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Sample records for alters secondary active

  1. Textures of Secondary Alteration Zones in Nakhla

    NASA Technical Reports Server (NTRS)

    McKay, D. S.; Wentworth, S. J.; Longazo, T. G.; Thomas-Keprta, K.; Gibson, E. K.

    2001-01-01

    Textures of secondary minerals in cracks in Nakhla are described and illustrated with high resolution Scanning Electron Microscopy (SEM) and BSE. Some Nakhla textures resemble alteration textures of glass in seafloor basalts. Criteria for inorganic vs. biogenic alteration are discussed. Additional information is contained in the original extended abstract.

  2. [FLS - three letters alter secondary fracture prevention].

    PubMed

    Suhm, N; Meier, C; Kraenzlin, M; Kungler, E; Savic, B; Mueller, S; Jakob, M; Rikli, D

    2016-01-01

    The increasing importance of preventive measures in the field of orthopedics and trauma surgery becomes apparent because of the demographic changes and the high risk for secondary fractures following osteoporotic fractures. Within the fracture treatment chain, orthopedics and trauma surgery are in the "pole position" to initiate these measures in geriatric patients. In the past orthopedists and trauma surgeons have constantly accused of neglecting secondary fracture prevention in fragility fracture patients. There are several reasons that speak in favor of us undertaking a role in secondary fracture prevention: osteoporosis medication is highly effective in fracture prevention when correctly indicated, the positive effects of osteoporosis therapy on fracture healing and legal issues. Arguments that have been used to justify neglect of secondary fracture prevention are undesired side effects related to osteoporosis medications, such as atypical femoral fractures and osteonecrosis of the jaws, interference of some specific drugs with fracture healing and the working conditions in emergency departments. These run contrary to the consideration of chronic diseases such as osteoporosis, secondary osteoporosis and the underlying disease could be overlooked and the increasing complexity of medicinal osteoporosis therapy. In the first part of the article these arguments are weighed against each other. In the second part the concept of a fracture liaison service (FLS) is discussed. The FLS framework now allows an active role to be taken with respect to secondary fracture prevention despite the busy daily routine schedule. Implementation of an FLS is facilitated by dedicated instruction protocols and programs. Self-financing of an FLS is currently possible only in some specific healthcare systems. In healthcare systems in German-speaking areas a cross-financing must be available and the value of an FLS indirectly presented. Apart from the financial aspects, implementation of

  3. Enhancement of Anti-Inflammatory Activity of Aloe vera Adventitious Root Extracts through the Alteration of Primary and Secondary Metabolites via Salicylic Acid Elicitation

    PubMed Central

    Lee, Yun Sun; Ju, Hyun Kyoung; Kim, Yeon Jeong; Lim, Tae-Gyu; Uddin, Md Romij; Kim, Yeon Bok; Baek, Jin Hong; Kwon, Sung Won; Lee, Ki Won; Seo, Hak Soo; Park, Sang Un; Yang, Tae-Jin

    2013-01-01

    Aloe vera (Asphodeloideae) is a medicinal plant in which useful secondary metabolites are plentiful. Among the representative secondary metabolites of Aloe vera are the anthraquinones including aloe emodin and chrysophanol, which are tricyclic aromatic quinones synthesized via a plant-specific type III polyketide biosynthesis pathway. However, it is not yet clear which cellular responses can induce the pathway, leading to production of tricyclic aromatic quinones. In this study, we examined the effect of endogenous elicitors on the type III polyketide biosynthesis pathway and identified the metabolic changes induced in elicitor-treated Aloe vera adventitious roots. Salicylic acid, methyl jasmonate, and ethephon were used to treat Aloe vera adventitious roots cultured on MS liquid media with 0.3 mg/L IBA for 35 days. Aloe emodin and chrysophanol were remarkably increased by the SA treatment, more than 10–11 and 5–13 fold as compared with untreated control, respectively. Ultra-performance liquid chromatography-electrospray ionization mass spectrometry analysis identified a total of 37 SA-induced compounds, including aloe emodin and chrysophanol, and 3 of the compounds were tentatively identified as tricyclic aromatic quinones. Transcript accumulation analysis of polyketide synthase genes and gas chromatography mass spectrometry showed that these secondary metabolic changes resulted from increased expression of octaketide synthase genes and decreases in malonyl-CoA, which is the precursor for the tricyclic aromatic quinone biosynthesis pathway. In addition, anti-inflammatory activity was enhanced in extracts of SA-treated adventitious roots. Our results suggest that SA has an important role in activation of the plant specific-type III polyketide biosynthetic pathway, and therefore that the efficacy of Aloe vera as medicinal agent can be improved through SA treatment. PMID:24358188

  4. Alteration of Tephra Conductivity Resulting From Secondary Pyroclast Disaggregation

    NASA Astrophysics Data System (ADS)

    Genareau, K. D.; Farley, A. W.

    2014-12-01

    In addition to influencing the electrical conductivity of volcanic ash, leachates bound to ash grain surfaces may pose significant hazards to water quality through the contribution of sulfates, fluoride, metals, and acidic compounds to local water supplies by either direct ash fallout or incorporation into precipitation runoff. In regions of active volcanism, remobilization of pyroclastic units may be a regular occurrence due to landslides or lahars, but the resultant effects of secondary disaggregation of pyroclasts have not been examined. Laboratory analyses of tephras from several eruptive centers have revealed variations in the pH, conductivity, and total dissolved solid (TDS) concentration of water-soluble compounds as a result of pyroclast disaggregation. Analyses were conducted using the standardized protocols for ash leachate analysis. TDS, conductivity, and pH were then measured and the tephra samples were allowed to air dry before being retested using identical methods. When pyroclast disaggregation was not performed, results show a progressive decrease in water conductivity, acidity, and TDS concentration following each stage of sonication. However, when an additional step of clast disaggregation (through crushing and grinding of samples) preceded the sonication step, water samples showed increases in measured properties. Mass spectroscopic analyses of water samples are in progress and results will be presented. These results indicate that secondary comminution of pyroclastic deposits will release water-soluble components from the pyroclast interior that may result in a renewed series of environmental hazards many years after the initial eruptive event. Break up of pyroclasts during transport in landslides or lahars (or even during cleanup efforts) will not only alter the size distribution of the deposit, but will also release metals, sulfates, and fluoride from the tephra interiors, altering the chemical and electrical properties of the tephra. This

  5. Short Term, Low Dose Simvastatin Pretreatment Alters Memory Immune Function Following Secondary Staphylococcus aureus Infection.

    PubMed

    Smelser, Lisa K; Walker, Callum; Burns, Erin M; Curry, Michael; Black, Nathanael; Metzler, Jennifer A; McDowell, Susan A; Bruns, Heather A

    2016-01-01

    Statins are potent modulators of immune responses, resulting in their ability to enhance host survival from primary bacterial infections. Alterations in primary immune responses that may be beneficial for survival following infection may also result in alterations in the generation of the immunologic memory response and subsequently affect immune responses mounted during secondary bacterial infection. In this study, we report that levels of total serum IgG2c, following primary infection, were decreased in simvastatin pretreated mice, and investigate the effect of simvastatin treatment, prior to primary infection, on immune responses activated during secondary S. aureus infection. A secondary infection model was implemented whereby simvastatin pretreated and control mice were reinfected with S. aureus 14 days after primary infection, with no additional simvastatin treatment, and assessed for survival and alterations in immune function. While survivability to secondary S. aureus infection was not different between simvastatin pretreated and control mice, memory B and T lymphocyte functions were altered. Memory B cells, isolated 14 days after secondary infection, from simvastatin pretreated mice and stimulated ex vivo produced increased levels of IgG1 compared to memory B cells isolated from control mice, while levels of IgM and IgG2c remained similar. Furthermore, memory B and T lymphocytes from simvastatin pretreated mice exhibited a decreased proliferative response when stimulated ex vivo compared to memory cells isolated from control mice. These findings demonstrate the ability of a short term, low dose simvastatin treatment to modulate memory immune function. PMID:26927218

  6. Acid sulfate alteration of fluorapatite, basaltic glass and olivine by hydrothermal vapors and fluids: Implications for fumarolic activity and secondary phosphate phases in sulfate-rich Paso Robles soil at Gusev Crater, Mars

    NASA Astrophysics Data System (ADS)

    Hausrath, E. M.; Golden, D. C.; Morris, R. V.; Agresti, D. G.; Ming, D. W.

    2013-01-01

    Phosphate-rich rocks and a nearby phosphate-rich soil, Paso Robles, were analyzed in Gusev Crater, Mars, by the Mars Exploration Rover Spirit and interpreted to be highly altered, possibly by hydrothermal or fumarolic alteration of primary, phosphate-rich material. To test mineral phases resulting from such alteration, we performed hydrothermal acid-vapor and acid-fluid experiments on olivine (Ol), fluorapatite (Ap), and basaltic glass (Gl) as single phases and a mixture of phases. Minerals formed include Ca-, Al-, Fe- and Mg-sulfates with different hydration states (anhydrite, bassanite, gypsum; alunogen; hexahydrite, and pentahydrite). Phosphate-bearing minerals formed included monocalcium phosphate monohydrate (MCP) (acid-vapor and acid-fluid alteration of fluorapatite only) and ferrian giniite (acid-fluid alteration of the Ol + Gl + Ap mixture). MCP is likely present in Paso Robles if primary Ca-phosphate minerals reacted with sulfuric acid with little transport of phosphate. Under fluid:rock ratios allowing transport of phosphate, a ferric phosphate phase such as ferrian giniite might form instead. Mössbauer measurements of ferrian giniite-bearing alteration products and synthetic ferrian giniite are consistent with Spirit's Mössbauer measurements of the ferric-bearing phase in Paso Robes soil, but are also consistent with ferric sulfate phases in the low-P soil Arad_Samra. Therefore, Mössbauer data alone do not constrain the fluid:rock ratio. However, the excess iron (hematite) in Paso Robles soil, which implies aqueous transport, combined with our laboratory experiments, suggest acid-sulfate alteration in a hydrothermal (fumarolic) environment at fluid:rock ratios sufficient to allow dissolution, transport, and precipitation of secondary chemical components including a ferric phosphate such as ferrian giniite.

  7. Bisphosphonates do not alter the rate of secondary mineralization

    SciTech Connect

    Fuchs R. K.; Miller L.; Faillace M.E.; Allen M.R.; Phipps R.J. and Burr D.B.

    2011-05-18

    Bisphosphonates function to reduce bone turnover, which consequently increases the mean degree of tissue mineralization at an organ level. However, it is not clear if bisphosphonates alter the length of time required for an individual bone-modeling unit (BMU) to fully mineralize. We have recently demonstrated that it takes {approx}350 days (d) for normal, untreated cortical bone to fully mineralize. The aim of this study was to determine the rate at which newly formed trabecular BMUs become fully mineralized in rabbits treated for up to 414 d with clinical doses of either risedronate (RIS) or alendronate (ALN). Thirty-six, 4-month old virgin female New Zealand white rabbits were allocated to RIS (n = 12; 2.4 {micro}g/kg body weight), ALN (n = 12; 2.4 {micro}g/kg body weight), or volume-matched saline controls (CON; n = 12). Fluorochrome labels were administered at specific time intervals to quantify the rate and level of mineralization of trabecular bone from the femoral neck (FN) by Fourier transform infrared microspectroscopy (FTIRM). The organic (collagen) and inorganic (phosphate and carbonate) IR spectral characteristics of trabecular bone from undecalcified 4 micron thick tissue sections were quantified from fluorescently labels regions that had mineralized for 1, 8, 18, 35, 70, 105, 140, 210, 280, and 385 d (4 rabbits per time point and treatment group). All groups exhibited a rapid increase in mineralization over the first 18 days, the period of primary mineralization, with no significant differences between treatments. Mineralization continued to increase, at a slower rate up, to 385 days (secondary mineralization), and was not different among treatments. There were no significant differences between treatments for the rate of mineralization within an individual BMU; however, ALN and RIS both increased global tissue mineralization as demonstrated by areal bone mineral density from DXA. We conclude that increases in tissue mineralization that occur

  8. Bisphosphonates do not Alter the Rate of Secondary Mineralization

    SciTech Connect

    R Fuchs; M Faillace; M Allen; R Phipps; L Miller; D Burr

    2011-12-31

    Bisphosphonates function to reduce bone turnover, which consequently increases the mean degree of tissue mineralization at an organ level. However, it is not clear if bisphosphonates alter the length of time required for an individual bone-modeling unit (BMU) to fully mineralize. We have recently demonstrated that it takes {approx}350 days (d) for normal, untreated cortical bone to fully mineralize. The aim of this study was to determine the rate at which newly formed trabecular BMUs become fully mineralized in rabbits treated for up to 414 d with clinical doses of either risedronate (RIS) or alendronate (ALN). Thirty-six, 4-month old virgin female New Zealand white rabbits were allocated to RIS (n=12; 2.4 {mu}g/kg body weight), ALN (n=12; 2.4 {mu}g/kg body weight), or volume-matched saline controls (CON; n=12). Fluorochrome labels were administered at specific time intervals to quantify the rate and level of mineralization of trabecular bone from the femoral neck (FN) by Fourier transform infrared microspectroscopy (FTIRM). The organic (collagen) and inorganic (phosphate and carbonate) IR spectral characteristics of trabecular bone from undecalcified 4 micron thick tissue sections were quantified from fluorescently labels regions that had mineralized for 1, 8, 18, 35, 70, 105, 140, 210, 280, and 385 d (4 rabbits per time point and treatment group). All groups exhibited a rapid increase in mineralization over the first 18 days, the period of primary mineralization, with no significant differences between treatments. Mineralization continued to increase, at a slower rate up, to 385 days (secondary mineralization), and was not different among treatments. There were no significant differences between treatments for the rate of mineralization within an individual BMU; however, ALN and RIS both increased global tissue mineralization as demonstrated by areal bone mineral density from DXA. We conclude that increases in tissue mineralization that occur following a period

  9. [Secondary Career Education Activities: Science.

    ERIC Educational Resources Information Center

    Radford City Schools, VA.

    The guide is one of a series developed in a pilot project to integrate career education concepts with subject matter in secondary grades. The units are designed to reveal career orientation aspects of traditional topics within five major subject areas: English, social studies, mathematics, science, and health and physical education. The lesson…

  10. Mount St. Helens Classroom Activities: Secondary.

    ERIC Educational Resources Information Center

    Washington State Educational Service District 112, Vancouver.

    This teacher's guide is designed to provide secondary teachers with an assortment of classroom activities dealing with the Mt. St. Helens eruption of May 18, 1980, in the areas of science, social studies, math, language arts and school newspaper activities. Copy masters and teacher versions of all activities are contained within this guide,…

  11. Coal Activities for Secondary Students.

    ERIC Educational Resources Information Center

    American Coal Foundation, Washington, DC.

    This collection of lesson plans designed for teachers of 4th- through 12th-grade students utilizes an assortment of teaching strategies for topics related to coal and the coal industry. Activities cover the following topics: coal formation; coal identification; "the geologist's dilemma" (a supply and demand activity); geologic time and the…

  12. Hydrothermal Alteration in the Logatchev Hydrothermal Field: Implications From Secondary Mineral Assemblages and Mineral Chemistry

    NASA Astrophysics Data System (ADS)

    Lackschewitz, K. S.; Augustin, N.; Devey, C. W.; Eisenhauer, A.; Garbe-Schoenberg, D.; James, R.

    2005-12-01

    We present new data on secondary mineral assemblages, clay and whole rock chemistry and clay mineral strontium and lithium isotopic compositions of altered rocks and sediments from the active, ultramafic-hosted Logatchev hydrothermal field reflecting various alteration conditions (e.g. fluid mixing, water-rock interaction). The altered ultramafic rocks are mainly consist of lizardite, chrysotile whereas magnetite and pyrite are minor minerals. Chlorite, chlorite-smectite mixed-layer (e.g., corrensite), smectite and talc are additional common phases in the clay fraction of most of these samples.Iron-hydroxides and iron sulfides are the main components of the hydrothermal crusts, with some amounts of pyroxene, chlorite, illite and pyrite. The hydrothermal sediments beneath the crusts are characterized by quartz, smectite and chlorite as main minerals. Analyses of clay separates representing a variety of alteration styles demonstrates that significant and characteristic changes in the bulk rock chemical composition are associated with various alteration conditions. The elements Cr, Cu, Pb and U appears to have a general enrichment in the lizardite and chlorite concentrates in comparison to a depleted mantle. 87Sr/86Sr ratios of clay concentrates vary between 0.7083 and 0.7096 suggesting that the clays either formed as a result of seawater alteration or hydrothermal alteration with various portions of seawater. The strontium isotopic ratio of a chlorite sample from hydrothermal sediments beneath the hydrothermal crust is much lower than the isotopic data reported for the lizardites suggesting precipitation from fluid with lower seawater content. The Li isotopic composition (δ7Li) of the clay separates varies between -5.4 and +6.4‰. Thus, the clays are enriched in 6Li relative to both seawater (~31‰) and hydrothermal vent fluids from the Logatchev field (~6‰) suggesting that 6Li is preferentially retained in alteration products. When considered together with the

  13. Instructional Activities Series. Elementary and Secondary Sections.

    ERIC Educational Resources Information Center

    National Council for Geographic Education.

    Twenty teacher-developed elementary and secondary instructional activities on geography-related topics are available in a single activity, loose-leaf format as an on-going series. Simulations, role playing, mapping, group discussion, experiential learning, and field excursions are some of the instructional approaches. Materials include case…

  14. Cocurricular Activity Programs in Secondary Schools.

    ERIC Educational Resources Information Center

    Gholson, Ronald E.; Buser, Robert L.

    This booklet provides a history of the role played by extracurricular activities in American secondary education, summarizing their objectives, principles, and problems, and classifying their types. The student-activity concept is traced through four stages of historical development in the United States. Noting that the objectives of cocurricular…

  15. Hydrothermal Alteration in the PACMANUS Hydrothermal Field: Implications From Secondary Mineral Assemblages and Mineral Chemistry, OPD Leg 193

    NASA Astrophysics Data System (ADS)

    Lackschewitz, K. S.; Kummetz, M.; Kummetz, M.; Ackermand, D.; Botz, R.; Devey, C. W.; Singer, A.; Stoffers, P.

    2001-12-01

    Leg 193 of the Ocean Drilling Program investigated the subsurface nature of the active PACMANUS hydrothermal field in the Manus backarc basin near Papua New Guinea. Drilling in different areas on the felsic neovolcanic Pual Ridge, including the high-temperature black smoker complex of Roman Ruins and the low-temperature Snowcap site with diffusive discharge yielded a complex alteration history with a regional primary alteration being overprinted by a secondary mineralogy. The intense hydrothermal alteration at both sites shows significant differences in the secondary mineralogy. At Roman Ruins, the upper 25 m of hydrothermally altered rocks are characterized by a rapid change from secondary cristobalite to quartz, implying a high temperature gradient. From 10 to 120 mbsf the clay mineralogy is dominated by illite and chlorite. The chlorite formation temperature calculated from oxygen isotope data lies at 250° C in 116 mbsf which is similar to the present fluid outflow temperatures of 240-250° C (Douville et al., 1999, Geochim. Cosmochim. Acta, 63, 627-643). Drilling in the Snowcap field recovered evidence for several stages of hydrothermal alteration. Between 50 and 150 mbsf, cristobalite and chlorite are the most abundant alteration minerals while hydrothermal pyrophyllite becomes abundant in some places At 67 mbsf, the isotopic composition of pyrophyllite gives a temperature for ist formation at 260° C whereas at 77 and 116 mbsf the pyrophyllite displays the highest temperatures of formation (>300° C). These temperatures are close to the maximum measured borehole temperatures of 313° C. The appearance of assemblages of chlorite, chlorite-vermiculite, chlorite-vermiculite-smectite and illite-smectite as well as the local development of corrensite below 150 mbsf suggests that the alteration at Snowcap may be more complex than that beneath Roman Ruins. Detailed geochemical studies of the authigenic clay mineral phases will provide further insights into the

  16. Alterations in lipid signaling underlie lipodystrophy secondary to AGPAT2 mutations.

    PubMed

    Subauste, Angela R; Das, Arun K; Li, Xiangquan; Elliott, Brandon G; Elliot, Brandon; Evans, Charles; El Azzouny, Mahmoud; Treutelaar, Mary; Oral, Elif; Leff, Todd; Burant, Charles F

    2012-11-01

    Congenital generalized lipodystrophy (CGL), secondary to AGPAT2 mutation is characterized by the absence of adipocytes and development of severe insulin resistance. In the current study, we investigated the adipogenic defect associated with AGPAT2 mutations. Adipogenesis was studied in muscle-derived multipotent cells (MDMCs) isolated from vastus lateralis biopsies obtained from controls and subjects harboring AGPAT2 mutations and in 3T3-L1 preadipocytes after knockdown or overexpression of AGPAT2. We demonstrate an adipogenic defect using MDMCs from control and CGL human subjects with mutated AGPAT2. This defect was rescued in CGL MDMCs with a retrovirus expressing AGPAT2. Both CGL-derived MDMCs and 3T3-L1 cells with knockdown of AGPAT2 demonstrated an increase in cell death after induction of adipogenesis. Lack of AGPAT2 activity reduces Akt activation, and overexpression of constitutively active Akt can partially restore lipogenesis. AGPAT2 modulated the levels of phosphatidic acid, lysophosphatidic acid, phosphatidylinositol species, as well as the peroxisome proliferator-activated receptor γ (PPARγ) inhibitor cyclic phosphatidic acid. The PPARγ agonist pioglitazone partially rescued the adipogenic defect in CGL cells. We conclude that AGPAT2 regulates adipogenesis through the modulation of the lipome, altering normal activation of phosphatidylinositol 3-kinase (PI3K)/Akt and PPARγ pathways in the early stages of adipogenesis. PMID:22872237

  17. DENSITY CURRENTS IN ACTIVATED SLUDGE SECONDARY CLARIFIERS

    EPA Science Inventory

    Density currents form in activated sludge secondary clarifiers because the mixed liquor has a density greater than the treated wastewater in the clarifier. This causes the mixed liquor to plunge to the bottom of the clarifier establishing relatively high velocity currents within ...

