua

    2016-05-01

    Urokinase-type plasminogen activator (uPA) acts by breaking down the basement membrane and is involved in cell proliferation, migration and invasion. These actions are mediated by binding to the uPA receptor (uPAR) via its growth factor domain (GFD). The present study evaluated the effects of uPAg-KPI, a fusion protein of uPA-GFD and a kunitz protease inhibitor (KPI) domain that is present in the amyloid β-protein precursor. Using SKOV-3 cells, an ovarian cancer cell line, we examined cell viability, migration, invasion and also protein expression. Furthermore, we examined wound healing, and migration and invasion using a Transwell assay. Our data showed that uPAg-KPI treatment reduced the viability of ovarian cancer SKOV-3 cells in both a concentration and time-dependent manner by arresting tumor cells at G1/G0 phase of the cell cycle. The IC50 of uPAg-KPI was 0.5 µg/µl after 48 h treatment. At this concentration, uPAg-KPI also inhibited tumor cell colony formation, wound closure, as well as cell migration and invasion capacity. At the protein level, western blot analysis demonstrated that uPAg-KPI exerted no significant effect on the expression of total extracellular signal-regulated kinase (ERK)1/ERK2 and AKT, whereas it suppressed levels of phosphorylated ERK1/ERK2 and AKT. Thus, we suggest that this novel uPAg-KPI fusion protein reduced cell viability, colony formation, wound healing and the invasive ability of human ovarian cancer SKOV-3 cells in vitro by regulating ERK and AKT signaling. Further studies using other cell lines will confirm these findings.

  7. A novel uPAg-KPI fusion protein inhibits the growth and invasion of human ovarian cancer cells in vitro

    PubMed Central

    ZHAO, LI-PING; XU, TIAN-MIN; KAN, MU-JIE; XIAO, YE-CHEN; CUI, MAN-HUA

    2016-01-01

    Urokinase-type plasminogen activator (uPA) acts by breaking down the basement membrane and is involved in cell proliferation, migration and invasion. These actions are mediated by binding to the uPA receptor (uPAR) via its growth factor domain (GFD). The present study evaluated the effects of uPAg-KPI, a fusion protein of uPA-GFD and a kunitz protease inhibitor (KPI) domain that is present in the amyloid β-protein precursor. Using SKOV-3 cells, an ovarian cancer cell line, we examined cell viability, migration, invasion and also protein expression. Furthermore, we examined wound healing, and migration and invasion using a Transwell assay. Our data showed that uPAg-KPI treatment reduced the viability of ovarian cancer SKOV-3 cells in both a concentration and time-dependent manner by arresting tumor cells at G1/G0 phase of the cell cycle. The IC50 of uPAg-KPI was 0.5 µg/µl after 48 h treatment. At this concentration, uPAg-KPI also inhibited tumor cell colony formation, wound closure, as well as cell migration and invasion capacity. At the protein level, western blot analysis demonstrated that uPAg-KPI exerted no significant effect on the expression of total extracellular signal-regulated kinase (ERK)1/ERK2 and AKT, whereas it suppressed levels of phosphorylated ERK1/ERK2 and AKT. Thus, we suggest that this novel uPAg-KPI fusion protein reduced cell viability, colony formation, wound healing and the invasive ability of human ovarian cancer SKOV-3 cells in vitro by regulating ERK and AKT signaling. Further studies using other cell lines will confirm these findings. PMID:27035617

  8. A Rapid Laser Probing Method Facilitates the Non-invasive and Contact-free Determination of Leaf Thermal Properties.

    PubMed

    Buyel, Johannes F; Gruchow, Hannah M; Wehner, Martin

    2017-01-07

    Plants can produce valuable substances such as secondary metabolites and recombinant proteins. The purification of the latter from plant biomass can be streamlined by heat treatment (blanching). A blanching apparatus can be designed more precisely if the thermal properties of the leaves are known in detail, i.e., the specific heat capacity and thermal conductivity. The measurement of these properties is time consuming and labor intensive, and usually requires invasive methods that contact the sample directly. This can reduce the product yield and may be incompatible with containment requirements, e.g., in the context of good manufacturing practice. To address these issues, a non-invasive, contact-free method was developed that determines the specific heat capacity and thermal conductivity of an intact plant leaf in about one minute. The method involves the application of a short laser pulse of defined length and intensity to a small area of the leaf sample, causing a temperature increase that is measured using a near infrared sensor. The temperature increase is combined with known leaf properties (thickness and density) to determine the specific heat capacity. The thermal conductivity is then calculated based on the profile of the subsequent temperature decline, taking thermal radiation and convective heat transfer into account. The associated calculations and critical aspects of sample handling are discussed.