  18. Growth under elevated air temperature alters secondary metabolites in Robinia pseudoacacia L. seedlings in Cd- and Pb-contaminated soils.

    PubMed

    Zhao, Y H; Jia, X; Wang, W K; Liu, T; Huang, S P; Yang, M Y

    2016-09-15

    Plant secondary metabolites play a pivotal role in growth regulation, antioxidant activity, pigment development, and other processes. As the global climate changes, increasing atmospheric temperatures and contamination of soil by heavy metals co-occur in natural ecosystems, which alters the pH of rhizosphere soil and influences the bioavailability and mobility of metals. Elevated temperatures in combination with heavy metals are expected to affect plant secondary metabolites, but this issue has not been extensively examined. Here, we investigated secondary metabolites in Robiniapseudoacacia seedlings exposed to elevated temperatures using a passive warming device in combination with Cd- and Pb-contaminated soils. Heavy metals significantly stimulated the accumulation of saponins, phenolic compounds, and flavonoids in leaves and stems; alkaloid compounds increased in leaves and decreased in stems, and condensed tannins fluctuated. Elevated temperatures, alone and in combination with Cd and Pb, caused increases in secondary metabolites in the plant tissues. Phenolic compounds showed the greatest changes among the secondary metabolites and significant interactive effects of temperature and metals were observed. These results suggest that slightly elevated temperature could enhance protective and defense mechanisms of Robinia pseudoacacia seedlings exposed to heavy metals by stimulating the production of secondary metabolites. PMID:27203519

  19. Protein kinase activators alter glial cholesterol esterification

    SciTech Connect

    Jeng, I.; Dills, C.; Klemm, N.; Wu, C.

    1986-05-01

    Similar to nonneural tissues, the activity of glial acyl-CoA cholesterol acyltransferase is controlled by a phosphorylation and dephosphorylation mechanism. Manipulation of cyclic AMP content did not alter the cellular cholesterol esterification, suggesting that cyclic AMP is not a bioregulator in this case. Therefore, the authors tested the effect of phorbol-12-myristate 13-acetate (PMA) on cellular cholesterol esterification to determine the involvement of protein kinase C. PMA has a potent effect on cellular cholesterol esterification. PMA depresses cholesterol esterification initially, but cells recover from inhibition and the result was higher cholesterol esterification, suggesting dual effects of protein kinase C. Studies of other phorbol analogues and other protein kinase C activators such as merezein indicate the involvement of protein kinase C. Oleoyl-acetyl glycerol duplicates the effect of PMA. This observation is consistent with a diacyl-glycerol-protein kinase-dependent reaction. Calcium ionophore A23187 was ineffective in promoting the effect of PMA. They concluded that a calcium-independent and protein C-dependent pathway regulated glial cholesterol esterification.

  20. Redox activity of naphthalene secondary organic aerosol

    NASA Astrophysics Data System (ADS)

    McWhinney, R. D.; Zhou, S.; Abbatt, J. P. D.

    2013-04-01

    Chamber secondary organic aerosol (SOA) from low-NOx photooxidation of naphthalene by hydroxyl radical was examined with respect to its redox cycling behaviour using the dithiothreitol (DTT) assay. Naphthalene SOA was highly redox active, consuming DTT at an average rate of 118 ± 14 pmol per minute per μg of SOA material. Measured particle-phase masses of the major previously identified redox active products, 1,2- and 1,4-naphthoquinone, accounted for only 21 ± 3% of the observed redox cycling activity. The redox-active 5-hydroxy-1,4-naphthoquinone was identified as a new minor product of naphthalene oxidation, and including this species in redox activity predictions increased the predicted DTT reactivity to 30 ± 5% of observations. Similar attempts to predict redox behaviour of oxidised two-stroke engine exhaust particles by measuring 1,2-naphthoquinone, 1,4-naphthoquinone and 9,10-phenanthrenequinone predicted DTT decay rates only 4.9 ± 2.5% of those observed. Together, these results suggest that there are substantial unidentified redox-active SOA constituents beyond the small quinones that may be important toxic components of these particles. A gas-to-SOA particle partitioning coefficient was calculated to be (7.0 ± 2.5) × 10-4 m3 μg-1 for 1,4-naphthoquinone at 25 °C. This value suggests that under typical warm conditions, 1,4-naphthoquinone is unlikely to contribute strongly to redox behaviour of ambient particles, although further work is needed to determine the potential impact under conditions such as low temperatures where partitioning to the particle is more favourable. As well, higher order oxidation products that likely account for a substantial fraction of the redox cycling capability of the naphthalene SOA are likely to partition much more strongly to the particle phase.

  1. Cyanotic congenital heart disease (CCHD): focus on hypoxemia, secondary erythrocytosis, and coagulation alterations.

    PubMed

    Zabala, Luis M; Guzzetta, Nina A

    2015-10-01

    Children with cyanotic congenital heart disease (CCHD) have complex alterations in their whole blood composition and coagulation profile due to long-standing hypoxemia. Secondary erythrocytosis is an associated physiological response intended to increase circulating red blood cells and oxygen carrying capacity. However, this response is frequently offset by an increase in whole blood viscosity that paradoxically reduces blood flow and tissue perfusion. In addition, the accompanying reduction in plasma volume leads to significant deficiencies in multiple coagulation proteins including platelets, fibrinogen and other clotting factors. On the one hand, these patients may suffer from severe hyperviscosity and subclinical 'sludging' in the peripheral vasculature with an increased risk of thrombosis. On the other hand, they are at an increased risk for postoperative hemorrhage due to a complex derangement in their hemostatic profile. Anesthesiologists caring for children with CCHD and secondary erythrocytosis need to understand the pathophysiology of these alterations and be aware of available strategies that lessen the risk of bleeding and/or thrombosis. The aim of this review is to provide an updated analysis of the systemic effects of long-standing hypoxemia in children with primary congenital heart disease with a specific focus on secondary erythrocytosis and hemostasis. PMID:26184479

  2. Stochastic steps in secondary active sugar transport.

    PubMed

    Adelman, Joshua L; Ghezzi, Chiara; Bisignano, Paola; Loo, Donald D F; Choe, Seungho; Abramson, Jeff; Rosenberg, John M; Wright, Ernest M; Grabe, Michael

    2016-07-01

    Secondary active transporters, such as those that adopt the leucine-transporter fold, are found in all domains of life, and they have the unique capability of harnessing the energy stored in ion gradients to accumulate small molecules essential for life as well as expel toxic and harmful compounds. How these proteins couple ion binding and transport to the concomitant flow of substrates is a fundamental structural and biophysical question that is beginning to be answered at the atomistic level with the advent of high-resolution structures of transporters in different structural states. Nonetheless, the dynamic character of the transporters, such as ion/substrate binding order and how binding triggers conformational change, is not revealed from static structures, yet it is critical to understanding their function. Here, we report a series of molecular simulations carried out on the sugar transporter vSGLT that lend insight into how substrate and ions are released from the inward-facing state of the transporter. Our simulations reveal that the order of release is stochastic. Functional experiments were designed to test this prediction on the human homolog, hSGLT1, and we also found that cytoplasmic release is not ordered, but we confirmed that substrate and ion binding from the extracellular space is ordered. Our findings unify conflicting published results concerning cytoplasmic release of ions and substrate and hint at the possibility that other transporters in the superfamily may lack coordination between ions and substrate in the inward-facing state. PMID:27325773

  3. A MYLK variant regulates asthmatic inflammation via alterations in mRNA secondary structure.

    PubMed

    Wang, Ting; Zhou, Tong; Saadat, Laleh; Garcia, Joe G N

    2015-06-01

    Myosin light-chain kinase (MYLK) is a gene known to be significantly associated with severe asthma in African Americans. Here we further examine the molecular function of a single-nucleotide polymorphism (SNP), located in the non-muscle myosin light-chain kinase isoform (nmMLCK), in asthma susceptibility and pathobiology. We identified nmMLCK variant (reference SNP: rs9840993, NM_053025: 721C>T, c.439C>T) with a distinct mRNA secondary structure from the other variants. The nmMLCK variant (721C) secondary structure exhibits increased stability with an elongated half-life in the human endothelial cell, and greater efficiency in protein translation initiation owing to an increased accessibility to translation start site. Finally, nmMLCK expression of 721C- and 721T-containing MYLK transgenes were compared in nmMLCK(-/-) mice and confirmed deleterious effects of nmMLCK expression on asthmatic indices and implicated the augmented influence of MYLK 721C>T (c.439C>T) SNP on asthma severity. The confirmation of the novel mechanism of the regulation of asthmatic inflammation by a MYLK advances knowledge of the genetic basis for asthma disparities, and further suggests the potential of nmMLCK as a therapeutic target. Our study suggests that in addition to altering protein structure and function, non-synonymous SNPs may also lead to phenotypic disparity by altering protein expression. PMID:25271083

  4. Hydrothermal alteration in Oregon's Newberry Volcano No. 2: fluid chemistry and secondary-mineral distribution

    SciTech Connect

    Keith, T.E.C.; Mariner, R.H.; Bargar, K.E.; Evans, W.C.; Presser, T.S.

    1984-04-01

    Newberry 2 was drilled in the caldera floor of Newberry Volcano, Oregon, by the US Geological Survey during 1979-81. The maximum temperature measured was 265C at the bottom of the hole, 932 m below the surface. Rocks recovered fr9om the drill hole are divided into three intervals on the basis of hydrothermal alteration and mineral deposition: (1) 0-290 m consists of unaltered, largely glassy volcanic material, with present temperatures ranging from 20 to 40C; (2) 290-700 m consists of permeable tuff layers, tuff breccia units, and brecciated and fractured rhyodacitic to dacitic lava flows, with temperatures ranging from 40 to 100C; (3) 700-932 m consists of impermeable andesitic to basaltic lava flows that generally show little effect of alteration, interlayered with permeable hydrothermally altered flow breccia, with temperatures gradually increasing from 100 at 700 m to 265C at 932 m. Hydrothermal alteration throughout the system is controlled by rock permeability, temperature, composition of geothermal fluids, and composition and crystallinity of host rocks. Rock alteration consists mainly of replacement of glass by clay minerals and, locally, zeolites, partial replacement of plagioclase phenocrysts by calcite +/- epidote +/- illite, and whole-rock leaching adjacent to fluids channels. Open-space deposition of hydrothermal minerals in fractures, vesicles, and interbreccia pore space is far more abundant than replacement. A cooling shallow convection system in the upper 700 m is indicated by the occurrence of hydrothermal minerals that were deposited in a slightly higher temperature environment than presently exists. Below 700 m, the heat flow is conductive, and fluid flow is controlled by horizontal lava flows. Homogenization temperatures of secondary quartz fluid inclusions were as high as 370C.

  5. Nectar microbes can reduce secondary metabolites in nectar and alter effects on nectar consumption by pollinators.

    PubMed

    Vannette, Rachel L; Fukami, Tadashi

    2016-06-01

    Secondary metabolites that are present in floral nectar have been hypothesized to enhance specificity in plant-pollinator mutualism by reducing larceny by non-pollinators, including microorganisms that colonize nectar. However, few studies have tested this hypothesis. Using synthetic nectar, we conducted laboratory and field experiments to examine the effects of five chemical compounds found in nectar on the growth and metabolism of nectar-colonizing yeasts and bacteria, and the interactive effects of these compounds and nectar microbes on the consumption of nectar by pollinators. In most cases, focal compounds inhibited microbial growth, but the extent of these effects depended on compound identity, concentration, and microbial species. Moreover, most compounds did not substantially decrease sugar metabolism by microbes, and microbes reduced the concentration of some compounds in nectar. Using artificial flowers in the field, we also found that the common nectar yeast Metschnikowia reukaufii altered nectar consumption by small floral visitors, but only in nectar containing catalpol. This effect was likely mediated by a mechanism independent of catalpol metabolism. Despite strong compound-specific effects on microbial growth, our results suggest that the secondary metabolites tested here are unlikely to be an effective general defense mechanism for preserving nectar sugars for pollinators. Instead, our results indicate that microbial colonization of nectar could reduce the concentration of secondary compounds in nectar and, in some cases, reduce deterrence to pollinators. PMID:27459772

  6. Disruption of secondary wall cellulose biosynthesis alters cadmium translocation and tolerance in rice plants.

    PubMed

    Song, Xue-Qin; Liu, Li-Feng; Jiang, Yi-Jun; Zhang, Bao-Cai; Gao, Ya-Ping; Liu, Xiang-Ling; Lin, Qing-Shan; Ling, Hong-Qing; Zhou, Yi-Hua

    2013-05-01

    Tricheary elements (TEs), wrapped by secondary cell wall, play essential roles in water, mineral, and nutrient transduction. Cadmium (Cd) is a toxic heavy metal that is absorbed by roots and transported to shoot, leaves, and grains through vascular systems in plants. As rice is a major source of Cd intake, many efforts have been made to establish 'low-Cd rice'. However, no links have been found between cellulose biosynthesis and cadmium accumulation. We report here a rice brittle culm13 mutant, resulting from a novel missense mutation (E101K) [corrected] in the N-terminus of cellulose synthase subunit 9 (CESA9). Except for the abnormal mechanical strength, the mutant plants are morphologically indistinguishable from the wild-type plants. Transmission electron microscopy (TEM) and chemical analyses showed a slight reduction in secondary wall thickness and 22% decrease in cellulose content in bc13 plants. Moreover, this mutation unexpectedly confers the mutant plants Cd tolerance due to less Cd accumulation in leaves. Expression analysis of the genes required for Cd uptake and transport revealed complicated alterations after applying Cd to wild-type and bc13. The mutants were further found to have altered vascular structure. More importantly, Cd concentration in the xylem saps from the bc13 plants was significantly lower than that from the wild-type. Combining the analyses of CESA9 gene expression and Cd content retention in the cell-wall residues, we conclude that CESA9(E101K) [corrected] mutation alters cell-wall properties in the conducting tissues, which consequently affects Cd translocation efficiency that largely contributes to the low Cd accumulation in the mutant plants. PMID:23376772

  7. Alterations in the activity and structure of pectin methylesterase treated by high pressure carbon dioxide.

    PubMed

    Zhou, Linyan; Wu, Jihong; Hu, Xiaosong; Zhi, Xian; Liao, Xiaojun

    2009-03-11

    The influence of high pressure carbon dioxide (HPCD) on the activity and structure of pectin methylesterase (PME) from orange was investigated. The pressures were 8-30 MPa, temperature 55 degrees C and time 10 min. HPCD caused significant inactivation on PME, the lowest residual activity was about 9.3% at 30 MPa. The SDS-PAGE electrophoretic behavior of HPCD-treated PME was not altered, while changes in the secondary and tertiary structures were found. The beta-structure fraction in the secondary structure decreased and the fluorescence intensity increased as HPCD pressures were elevated. After 7-day storage at 4 degrees C, no alteration of its activity and no reversion of its beta-structure fraction were observed, while its fluorescence intensity further decreased. PMID:19256556

  8. The Infusion of Environmental Activities into a Secondary Biology Curriculum

    ERIC Educational Resources Information Center

    Foster, Helen M.

    1976-01-01

    Reviewed are "adventure-type" environmental education activities incorporated into a secondary level biology course. Student wilderness experiences included 24 weekend activities of hiking, bird watching, camping, and cross-country skiing. (SL)

  9. Peptide fibrils with altered stability, activity, and cell selectivity

    PubMed Central

    Chen, Long; Liang, Jun F.

    2014-01-01

    Peptides have some unique and superior features compared to proteins. However, the use of peptides as therapeutics is hampered by their low stability and cell selectivity. In this study, a new lytic peptide (CL-1, FLGALFRALSRLL) was constructed. Under the physiological condition, peptide CL-1 self-assembled into dynamically stable aggregates with fibrils-like structures. Aggregated CL-1 demonstrated dramatically altered activity and stability in comparison with single molecule CL-1 and other lytic peptides: when incubated with co-cultured bacteria and tissue cells, CL-1 aggregates killed bacteria selectively but spared co-cultured human cells; CL-1 aggregates kept intact in human serum for more than five hours. Peptide-cell interaction studies performed on lipid monolayers and live human tissue cells revealed that in comparison with monomeric CL-1, aggregated CL-1 had decreased cell affinity and membrane insertion capability on tissue cells. A dynamic process involving aggregate dissociation and rearrangement seemed to be an essential step for membrane bound CL-1 aggregates to realize its cytotoxicity to tissue cells. Our study suggests that peptide aggregation could be as important as the charge and secondary structure of a peptide in affecting peptide-cell interactions. Controlling peptide self-assembly represents a new way to increase the stability and cell selectivity of bioactive peptides for wide biomedical applications. PMID:23713839

  10. Essential Laboratory Activities Guide. Secondary Science.

    ERIC Educational Resources Information Center

    Duval County Schools, Jacksonville, FL.

    This teacher's guide was developed for use in junior and senior high schools in Duval County, Jacksonville, Florida, for the purpose of identifying those secondary science laboratory experiences which are essential to the development of science content knowledge and competency in handling science laboratory equipment and consumables. The guide…

  11. Computer Activities in Illinois Secondary Schools.

    ERIC Educational Resources Information Center

    Dennis, J. Richard; And Others

    A brief, non-technical questionnaire was sent to 875 secondary school administrators (primarily principals) in the State of Illinois. Information was collected in four areas: (1) general school characteristics, (2) availability and use of computers, (3) perceived need for and qualifications of teachers of computer science, and (4) perceived need…

  12. [Secondary Career Education Activities: Social Studies.

    ERIC Educational Resources Information Center

    Radford City Schools, VA.

    The guide is one of a series developed in a pilot project to integrate career education concepts with subject matter in secondary grades. The units are designed to reveal career orientation aspects of traditional topics within five major subject areas: English, social studies, mathematics, science, and health and physical education. The lesson…

  13. Metabolic profiling reveals altered sugar and secondary metabolism in response to UGPase overexpression in Populus

    DOE PAGESBeta

    Payyavula, Raja S.; Tschaplinski, Timothy J.; Jawdy, Sara; Sykes, Robert; Tuskan, Gerald A.; Kalluri, Udaya C.

    2014-10-07

    Background: UDP-glucose pyrophopharylase (UGPase) is a sugar metabolizing enzyme (E.C. 2.7.7.9) that catalyzes a reversible reaction of UDP-glucose and pyrophosphate from glucose-1-phosphate and uridine triphosphate glucose. UDP-glucose is a key intermediate sugar that is channeled to multiple metabolic pathways. The functional role of UGPase in woody plants such as Populus is poorly understood. Results: We characterized the functional role of UGPase in Populus deltoides by overexpressing a native gene. Overexpression of the native gene resulted in increased leaf area and leaf-to-shoot biomass ratio but decreased shoot and root growth. Metabolomic analyses showed that manipulation of UGPase results in perturbations inmore » primary as well as secondary metabolism resulting in reduced sugar and starch levels and increased phenolics such as caffeoyl- and feruloyl conjugates. While cellulose and lignin levels in the cell walls were not significantly altered, the syringyl-to-guaiacyl ratio was significantly reduced. Conclusions: These results demonstrate that UGPase plays a key role in the tightly coupled primary and secondary metabolic pathways and perturbation in its function results in pronounced effects on growth and metabolism outside of cell wall biosynthesis of Populus.« less

  14. Metabolic profiling reveals altered sugar and secondary metabolism in response to UGPase overexpression in Populus

    SciTech Connect

    Payyavula, Raja S.; Tschaplinski, Timothy J.; Jawdy, Sara; Sykes, Robert; Tuskan, Gerald A.; Kalluri, Udaya C.

    2014-10-07

    Background: UDP-glucose pyrophopharylase (UGPase) is a sugar metabolizing enzyme (E.C. 2.7.7.9) that catalyzes a reversible reaction of UDP-glucose and pyrophosphate from glucose-1-phosphate and uridine triphosphate glucose. UDP-glucose is a key intermediate sugar that is channeled to multiple metabolic pathways. The functional role of UGPase in woody plants such as Populus is poorly understood. Results: We characterized the functional role of UGPase in Populus deltoides by overexpressing a native gene. Overexpression of the native gene resulted in increased leaf area and leaf-to-shoot biomass ratio but decreased shoot and root growth. Metabolomic analyses showed that manipulation of UGPase results in perturbations in primary as well as secondary metabolism resulting in reduced sugar and starch levels and increased phenolics such as caffeoyl- and feruloyl conjugates. While cellulose and lignin levels in the cell walls were not significantly altered, the syringyl-to-guaiacyl ratio was significantly reduced. Conclusions: These results demonstrate that UGPase plays a key role in the tightly coupled primary and secondary metabolic pathways and perturbation in its function results in pronounced effects on growth and metabolism outside of cell wall biosynthesis of Populus.

  15. Origin of secondary sulfate minerals on active andesitic stratovolcanoes

    USGS Publications Warehouse

    Zimbelman, D.R.; Rye, R.O.; Breit, G.N.

    2005-01-01

    Sulfate minerals in altered rocks on the upper flanks and summits of active andesitic stratovolcanoes result from multiple processes. The origin of these sulfates at five active volcanoes, Citlalte??petl (Mexico), and Mount Adams, Hood, Rainier, and Shasta (Cascade Range, USA), was investigated using field observations, petrography, mineralogy, chemical modeling, and stable-isotope data. The four general groups of sulfate minerals identified are: (1) alunite group, (2) jarosite group, (3) readily soluble Fe- and Al-hydroxysulfates, and (4) simple alkaline-earth sulfates such as anhydrite, gypsum, and barite. Generalized assemblages of spatially associated secondary minerals were recognized: (1) alunite+silica??pyrite??kaolinite?? gypsum??sulfur, (2) jarosite+alunite+silica; (3) jarosite+smectite+silica??pyrite, (4) Fe- and Al-hydroxysulfates+silica, and (5) simple sulfates+silica??Al-hydroxysulfates??alunite. Isotopic data verify that all sulfate and sulfide minerals and their associated alteration assemblages result largely from the introduction of sulfur-bearing magmatic gases into meteoric water in the upper levels of the volcanoes. The sulfur and oxygen isotopic data for all minerals indicate the general mixing of aqueous sulfate derived from deep (largely disproportionation of SO2 in magmatic vapor) and shallow (oxidation of pyrite or H2S) sources. The hydrogen and oxygen isotopic data of alunite indicate the mixing of magmatic and meteoric fluids. Some alunite-group minerals, along with kaolinite, formed from sulfuric acid created by the disproportionation of SO2 in a condensing magmatic vapor. Such alunite, observed only in those volcanoes whose interiors are exposed by erosion or edifice collapse, may have ??34S values that reflect equilibrium (350??50 ??C) between aqueous sulfate and H2S. Alunite with ??34S values indicating disequilibrium between parent aqueous sulfate and H2S may form from aqueous sulfate created in higher level low

  16. Does mental exertion alter maximal muscle activation?

    PubMed Central

    Rozand, Vianney; Pageaux, Benjamin; Marcora, Samuele M.; Papaxanthis, Charalambos; Lepers, Romuald

    2014-01-01

    Mental exertion is known to impair endurance performance, but its effects on neuromuscular function remain unclear. The purpose of this study was to test the hypothesis that mental exertion reduces torque and muscle activation during intermittent maximal voluntary contractions of the knee extensors. Ten subjects performed in a randomized order three separate mental exertion conditions lasting 27 min each: (i) high mental exertion (incongruent Stroop task), (ii) moderate mental exertion (congruent Stroop task), (iii) low mental exertion (watching a movie). In each condition, mental exertion was combined with 10 intermittent maximal voluntary contractions of the knee extensor muscles (one maximal voluntary contraction every 3 min). Neuromuscular function was assessed using electrical nerve stimulation. Maximal voluntary torque, maximal muscle activation and other neuromuscular parameters were similar across mental exertion conditions and did not change over time. These findings suggest that mental exertion does not affect neuromuscular function during intermittent maximal voluntary contractions of the knee extensors. PMID:25309404

  17. Antibiotic-Induced Alterations of the Gut Microbiota Alter Secondary Bile Acid Production and Allow for Clostridium difficile Spore Germination and Outgrowth in the Large Intestine

    PubMed Central

    Bowman, Alison A.; Young, Vincent B.

    2016-01-01

    ABSTRACT It is hypothesized that the depletion of microbial members responsible for converting primary bile acids into secondary bile acids reduces resistance to Clostridium difficile colonization. To date, inhibition of C. difficile growth by secondary bile acids has only been shown in vitro. Using targeted bile acid metabolomics, we sought to define the physiologically relevant concentrations of primary and secondary bile acids present in the murine small and large intestinal tracts and how these impact C. difficile dynamics. We treated mice with a variety of antibiotics to create distinct microbial and metabolic (bile acid) environments and directly tested their ability to support or inhibit C. difficile spore germination and outgrowth ex vivo. Susceptibility to C. difficile in the large intestine was observed only after specific broad-spectrum antibiotic treatment (cefoperazone, clindamycin, and vancomycin) and was accompanied by a significant loss of secondary bile acids (deoxycholate, lithocholate, ursodeoxycholate, hyodeoxycholate, and ω-muricholate). These changes were correlated to the loss of specific microbiota community members, the Lachnospiraceae and Ruminococcaceae families. Additionally, physiological concentrations of secondary bile acids present during C. difficile resistance were able to inhibit spore germination and outgrowth in vitro. Interestingly, we observed that C. difficile spore germination and outgrowth were supported constantly in murine small intestinal content regardless of antibiotic perturbation, suggesting that targeting growth of C. difficile will prove most important for future therapeutics and that antibiotic-related changes are organ specific. Understanding how the gut microbiota regulates bile acids throughout the intestine will aid the development of future therapies for C. difficile infection and other metabolically relevant disorders such as obesity and diabetes. IMPORTANCE Antibiotics alter the gastrointestinal

  18. Antibiotic-Induced Alterations of the Gut Microbiota Alter Secondary Bile Acid Production and Allow for Clostridium difficile Spore Germination and Outgrowth in the Large Intestine.

    PubMed

    Theriot, Casey M; Bowman, Alison A; Young, Vincent B

    2016-01-01

    It is hypothesized that the depletion of microbial members responsible for converting primary bile acids into secondary bile acids reduces resistance to Clostridium difficile colonization. To date, inhibition of C. difficile growth by secondary bile acids has only been shown in vitro. Using targeted bile acid metabolomics, we sought to define the physiologically relevant concentrations of primary and secondary bile acids present in the murine small and large intestinal tracts and how these impact C. difficile dynamics. We treated mice with a variety of antibiotics to create distinct microbial and metabolic (bile acid) environments and directly tested their ability to support or inhibit C. difficile spore germination and outgrowth ex vivo. Susceptibility to C. difficile in the large intestine was observed only after specific broad-spectrum antibiotic treatment (cefoperazone, clindamycin, and vancomycin) and was accompanied by a significant loss of secondary bile acids (deoxycholate, lithocholate, ursodeoxycholate, hyodeoxycholate, and ω-muricholate). These changes were correlated to the loss of specific microbiota community members, the Lachnospiraceae and Ruminococcaceae families. Additionally, physiological concentrations of secondary bile acids present during C. difficile resistance were able to inhibit spore germination and outgrowth in vitro. Interestingly, we observed that C. difficile spore germination and outgrowth were supported constantly in murine small intestinal content regardless of antibiotic perturbation, suggesting that targeting growth of C. difficile will prove most important for future therapeutics and that antibiotic-related changes are organ specific. Understanding how the gut microbiota regulates bile acids throughout the intestine will aid the development of future therapies for C. difficile infection and other metabolically relevant disorders such as obesity and diabetes. IMPORTANCE Antibiotics alter the gastrointestinal microbiota

  19. Physical Activity and Environmental Influences during Secondary School Physical Education

    ERIC Educational Resources Information Center

    Chow, Bik C.; McKenzie, Thomas L.; Louie, Lobo

    2009-01-01

    Physical activity engagement during physical education is important for many reasons, including developing physical fitness and movement skills and promoting health. Much more is known about physical activity in elementary than secondary schools. We examined physical activity and how it was influenced by instructor-related and environmental…

  20. HYDRAULIC CHARACTERISTICS OF ACTIVATED SLUDGE SECONDARY CLARIFIERS

    EPA Science Inventory

    This study documented the hydraulic characteristics of typical activated sludge clarifiers. Modifications to the clarifier structures were made in an attempt to improve clarifier hydraulic characteristics and performance. Innovative fluorometric dye tracer studies were used to ob...

  1. Overexpression of SbMyb60 impacts phenylpropanoid biosynthesis and alters secondary cell wall composition in Sorghum bicolor.

    PubMed

    Scully, Erin D; Gries, Tammy; Sarath, Gautam; Palmer, Nathan A; Baird, Lisa; Serapiglia, Michelle J; Dien, Bruce S; Boateng, Akwasi A; Ge, Zhengxiang; Funnell-Harris, Deanna L; Twigg, Paul; Clemente, Thomas E; Sattler, Scott E

    2016-02-01

    The phenylpropanoid biosynthetic pathway that generates lignin subunits represents a significant target for altering the abundance and composition of lignin. The global regulators of phenylpropanoid metabolism may include MYB transcription factors, whose expression levels have been correlated with changes in secondary cell wall composition and the levels of several other aromatic compounds, including anthocyanins and flavonoids. While transcription factors correlated with downregulation of the phenylpropanoid biosynthesis pathway have been identified in several grass species, few transcription factors linked to activation of this pathway have been identified in C4 grasses, some of which are being developed as dedicated bioenergy feedstocks. In this study we investigated the role of SbMyb60 in lignin biosynthesis in sorghum (Sorghum bicolor), which is a drought-tolerant, high-yielding biomass crop. Ectopic expression of this transcription factor in sorghum was associated with higher expression levels of genes involved in monolignol biosynthesis, and led to higher abundances of syringyl lignin, significant compositional changes to the lignin polymer and increased lignin concentration in biomass. Moreover, transgenic plants constitutively overexpressing SbMyb60 also displayed ectopic lignification in leaf midribs and elevated concentrations of soluble phenolic compounds in biomass. Results indicate that overexpression of SbMyb60 is associated with activation of monolignol biosynthesis in sorghum. SbMyb60 represents a target for modification of plant cell wall composition, with the potential to improve biomass for renewable uses. PMID:26712107

  2. SECONDARY WASTE MANAGEMENT STRATEGY FOR EARLY LOW ACTIVITY WASTE TREATMENT

    SciTech Connect

    TW, CRAWFORD

    2008-07-17

    This study evaluates parameters relevant to River Protection Project secondary waste streams generated during Early Low Activity Waste operations and recommends a strategy for secondary waste management that considers groundwater impact, cost, and programmatic risk. The recommended strategy for managing River Protection Project secondary waste is focused on improvements in the Effiuent Treatment Facility. Baseline plans to build a Solidification Treatment Unit adjacent to Effluent Treatment Facility should be enhanced to improve solid waste performance and mitigate corrosion of tanks and piping supporting the Effiuent Treatment Facility evaporator. This approach provides a life-cycle benefit to solid waste performance and reduction of groundwater contaminants.

  3. Teaching about Korea: Elementary and Secondary Activities.

    ERIC Educational Resources Information Center

    Lee, Yong-sook, Ed.; And Others

    The classroom activities in this book focus on teaching about Korean culture and society within the context of larger social science units. Also, some of the lessons may be taught within the context of the humanities and fine arts. An historical overview and a list of suggestions for working with small groups introduces the 18 lessons. The format…

  4. Microdistributions of Rb and Sr in ALH84001 carbonates: Chronological implications for secondary alteration on Mars

    SciTech Connect

    Wadhwa, M.; Sutton, S.R.; Flynn, G.J.

    2005-04-22

    Concentrations of Rb and Sr were analyzed on the micron-scale in various compositional zones of the ALH84001 carbonates. Implications of the measured Rb/Sr ratios for the chronology of these carbonates are discussed. ALH84001 is unique among the Martian meteorites in that it has an ancient crystallization age of {approx}4.5 Ga defined by Sm-Nd isotope systematics. Another aspect that differentiates this Martian meteorite from the others is the presence of Ca-Fe-Mg carbonates (modal abundance {approx}1%) that are thought to have been precipitated during alteration in a near-surface environment. Precise age dating of these carbonates is important since it could provide constraints on the timing of surficial secondary alteration processes on Mars. However, this has been a challenging problem owing to the relatively small abundance of the carbonates in ALH84001 and because these carbonates are difficult to separate from the other minerals in the rock by physical and chemical means. Previous investigations have attempted to separate the carbonates by leaching of carbonate-rich mineral fractions. The single 'bulk carbonate' fraction analyzed by Wadhwa and Lugmair was characterized by a low {sup 87}Rb/{sup 86}Sr ratio of {approx}0.05, the lowest of any mineral in ALH84001, and the corresponding Rb-Sr age estimate ({approx}1.39 Ga) was dependent on the assumption of isotopic equilibrium between the carbonates and plagioclase. As pointed out by Borg et al., such an assumption may not be assured and, therefore, they obtained multiple carbonate-rich leachates with a range of {sup 87}Rb/{sup 86}Sr ratios (0.12-2.62) from which they estimated an age of {approx}3.9 Ga. Although these authors performed painstaking chemical characterization to determine contributions in the leachates from minerals such as phosphates and silicates, it is nevertheless difficult to positively rule out contributions from other as yet unidentified phases. Therefore, the goal of the present

  5. Northwest Africa 5738: Multistage fluid-driven secondary alteration in an extraordinarily evolved eucrite

    NASA Astrophysics Data System (ADS)

    Warren, Paul H.; Rubin, Alan E.; Isa, Junko; Gessler, Nicholas; Ahn, Insu; Choi, Byeon-Gak

    2014-09-01

    The Northwest Africa 5738 eucrite contains a record of unprecedented geochemical complexity for a sample from the HED asteroid. It originated with a uniquely evolved (Stannern Trend) primary igneous composition, combining ultra-high bulk incompatible element and Na2O concentrations with a relatively low mg. Its bulk oxygen-isotopic composition (Δ‧17O = -0.27‰), as well as its trace element composition (e.g., Ga/Al), confirm other evidence for classification as a eucrite. Pyroxene mg equilibration, exsolution and “cloudy” inclusions, all reflect a typical eucritic degree of thermal metamorphism. The rock contains an unprecedented array of microscopic fluid-metasomatic vein deposits. Most common are curvy microveins within pyroxene, which consist dominantly of Ca-plagioclase (typically An95, in stark contrast with the rock’s An68-78 primary-igneous plagioclase), with Fe-olivine (Fo14) and Cr-spinel as additional major constituents. Likely related to these microveins are small masses of intergrown Ca-plagioclase (again roughly An95) and silica (or high-Si glass). Analyses of the microvein Cr-spinels show stoichiometry implying a significant Fe3+ content (Fe2O3 0.7-2.3 wt.%), and fO2 up to roughly IW+3; clearly elevated in comparison to the normal HED fO2 of about IW-1. The fO2 results show an anticorrelation with equilibration T (and with Mg/Fe), which suggests the parent fluid system became more oxidizing as it cooled. NWA 5738 also contains apparent secondary iron metal. The Fe-metals are very pure, with Ni consistently below an EPMA detection limit of ∼0.01 wt.%. The vein-like shapes of roughly 1/3 of the largest Fe-metals suggest origin by deposition from a fluid. The role of pyroxene exsolution as template for a denticular (sawtooth) Fe-metal edge shape, and the survival of Fo14 olivine in a rock with abundant silica and a far higher bulk mg, suggest that the most intense thermal metamorphism occurred no later than the secondary alteration. Near

  6. Whirling Dervish Dynamos: Magnetic Activity in CV Secondaries

    NASA Astrophysics Data System (ADS)

    Saar, Steven

    2003-07-01

    The mass-losing secondary stars of cataclysmic variables {CVs} are the most rapidly rotating cool dwarfs observable. Other rapid rotators show a maximal, "saturated" level of magnetic activity {e.g., X-ray emission}, but there are hints from contact binaries and young clusters that activity may be suppressed at the highest rotation rates. CV secondaries are thus important probes of magnetic dynamos at rotational extremes. Implications for CV evolution {e.g., the ``period gap", accretion variability} may also be profound. Unfortunately, study of CV secondaries is hampered by pesky accretion-related phenomena and reflection effects. As a result, little systematic work has been done. To explore activity in these stars, we therefore propose to study far-UV spectra of AM Her-type systems {which have no accretion disks} in deep photometric minima in which accretion is shut off. Magnetic-related emission from the secondary will be separated {in velocity} from residual accretion emission by observations near quadratures. Lower chromospheric irradiation due to the white dwarf primary will be removed by modeling, yielding the true level of magnetic activity on the secondary. We will compare the results to other dMe stars and draw implications for magnetic dynamos and activity at rotational extremes, and for CV evolution and behavior.

  7. Above and Beyond: Secondary Activities for Peace Corps Volunteers.

    ERIC Educational Resources Information Center

    Benjamin, Judy; And Others

    This manual focuses on what prompts Peace Corps volunteers to get involved, activities that volunteers have tried while on assignment, and a series of guidelines volunteers can apply to secondary activity, which is organized during school recesses or at times when the Volunteer is otherwise unoccupied. The book is divided into three sections. Part…

  8. Chronic ozone exposure alters the secondary metabolite profile, antioxidant potential, anti-inflammatory property, and quality of red pepper fruit from Capsicum baccatum.

    PubMed

    Bortolin, Rafael Calixto; Caregnato, Fernanda Freitas; Divan Junior, Armando Molina; Zanotto-Filho, Alfeu; Moresco, Karla Suzana; de Oliveira Rios, Alessandro; de Oliveira Salvi, Aguisson; Ortmann, Caroline Flach; de Carvalho, Pâmela; Reginatto, Flávio Henrique; Gelain, Daniel Pens; Fonseca Moreira, José Cláudio

    2016-07-01

    Tropospheric ozone (O3) background concentrations have increased since pre-industrial times, reaching phytotoxic concentrations in many regions globally. However, the effect of high O3 concentrations on quality of fruit and vegetables remains unknown. Here, we evaluated whether O3 pollution alters the quality of Capsicum baccatum peppers by changing the secondary compound profiles and biological activity of the fruit. C. baccatum pepper plants were exposed to ozone for 62 days in an open-top chamber at a mean O3 concentration of 171.6µg/m(3). Capsaicin levels decreased by 50% in the pericarp, but remained unchanged in the seeds. In contrast, the total carotenoid content increased by 52.8% in the pericarp. The content of total phenolic compounds increased by 17% in the pericarp. The total antioxidant potential decreased by 87% in seeds of O3-treated plants. The seeds contributed more than the pericarp to the total radical-trapping antioxidant potential and total antioxidant reactivity. O3 treatment impaired the ferric-reducing antioxidant power of the seeds and reduced NO(•)-scavenging activity in the pericarp. However, O3 treatment increased ferrous ion-chelating activity and hydroxyl radical-scavenging activity in the pericarp. Our results confirm that O3 alters the secondary metabolite profile of C. baccatum pepper fruits and, consequently, their biological activity profile. PMID:26970882

  9. Identification of secondary minerals crystallized by low and high temperature alteration in the Northern Kyushu-Palau Ridge volcanic rocks

    NASA Astrophysics Data System (ADS)

    Haraguchi, S.

    2008-12-01

    Seafloor rocks were affected by hydrothermal alteration and low temperature seawater weathering display various elemental behaviors, necessitating detailed investigations to evaluate primary bulk rock compositions without the effect of elemental behaviors during alteration. Seafloor alteration entails primary minerals being changed into hydrous minerals. Bulk chemical compositions of seafloor igneous rocks are changed by high- temperature hydrothermal alteration and low-temperature seafloor weathering. In this study, I report the secondary mineral identifications by XRD analyses in the rocks from the northern Kyushu-Palau Ridge, and consider to condition of alteration processes. Volcanic rocks dredged from the Northern Kyushu Palau Ridge during cruise by Tansei-maru, ORI, University of Tokyo show petrological and geochemical characteristics of low and high temperature alterations. These rocks are classified into bulk water content, that is, low H2O- and LOI samples at the Miyazaki Seamount, high H2O- samples at the Nichinan Seamount, and high LOI samples at the Komahashi-Daini Seamount. The Nichinan Seamount samples show flesh phenocrysts, low altered groundmass minerals, and high degree alteration of groundmass glass, assumed to replace into clay minerals. These altered phenocrysts are identified by XRD to be serpentine, saponite, and talc. And these altered groundmasses are identified by XRD to be saponite with primary plagioclase and clinopyroxene. These results are assumed to replacement of glass into clay minerals under low temperature seafloor weathering. Nichinan Seamount rocks show high alkali-elements contents. The remarkable movement of bulk composition is not occur under the low temperature seafloor weathering except for K and Rb, and these enrichments reflect secondary deposition of celadonite, K-rich smectite (e.g. Nakamura, 2001). Saponite is typical identified, but celadonite is not identified in the Nichinan Seamount rocks. Therefore, the

  10. Morphine treatment alters nucleotidase activities in rat blood serum

    PubMed Central

    Rozisky, Joanna Ripoll; Nonose, Yasmine; Laste, Gabriela; dos Santos, Vinicius Souza; de Macedo, Isabel Cristina; Battastini, Ana Maria Oliveira; Caumo, Wolnei; Torres, Iraci LS

    2012-01-01

    Morphine has been widely used in neonatal pain management. However, this treatment may produce adaptive changes in several physiologic systems. Our laboratory has demonstrated that morphine treatment in neonate rats alters nucleoside triphosphate diphosphohydrolase (NTPDase) activity and gene expression in central nervous system structures. Considering the relationship between the opioid and purinergic systems, our aim was to verify whether treatment with morphine from postnatal days 8 (P8) through 14 (P14) at a dose of 5 µg per day alters NTPDase and 5′-nucleotidase activities in rat serum over the short, medium, and long terms. After the in vivo assay, the morphine group showed increased hydrolysis of all nucleotides at P30, and a decrease in adenosine 5′-diphosphate hydrolysis at P60. Moreover, we found that nucleotidase activities change with age; adenosine 5′-triphosphate hydrolysis activity was lower at P16, and adenosine 5′-monophosphate hydrolysis activity was higher at P60. These changes are very important because these enzymes are the main regulators of blood nucleotide levels and, consequently, nucleotide signaling. Our findings showed that in vivo morphine treatment alters nucleotide hydrolysis in rat blood serum, suggesting that purine homeostasis can be influenced by opioid treatment during the neonatal period.

  11. Intrinsic Brain Activity in Altered States of Consciousness

    PubMed Central

    Boly, M.; Phillips, C.; Tshibanda, L.; Vanhaudenhuyse, A.; Schabus, M.; Dang-Vu, T.T.; Moonen, G.; Hustinx, R.; Maquet, P.; Laureys, S.