  9. [Combination therapy for invasive aspergillosis].

    PubMed

    Ruiz-Camps, Isabel

    2011-03-01

    The frequency of invasive fungal infections, and specifically invasive aspergillosis, has increased in the last few decades. Despite the development of new antifungal agents, these infections are associated with high mortality, ranging from 40% to 80%, depending on the patient and the localization of the infection. To reduce these figures, several therapeutic strategies have been proposed, including combination therapy. Most of the available data on the efficacy of these combinations are from experimental models, in vitro data and retrospective observational studies or studies with a small number of patients that have included both patients in first-line treatment and those receiving rescue therapy; in addition there are many patients with possible forms of aspergillosis and few with demonstrated or probable forms. To date, there is no evidence that combination therapy has significantly higher efficacy than monotherapy; however, combination therapy could be indicated in severe forms of aspergillosis, or forms with central nervous involvement or extensive pulmonary involvement with respiratory insufficiency, etc. Among the combinations, the association of an echinocandin--the group that includes micafungin--with voriconazole or liposomal amphotericin B seems to show synergy. These combinations are those most extensively studied in clinical trials and therefore, although the grade of evidence is low, are recommended by the various scientific societies.

  10. Early Primary Invasion Scientists

    ERIC Educational Resources Information Center

    Spellman, Katie V.; Villano, Christine P.

    2011-01-01

    "We really need to get the government involved," said one student, holding his graph up to USDA scientist Steve Seefeldt. Dr. Steve studies methods to control "invasive" plants, plants that have been introduced to an area by humans and have potential to spread rapidly and negatively affect ecosystems. The first grader and his…

  11. Minimally invasive valve surgery.

    PubMed

    Woo, Y Joseph

    2009-08-01

    Traditional cardiac valve replacement surgery is being rapidly supplanted by innovative, minimally invasive approaches toward the repair of these valves. Patients are experiencing benefits ranging from less bleeding and pain to faster recovery and greater satisfaction. These operations are proving to be safe, highly effective, and durable, and their use will likely continue to increase and become even more widely applicable.

  12. Refinery Capacity Report

    EIA Publications

    2016-01-01

    Data series include fuel, electricity, and steam purchased for consumption at the refinery; refinery receipts of crude oil by method of transportation; and current and projected atmospheric crude oil distillation, downstream charge, and production capacities. Respondents are operators of all operating and idle petroleum refineries (including new refineries under construction) and refineries shut down during the previous year, located in the 50 states, the District of Columbia, Puerto Rico, the Virgin Islands, Guam, and other U.S. possessions. The Refinery Capacity Report does not contain working and shell storage capacity data. This data is now being collected twice a year as of March 31 and September 30 on the Form EIA-810, "Monthly Refinery Report", and is now released as a separate report Working and Net Available Shell Storage Capacity.

  13. Salmonella Adhesion, Invasion and Cellular Immune Responses Are Differentially Affected by Iron Concentrations in a Combined In Vitro Gut Fermentation-Cell Model

    PubMed Central

    Dostal, Alexandra; Gagnon, Mélanie; Chassard, Christophe; Zimmermann, Michael Bruce; O'Mahony, Liam; Lacroix, Christophe