    2010-01-01

    Spontaneous brain activity has recently received increasing interest in the neuroimaging community. However, the value of resting-state studies to a better understanding of brain–behavior relationships has been challenged. That altered states of consciousness are a privileged way to study the relationships between spontaneous brain activity and behavior is proposed, and common resting-state brain activity features observed in various states of altered consciousness are reviewed. Early positron emission tomography studies showed that states of extremely low or high brain activity are often associated with unconsciousness. However, this relationship is not absolute, and the precise link between global brain metabolism and awareness remains yet difficult to assert. In contrast, voxel-based analyses identified a systematic impairment of associative frontoparieto–cingulate areas in altered states of consciousness, such as sleep, anesthesia, coma, vegetative state, epileptic loss of consciousness, and somnambulism. In parallel, recent functional magnetic resonance imaging studies have identified structured patterns of slow neuronal oscillations in the resting human brain. Similar coherent blood oxygen level–dependent (BOLD) systemwide patterns can also be found, in particular in the default-mode network, in several states of unconsciousness, such as coma, anesthesia, and slow-wave sleep. The latter results suggest that slow coherent spontaneous BOLD fluctuations cannot be exclusively a reflection of conscious mental activity, but may reflect default brain connectivity shaping brain areas of most likely interactions in a way that transcends levels of consciousness, and whose functional significance remains largely in the dark. PMID:18591474

  12. Activated oxygen alters cerebral microvascular responses in newborn pigs

    SciTech Connect

    Leffler, C.W.; Busiia, D.W.; Armstead, W.M.; Mirro, R.; Thelin, O. )

    1990-02-26

    In piglets, cerebral ischemia/reperfusion blocks prostanoid dependent cerebral vasodilation to hypercapnia (CO{sub 2}) and hypotension but not prostanoid independent dilation to isoproterenol (Isu) or constriction to norepinephrine (NE). Ischemia/reperfusion increases activated-O{sub 2} production by piglet brains. Using cranial windows in piglets, the authors investigated the hypothesis that activated oxygen can block prostanoid dependent cerebral vasodilator responses to CO{sub 2} and hypotension without altering responses to Isu and NE. Exposure to an activated oxygen generating system of xanthine oxidase, hypoxanthine, and Fe that made about 3 times the activated-O{sub 2} on the brain surface as ischemia/reperfusion caused reversible pial arteriolar dilation. After exposure, pial arteriolar dilation was reduced to CO{sub 2} and hypotension but not to Isu. NE constrictor responses were also unaltered. H{sub 2}O{sub 2} or H{sub 2}O{sub 2} + Fe caused constriction followed by reversible dilation. After exposure, pial arteriolar dilation in response to CO{sub 2} and hypotension was not altered. However, addition of xanthine oxidase and hypoxanthine with H{sub 2}O{sub 2} and Fe totally eliminated pial arteriolar dilator responses to CO{sub 2} and hypotension but did not decrease dilation caused by Isu or constriction caused by NE. The authors conclude that activated oxygen could produce the altered prostanoid dependent pial arteriolar responses observed following ischemia in piglets.

  13. Human activities change marine ecosystems by altering predation risk.

    PubMed

    Madin, Elizabeth M P; Dill, Lawrence M; Ridlon, April D; Heithaus, Michael R; Warner, Robert R

    2016-01-01

    In ocean ecosystems, many of the changes in predation risk - both increases and decreases - are human-induced. These changes are occurring at scales ranging from global to local and across variable temporal scales. Indirect, risk-based effects of human activity are known to be important in structuring some terrestrial ecosystems, but these impacts have largely been neglected in oceans. Here, we synthesize existing literature and data to explore multiple lines of evidence that collectively suggest diverse human activities are changing marine ecosystems, including carbon storage capacity, in myriad ways by altering predation risk. We provide novel, compelling evidence that at least one key human activity, overfishing, can lead to distinct, cascading risk effects in natural ecosystems whose magnitude exceeds that of presumed lethal effects and may account for previously unexplained findings. We further discuss the conservation implications of human-caused indirect risk effects. Finally, we provide a predictive framework for when human alterations of risk in oceans should lead to cascading effects and outline a prospectus for future research. Given the speed and extent with which human activities are altering marine risk landscapes, it is crucial that conservation and management policy considers the indirect effects of these activities in order to increase the likelihood of success and avoid unfortunate surprises. PMID:26448058

  14. Altered combustion characteristics of metallized energetics due to stable secondary material inclusion

    NASA Astrophysics Data System (ADS)

    Terry, Brandon C.

    Though metals and metalloids have been widely considered as reactive fuels, the ability to tune their ignition and combustion characteristics remains challenging. One means to accomplish this may be through low-level inclusion of secondary materials into the metallized fuel. While there are several potential methods to stably introduce secondary inclusion materials, this work focuses on the use of mechanical activation (MA) and metal alloys. Recent work has shown that low-level inclusion of fluoropolymers into aluminum particles can have a substantial effect on their combustion characteristics. The reflected shock ignition of mechanically activated aluminum/polytetrafluoroethylene (MA Al/PTFE) is compared to a physical mixture (PM) of Al/PTFE, neat spherical aluminum, and flake aluminum. It was found that the powders with higher specific surface areas ignited faster than the spherical particles of the same size, and had ignition delay times comparable to agglomerates of aluminum particles that were two orders of magnitude smaller in size. Flake aluminum powder had the same ignition delay as MA Al/PTFE, indicating that any initial aluminum/fluoropolymer reactions did not yield an earlier onset of aluminum oxidation. However, MA Al/PTFE did have a shorter total burn time. The PM of Al/PTFE powder had a shorter ignition delay than neat spherical aluminum due to the rapid decomposition of PTFE into reactive fluorocarbon compounds, but the subsequent fluorocarbon reactions also created a secondary luminosity profile that significantly increased the total burn time of the system. The explosive shock ignition of aluminum and aluminum-silicon eutectic alloy compacts was evaluated with and without polymer inclusions. A statistical analysis was completed, investigating the effects of: detonation train orientation (into or not into a hard surface); the high explosive driver; whether the metal/polymer system is mechanically activated; particle size; particle morphology

  15. Altered cell shapes, hyperplasia, and secondary growth in Arabidopsis caused by beet curly top geminivirus infection.

    PubMed

    Park, Jongbum; Hwang, Hyunsik; Shim, Haekyung; Im, Kyunghoan; Auh, Chung-Kyoon; Lee, Sukchan; Davis, Keith R

    2004-02-29

    Arabidopsis Sei-O ecotype was found to be hypersusceptible to the BCTV-Logan strain in that it developed very severe symptoms, including severely deformed inflorescences with the callus-like structure, and accumulated high level of viral DNA. Microscopic studies of the BCTV-induced cell divisions demonstrated that the activation of cell divisions was preceded by the phloem disruption and the callus-like structure seemed to be originated from the cortex nearby disrupted phloem. We have further defined the callus-like structure formed by BCTV infection using molecular and histochemical analyses. Results indicate that BCTV infection causes the phloem disruption, following by cell enlargement and elongation in cortex and even epidermis. Finally, BCTV induced symptomatic secondary growth in cortex by de novo anticlinal and periclinal cell divisions. Expression of cdc2 and saur from BCTV-infected Arabidopsis correlates with symptom development. These results suggest a critical role of auxin in symptom development in the interactions between Arabidopsis and BCTV. PMID:15055537

  16. EVALUATION OF AN ACTIVATED SLUDGE SECONDARY CLARIFIER DISTRIBUTED INLET

    EPA Science Inventory

    Secondary clarifiers are crucial to the overall performance of the activated sludge process. Research over the last 40 years indicates that density currents are factors which degrade clarifier performance when not considered in design. However, present designs of most center-feed...

  17. Thinking Science: Classroom Activities in Secondary Science. Teacher's Guide.

    ERIC Educational Resources Information Center

    Adey, Philip; And Others

    This teacher's guide is part of a program of activities that help secondary-level students develop the complex thinking skills needed to succeed in science. This program can be used with current curriculum materials. It is designed to help students integrate ideas and develop concepts that demonstrate higher level thinking. A rich environment of…

  18. Physical Activity Breaks and Facilities in US Secondary Schools

    ERIC Educational Resources Information Center

    Hood, Nancy E.; Colabianchi, Natalie; Terry-McElrath, Yvonne M.; O'Malley, Patrick M.; Johnston, Lloyd D.

    2014-01-01

    Background: Research on physical activity breaks and facilities (indoor and outdoor) in secondary schools is relatively limited. Methods: School administrators and students in nationally representative samples of 8th (middle school) and 10th/12th grade (high school) students were surveyed annually from 2008-2009 to 2011-2012. School administrators…

  19. Platelet Activation in Human Immunodeficiency Virus Type-1 Patients Is Not Altered with Cocaine Abuse

    PubMed Central

    Kiebala, Michelle; Singh, Meera V.; Piepenbrink, Michael S.; Qiu, Xing; Kobie, James J.; Maggirwar, Sanjay B.

    2015-01-01

    Recent work has indicated that platelets, which are anucleate blood cells, significantly contribute to inflammatory disorders. Importantly, platelets also likely contribute to various inflammatory secondary disorders that are increasingly associated with Human Immunodeficiency Virus Type-1 (HIV) infection including neurological impairments and cardiovascular complications. Indeed, HIV infection is often associated with increased levels of platelet activators. Additionally, cocaine, a drug commonly abused by HIV-infected individuals, leads to increased platelet activation in humans. Considering that orchestrated signaling mechanisms are essential for platelet activation, and that nuclear factor-kappa B (NF-κB) inhibitors can alter platelet function, the role of NF-κB signaling in platelet activation during HIV infection warrants further investigation. Here we tested the hypothesis that inhibitory kappa B kinase complex (IKK) activation would be central for platelet activation induced by HIV and cocaine. Whole blood from HIV-positive and HIV-negative individuals, with or without cocaine abuse was used to assess platelet activation via flow cytometry whereas IKK activation was analyzed by performing immunoblotting and in vitro kinase assays. We demonstrate that increased platelet activation in HIV patients, as measured by CD62P expression, is not altered with reported cocaine use. Furthermore, cocaine and HIV do not activate platelets in whole blood when treated ex vivo. Finally, HIV-induced platelet activation does not involve the NF-κB signaling intermediate, IKKβ. Platelet activation in HIV patients is not altered with cocaine abuse. These results support the notion that non-IKK targeting approaches will be better suited for the treatment of HIV-associated inflammatory disorders. PMID:26076359

  20. Altered Spontaneous Brain Activity in Betel Quid Dependence

    PubMed Central

    Liu, Tao; Li, Jian-jun; Zhao, Zhong-yan; Yang, Guo-shuai; Pan, Meng-jie; Li, Chang-qing; Pan, Su-yue; Chen, Feng

    2016-01-01

    Abstract It has been suggested by the first voxel-based morphometry investigation that betel quid dependence (BQD) individuals are presented with brain structural changes in previous reports, and there may be a neurobiological basis for BQD individuals related to an increased risk of executive dysfunction and disinhibition, subjected to the reward system, cognitive system, and emotion system. However, the effects of BQD on neural activity remain largely unknown. Individuals with impaired cognitive control of behavior often reveal altered spontaneous cerebral activity in resting-state functional magnetic resonance imaging and those changes are usually earlier than structural alteration. Here, we examined BQD individuals (n = 33) and age-, sex-, and education-matched healthy control participants (n = 32) in an resting-state functional magnetic resonance imaging study to observe brain function alterations associated with the severity of BQD. Amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) values were both evaluated to stand for spontaneous cerebral activity. Gray matter volumes of these participants were also calculated for covariate. In comparison with healthy controls, BQD individuals demonstrated dramatically decreased ALFF and ReHo values in the prefrontal gurus along with left fusiform, and increased ALFF and ReHo values in the primary motor cortex area, temporal lobe as well as some regions of occipital lobe. The betel quid dependence scores (BQDS) were negatively related to decreased activity in the right anterior cingulate. The abnormal spontaneous cerebral activity revealed by ALFF and ReHo calculation excluding the structural differences in patients with BQD may help us probe into the neurological pathophysiology underlying BQD-related executive dysfunction and disinhibition. Diminished spontaneous brain activity in the right anterior cingulate cortex may, therefore, represent a biomarker of BQD individuals. PMID

  1. Alteration of Electro-Cortical Activity in Microgravity

    NASA Astrophysics Data System (ADS)

    Schneider, Stefan; Brummer, Vera; Carnahan, Heather; Askew, Christopher D.; Guardiera, Simon; Struder, Heiko K.

    2008-06-01

    There is growing interest in the effects of weightlessness on central nervous system (CNS) activity. Due to technical and logistical limitations it presently seems impossible to apply imaging techniques as fMRI or PET in weightless environments e.g. on ISS or during parabolic flights. Within this study we evaluated changes in brain cortical activity using low resolution brain electromagnetic tomography (LORETA) during parabolic flights. Results showed a distinct inhibition of right frontal area activity >12Hz during phases of microgravity compared to normal gravity. We conclude that the inhibition of high frequency frontal activity during microgravity may serve as a marker of emotional anxiety and/or indisposition associated with weightlessness. This puts a new light on the debate as to whether cognitive and sensorimotor impairments are attributable to primary physiological effects or secondary psychological effects of a weightless environment.

  2. CHARACTERIZATION OF SECONDARY ALTERATION IN THE COLUMBIA RIVER BASALT BY BACKSCATTERED ELECTRON IMAGING AND ENERGY-DISPERSIVE X-RAY SPECTROSCOPY.

    USGS Publications Warehouse

    Hearn, P.P.; Steinkampf, W.C.; Brown, Z.A.

    1984-01-01

    The thick sequences of flood basalts which underlie the Columbia River basin are important aquifiers, providing water for both agricultural and domestic use. Secondary alteration in these rocks occurs primarily as coatings or fillings in fractures and vesicles; alteration is generally believed to have occurred at low temperatures ( less than 100 C) by reaction with meteroic waters. The distribution and compositional variation of secondary minerals are therefore of major interest. This paper focuses on the compositional variation of the major alteration products and on present formulas based on the mean composition of these phases, and suggests possible reactions for the observed sequence of alteration.

  3. Biophysical and mutagenic analysis of Thermoanaerobacter ethanolicus secondary-alcohol dehydrogenase activity and specificity.

    PubMed Central

    Burdette, D S; Secundo, F; Phillips, R S; Dong, J; Scott, R A; Zeikus, J G

    1997-01-01

    The Thermoanaerobacter ethanolicus 39E adhB gene encoding the secondary-alcohol dehydrogenase (secondary ADH) was overexpressed in Escherichia coli at more than 10% of total protein. The recombinant enzyme was purified in high yield (67%) by heat-treatment at 85 degrees C and (NH4)2SO4 precipitation. Site-directed mutants (C37S, H59N, D150N, D150Eand D150C were analysed to test the peptide sequence comparison-based predictions of amino acids responsible for putative catalytic Zn binding. X-ray absorption spectroscopy confirmed the presence of a protein-bound Zn atom with ZnS1(imid)1(N,O)3 co-ordination sphere. Inductively coupled plasma atomic emission spectrometry measured 0.48 Zn atoms per wild-type secondary ADH subunit. The C37S, H59N and D150N mutant enzymes bound only 0.11, 0.13 and 0.33 Zn per subunit respectively,suggesting that these residues are involved in Zn liganding. The D150E and D150C mutants retained 0.47 and 1.2 Zn atoms per subunit, indicating that an anionic side-chain moiety at this position preserves the bound Zn. All five mutant enzymes had activity, suggesting that the T. ethanolicus secondary ADH requires a properly co-ordinated catalytic Zn atom. The His-59 and Asp-150 mutations also altered secondary ADH affinity for propan-2-ol over a 140-fold range, whereas the overall change in affinity for ethanol spanned a range of only 7-fold, supporting the importance of the metal in secondary ADH substrate binding. The lack of significant changes in cofactor affinity as a result of these catalytic Zn ligand mutations suggested that secondary ADH substrate-and cofactor-binding sites are structurally distinct. Altering Gly198 to Asp reduced the enzyme specific activity 2.7-fold, increased the Km(app) for NADP+ 225-fold, and decreased the Km(app) for NAD+ 3-fold, supporting the prediction that the enzyme binds nicotinamide cofactor in a Rossmann fold. Our data indicate therefore that, unlike the liver primary ADH

  4. Problems Encountered by Religious Vocational Secondary School and Other Secondary School Students in Physical Education and Sports Activities

    ERIC Educational Resources Information Center

    Bar, Mustafa; Yaman, Menzure Sibel; Hergüner, Gülten

    2016-01-01

    The study aimed to determine problems encountered by Religious Vocational Secondary School and other Secondary School students in physical education and sports activities and to compare these problems according to school type and gender. A questionnaire named "Problems encountered in attending to physical education and sports activities"…

  5. Environmental noise alters gastric myoelectrical activity: Effect of age

    PubMed Central

    Castle, James S; Xing, Jin-Hong; Warner, Mark R; Korsten, Mark A

    2007-01-01

    AIM: To evaluate the effect of age and acoustic stress on gastric myoelectrical activity (GMA) and autonomic nervous system function. METHODS: Twenty-one male subjects (age range 22-71 years, mean 44 years) were recruited and exposed, in random order, to three auditory stimuli (Hospital noise, conversation babble and traffic noise) after a 20-min baseline. All periods lasted 20 min and were interspersed with a 10 min of recovery. GMA was obtained using a Synectics Microdigitrapper. Autonomic nerve function was assessed by monitoring blood pressure and heart rate using an automatic recording device. RESULTS: Dominant power tended to decrease with increase of age (P < 0.05). The overall percentage of three cycle per minute (CPM) activity decreased during exposure to hospital noise (12.0%, P < 0.05), traffic noise (13.9%, P < 0.05), and conversation babble (7.1%). The subjects in the younger group (< 50 years) showed a consistent reduction in the percentage of 3 CPM activity during hospital noise (22.9%, P < 0.05), traffic noise (19.0%, P < 0.05), and conversation babble (15.5%). These observations were accompanied by a significant increase in bradygastria: hospital noise (P < 0.05) and traffic noise (P < 0.05). In contrast, the subjects over 50 years of age did not exhibit a significant decrease in 3 CPM activity. Regardless of age, noise did not alter blood pressure or heart rate. CONCLUSION: GMA changes with age. Loud noise can alter GMA, especially in younger individuals. Our data indicate that even short-term exposure to noise may alter the contractility of the stomach. PMID:17230609

  6. Physical activity breaks and facilities in US secondary schools

    PubMed Central

    Hood, Nancy E.; Colabianchi, Natalie; Terry-McElrath, Yvonne M.; O’Malley, Patrick M.; Johnston, Lloyd D.

    2014-01-01

    BACKGROUND Research on physical activity breaks and facilities (indoor and outdoor) in secondary schools is relatively limited. METHODS School administrators and students in nationally representative samples of 8th (middle school) and 10th/12th grade (high school) students were surveyed annually from 2008-09 through 2011-12. School administrators reported information about physical activity breaks and facilities. Students self-reported height, weight, and physical activity. RESULTS The prevalence of physical activity breaks and indoor and outdoor facilities (dichotomized by median split) differed significantly by region of the country, school size, student race/ethnicity, and school socioeconomic status (SES). Breaks were associated with lower odds of overweight (adjusted odds ratio (AOR) = 0.91, 95% confidence interval (CI): 0.83-1.00) and obesity (AOR = 0.86, 95% CI: 0.75-0.99) among middle school students. Among low-SES middle school students and schools, higher indoor facilities were associated with lower rates of overweight and obesity. Among high school students, higher indoor and outdoor facilities were associated with 19%-42% higher odds of moderate-to-vigorous physical activity. CONCLUSIONS Physical activity breaks and school facilities may help to address high rates of overweight/obesity and low physical activity levels among secondary students, especially lower-SES students. Students in all schools should have equal access to these resources. PMID:25274169

  7. Altered Amphibian Secondary Sex Characteristics following Exposure to Model Endocrine Disruptors

    EPA Science Inventory

    The formation of the secondary sex characteristics, oviducts and nuptial pads, are under the control of steroid hormones in frogs and as such are potential targets for endocrine-disrupting compounds. Oviducts are large, convoluted tubules derived from the Mullerian ducts in whic...

  8. Seasonal Variation in Seed Dispersal by Tamarins Alters Seed Rain in a Secondary Rain Forest

    PubMed Central

    Muñoz Lazo, Fernando Julio João; Huynen, Marie-Claude; Poncin, Pascal; Heymann, Eckhard W.

    2010-01-01

    Reduced dispersal of large seeds into degraded areas is one of the major factors limiting rain forest regeneration, as many seed dispersers capable of transporting large seeds avoid these sites with a limited forest cover. However, the small size of tamarins allows them to use small trees, and hence to disperse seeds into young secondary forests. Seasonal variations in diet and home range use might modify their contribution to forest regeneration through an impact on the seed rain. For a 2-yr period, we followed a mixed-species group of tamarins in Peru to determine how their role as seed dispersers in a 9-yr-old secondary-growth forest varied across seasons. These tamarins dispersed small to large seeds of 166 tree species, 63 of which were into a degraded area. Tamarins’ efficiency in dispersing seeds from primary to secondary forest varied across seasons. During the late wet season, high dietary diversity and long forays in secondary forest allowed them to disperse large seeds involved in later stages of regeneration. This occurred precisely when tamarins spent a more equal amount of time eating a high diversity of fruit species in primary forest and pioneer species in secondary forest. We hypothesized that well-balanced fruit availability induced the movement of seed dispersers between these 2 habitats. The noteworthy number of large-seeded plant species dispersed by such small primates suggests that tamarins play an important, but previously neglected, role in the regeneration and maintenance of forest structure. Electronic supplementary material The online version of this article (doi:10.1007/s10764-010-9413-7) contains supplementary material, which is available to authorized users. PMID:20651905

  9. Myelin alters the inflammatory phenotype of macrophages by activating PPARs

    PubMed Central

    2013-01-01

    Background Foamy macrophages, containing myelin degradation products, are abundantly found in active multiple sclerosis (MS) lesions. Recent studies have described an altered phenotype of macrophages after myelin internalization. However, mechanisms by which myelin affects the phenotype of macrophages and how this phenotype influences lesion progression remain unclear. Results We demonstrate that myelin as well as phosphatidylserine (PS), a phospholipid found in myelin, reduce nitric oxide production by macrophages through activation of peroxisome proliferator-activated receptor β/δ (PPARβ/δ). Furthermore, uptake of PS by macrophages, after intravenous injection of PS-containing liposomes (PSLs), suppresses the production of inflammatory mediators and ameliorates experimental autoimmune encephalomyelitis (EAE), an animal model of MS. The protective effect of PSLs in EAE animals is associated with a reduced immune cell infiltration into the central nervous system and decreased splenic cognate antigen specific proliferation. Interestingly, PPARβ/δ is activated in foamy macrophages in active MS lesions, indicating that myelin also activates PPARβ/δ in macrophages in the human brain. Conclusion Our data show that myelin modulates the phenotype of macrophages by PPAR activation, which may subsequently dampen MS lesion progression. Moreover, our results suggest that myelin-derived PS mediates PPARβ/δ activation in macrophages after myelin uptake. The immunoregulatory impact of naturally-occurring myelin lipids may hold promise for future MS therapeutics. PMID:24252308

  10. Immunosenescence is associated with altered gene expression and epigenetic regulation in primary and secondary immune organs

    PubMed Central

    Sidler, Corinne; Wóycicki, Rafał; Ilnytskyy, Yaroslav; Metz, Gerlinde; Kovalchuk, Igor; Kovalchuk, Olga

    2013-01-01

    Deterioration of the immune system (immunosenescence) with age is associated with an increased susceptibility to infection, autoimmune disease and cancer, and reduced responsiveness to vaccination. Immunosenescence entails a reduced supply of naïve T cells from the thymus and increased specialization of peripheral T cell clones. Both thymic involution and peripheral T cell homeostasis are thought to involve cellular senescence. In order to analyze this at the molecular level, we studied gene expression profiles, epigenetic status, and genome stability in the thymus and spleen of 1-, 4-, and 18-month-old Long Evans rats. In the thymus, altered gene expression, DNA and histone H3K9 hypomethylation, increased genome instability, and apoptosis were observed in 18-month-old animals compared to 1- and 4-month-old animals. In the spleen, alterations in gene expression and epigenetic regulation occurred already by the age of 4 months compared to 1 month and persisted in 18-month-old compared to 1-month-old rats. In both organs, these changes were accompanied by the altered composition of resident T cell populations. Our study suggests that both senescence and apoptosis may be involved in altered organ function. PMID:24151501

  11. Altered brain activity for phonological manipulation in dyslexic Japanese children

    PubMed Central

    Yamamoto, Hisako; Oba, Kentaro; Terasawa, Yuri; Moriguchi, Yoshiya; Uchiyama, Hitoshi; Seki, Ayumi; Koeda, Tatsuya; Inagaki, Masumi

    2013-01-01

    Because of unique linguistic characteristics, the prevalence rate of developmental dyslexia is relatively low in the Japanese language. Paradoxically, Japanese children have serious difficulty analysing phonological processes when they have dyslexia. Neurobiological deficits in Japanese dyslexia remain unclear and need to be identified, and may lead to better understanding of the commonality and diversity in the disorder among different linguistic systems. The present study investigated brain activity that underlies deficits in phonological awareness in Japanese dyslexic children using functional magnetic resonance imaging. We developed and conducted a phonological manipulation task to extract phonological processing skills and to minimize the influence of auditory working memory on healthy adults, typically developing children, and dyslexic children. Current experiments revealed that several brain regions participated in manipulating the phonological information including left inferior and middle frontal gyrus, left superior temporal gyrus, and bilateral basal ganglia. Moreover, dyslexic children showed altered activity in two brain regions. They showed hyperactivity in the basal ganglia compared with the two other groups, which reflects inefficient phonological processing. Hypoactivity in the left superior temporal gyrus was also found, suggesting difficulty in composing and processing phonological information. The altered brain activity shares similarity with those of dyslexic children in countries speaking alphabetical languages, but disparity also occurs between these two populations. These are initial findings concerning the neurobiological impairments in dyslexic Japanese children. PMID:24052613

  12. Microgravity: a Teacher's Guide with Activities, Secondary Level

    NASA Technical Reports Server (NTRS)

    Vogt, Gregory L. (Editor); Wargo, Michael J. (Editor)

    1992-01-01

    This NASA Educational Publication is a teacher's guide that focuses on microgravity for the secondary level student. The introduction answers the question 'What is microgravity?', as well as describing gravity and creating microgravity. Following the introduction is a microgravity primer which covers such topics as the fluid state, combustion science, materials science, biotechnology, as well as microgravity and space flight. Seven different activities are described in the activities section and are written by authors prominent in the field. The concluding sections of the book include a glossary, microgravity references, and NASA educational resources.

  13. Local school policies increase physical activity in Norwegian secondary schools

    PubMed Central

    Haug, Ellen; Torsheim, Torbjørn; Samdal, Oddrun

    2010-01-01

    SUMMARY The implementation of school policies to support the adoption of physical activity is one of the main strategies recommended to increase physical activity levels among this age group. However, documentation of the effect of such policies is so far limited. The purpose of this study was to explore policy-related practices to support physical activity in Norwegian secondary schools and their association with recess physical activity. Emphasis was given to examine the association between policies and physical activity, over and beyond, individual level interests and environmental factors and to examine cross-level interaction effects. This cross-sectional study was based on a nationally representative sample of Norwegian secondary schools and grade 8 students who participated in the Health Behaviour in School-aged Children (HBSC) 2005/06 study. The final sample comprised 68 schools and 1347 students. Data were collected through questionnaires. The results showed that schools with a written policy for physical activity and schools offering organized non-curricular physical activity several times a week had a higher proportion of students reporting daily participation in recess physical activity. Multilevel logistic regression analysis demonstrated a cross-level main effect of the policy index after controlling for sex, socio-economic status, individual-level interests and the physical environment. A significant contribution of adding the policy index to the prediction of recess physical activity above that provided by the individual-level interests and the physical environment was demonstrated. The results are encouraging and give scientific support to policy documents recommending the implementation of school policies to increase physical activity. PMID:19884244

  14. Gut passage and secondary metabolites alter the source of post-dispersal predation for bird-dispersed chili seeds.

    PubMed

    Fricke, Evan C; Haak, David C; Levey, Douglas J; Tewksbury, Joshua J

    2016-07-01

    Plants can influence the source and severity of seed predation through various mechanisms; the use of secondary metabolites for chemical defense, for example, is well documented. Gut passage by frugivores can also reduce mortality of animal-dispersed seeds, although this mechanism has gained far less attention than secondary metabolites. Apart from influencing the severity of seed predation, gut passage may also influence the source of seed predation. In Bolivia, we compared impacts of these two mechanisms, gut passage and secondary metabolites, on the source of seed predation in Capsicum chacoense, a wild chili species that is polymorphic for pungency (individual plants either produce fruits and seeds containing or lacking capsaicinoids). Using physical exclosures, we isolated seed removal by insects, mammals, and birds; seeds in the trials were from either pungent or non-pungent fruits and were either passed or not passed by seed-dispersing birds. Pungency had little influence on total short-term seed removal by animals, although prior work on this species indicates that capsaicin reduces mortality caused by fungi at longer time scales. Gut passage strongly reduced removal by insects, altering the relative impact of the three predator types. The weak impact of pungency on short-term predation contrasts with previous studies, highlighting the context dependence of secondary metabolites. The strong impact of gut passage demonstrates that this mechanism alone can influence which seed predators consume seeds, and that impacts of gut passage can be larger than those of secondary metabolites, which are more commonly acknowledged as a defense mechanism. PMID:27016078

  15. Hsp90 Activity Modulation by Plant Secondary Metabolites.

    PubMed

    Dal Piaz, Fabrizio; Terracciano, Stefania; De Tommasi, Nunziatina; Braca, Alessandra

    2015-09-01

    Hsp90 is an evolutionarily conserved adenosine triphosphate-dependent molecular chaperone and is one of the most abundant proteins in the cells (1-3 %). Hsp90 is induced when a cell undergoes various types of environmental stresses such as heat, cold, or oxygen deprivation. It is involved in the turnover, trafficking, and activity of client proteins, including apoptotic factors, protein kinases, transcription factors, signaling proteins, and a number of oncoproteins. Most of the Hsp90 client proteins are involved in cell growth, differentiation, and survival, and include kinases, nuclear hormone receptors, transcription factors, and other proteins associated with almost all the hallmarks of cancer. Consistent with these diverse activities, genetic and biochemical studies have demonstrated the implication of Hsp90 in a range of diseases, including cancer, making this chaperone an interesting target for drug research.During the last few decades, plant secondary metabolites have been studied as a major source for lead compounds in drug discovery. Recently, several plant-derived small molecules have been discovered exhibiting inhibitory activity towards Hsp90, such as epigallocatechin gallate, gedunin, lentiginosine, celastrol, and deguelin. In this work, an overview of plant secondary metabolites interfering with Hsp90 activities is provided. PMID:26227505

  16. Active optics control of VST telescope secondary mirror.

    PubMed

    Schipani, Pietro; D'Orsi, Sergio; Fierro, Davide; Marty, Laurent

    2010-06-01

    In telescopes based on active optics, defocus and coma are usually compensated for by secondary mirror movements. They are performed at the Very Large Telescope Survey Telescope (VST) with a hexapod--a parallel robot with six degrees of freedom positioning capability. We describe the application of the two-mirror telescope theory to the VST case and the solutions adopted for the hexapod control. We present the results of performance and reliability tests performed both in the laboratory and at the telescope. PMID:20517391

  17. Environmental enrichment alters splenic immune cell composition and enhances secondary influenza vaccine responses in mice.

    PubMed

    Gurfein, Blake T; Davidenko, Olga; Premenko-Lanier, Mary; Milush, Jeffrey M; Acree, Michael; Dallman, Mary F; Touma, Chadi; Palme, Rupert; York, Vanessa A; Fromentin, Gilles; Darcel, Nicolas; Nixon, Douglas F; Hecht, Frederick M

    2014-01-01

    Chronic stress has deleterious effects on immune function, which can lead to adverse health outcomes. However, studies investigating the impact of stress reduction interventions on immunity in clinical research have yielded divergent results, potentially stemming from differences in study design and genetic heterogeneity, among other clinical research challenges. To test the hypothesis that reducing glucocorticoid levels enhances certain immune functions, we administered influenza vaccine once (prime) or twice (boost) to mice housed in either standard control caging or environmental enrichment (EE) caging. We have shown that this approach reduces mouse corticosterone production. Compared with controls, EE mice had significantly lower levels of fecal corticosterone metabolites (FCMs) and increased splenic B and T lymphocyte numbers. Corticosterone levels were negatively associated with the numbers of CD19(+) (r(2) = 0.43, p = 0.0017), CD4(+) (r(2) = 0.28, p = 0.0154) and CD8(+) cells (r(2) = 0.20, p = 0.0503). Vaccinated mice showed nonsignificant differences in immunoglobulin G (IgG) titer between caging groups, although EE mice tended to exhibit larger increases in titer from prime to boost than controls; the interaction between the caging group (control versus EE) and vaccine group (prime versus boost) showed a strong statistical trend (cage-group*vaccine-group, F = 4.27, p = 0.0555), suggesting that there may be distinct effects of EE caging on primary versus secondary IgG vaccine responses. Vaccine-stimulated splenocytes from boosted EE mice had a significantly greater frequency of interleukin 5 (IL-5)-secreting cells than boosted controls (mean difference 7.7, IL-5 spot-forming units/10(6) splenocytes, 95% confidence interval 0.24-135.1, p = 0.0493) and showed a greater increase in the frequency of IL-5-secreting cells from prime to boost. Our results suggest that corticosterone reduction via EE caging was associated with enhanced secondary vaccine responses

  18. Environmental Enrichment Alters Splenic Immune Cell Composition and Enhances Secondary Influenza Vaccine Responses in Mice

    PubMed Central

    Gurfein, Blake T; Davidenko, Olga; Premenko-Lanier, Mary; Milush, Jeffrey M; Acree, Michael; Dallman, Mary F; Touma, Chadi; Palme, Rupert; York, Vanessa A; Fromentin, Gilles; Darcel, Nicolas; Nixon, Douglas F; Hecht, Frederick M

    2014-01-01

    Chronic stress has deleterious effects on immune function, which can lead to adverse health outcomes. However, studies investigating the impact of stress reduction interventions on immunity in clinical research have yielded divergent results, potentially stemming from differences in study design and genetic heterogeneity, among other clinical research challenges. To test the hypothesis that reducing glucocorticoid levels enhances certain immune functions, we administered influenza vaccine once (prime) or twice (boost) to mice housed in either standard control caging or environmental enrichment (EE) caging. We have shown that this approach reduces mouse corticosterone production. Compared with controls, EE mice had significantly lower levels of fecal corticosterone metabolites (FCMs) and increased splenic B and T lymphocyte numbers. Corticosterone levels were negatively associated with the numbers of CD19+ (r2 = 0.43, p = 0.0017), CD4+ (r2 = 0.28, p = 0.0154) and CD8+ cells (r2 = 0.20, p = 0.0503). Vaccinated mice showed nonsignificant differences in immunoglobulin G (IgG) titer between caging groups, although EE mice tended to exhibit larger increases in titer from prime to boost than controls; the interaction between the caging group (control versus EE) and vaccine group (prime versus boost) showed a strong statistical trend (cage-group*vaccine-group, F = 4.27, p = 0.0555), suggesting that there may be distinct effects of EE caging on primary versus secondary IgG vaccine responses. Vaccine-stimulated splenocytes from boosted EE mice had a significantly greater frequency of interleukin 5 (IL-5)-secreting cells than boosted controls (mean difference 7.7, IL-5 spot-forming units/106 splenocytes, 95% confidence interval 0.24–135.1, p = 0.0493) and showed a greater increase in the frequency of IL-5–secreting cells from prime to boost. Our results suggest that corticosterone reduction via EE caging was associated with enhanced secondary vaccine responses, but had

  19. Pharmacological activity of metal binding agents that alter copper bioavailability

    PubMed Central

    Helsel, Marian E.

    2015-01-01

    Iron, copper and zinc are required nutrients for many organisms but also potent toxins if misappropriated. An overload of any of these metals can be cytotoxic and ultimately lead to organ failure, whereas deficiencies can result in anemia, weakened immune system function, and other medical conditions. Cellular metal imbalances have been implicated in neurodegenerative diseases, cancer and infection. It is therefore critical for living organisms to maintain careful control of both the total levels and subcellular distributions of these metals to maintain healthy function. This perspective explores several strategies envisioned to alter the bioavailability of metal ions by using synthetic metal-binding agents targeted for diseases where misappropriated metal ions are suspected of exacerbating cellular damage. Specifically, we discuss chemical properties that influence the pharmacological outcome of a subset of metal-binding agents known as ionophores, and review several examples that have shown multiple pharmacological activities in metal-related diseases, with a specific focus on copper. PMID:25797044

  20. Exposure to mercury alters early activation events in fish leukocytes.

    PubMed Central

    MacDougal, K C; Johnson, M D; Burnett, K G

    1996-01-01

    Although fish in natural populations may carry high body burdens of both organic and inorganic mercury, the effects of this divalent metal on such lower vertebrates is poorly understood. In this report, inorganic mercury in the form of mercuric chloride (HgCl2) is shown to produce both high-dose inhibition and low-dose activation of leukocytes in a marine teleost fish, Sciaenops ocellatus. Concentrations of inorganic mercury > or = 10 microM suppressed DNA synthesis and induced rapid influx of radiolabeled calcium, as well as tyrosine phosphorylation of numerous cellular proteins. Lower concentrations (0.1-1 microM) of HgCl2 that activated cell growth also induced a slow sustained rise in intracellular calcium in cells loaded with the calcium indicator dye fura-2, but did not produce detectable tyrosine phosphorylation of leukocyte proteins. These studies support the possibility that subtoxic doses of HgCl2 may inappropriately activate teleost leukocytes, potentially altering the processes that regulate the magnitude and specificity of the fish immune response to environmental pathogens. Images Figure 1. Figure 2. Figure 3. Figure 4. Figure 5. Figure 6. Figure 7. PMID:8930553

  1. Alteration of biophysical activity of pulmonary surfactant by aluminosilicate nanoparticles.

    PubMed

    Kondej, Dorota; Sosnowski, Tomasz R

    2013-02-01

    The influence of five different types of aluminosilicate nanoparticles (NPs) on the dynamic surface activity of model pulmonary surfactant (PS) (Survanta) was studied experimentally using oscillating bubble tensiometry. Bentonite, halloysite and montmorillonite (MM) NPs, which are used as fillers of polymer composites, were characterized regarding the size distribution, morphology and surface area. Particle doses applied in the studies were estimated based on the inhalation rate and duration, taking into account the expected aerosol concentration and deposition efficiency after penetration of NPs into the alveolar region. The results indicate that aluminosilicate NPs at concentrations in the pulmonary liquid above 0.1 mg cm(-3) are capable of promoting alterations of the original dynamic biophysical activity of the PS. This effect is indicated by deviation of the minimum surface tension, stability index and the size of surface tension hysteresis. Such response is dependent on the type of NPs present in the system and is stronger when particle concentration increases. It is suggested that interactions between NPs and the PS must be related to the surfactant adsorption on the suspended particles, while in the case of surface-modified clay NPs the additional washout of surface-active components may be expected. It is speculated that observed changes in surface properties of the surfactant may be associated with undesired health effects following extensive inhalation of aluminosilicate NPs in the workplace. PMID:23363039

  2. Mutagenic activity of austocystins - secondary metabolites of Aspergillus ustus

    SciTech Connect

    Kfir, R.; Johannsen, E.; Vleggaar, R.

    1986-11-01

    Mycotoxins constitute a group of toxic secondary fungal metabolites. Fungi that produce these toxins frequently contaminate food and feed, creating a potential threat to human and animal health. Biological activities of mycotoxins include, amongst others: toxicity, mutagenicity and carcinogenicity, which can be expressed with or without metabolic activation. Austocystins are similar in structure to aflatoxin B/sup 1/ and are probably synthesized in a similar manner. The Ames Salmonella test, a widely accepted method employed for the detection of mutagenic activity of various chemical compounds was used for testing the mutagenic activity of different mycotoxins. As aflatoxin B/sup 1/ was found by the Ames test to be highly mutagenic, the same test was applied for the study of possible mutagenicity of the austocystins. The mutagenic activity of these compounds was studied with and without metabolic activation using two tester strains of S. typhimurium, one capable of detecting frame shift mutation (strain TA98) and the other capable of detecting base pair substitution (strain TA100).

  3. The plant secondary metabolite citral alters water status and prevents seed formation in Arabidopsis thaliana.

    PubMed

    Graña, E; Díaz-Tielas, C; López-González, D; Martínez-Peñalver, A; Reigosa, M J; Sánchez-Moreiras, A M

    2016-05-01

    Based on previous results, which showed that the secondary metabolite citral causes disturbances to plant water status, the present study is focused on demonstrating and detailing these effects on the water-related parameters of Arabidopsis thaliana adult plants, and their impact on plant fitness. Clear evidence of effects on water status and fitness were observed: plants treated with 1200 and 2400 μm citral showed decreased RWC, reduced Ψs , increased Ψw and reduced stomatal opening, even 7 days after the beginning of the experiment. Plant protection signals, such as leaf rolling or increased anthocyanin content, were also detected in these plants. In contrast, 14 days after beginning the treatment, treated plants showed signs of citral-related damage. Moreover, the reproductive success of treated plants was critically compromised, with prematurely withered flowers and no silique or seed development. This effect of citral on fitness of adult plants suggests a promising application of this natural compound in weed management by reducing the weed seed bank in the soil. PMID:26587965

  4. Pseudorabies Virus Infection Alters Neuronal Activity and Connectivity In Vitro

    PubMed Central

    McCarthy, Kelly M.; Tank, David W.; Enquist, Lynn W.