    2014-01-01

    In regions with a high infectious disease burden, concerns have been raised about the safety of iron supplementation because higher iron concentrations in the gut lumen may increase risk of enteropathogen infection. The aim of this study was to investigate interactions of the enteropathogen Salmonella enterica ssp. enterica Typhimurium with intestinal cells under different iron concentrations encountered in the gut lumen during iron deficiency and supplementation using an in vitro colonic fermentation system inoculated with immobilized child gut microbiota combined with Caco-2/HT29-MTX co-culture monolayers. Colonic fermentation effluents obtained during normal, low (chelation by 2,2'-dipyridyl) and high iron (26.5 mg iron/L) fermentation conditions containing Salmonella or pure Salmonella cultures with similar iron conditions were applied to cellular monolayers. Salmonella adhesion and invasion capacity, cellular integrity and immune response were assessed. Under high iron conditions in pure culture, Salmonella adhesion was 8-fold increased compared to normal iron conditions while invasion was not affected leading to decreased invasion efficiency (−86%). Moreover, cellular cytokines IL-1β, IL-6, IL-8 and TNF-α secretion as well as NF-κB activation in THP-1 cells were attenuated under high iron conditions. Low iron conditions in pure culture increased Salmonella invasion correlating with an increase in IL-8 release. In fermentation effluents, Salmonella adhesion was 12-fold and invasion was 428-fold reduced compared to pure culture. Salmonella in high iron fermentation effluents had decreased invasion efficiency (−77.1%) and cellular TNF-α release compared to normal iron effluent. The presence of commensal microbiota and bacterial metabolites in fermentation effluents reduced adhesion and invasion of Salmonella compared to pure culture highlighting the importance of the gut microbiota as a barrier during pathogen invasion. High iron concentrations as

  14. Panama Canal capacity analysis

    SciTech Connect

    Bronzini, M.S.

    1995-04-27

    Predicting the transit capacities of the various Panama Canal alternatives required analyzing data on present Canal operations, adapting and extending an existing computer simulation model, performing simulation runs for each of the alternatives, and using the simulation model outputs to develop capacity estimates. These activities are summarized in this paper. A more complete account may be found in the project final report (TAMS 1993). Some of the material in this paper also appeared in a previously published paper (Rosselli, Bronzini, and Weekly 1994).

  15. Functional capacity evaluation: an empirical approach.

    PubMed

    Jette, A M

    1980-02-01

    This paper presents an empirical approach to selecting activities of daily living (ADL) to assess the functional capacity of noninstitutionalized individuals with polyarticular disability. The results of structural analyses illustrate the feasibility of substantially reducing the task of assessing functional capacity with a subset of ADL items without sacrificing the comprehensiveness of the assessment. The analyses reveal 5 common functional categories: physical mobility, transfers, home chores, kitchen chores, and personal care, which account for over 50% of the variance in the data.

  16. Reduced repair capacity of a DNA clustered damage site comprised of 8-oxo-7,8-dihydro-2'-deoxyguanosine and 2-deoxyribonolactone results in an increased mutagenic potential of these lesions

    DOE PAGES

    Cunniffe, Siobhan; O’Neill, Peter; Greenberg, Marc M.; ...

    2014-04-01

    A signature of ionizing radiation is the induction of DNA clustered damaged sites. Non-double strand break (DSB) clustered damage has been shown to compromise the base excision repair pathway, extending the lifetimes of the lesions within the cluster, compared to isolated lesions. This increases the likelihood the lesions persist to replication and thus increasing the mutagenic potential of the lesions within the cluster. Lesions formed by ionizing radiation include 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) and 2-deoxyribonolactone (dL). dL poses an additional challenge to the cell as it is not repaired by the short-patch base excision repair pathway. Here we show recalcitrant dL repairmore » is reflected in mutations observed when DNA containing it and a proximal 8-oxodGuo is replicated in Escherichia coli. 8-oxodGuo in close proximity to dL on the opposing DNA strand results in an enhanced frequency of mutation of the lesions within the cluster and a 20 base sequence flanking the clustered damage site in an E. coli based plasmid assay. In vitro repair of a dL lesion is reduced when compared to the repair of an abasic (AP) site and a tetrahydrofuran (THF), and this is due mainly to a reduction in the activity of polymerase β, leading to retarded FEN1 and ligase 1 activities. This study has given insights in to the biological effects of clusters containing dL.« less

  17. REDUCTION CAPACITY OF SALTSTONE AND SALTSTONE COMPONENTS

    SciTech Connect

    Roberts, K.; Kaplan, D.