    2009-01-01

    Alpha-herpesviruses, including human herpes simplex virus 1 & 2, varicella zoster virus and the swine pseudorabies virus (PRV), infect the peripheral nervous system of their hosts. Symptoms of infection often include itching, numbness, or pain indicative of altered neurological function. To determine if there is an in vitro electrophysiological correlate to these characteristic in vivo symptoms, we infected cultured rat sympathetic neurons with well-characterized strains of PRV known to produce virulent or attenuated symptoms in animals. Whole-cell patch clamp recordings were made at various times after infection. By 8 hours of infection with virulent PRV, action potential (AP) firing rates increased substantially and were accompanied by hyperpolarized resting membrane potentials and spikelet-like events. Coincident with the increase in AP firing rate, adjacent neurons exhibited coupled firing events, first with AP-spikelets and later with near identical resting membrane potentials and AP firing. Small fusion pores between adjacent cell bodies formed early after infection as demonstrated by transfer of the low molecular weight dye, Lucifer Yellow. Later, larger pores formed as demonstrated by transfer of high molecular weight Texas red-dextran conjugates between infected cells. Further evidence for viral-induced fusion pores was obtained by infecting neurons with a viral mutant defective for glycoprotein B, a component of the viral membrane fusion complex. These infected neurons were essentially identical to mock infected neurons: no increased AP firing, no spikelet-like events, and no electrical or dye transfer. Infection with PRV Bartha, an attenuated circuit-tracing strain delayed, but did not eliminate the increased neuronal activity and coupling events. We suggest that formation of fusion pores between infected neurons results in electrical coupling and elevated firing rates, and that these processes may contribute to the altered neural function seen in PRV

  5. Small Chemical Chromatin Effectors Alter Secondary Metabolite Production in Aspergillus clavatus

    PubMed Central

    Zutz, Christoph; Gacek, Agnieszka; Sulyok, Michael; Wagner, Martin; Strauss, Joseph; Rychli, Kathrin

    2013-01-01

    The filamentous fungus Aspergillus clavatus is known to produce a variety of secondary metabolites (SM) such as patulin, pseurotin A, and cytochalasin E. In fungi, the production of most SM is strongly influenced by environmental factors and nutrients. Furthermore, it has been shown that the regulation of SM gene clusters is largely based on modulation of a chromatin structure. Communication between fungi and bacteria also triggers chromatin-based induction of silent SM gene clusters. Consequently, chemical chromatin effectors known to inhibit histone deacetylases (HDACs) and DNA-methyltransferases (DNMTs) influence the SM profile of several fungi. In this study, we tested the effect of five different chemicals, which are known to affect chromatin structure, on SM production in A. clavatus using two growth media with a different organic nitrogen source. We found that production of patulin was completely inhibited and cytochalasin E levels strongly reduced, whereas growing A. clavatus in media containing soya-derived peptone led to substantially higher pseurotin A levels. The HDAC inhibitors valproic acid, trichostatin A and butyrate, as well as the DNMT inhibitor 5-azacytidine (AZA) and N-acetyl-d-glucosamine, which was used as a proxy for bacterial fungal co-cultivation, had profound influence on SM accumulation and transcription of the corresponding biosynthetic genes. However, the repressing effect of the soya-based nitrogen source on patulin production could not be bypassed by any of the small chemical chromatin effectors. Interestingly, AZA influenced some SM cluster genes and SM production although no Aspergillus species has yet been shown to carry detectable DNA methylation. PMID:24105402

  6. Alteration of spontaneous brain activity in COPD patients

    PubMed Central

    Zhang, Jiaxing; Chen, Ji; Yu, Qian; Fan, Cunxiu; Zhang, Ran; Lin, Jianzhong; Yang, Tianhe; Fan, Ming

    2016-01-01

    Background and objective Airflow limitation in chronic obstructive pulmonary disease (COPD) results in a decrease in oxygen transport to the brain. The aim of the present study was to explore the alteration of spontaneous brain activity induced by hypoxia in patients with COPD. Patients and methods Twenty-five stable patients with COPD and 25 matching healthy volunteers were investigated. Amplitude of low-frequency fluctuation (ALFF) of blood oxygenation level-dependent signal at resting state in the brain was analyzed using functional magnetic resonance imaging. Results Whole-brain analysis using functional magnetic resonance imaging revealed significant decreases in ALFF in the bilateral posterior cingulate gyri and right lingual gyrus and an increase in ALFF in the left postcentral gyrus of patients with COPD. After controlling for SaO2, patients with COPD only showed an increase in ALFF in the left postcentral gyrus. Region of interest analysis showed a decrease in ALFF in the left precentral gyrus and an increase in ALFF in the left caudate nucleus of patients with COPD. In all subjects, ALFF in the bilateral posterior cingulate gyri and right lingual gyrus showed positive correlations with visual reproduction. Conclusion We demonstrated abnormal spontaneous brain activity of patients with COPD, which may have a pathophysiologic meaning. PMID:27555761

  7. Disruption of secondary structure by oxidative stress alters the cross-linking pattern of myosin by microbial transglutaminase.

    PubMed

    Li, Chunqiang; Xiong, Youling L

    2015-10-01

    Porcine myofibrillar protein (MP) was oxidatively stressed in an iron-H2O2 radical-producing system then subjected to microbial transglutaminase (TGase, E:S=1:20) at 4°C. Changes in the MP secondary structure and cross-linking site on myosin (subfragments S1, S2, rod, light meromyosin, and heavy meromyosin) after TGase treatment were investigated. Circular dichroism and FTIR recorded unraveling of helixes caused by both oxidation and TGase. The loss of α-helix due to TGase treatment was oxidation-dependent, namely, mild oxidation (0.1-1mM H2O2)>non-oxidation>moderate oxidation (5-20mM H2O2). Moreover, oxidation altered the myosin cross-linking pattern: TGase-initiated S1 cross-linking (which dominated non-oxidized MP) partially shifted to the rod under 0.1-0.5mM H2O2 and extensively to the S2 site with 20mM H2O2. Unraveling of the helical structure and formation of disulfide bonds due to oxidation were implicated in the altered myosin cross-linking pattern during subsequent TGase reactions. PMID:26068405

  8. Phenol oxidase activity in secondary transformed peat-moorsh soils

    NASA Astrophysics Data System (ADS)

    Styła, K.; Szajdak, L.

    2009-04-01

    The chemical composition of peat depends on the geobotanical conditions of its formation and on the depth of sampling. The evolution of hydrogenic peat soils is closely related to the genesis of peat and to the changes in water conditions. Due to a number of factors including oscillation of ground water level, different redox potential, changes of aerobic conditions, different plant communities, and root exudes, and products of the degradation of plant remains, peat-moorsh soils may undergo a process of secondary transformation conditions (Sokolowska et al. 2005; Szajdak et al. 2007). Phenol oxidase is one of the few enzymes able to degrade recalcitrant phenolic materials as lignin (Freeman et al. 2004). Phenol oxidase enzymes catalyze polyphenol oxidation in the presence of oxygen (O2) by removing phenolic hydrogen or hydrogenes to from radicals or quinines. These products undergo nucleophilic addition reactions in the presence or absence of free - NH2 group with the eventual production of humic acid-like polymers. The presence of phenol oxidase in soil environments is important in the formation of humic substances a desirable process because the carbon is stored in a stable form (Matocha et al. 2004). The investigations were carried out on the transect of peatland 4.5 km long, located in the Agroecological Landscape Park host D. Chlapowski in Turew (40 km South-West of Poznań, West Polish Lowland). The sites of investigation were located along Wyskoć ditch. The following material was taken from four chosen sites marked as Zbechy, Bridge, Shelterbelt and Hirudo in two layers: cartel (0-50cm) and cattle (50-100cm). The object of this study was to characterize the biochemical properties by the determination of the phenol oxidize activity in two layers of the four different peat-moors soils used as meadow. The phenol oxidase activity was determined spectrophotometrically by measuring quinone formation at λmax=525 nm with catechol as substrate by method of Perucci

  9. School grounds and physical activity: Associations at secondary schools, and over the transition from primary to secondary schools.

    PubMed

    Harrison, Flo; van Sluijs, Esther M F; Corder, Kirsten; Jones, Andy

    2016-05-01

    This paper aims to further understanding of the physical environments of secondary schools and their associations with young peoples' physical activity. Accelerometer-derived physical activity measurements from 299 participants in the SPEEDY study (Norfolk, UK) were obtained from baseline measurements (age 9-10y) and +4y follow-up. These were linked to objective measures of primary and secondary school environments as measured by the SPEEDY grounds audit tool. We saw considerable differences in the nature of school grounds between primary and secondary schools. Cross-sectional associations were seen between active travel provision scores and commuting time moderate-to-vigorous physical activity (MVPA) for 13-14 year old boys and adolescents living further from school. However, few associations were seen between changes in school grounds scores and changes in school-based MVPA. PMID:26922516

  10. Characterization of a novel RNA polymerase mutant that alters DksA activity.

    PubMed

    Satory, Dominik; Halliday, Jennifer A; Sivaramakrishnan, Priya; Lua, Rhonald C; Herman, Christophe

    2013-09-01

    The auxiliary factor DksA is a global transcription regulator and, with the help of ppGpp, controls the nutritional stress response in Escherichia coli. Although the consequences of its modulation of RNA polymerase (RNAP) are becoming better explained, it is still not fully understood how the two proteins interact. We employed a series of genetic suppressor selections to find residues in RNAP that alter its sensitivity to DksA. Our approach allowed us to identify and genetically characterize in vivo three single amino acid substitutions: β' E677G, β V146F, and β G534D. We demonstrate that the mutation β' E677G affects the activity of both DksA and its homolog, TraR, but does not affect the action of other secondary interactors, such as GreA or GreB. Our mutants provide insight into how different auxiliary transcription factors interact with RNAP and contribute to our understanding of how different stages of transcription are regulated through the secondary channel of RNAP in vivo. PMID:23852871

  11. Secondary Metabolites from Three Florida Sponges with Antidepressant Activity

    PubMed Central

    Kochanowska, Anna J.; Rao, Karumanchi V.; Childress, Suzanne; El-Alfy, Abir; Matsumoto, Rae R.; Kelly, Michelle; Stewart, Gina S.; Sufka, Kenneth J.; Hamann, Mark T.

    2016-01-01

    Brominated indole alkaloids are a common class of metabolites reported from sponges of the order Verongida. Herein we report the isolation, structure determination, and activity of metabolites from three Florida sponges, namely, Verongula rigida (order Verongida, family Aplysinidae), Smenospongia aurea, and S. cerebriformis (order Dictyoceratida, family Thorectidae). All three species were investigated chemically, revealing similarities in secondary metabolites. Brominated compounds, as well as sesquiterpene quinones and hydroquinones, were identified from both V. rigida and S. aurea despite their apparent taxonomic differences at the ordinal level. Similar metabolites found in these distinct sponge species of two different genera provide evidence for a microbial origin of the metabolites. Isolated compounds were evaluated in the Porsolt forced swim test (FST) and the chick anxiety–depression continuum model. Among the isolated compounds, 5,6-dibromo-N,N-dimethyltryptamine (1) exhibited significant antidepressant-like action in the rodent FST model, while 5-bromo-N,N-dimethyltryptamine (2) caused significant reduction of locomotor activity indicative of a potential sedative action. The current study provides ample evidence that marine natural products with the diversity of brominated marine alkaloids will provide potential leads for antidepressant and anxiolytic drugs. PMID:18217716

  12. Chronic neck pain alters muscle activation patterns to sudden movements.

    PubMed

    Boudreau, Shellie A; Falla, Deborah

    2014-06-01

    The aim of this study was to assess the activation of the sternocleidomastoid (SCM) and splenius capitis (SC) muscles in response to unanticipated, full body perturbations in individuals with chronic neck pain (NP) and age-matched healthy controls (HC). Individuals with NP had a history of NP for 8.9 ± 7.8 years, rated the intensity of NP as 4.2 ± 2.0 (score out of 10), and scored 15.3 ± 6.5 on the Neck Disability Index. Participants stood on a moveable platform during which 32 randomized postural perturbations (eight repetitions of four perturbation types: 8 cm forward slide (FS), 8 cm backward slides, 10° forward tilt, and 10° backward tilt) with varying inter-perturbation time intervals were performed over a period of 5 min. Bilateral surface electromyography (EMG) from the SCM and SC was recorded, and the onset time and the average rectified value of the EMG signal was determined for epochs of 100 ms; starting 100 ms prior to and 500 ms after the perturbation onset. Individuals with NP, as compared to HC, demonstrated delayed onset times and reduced EMG amplitude of the SCM and SC muscles in response to all postural perturbations. Such findings were most pronounced following the FS postural perturbation (healthy vs. NP for SCM 83.3 ± 8.0 vs. 86.3 ± 4.4 and SC 75.6 ± 3.5 vs. 89.3 ± 4.2), which was also associated with the greatest change (expressed in % relative to baseline) in EMG amplitude (healthy vs. NP for SCM 206.6 ± 50.4 vs. 115.9 ± 15.7 and SC 83.4 ± 19.2 vs. 69.2 ± 10.9) across all postural perturbations types. Individuals with NP display altered neural control of the neck musculature in response to rapid, unanticipated full body postural perturbations. Although the relative timing of neck musculature activity in individuals with NP appears to be intact, simultaneous co-activation of the neck musculature emerges for unanticipated anterior-posterior postural perturbations. PMID:24632836

  13. Evidence for altered opioid activity in patients with cancer.

    PubMed Central

    Lissoni, P.; Barni, S.; Paolorossi, F.; Crispino, S.; Rovelli, F.; Ferri, L.; Delitala, G.; Tancini, G.

    1987-01-01

    Endogenous opioid peptides have been shown to be involved in the regulation of tumour growth. At present, however, no data are available about the secretion of opioid peptides in cancer patients. To draw some preliminary conclusions on opioid brain function in human neoplasms, we evaluated hypophyseal hormone responses to the administration of a met-enkephalin analogue, FK 33-824. The study included 14 patients affected by early or advanced neoplastic disease, 12 healthy subjects and 7 patients with a chronic medical illness other than cancer. FK 33-824 was given intravenously at a dose of 0.3 mg. Venous blood samples were collected at zero time, and 30, 60 and 120 min after drug administration. In each sample, PRL, GH, LH, cortisol and beta-endorphin levels were measured by RIA. In all normal subjects and in patients with non-neoplastic chronic illness, FK 33-824 induced a rise in PRL and GH levels, and a decrease in LH, cortisol and beta-endorphin. A normal endocrine response to FK 33-824 was seen in our cancer patient only, while in the other cases with tumour no hormonal changes or a paradoxical response were seen after FK 33-824. Based on the fact that an abnormal endocrine response to FK 33-824 has been described in hypothalamic-pituitary disorders, in which anomalous brain opioid activity has been demonstrated, these results suggest the existence of an altered function of the opioid system in cancer patients, the clinical importance of which remains to be determined. PMID:2963662

  14. SECONDARY WASTE MANAGEMENT FOR HANFORD EARLY LOW ACTIVITY WASTE VITRIFICATION

    SciTech Connect

    UNTERREINER BJ

    2008-07-18

    More than 200 million liters (53 million gallons) of highly radioactive and hazardous waste is stored at the U.S. Department of Energy's Hanford Site in southeastern Washington State. The DOE's Hanford Site River Protection Project (RPP) mission includes tank waste retrieval, waste treatment, waste disposal, and tank farms closure activities. This mission will largely be accomplished by the construction and operation of three large treatment facilities at the Waste Treatment and Immobilization Plant (WTP): (1) a Pretreatment (PT) facility intended to separate the tank waste into High Level Waste (HLW) and Low Activity Waste (LAW); (2) a HLW vitrification facility intended to immobilize the HLW for disposal at a geologic repository in Yucca Mountain; and (3) a LAW vitrification facility intended to immobilize the LAW for shallow land burial at Hanford's Integrated Disposal Facility (IDF). The LAW facility is on target to be completed in 2014, five years prior to the completion of the rest of the WTP. In order to gain experience in the operation of the LAW vitrification facility, accelerate retrieval from single-shell tank (SST) farms, and hasten the completion of the LAW immobilization, it has been proposed to begin treatment of the low-activity waste five years before the conclusion of the WTP's construction. A challenge with this strategy is that the stream containing the LAW vitrification facility off-gas treatment condensates will not have the option of recycling back to pretreatment, and will instead be treated by the Hanford Effluent Treatment Facility (ETF). Here the off-gas condensates will be immobilized into a secondary waste form; ETF solid waste.

  15. School Sports Opportunities Influence Physical Activity in Secondary School and beyond

    ERIC Educational Resources Information Center

    Fuller, Daniel; Sabiston, Catherine; Karp, Igor; Barnett, Tracie; O'Loughlin, Jennifer

    2011-01-01

    Background: The purpose of the present study was to examine whether the availability of intramural or extramural sports in secondary schools is associated with physical activity levels in youth throughout secondary school and at age 20. Methods: Eight hundred and eight adolescents from 10 secondary schools in Montreal, Canada, provided physical…

  16. Altered sensorimotor activation patterns in idiopathic dystonia—an activation likelihood estimation meta‐analysis of functional brain imaging studies

    PubMed Central

    Herz, Damian M.; Haagensen, Brian N.; Lorentzen, Anne K.; Eickhoff, Simon B.; Siebner, Hartwig R.

    2015-01-01

    Abstract Dystonia is characterized by sustained or intermittent muscle contractions causing abnormal, often repetitive, movements or postures. Functional neuroimaging studies have yielded abnormal task‐related sensorimotor activation in dystonia, but the results appear to be rather variable across studies. Further, study size was usually small including different types of dystonia. Here we performed an activation likelihood estimation (ALE) meta‐analysis of functional neuroimaging studies in patients with primary dystonia to test for convergence of dystonia‐related alterations in task‐related activity across studies. Activation likelihood estimates were based on previously reported regional maxima of task‐related increases or decreases in dystonia patients compared to healthy controls. The meta‐analyses encompassed data from 179 patients with dystonia reported in 18 functional neuroimaging studies using a range of sensorimotor tasks. Patients with dystonia showed bilateral increases in task‐related activation in the parietal operculum and ventral postcentral gyrus as well as right middle temporal gyrus. Decreases in task‐related activation converged in left supplementary motor area and left postcentral gyrus, right superior temporal gyrus and dorsal midbrain. Apart from the midbrain cluster, all between‐group differences in task‐related activity were retrieved in a sub‐analysis including only the 14 studies on patients with focal dystonia. For focal dystonia, an additional cluster of increased sensorimotor activation emerged in the caudal cingulate motor zone. The results show that dystonia is consistently associated with abnormal somatosensory processing in the primary and secondary somatosensory cortex along with abnormal sensorimotor activation of mesial premotor and right lateral temporal cortex. Hum Brain Mapp 37:547–557, 2016. © 2015 Wiley Periodicals, Inc. PMID:26549606

  17. Altered sensorimotor activation patterns in idiopathic dystonia-an activation likelihood estimation meta-analysis of functional brain imaging studies.

    PubMed

    Løkkegaard, Annemette; Herz, Damian M; Haagensen, Brian N; Lorentzen, Anne K; Eickhoff, Simon B; Siebner, Hartwig R

    2016-02-01

    Dystonia is characterized by sustained or intermittent muscle contractions causing abnormal, often repetitive, movements or postures. Functional neuroimaging studies have yielded abnormal task-related sensorimotor activation in dystonia, but the results appear to be rather variable across studies. Further, study size was usually small including different types of dystonia. Here we performed an activation likelihood estimation (ALE) meta-analysis of functional neuroimaging studies in patients with primary dystonia to test for convergence of dystonia-related alterations in task-related activity across studies. Activation likelihood estimates were based on previously reported regional maxima of task-related increases or decreases in dystonia patients compared to healthy controls. The meta-analyses encompassed data from 179 patients with dystonia reported in 18 functional neuroimaging studies using a range of sensorimotor tasks. Patients with dystonia showed bilateral increases in task-related activation in the parietal operculum and ventral postcentral gyrus as well as right middle temporal gyrus. Decreases in task-related activation converged in left supplementary motor area and left postcentral gyrus, right superior temporal gyrus and dorsal midbrain. Apart from the midbrain cluster, all between-group differences in task-related activity were retrieved in a sub-analysis including only the 14 studies on patients with focal dystonia. For focal dystonia, an additional cluster of increased sensorimotor activation emerged in the caudal cingulate motor zone. The results show that dystonia is consistently associated with abnormal somatosensory processing in the primary and secondary somatosensory cortex along with abnormal sensorimotor activation of mesial premotor and right lateral temporal cortex. Hum Brain Mapp 37:547-557, 2016. © 2015 Wiley Periodicals, Inc. PMID:26549606

  18. Cloud condensation nuclei activity of aliphatic amine secondary aerosol

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Aliphatic amines can form secondary aerosol via oxidation with atmospheric radicals (e.g. hydroxyl radical and nitrate radical). The resulting particle composition can contain both secondary organic aerosol (SOA) and inorganic salts. The fraction of organic to inorganic materials in the particulate ...

  19. The Physically Active Lifestyle of Flemish Secondary School Teachers: A Mixed-Methods Approach towards Developing a Physical Activity Intervention

    ERIC Educational Resources Information Center

    Bogaert, Inge; De Martelaer, Kristine; Deforche, Benedicte; Clarys, Peter; Zinzen, Evert

    2015-01-01

    Objective: The primary aim of this study was to describe and analyse the physical activity and sedentary levels of secondary school teachers in Flanders. A secondary aim was to collect information regarding a possible worksite intervention of special relevance to secondary school teachers. Design: Mixed-methods quantitative and qualitative…

  20. High physical activity in young children suggests positive effects by altering autoantigen-induced immune activity.

    PubMed

    Carlsson, E; Ludvigsson, J; Huus, K; Faresjö, M

    2016-04-01

    Physical activity in children is associated with several positive health outcomes such as decreased cardiovascular risk factors, improved lung function, enhanced motor skill development, healthier body composition, and also improved defense against inflammatory diseases. We examined how high physical activity vs a sedentary lifestyle in young children influences the immune response with focus on autoimmunity. Peripheral blood mononuclear cells, collected from 55 5-year-old children with either high physical activity (n = 14), average physical activity (n = 27), or low physical activity (n = 14), from the All Babies In Southeast Sweden (ABIS) cohort, were stimulated with antigens (tetanus toxoid and beta-lactoglobulin) and autoantigens (GAD65 , insulin, HSP60, and IA-2). Immune markers (cytokines and chemokines), C-peptide and proinsulin were analyzed. Children with high physical activity showed decreased immune activity toward the autoantigens GAD65 (IL-5, P < 0.05), HSP60 and IA-2 (IL-10, P < 0.05) and also low spontaneous pro-inflammatory immune activity (IL-6, IL-13, IFN-γ, TNF-α, and CCL2 (P < 0.05)) compared with children with an average or low physical activity. High physical activity in young children seems to have positive effects on the immune system by altering autoantigen-induced immune activity. PMID:25892449

  1. Possible secondary apatite fission track age standard from altered volcanic ash beds in the middle Jurassic Carmel Formation, Southwestern Utah

    USGS Publications Warehouse

    Kowallis, B.J.; Christiansen, E.H.; Everett, B.H.; Crowley, K.D.; Naeser, C.W.; Miller, D.S.; Deino, A.L.