    2009-11-30

    The duration that saltstone retains its ability to immobilize some key radionuclides, such as technetium (Tc), plutonium (Pu), and neptunium (Np), depends on its capacity to maintain a low redox status (or low oxidation state). The reduction capacity is a measure of the mass of reductants present in the saltstone; the reductants are the active ingredients that immobilize Tc, Pu, and Np. Once reductants are exhausted, the saltstone loses its ability to immobilize these radionuclides. The reduction capacity values reported here are based on the Ce(IV)/Fe(II) system. The Portland cement (198 {micro}eq/g) and especially the fly ash (299 {micro}eq/g) had a measurable amount of reduction capacity, but the blast furnace slag (820 {micro}eq/g) not surprisingly accounted for most of the reduction capacity. The blast furnace slag contains ferrous iron and sulfides which are strong reducing and precipitating species for a large number of solids. Three saltstone samples containing 45% slag or one sample containing 90% slag had essentially the same reduction capacity as pure slag. There appears to be some critical concentration between 10% and 45% slag in the Saltstone formulation that is needed to create the maximum reduction capacity. Values from this work supported those previously reported, namely that the reduction capacity of SRS saltstone is about 820 {micro}eq/g; this value is recommended for estimating the longevity that the Saltstone Disposal Facility will retain its ability to immobilize radionuclides.

  18. ODZ1 allows glioblastoma to sustain invasiveness through a Myc-dependent transcriptional upregulation of RhoA.

    PubMed

    Talamillo, A; Grande, L; Ruiz-Ontañon, P; Velasquez, C; Mollinedo, P; Torices, S; Sanchez-Gomez, P; Aznar, A; Esparis-Ogando, A; Lopez-Lopez, C; Lafita, C; Berciano, M T; Montero, J A; Vazquez-Barquero, A; Segura, V; Villagra, N T; Pandiella, A; Lafarga, M; Leon, J; Martinez-Climent, J A; Sanz-Moreno, V; Fernandez-Luna, J L

    2017-03-23

    Long-term survival remains low for most patients with glioblastoma (GBM), which reveals the need for markers of disease outcome and novel therapeutic targets. We describe that ODZ1 (also known as TENM1), a type II transmembrane protein involved in fetal brain development, plays a crucial role in the invasion of GBM cells. Differentiation of glioblastoma stem-like cells drives the nuclear translocation of an intracellular fragment of ODZ1 through proteolytic cleavage by signal peptide peptidase-like 2a. The intracellular fragment of ODZ1 promotes cytoskeletal remodelling of GBM cells and invasion of the surrounding environment both in vitro and in vivo. Absence of ODZ1 by gene deletion or downregulation of ODZ1 by small interfering RNAs drastically reduces the invasive capacity of GBM cells. This activity is mediated by an ODZ1-triggered transcriptional pathway, through the E-box binding Myc protein, that promotes the expression and activation of Ras homolog family member A (RhoA) and subsequent activation of Rho-associated, coiled-coil containing protein kinase (ROCK). Overexpression of ODZ1 in GBM cells reduced survival of xenografted mice. Consistently, analysis of 122 GBM tumour samples revealed that the number of ODZ1-positive cells inversely correlated with overall and progression-free survival. Our findings establish a novel marker of invading GBM cells and consequently a potential marker of disease progression and a therapeutic target in GBM.

  19. Near-infrared oxymeter biosensor prototype for non-invasive in vivo analysis of rat brain oxygenation: effects of drugs of abuse

    NASA Astrophysics Data System (ADS)

    Crespi, F.; Donini, M.; Bandera, A.; Congestri, F.; Formenti, F.; Sonntag, V.; Heidbreder, C.; Rovati, L.

    2006-07-01

    The feasibility of non-invasive analysis of brain activities was studied in the attempt to overcome the major limitation of actual in vivo methodologies, i.e. invasiveness. Optic fibre probes were used as the optical head of a novel, highly sensitive near-infrared continuous wave spectroscopy (CW-NIR) instrument. This prototype was designed for non-invasive analysis of the two main forms of haemoglobin: oxy-haemoglobin (HbO2) and deoxy-haemoglobin (Hb), chromophores present in biological tissues. It was tested in peripheral tissue (human gastrocnemius muscle) and then reset to perform the measurement on rat brain. In animal studies, the optical head was firmly placed using stereotaxic apparatus upon the sagittal line of the head of anaesthetized adult rats, without any surgery. Then pharmacological treatments with saline (300 µl s.c.) amphetamine (2 mg kg-1) or nicotine (0.4 mg kg-1) were performed. Within 10-20 min amphetamine substantially increased HbO2 and reduced Hb control levels. Nicotine produced a rapid initial increase followed by a decrease in HbO2. In contrast to amphetamine, nicotine treatment also reduced Hb and blood volume. These results support the capacity of our CW-NIR prototype to measure non-invasively HbO2 and Hb levels in the rat brain, that are markers of the degree of tissue oxygenation, thus providing an index of blood levels and therefore of brain metabolism.