    1993-01-01

    Secondary age standards are valuable in intra- and interlaboratory calibration. At present very few such standards are available for fission track dating that is older than Tertiary. Several altered volcanic ash beds occur in the Middle Jurassic Carmel Formation in southwestern Utah. The formation was deposited in a shallow marine/sabhka environment. Near Gunlock, Utah, eight ash beds have been identified. Sanidines from one of the ash beds (GUN-F) give a single-crystal laser-probe 40Ar/39Ar age of 166.3??0.8 Ma (2??). Apatite and zircon fission track ages range from 152-185 Ma with typically 15-20 Ma errors (2??). Track densities in zircons are high and most grains are not countable. Apatites are fairly common in most of the ash beds and have reasonable track densities ranging between 1.2-1.5 ?? 106 tracks/cm2. Track length distributions in apatites are unimodal, have standard deviations <1??m, and mean track lengths of about 14-14.5 ??m. High Cl apatites (F:Cl:OH ratio of 39:33:28) are particularly abundant and large in ash GUN-F, and are fairly easy to concentrate, but the concentrates contain some siderite, most of which can be removed by sieving. GUN-F shows evidence of some reworking and detriaal contamination based on older single grain 40Ar/39Ar analyses and some rounding of grains, but the apatite population appears to be largely uncontaminated. At present BJK has approximately 12 of apatite separate from GUN-F. ?? 1993.

  2. Altered baseline brain activity differentiates regional mechanisms subserving biological and psychological alterations in obese men

    PubMed Central

    Zhang, Bin; Tian, Derun; Yu, Chunshui; Li, Meng; Zang, Yufeng; Liu, Yijun; Walter, Martin

    2015-01-01

    Obesity as a chronic disease is a major factor for insulin resistance and Type 2 diabetes, which has become a global health problem. In the present study, we used resting state functional MRI to investigate the amplitude of low frequency fluctuations of spontaneous signal during both hunger and satiety states in 20 lean and 20 obese males. We found that, before food intake, obese men had significantly greater baseline activity in the precuneus and lesser activity in dorsal anterior cingulate cortex (dACC) relative to lean subjects. Furthermore, after food intake, obese males had significantly lesser activity in dACC than lean males. We further found a significant positive correlation between precuneus activation and hunger ratings before food intake, while dACC activity was negatively correlated with plasma insulin levels before and after food intake. These results indicated that both precuneus and dACC may play an important role in eating behavior. While precuneus rather seemed to mediate subjective satiety, dACC levels rather reflected indirect measures of glucose utilization. PMID:26099208

  3. Altered baseline brain activity differentiates regional mechanisms subserving biological and psychological alterations in obese men.

    PubMed

    Zhang, Bin; Tian, Derun; Yu, Chunshui; Li, Meng; Zang, Yufeng; Liu, Yijun; Walter, Martin

    2015-01-01

    Obesity as a chronic disease is a major factor for insulin resistance and Type 2 diabetes, which has become a global health problem. In the present study, we used resting state functional MRI to investigate the amplitude of low frequency fluctuations of spontaneous signal during both hunger and satiety states in 20 lean and 20 obese males. We found that, before food intake, obese men had significantly greater baseline activity in the precuneus and lesser activity in dorsal anterior cingulate cortex (dACC) relative to lean subjects. Furthermore, after food intake, obese males had significantly lesser activity in dACC than lean males. We further found a significant positive correlation between precuneus activation and hunger ratings before food intake, while dACC activity was negatively correlated with plasma insulin levels before and after food intake. These results indicated that both precuneus and dACC may play an important role in eating behavior. While precuneus rather seemed to mediate subjective satiety, dACC levels rather reflected indirect measures of glucose utilization. PMID:26099208

  4. 12 CFR 204.122 - Secondary market activities of international banking facilities.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 12 Banks and Banking 2 2013-01-01 2013-01-01 false Secondary market activities of international...) Interpretations § 204.122 Secondary market activities of international banking facilities. (a) Questions have been raised concerning the extent to which international banking facilities may purchase (or sell)...

  5. 12 CFR 204.122 - Secondary market activities of international banking facilities.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 12 Banks and Banking 2 2012-01-01 2012-01-01 false Secondary market activities of international...) Interpretations § 204.122 Secondary market activities of international banking facilities. (a) Questions have been raised concerning the extent to which international banking facilities may purchase (or sell)...

  6. 12 CFR 204.122 - Secondary market activities of international banking facilities.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 12 Banks and Banking 2 2014-01-01 2014-01-01 false Secondary market activities of international...) Interpretations § 204.122 Secondary market activities of international banking facilities. (a) Questions have been raised concerning the extent to which international banking facilities may purchase (or sell)...

  7. 12 CFR 204.122 - Secondary market activities of international banking facilities.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 12 Banks and Banking 2 2011-01-01 2011-01-01 false Secondary market activities of international...) Interpretations § 204.122 Secondary market activities of international banking facilities. (a) Questions have been raised concerning the extent to which international banking facilities may purchase (or sell)...

  8. 16 CFR 1211.13 - Inherent force activated secondary door sensors.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 16 Commercial Practices 2 2011-01-01 2011-01-01 false Inherent force activated secondary door... § 1211.13 Inherent force activated secondary door sensors. (a) Normal operation test. (1) A force... when the door applies a 15 pound (66.7 N) or less force in the down or closing direction and when...

  9. 16 CFR 1211.13 - Inherent force activated secondary door sensors.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 16 Commercial Practices 2 2013-01-01 2013-01-01 false Inherent force activated secondary door... § 1211.13 Inherent force activated secondary door sensors. (a) Normal operation test. (1) A force... when the door applies a 15 pound (66.7 N) or less force in the down or closing direction and when...

  10. 16 CFR 1211.13 - Inherent force activated secondary door sensors.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 16 Commercial Practices 2 2014-01-01 2014-01-01 false Inherent force activated secondary door... § 1211.13 Inherent force activated secondary door sensors. (a) Normal operation test. (1) A force... when the door applies a 15 pound (66.7 N) or less force in the down or closing direction and when...

  11. 16 CFR 1211.13 - Inherent force activated secondary door sensors.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 16 Commercial Practices 2 2012-01-01 2012-01-01 false Inherent force activated secondary door... § 1211.13 Inherent force activated secondary door sensors. (a) Normal operation test. (1) A force... when the door applies a 15 pound (66.7 N) or less force in the down or closing direction and when...

  12. 12 CFR 204.122 - Secondary market activities of international banking facilities.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 12 Banks and Banking 2 2010-01-01 2010-01-01 false Secondary market activities of international banking facilities. 204.122 Section 204.122 Banks and Banking FEDERAL RESERVE SYSTEM BOARD OF GOVERNORS OF...) Interpretations § 204.122 Secondary market activities of international banking facilities. (a) Questions have...

  13. Low molecular weight heparin restores antithrombin III activity from hyperglycemia induced alterations.

    PubMed

    Ceriello, A; Marchi, E; Palazzni, E; Quatraro, A; Giugliano, D

    1990-01-01

    Alteration of antithrombin III (ATIII) activity, glycemia level dependent, exists in diabetes mellitus. In this study the ability of a low molecular weight heparin (LMWH) (Fluxum, Alfa-Wassermann S.p.A., Bologna, Italy), as well as unfractioned héparin, to preserve ATIII activity from glucose-induced alterations, both in vitro and in vivo, is reported. The subcutaneous and intravenous LMWH and heparin administration increases basal depressed ATIII activity in diabetic patients. Heparin shows an equivalent effect on both anti-IIa and anti-Xa activity of ATIII, while LMWH is more effective in preserving the anti-Xa activity. Similarity, heparin preserves ATIII activity from hyperglycemia-induced alterations, during hyperglycemic clamp, and LMWH infusion is able to preserve a significant amount of anti-Xa activity from glucose-induced alterations. Since diabetic patients show a high incidence of thrombotic accidents, LMWH appears to be a promising innovation for the prevention of diabetic thrombophylia. PMID:2196192

  14. Chronic hyperammonemia alters the circadian rhythms of corticosteroid hormone levels and of motor activity in rats.

    PubMed

    Ahabrach, Hanan; Piedrafita, Blanca; Ayad, Abdelmalik; El Mlili, Nisrin; Errami, Mohammed; Felipo, Vicente; Llansola, Marta

    2010-05-15

    Patients with liver cirrhosis may present hepatic encephalopathy with a wide range of neurological disturbances and alterations in sleep quality and in the sleep-wake circadian rhythm. Hyperammonemia is a main contributor to the neurological alterations in hepatic encephalopathy. We have assessed, in an animal model of chronic hyperammonemia without liver failure, the effects of hyperammonemia per se on the circadian rhythms of motor activity, temperature, and plasma levels of adrenal corticosteroid hormones. Chronic hyperammonemia alters the circadian rhythms of locomotor activity and of cortisol and corticosterone levels in blood. Different types of motor activity are affected differentially. Hyperammonemia significantly alters the rhythm of spontaneous ambulatory activity, reducing strongly ambulatory counts and slightly average velocity during the night (the active phase) but not during the day, resulting in altered circadian rhythms. In contrast, hyperammonemia did not affect wheel running at all, indicating that it affects spontaneous but not voluntary activity. Vertical activity was affected only very slightly, indicating that hyperammonemia does not induce anxiety. Hyperammonemia abolished completely the circadian rhythm of corticosteroid hormones in plasma, completely eliminating the peaks of cortisol and corticosterone present in control rats at the start of the dark period. The data reported show that chronic hyperammonemia, similar to that present in patients with liver cirrhosis, alters the circadian rhythms of corticosteroid hormones and of motor activity. This suggests that hyperammonemia would be a relevant contributor to the alterations in corticosteroid hormones and in circadian rhythms in patients with liver cirrhosis. PMID:19998493

  15. Elections: Secondary Teaching Activities in the Participation Series.

    ERIC Educational Resources Information Center

    Schultz, John; Taft-Morales, Hugh

    One of a series of teacher-developed curriculum guides designed to encourage student participation and involvement in important social issues, this secondary level guide helps 7th through 12th grade English and social studies educators teach about the election process. An introductory section suggests practical considerations, means of enlisting…

  16. [Secondary Career Education Activities: Health and Physical Education.

    ERIC Educational Resources Information Center

    Radford City Schools, VA.

    The guide is one of a series developed in a pilot project to integrate career education concepts with subject matter in secondary grades. The units are designed to reveal career orientation aspects of traditional topics within five major subject areas: English, social studies, mathematics, science, and health and physical education. The lesson…

  17. Alcohol-induced alterations in dopamine modulation of prefrontal activity.

    PubMed

    Trantham-Davidson, Heather; Chandler, L Judson

    2015-12-01

    Long-term alcohol use leads to persistent cognitive deficits that may be associated with maladaptive changes in the neurocircuitry that mediates executive functions. Impairments caused by these changes can persist well into abstinence and have a negative impact on quality of life and job performance, and can increase the probability of relapse. Many of the changes that affect cognitive function appear to involve dysregulation of the mesocortical dopamine system. This includes changes in dopamine release and alterations in dopamine receptor expression and function in the medial prefrontal cortex (PFC). This review summarizes the cellular effects of acute and chronic ethanol exposure on dopamine release and dopamine receptor function in the PFC with the goal of providing greater understanding of the effects of alcohol-use disorders on the dopamine system and how this relates to deficits in the executive function of the PFC. PMID:26558348

  18. Autogenic training alters cerebral activation patterns in fMRI.

    PubMed

    Schlamann, Marc; Naglatzki, Ryan; de Greiff, Armin; Forsting, Michael; Gizewski, Elke R

    2010-10-01

    Cerebral activation patterns during the first three auto-suggestive phases of autogenic training (AT) were investigated in relation to perceived experiences. Nineteen volunteers trained in AT and 19 controls were studied with fMRI during the first steps of autogenic training. FMRI revealed activation of the left postcentral areas during AT in those with experience in AT, which also correlated with the level of AT experience. Activation of prefrontal and insular cortex was significantly higher in the group with experience in AT while insular activation was correlated with number years of simple relaxation exercises. Specific activation in subjects experienced in AT may represent a training effect. Furthermore, the correlation of insular activation suggests that these subjects are different from untrained subjects in emotional processing or self-awareness. PMID:20799123

  19. Altered Erythrocyte Glycolytic Enzyme Activities in Type-II Diabetes.

    PubMed

    Mali, Aniket V; Bhise, Sunita S; Hegde, Mahabaleshwar V; Katyare, Surendra S

    2016-07-01

    The activity of enzymes of glycolysis has been studied in erythrocytes from type-II diabetic patients in comparison with control. RBC lysate was the source of enzymes. In the diabetics the hexokinase (HK) activity increased 50 % while activities of phosphoglucoisomerase (PGI), phosphofructokinase (PFK) and aldolase (ALD) decreased by 37, 75 and 64 % respectively but were still several folds higher than that of HK. Hence, it is possible that in the diabetic erythrocytes the process of glycolysis could proceed in an unimpaired or in fact may be augmented due to increased levels of G6P. The lactate dehydrogenase (LDH) activity was comparatively high in both the groups; the diabetic group showed 85 % increase. In control group the HK, PFK and ALD activities showed strong positive correlation with blood sugar level while PGI activity did not show any correlation. In the diabetic group only PFK activity showed positive correlation. The LDH activity only in the control group showed positive correlation with marginal increase with increasing concentrations of glucose. PMID:27382204

  20. Energy Use and the Environment. Concepts & Activities for the Classroom: Secondary Social Studies Module.

    ERIC Educational Resources Information Center

    Hawaii State Dept. of Education, Honolulu. Office of Instructional Services.

    As part of a comprehensive, interdisciplinary environmental education program for elementary and secondary education in Hawaii, this teaching guide provides a variety of energy education activities for secondary social studies. An extensive introduction outlines the total program and how it fits into the general education program. It explains how…

  1. 78 FR 9048 - Agency Information Collection Activities; Elementary-Secondary Staff Information Report...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-07

    ... information collection--extension without change: The Elementary-Secondary Staff Information Report (EEO- 5). (77 FR 65548, October 29, 2012). No requests to present oral testimony at a hearing concerning the... COMMISSION Agency Information Collection Activities; Elementary-Secondary Staff Information...

  2. Complement Activation in Trauma Patients Alters Platelet Function.

    PubMed

    Atefi, Gelareh; Aisiku, Omozuanvbo; Shapiro, Nathan; Hauser, Carl; Dalle Lucca, Jurandir; Flaumenhaft, Robert; Tsokos, George C

    2016-09-01

    Trauma remains the main cause of death for both civilians and those in uniform. Trauma-associated coagulopathy is a complex process involving inflammation, coagulation, and platelet dysfunction. It is unknown whether activation of complement, which occurs invariably in trauma patients, is involved in the expression of trauma-associated coagulopathy. We designed a prospective study in which we enrolled 40 trauma patients and 30 healthy donors upon arrival to the emergency department of BIDMC. Platelets from healthy individuals were incubated with sera from trauma patients and their responsiveness to a thrombin receptor-activating peptide was measured using aggregometry. Complement deposition on platelets from trauma patients was measured by flow cytometry. Normal platelets displayed hypoactivity after incubation with trauma sera even though exposure to trauma sera resulted in increased agonist-induced calcium flux. Depletion of complement from sera further blocked activation of hypoactive platelets. Conversely, complement activation increased aggregation of platelets. Platelets from trauma patients were found to have significantly higher amounts of C3a and C4d on their surface compared with platelets from controls. Depletion of complement (C4d, C3a) reversed the ability of trauma sera to augment agonist-induced calcium flux in donor platelets. Our data indicate that complement enhances platelet aggregation. Despite its complement content, trauma sera render platelets hypoactive and complement depletion further blocks activation of hypoactive platelets. The defect in platelet activation induced by trauma sera is distal to receptor activation since agonist-induced Ca2+ flux is elevated in the presence of trauma sera owing to complement deposition. PMID:27355402

  3. Compendium of Interdisciplinary Activities for an Introductory Course in Communication Systems at the Secondary Level.

    ERIC Educational Resources Information Center

    Lasko, David J.

    This compendium of interdisciplinary learning activities is designed to assist technology education instructors who are conducting an introductory secondary-level course in communication technology. The 12 activities, which are sequenced from introductory, low-cost activities to more advanced and more involved activities, deal with the following…

  4. Altered Error-Related Activity in Patients with Schizophrenia

    ERIC Educational Resources Information Center

    Koch, Kathrin; Wagner, Gerd; Schultz, Christoph; Schachtzabel, Claudia; Nenadic, Igor; Axer, Martina; Reichenbach, Jurgen R.; Sauer, Heinrich; Schlosser, Ralf G. M.

    2009-01-01

    Deficits in working memory (WM) and executive cognitive control are core features of schizophrenia. However, findings regarding functional activation strengths are heterogeneous, partly due to differences in task demands and behavioral performance. Previous investigators proposed integrating these heterogeneous findings into a comprehensive model…

  5. Silver and Gold Nanoparticles Alter Cathepsin Activity In vitro

    NASA Astrophysics Data System (ADS)

    Speshock, Janice L.; Braydich-Stolle, Laura K.; Szymanski, Eric R.; Hussain, Saber M.

    2011-12-01

    Nanomaterials are being incorporated into many biological applications for use as therapeutics, sensors, or labels. Silver nanomaterials are being utilized for biological implants and wound dressings as an antiviral material, whereas gold nanomaterials are being used as biological labels or sensors due to their surface properties and biocompatibility. Cytotoxicity data of these materials are becoming more prevalent; however, little research has been performed to understand how the introduction of these materials into cells affects cellular processes. Here, we demonstrate the impact that silver and gold nanoparticles have on cathepsin activity in vitro. Cathepsins are important cellular proteases that are imperative for proper immune system function. We have selected to examine gold and silver nanoparticles due to the increased use of these materials in biological applications. This manuscript depicts how both of these types of nanomaterials affect cathepsin activity, which could impact the host's immune system and its ability to respond to pathogens. Cathepsin B activity decreases in a dose-dependent manner with all nanoparticles tested. Alternatively, the impact of nanoparticles on cathepsin L activity depends greatly on the type and size of the material.

  6. MICROBIOLOGICAL ALTERATIONS IN DISTRIBUTED WATER TREATED WITH GRANULAR ACTIVATED CARBON

    EPA Science Inventory

    The goal of this project was to examine the effect of granular activated carbon (GAC) treatment on the microbiological characteristics of potable water in distribution systems. Data was collected from both field and pilot plant studies. Field monitoring studies from two water tre...

  7. Acute neuroactive drug exposures alter locomotor activity in larval zebrafish

    EPA Science Inventory

    In an effort to develop a rapid in vivo screen for EPA's prioritization of toxic chemicals, we are characterizing the locomotor activity of zebrafish (Danio rerio) larvae after exposure to prototypic drugs that act on the central nervous system. MPTP (1-methyl-4phenyl- 1 ,2,3,6-...

  8. Acute Neuroactive Drug Exposures alter Locomotor Activity in Larval Zebrafish

    EPA Science Inventory

    As part of the development of a rapid in vivo screen for prioritization of toxic chemicals, we have begun to characterize the locomotor activity of zebrafish (Danio rerio) larvae by assessing the acute effects of prototypic drugs that act on the central nervous system. Initially,...

  9. 78 FR 37528 - Agency Information Collection Activities; Comment Request; Elementary and Secondary Improvement...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-21

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF EDUCATION Agency Information Collection Activities; Comment Request; Elementary and Secondary Improvement Formula... Improvement Formula Grants. OMB Control Number: 1810-0682. Type of Review: An extension of an...

  10. Japan in the Classroom: Elementary and Secondary Activities.

    ERIC Educational Resources Information Center

    Johnson, Jacquelyn; Parisi, Lynn S.

    The activities in this book focus on teaching about Japan within the context of larger social science units. Several of the lessons can be taught within the context of the humanities and fine arts. The book's 18 classroom activities are organized into three sections. Section 1, "Society and Culture," contains four activities in which students…

  11. Investigations of fungal secondary metabolites with potential anticancer activity.

    PubMed

    Balde, ElHadj Saidou; Andolfi, Anna; Bruyère, Céline; Cimmino, Alessio; Lamoral-Theys, Delphine; Vurro, Maurizio; Damme, Marc Van; Altomare, Claudio; Mathieu, Véronique; Kiss, Robert; Evidente, Antonio

    2010-05-28

    Fourteen metabolites, isolated from phytopathogenic and toxigenic fungi, were evaluated for their in vitro antigrowth activity for six distinct cancer cell lines, using the MTT colorimetric assay. Bislongiquinolide (1) and dihydrotrichodimerol (5), which belong to the bisorbicillinoid structural class, displayed significant growth inhibitory activity against the six cancer cell lines studied, while the remaining compounds displayed weak or no activity. The data show that 1 and 5 have similar growth inhibitory activities with respect to those cancer cell lines that display certain levels of resistance to pro-apoptotic stimuli or those that are sensitive to apoptosis. Quantitative videomicroscopy analysis revealed that 1 and 5 exert their antiproliferative effect through cytostatic and not cytotoxic activity. The preliminary results from the current study have stimulated further structure-activity investigations with respect to the growth inhibitory activity of compounds belonging to the bisorbicillinoid group. PMID:20415482

  12. Electrocatalytic activity of phthalocyanines in secondary lithium cells

    SciTech Connect

    Wohrle, D.; Kirchenmann, M.

    1985-05-01

    The feasibility of cathodes containing low molecular unsubstituted phthalocyanines in secondary lithium cells was studied by Yamaki and Yamaji. They reported values of discharge capacities of more than 17 electrons per molecule of phthalocyanine requiring the intercalation of the equivalent number of charge compensating lithium cations. The extensive literature concerning the properties of phthalocyanines, namely, electrochemical and chemical redox equilibria, suggests a reversible reduction of up to four electrons per molecule. The apparent discrepancies gave rise to a more detailed investigation of the electrochemistry of the cell. At the same time, the properties of low molecular copper octacyanophthalocyanine 2 and copperpolyphthalocyanine 3 were tested in the same cell reaction. The structures of the compounds are given.

  13. Alterations in electrodermal activity and cardiac parasympathetic tone during hypnosis.

    PubMed

    Kekecs, Zoltán; Szekely, Anna; Varga, Katalin

    2016-02-01

    Exploring autonomic nervous system (ANS) changes during hypnosis is critical for understanding the nature and extent of the hypnotic phenomenon and for identifying the mechanisms underlying the effects of hypnosis in different medical conditions. To assess ANS changes during hypnosis, electrodermal activity and pulse rate variability (PRV) were measured in 121 young adults. Participants either received hypnotic induction (hypnosis condition) or listened to music (control condition), and both groups were exposed to test suggestions. Blocks of silence and experimental sound stimuli were presented at baseline, after induction, and after de-induction. Skin conductance level (SCL) and high frequency (HF) power of PRV measured at each phase were compared between groups. Hypnosis decreased SCL compared to the control condition; however, there were no group differences in HF power. Furthermore, hypnotic suggestibility did not moderate ANS changes in the hypnosis group. These findings indicate that hypnosis reduces tonic sympathetic nervous system activity, which might explain why hypnosis is effective in the treatment of disorders with strong sympathetic nervous system involvement, such as rheumatoid arthritis, hot flashes, hypertension, and chronic pain. Further studies with different control conditions are required to examine the specificity of the sympathetic effects of hypnosis. PMID:26488759

  14. Postnatal foraging demands alter adrenocortical activity and psychosocial development.

    PubMed

    Lyons, D M; Kim, S; Schatzberg, A F; Levine, S

    1998-05-01

    Mother squirrel monkeys stop carrying infants at earlier ages in high-demand (HD) conditions where food is difficult to find relative to low-demand (LD) conditions. To characterize these transitions in psychosocial development, from 10- to 21-weeks postpartum we collected measures of behavior, adrenocortical activity, and social transactions coded for initiator (mother or infant), goal (make-contact or break-contact), and outcome (success or failure). Make-contact attempts were most often initiated by HD infants, but mothers often opposed these attempts and less than 50% were successful. Break-contact attempts were most often initiated by LD infants, but mothers often opposed these attempts and fewer LD than HD infant break-contact attempts were successful. Plasma levels of cortisol were significantly higher in HD than LD mothers, but differences in adrenocortical activity were less consistent in their infants. HD and LD infants also spent similar amounts of time nursing on their mothers and feeding on solid foods. By rescheduling some transitions in development (carry-->self-transport), and not others (nursing-->self-feeding), mothers may have partially protected infants from the immediate impact of an otherwise stressful foraging task. PMID:9589217

  15. Microglia mechanics: immune activation alters traction forces and durotaxis

    PubMed Central

    Bollmann, Lars; Koser, David E.; Shahapure, Rajesh; Gautier, Hélène O. B.; Holzapfel, Gerhard A.; Scarcelli, Giuliano; Gather, Malte C.; Ulbricht, Elke; Franze, Kristian

    2015-01-01

    Microglial cells are key players in the primary immune response of the central nervous system. They are highly active and motile cells that chemically and mechanically interact with their environment. While the impact of chemical signaling on microglia function has been studied in much detail, the current understanding of mechanical signaling is very limited. When cultured on compliant substrates, primary microglial cells adapted their spread area, morphology, and actin cytoskeleton to the stiffness of their environment. Traction force microscopy revealed that forces exerted by microglia increase with substrate stiffness until reaching a plateau at a shear modulus of ~5 kPa. When cultured on substrates incorporating stiffness gradients, microglia preferentially migrated toward stiffer regions, a process termed durotaxis. Lipopolysaccharide-induced immune-activation of microglia led to changes in traction forces, increased migration velocities and an amplification of durotaxis. We finally developed a mathematical model connecting traction forces with the durotactic behavior of migrating microglial cells. Our results demonstrate that microglia are susceptible to mechanical signals, which could be important during central nervous system development and pathologies. Stiffness gradients in tissue surrounding neural implants such as electrodes, for example, could mechanically attract microglial cells, thus facilitating foreign body reactions detrimental to electrode functioning. PMID:26441534

  16. New Aquatic Activities and Games for Secondary Physical Education

    ERIC Educational Resources Information Center

    Banks, Aaron; Reimann, Bonnie

    2012-01-01

    The purpose of this article is to provide educators with usable, nontraditional aquatic activities that can be adapted for swimmers and non-swimmers alike. Educators are oriented to a variety of aquatic techniques designed to challenge both health- and skill-related fitness components. By using a series of activity cards, the authors have blended…

  17. Japan in the Classroom: Elementary and Secondary Activities, Revised Edition.

    ERIC Educational Resources Information Center

    Parisi, Lynn; And Others

    This activity book is designed to present information and insights on Japanese culture and society. Because few teachers can devote entire units to the study of Japan, the activities focus on teaching about Japan within the context of larger social science units. Some of the lessons can be taught within the context of the humanities and fine arts,…

  18. Life Skills Activities for Secondary Students with Special Needs.

    ERIC Educational Resources Information Center

    Mannix, Darlene

    This resource for life skills activities for adolescents with special needs covers aspects of interpersonal relationships, communication skills, academic and school skills, practical living skills, vocational skills, problem-solving skills, and lifestyle choices. Included are 190 illustrated activity sheets with related exercises, discussion…

  19. Physical Activity & Sport for the Secondary School Student. Fifth Edition.

    ERIC Educational Resources Information Center

    Dougherty, Neil J., Ed.

    This collection of papers offers a comprehensive text about contemporary physical activities and sports forms. It provides students with an overview of the various physical activities, skill technique required, safety, scoring, rules and etiquette, strategies, equipment, and related terminology. The 26 papers are: (1) "Physical Fitness" (Carolyn…

  20. Altered behaviour in spotted hyenas associated with increased human activity

    USGS Publications Warehouse

    Boydston, E.E.; Kapheim, K.M.; Watts, H.E.; Szykman, M.; Holekamp, K.E.

    2003-01-01

    To investigate how anthropogenic activity might affect large carnivores, we studied the behaviour of spotted hyenas (Crocuta crocuta) during two time periods. From 1996 to 1998, we documented the ecological correlates of space utilization patterns exhibited by adult female hyenas defending a territory at the edge of a wildlife reserve in Kenya. Hyenas preferred areas near dense vegetation but appeared to avoid areas containing the greatest abundance of prey, perhaps because these were also the areas of most intensive livestock grazing. We then compared hyena behaviour observed in 1996-98 with that observed several years earlier and found many differences. Female hyenas in 1996-98 were found farther from dens, but closer to dense vegetation and to the edges of their territory, than in 1988-90. Recent females also had larger home ranges, travelled farther between consecutive sightings, and were more nocturnal than in 1988-90. Finally, hyenas occurred in smaller groups in 1996-98 than in 1988-90. We also found several changes in hyena demography between periods. We next attempted to explain differences observed between time periods by testing predictions of hypotheses invoking prey abundance, climate, interactions with lions, tourism and livestock grazing. Our data were consistent with the hypothesis that increased reliance on the reserve for livestock grazing was responsible for observed changes. That behavioural changes were not associated with decreased hyena population density suggests the behavioural plasticity typical of this species may protect it from extinction. ?? 2003 The Zoological Society of London.

  1. Altered host behaviour and brain serotonergic activity caused by acanthocephalans: evidence for specificity

    PubMed Central

    Tain, Luke; Perrot-Minnot, Marie-Jeanne; Cézilly, Frank

    2006-01-01

    Manipulative parasites can alter the phenotype of intermediate hosts in various ways. However, it is unclear whether such changes are just by-products of infection or adaptive and enhance transmission to the final host. Here, we show that the alteration of serotonergic activity is functionally linked to the alteration of specific behaviour in the amphipod Gammarus pulex infected with acanthocephalan parasites. Pomphorhynchus laevis and, to a lesser extent, Pomphorhynchus tereticollis altered phototactism, but not geotactism, in G. pulex, whereas the reverse was true for Polymorphus minutus. Serotonin (5-hydroxytryptamine, 5-HT) injected to uninfected G. pulex mimicked the altered phototactism, but had no effect on geotactism. Photophilic G. pulex infected with P. laevis or P. tereticollis showed a 40% increase in brain 5-HT immunoreactivity compared to photophobic, uninfected individuals. In contrast, brain 5-HT immunoreactivity did not differ between P. minutus-infected and uninfected G. pulex. Finally, brain 5-HT immunoreactivity differed significantly among P. tereticollis-infected individuals in accordance with their degree of manipulation. Our results demonstrate that altered 5-HT activity is not the mere consequence of infection by acanthocephalans but is specifically linked to the disruption of host photophobic behaviour, whereas the alteration of other behaviours such as geotactism may rely on distinct physiological routes. PMID:17015346

  2. CHARACTERIZATION ADN BIOLOGICAL ACTIVITY OF SECONDARY METABOLITES FROM ARMILLARIA TABESCENS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Ethyl acetate extracts from liquid cultures of Armillaria tabescens showed good antimicrobial activity against Candida albicans, Cryptococcus neoformans, Escherichia coli and Mycobacterium intracellulare. Chemical analyses of extract constituents led to the isolation and identification of two new co...

  3. Calcium alloy as active material in secondary electrochemical cell

    DOEpatents

    Roche, Michael F.; Preto, Sandra K.; Martin, Allan E.

    1976-01-01

    Calcium alloys such as calcium-aluminum and calcium-silicon, are employed as active material within a rechargeable negative electrode of an electrochemical cell. Such cells can use a molten salt electrolyte including calcium ions and a positive electrode having sulfur, sulfides, or oxides as active material. The calcium alloy is selected to prevent formation of molten calcium alloys resulting from reaction with the selected molten electrolytic salt at the cell operating temperatures.

  4. Quantification of primary versus secondary C-H bond cleavage in alkane activation: Propane on Pt

    SciTech Connect

    Weinberg, W.H.; Sun, Yongkui )

    1991-08-02

    The trapping-mediated dissociative chemisorption of three isotopes of propane (C{sub 3}H{sub 8}, CH{sub 3}, CD{sub 2}CH{sub 3}, and C{sub 3}D{sub 8}) has been investigated on the Pt(110)-(1 {times} 2) surface, and both the apparent activation energies and the preexponential factors of the surface reaction rate coefficients have been measured. In addition, the probabilities of primary and secondary C-H bond cleavage for alkane activation on a surface were evaluated. The activation energy for primary C-H bond cleavage was 425 calories per mole greater than that of secondary C-H bond cleavage, and the two true activation energies that embody the single measured activation energy were determined for each of the three isotopes. Secondary C-H bond cleavage is also preferred on entropic grounds, and the magnitude of the effect was quantified.

  5. ALTERATIONS IN CALCIUM ION ACTIVITY BY ELF AND RF ELECTROMAGNETIC FIELDS

    EPA Science Inventory



    Alterations in calcium ion activity by ELF and RF electromagnetic fields

    Introduction

    Calcium ions play many important roles in biological systems. For example, calcium ion activity can be used as an indicator of second-messenger signal-transduction processe...

  6. Secondary Path Modeling Method for Active Noise Control of Power Transformer

    NASA Astrophysics Data System (ADS)

    Zhao, Tong; Liang, Jiabi; Liang, Yuanbin; Wang, Lixin; Pei, Xiugao; Li, Peng

    The accuracy of the secondary path modeling is critical to the stability of active noise control system. On condition of knowing the input and output of the secondary path, system identification theory can be used to identify the path. Based on the experiment data, correlation analysis is adopted to eliminate the random noise and nonlinear harmonic in the output data in order to obtain the accurate frequency characteristic of the secondary path. After that, Levy's Method is applied to identify the transfer function of the path. Computer simulation results are given respectively, both showing the proposed off-line modeling method is feasible and applicable. At last, Levy's Method is used to attain an accurate secondary path model in the active control of transformer noise experiment and achieves to make the noise sound level decrease about 10dB.

  7. Springboards into Holocaust: Five Activities for Secondary Social Studies Students.

    ERIC Educational Resources Information Center

    Allen, Rodney

    2000-01-01

    Explains that in a study of the Holocaust teachers must connect the stories of the Holocaust to the lives of their students. Provides five activities about the Holocaust that focus upon teaching tolerance. Addresses the children of the Holocaust, difference versus deviance, social identity, and The Night of Broken Glass. (CMK)

  8. Extra-Curricular Activities and Academic Performance in Secondary Students

    ERIC Educational Resources Information Center

    Moriana, Juan Antonio; Alos, Francisco; Alcala, Rocio; Pino, Maria-Jose; Herruzo, Javier; Ruiz, Rosario

    2006-01-01

    Introduction: In this paper we study the possible influence of extra-curricular activities (study-related and/or sports) on academic performance of first- and second-year pupils in "Educacion Secundaria Obligatoria (ESO)" [N.T. seventh- and eighth-graders]. Method: We randomly selected 12 schools in the city (9 public and 3 private), and randomly…

  9. Setting the Stage for Physical Activity for Secondary Students

    ERIC Educational Resources Information Center

    Ciccomascolo, Lori; Riebe, Deborah

    2006-01-01

    Despite the positive long-term physiological and psychological effects of exercise, many young adults between the ages of 12 and 21 years do not participate in regular physical activity. With the time constraints and other challenges in teaching and assessing students, physical educators need realistic strategies that will help in their efforts to…

  10. Assessing Environmental Impact: A Secondary School Learning Activity

    ERIC Educational Resources Information Center

    Nous, Albert P.

    This packet contains information on teaching about environmental impact. Background information is included on the role of environmental impact on our society and environmental risk is also discussed. Environmental impacts are studied using Stages of Assessment. Learning activities and seven lesson plans include: (1) "The Community Initiative";…

  11. Metabolic alterations induced in cultured skeletal muscle by stretch-relaxation activity

    NASA Technical Reports Server (NTRS)

    Hatfaludy, Sophia; Shansky, Janet; Vandenburgh, Herman H.

    1989-01-01

    Muscle cells differentiated in vitro are repetitively stretched and relaxed in order to determine the presence of short- and long-term alterations occurring in glucose uptake and lactate efflux that are similar to the metabolic alterations occurring in stimulated organ-cultured muscle and in vivo skeletal muscle during the active state. It is observed that whereas mechanical stimulation increases these metabolic parameters within 4-6 h of starting activity, unstimulated basal rates in control cultures also increase during this period of time, and by 8 h, their rates have reached or exceeded the rates in continuously stimulated cells. Measurements of these parameters in media of different compositions show that activity-induced long-term alterations in the parameters occur independently of growth factors in serium and embryo extracts.

  12. Diversity of Secondary Metabolites from Marine Bacillus Species: Chemistry and Biological Activity

    PubMed Central

    Mondol, Muhammad Abdul Mojid; Shin, Hee Jae; Islam, Mohammad Tofazzal

    2013-01-01

    Marine Bacillus species produce versatile secondary metabolites including lipopeptides, polypeptides, macrolactones, fatty acids, polyketides, and isocoumarins. These structurally diverse compounds exhibit a wide range of biological activities, such as antimicrobial, anticancer, and antialgal activities. Some marine Bacillus strains can detoxify heavy metals through reduction processes and have the ability to produce carotenoids. The present article reviews the chemistry and biological activities of secondary metabolites from marine isolates. Side by side, the potential for application of these novel natural products from marine Bacillus strains as drugs, pesticides, carotenoids, and tools for the bioremediation of heavy metal toxicity are also discussed. PMID:23941823

  13. Diversity of secondary metabolites from marine Bacillus species: chemistry and biological activity.

    PubMed

    Mondol, Muhammad Abdul Mojid; Shin, Hee Jae; Islam, Mohammad Tofazzal

    2013-08-01

    Marine Bacillus species produce versatile secondary metabolites including lipopeptides, polypeptides, macrolactones, fatty acids, polyketides, and isocoumarins. These structurally diverse compounds exhibit a wide range of biological activities, such as antimicrobial, anticancer, and antialgal activities. Some marine Bacillus strains can detoxify heavy metals through reduction processes and have the ability to produce carotenoids. The present article reviews the chemistry and biological activities of secondary metabolites from marine isolates. Side by side, the potential for application of these novel natural products from marine Bacillus strains as drugs, pesticides, carotenoids, and tools for the bioremediation of heavy metal toxicity are also discussed. PMID:23941823

  14. Dynamic transcription factor activity networks in response to independently altered mechanical and adhesive microenvironmental cues.

    PubMed

    Peñalver Bernabé, Beatriz; Shin, Seungjin; Rios, Peter D; Broadbelt, Linda J; Shea, Lonnie D; Seidlits, Stephanie K

    2016-08-01

    Multiple aspects of the local extracellular environment profoundly affect cell phenotype and function. Physical and chemical cues in the environment trigger intracellular signaling cascades that ultimately activate transcription factors (TFs) - powerful regulators of the cell phenotype. TRACER (TRanscriptional Activity CEll aRrays) was employed for large-scale, dynamic quantification of TF activity in human fibroblasts cultured on hydrogels with a controlled elastic modulus and integrin ligand density. We identified three groups of TFs: responders to alterations in ligand density alone, substrate stiffness or both. Dynamic networks of regulatory TFs were constructed computationally and revealed distinct TF activity levels, directionality (i.e., activation or inhibition), and dynamics for adhesive and mechanical cues. Moreover, TRACER networks predicted conserved hubs of TF activity across multiple cell types, which are significantly altered in clinical fibrotic tissues. Our approach captures the distinct and overlapping effects of adhesive and mechanical stimuli, identifying conserved signaling mechanisms in normal and disease states. PMID:27470442

  15. Secondary School Students' Physical Activity Participation across Physical Education Classes: The Expectancy-Value Theory Approach

    ERIC Educational Resources Information Center

    Gråstén, Arto; Watt, Anthony; Hagger, Martin; Jaakkola, Timo; Liukkonen, Jarmo

    2015-01-01

    The primary purpose of this study was to analyze the link between students' expectancy beliefs, subjective task values, out-of-school activity, and moderate to vigorous physical activity (MVPA) participation across secondary school physical education (PE) classes. The sample comprised 96 students (58 girls, 38 boys; Mage = 15.03, SD = 0.94) from…

  16. 16 CFR 1211.13 - Inherent force activated secondary door sensors.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... sensors. 1211.13 Section 1211.13 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT... § 1211.13 Inherent force activated secondary door sensors. (a) Normal operation test. (1) A force activated door sensor of a door system installed according to the installation instructions shall...

  17. Stable Isotope Signatures of Middle Palaeozoic Ahermatypic Rugose Corals – Deciphering Secondary Alteration, Vital Fractionation Effects, and Palaeoecological Implications

    PubMed Central

    Jakubowicz, Michal; Berkowski, Blazej; López Correa, Matthias; Jarochowska, Emilia; Joachimski, Michael; Belka, Zdzislaw

    2015-01-01

    This study investigates stable isotope signatures of five species of Silurian and Devonian deep-water, ahermatypic rugose corals, providing new insights into isotopic fractionation effects exhibited by Palaeozoic rugosans, and possible role of diagenetic processes in modifying their original isotopic signals. To minimize the influence of intraskeletal cements on the observed signatures, the analysed specimens included unusual species either devoid of large intraskeletal open spaces ('button corals': Microcyclus, Palaeocyclus), or typified by particularly thick corallite walls (Calceola). The corals were collected at four localities in the Holy Cross Mountains (Poland), Mader Basin (Morocco) and on Gotland (Sweden), representing distinct diagenetic histories and different styles of diagenetic alteration. To evaluate the resistance of the corallites to diagenesis, we applied various microscopic and trace element preservation tests. Distinct differences between isotopic compositions of the least-altered and most-altered skeleton portions emphasise a critical role of material selection for geochemical studies of Palaeozoic corals. The least-altered parts of the specimens show marine or near-marine stable isotope signals and lack positive correlation between δ13C and δ18O. In terms of isotopic fractionation mechanisms, Palaeozoic rugosans must have differed considerably from modern deep-water scleractinians, typified by significant depletion in both 18O and 13C, and pronounced δ13C-δ18O co-variance. The fractionation effects exhibited by rugosans seem similar rather to the minor isotopic effects typical of modern non-scleractinian corals (octocorals and hydrocorals). The results of the present study add to growing evidence for significant differences between Scleractinia and Rugosa, and agree with recent studies indicating that calcification mechanisms developed independently in these two groups of cnidarians. Consequently, particular caution is needed in using

  18. Prediction of adolescents doing physical activity after completing secondary education.

    PubMed

    Moreno-Murcia, Juan Antonio; Huéscar, Elisa; Cervelló, Eduardo

    2012-03-01

    The purpose of this study, based on the self-determination theory (Ryan & Deci, 2000) was to test the prediction power of student's responsibility, psychological mediators, intrinsic motivation and the importance attached to physical education in the intention to continue to practice some form of physical activity and/or sport, and the possible relationships that exist between these variables. We used a sample of 482 adolescent students in physical education classes, with a mean age of 14.3 years, which were measured for responsibility, psychological mediators, sports motivation, the importance of physical education and intention to be physically active. We completed an analysis of structural equations modelling. The results showed that the responsibility positively predicted psychological mediators, and this predicted intrinsic motivation, which positively predicted the importance students attach to physical education, and this, finally, positively predicted the intention of the student to continue doing sport. Results are discussed in relation to the promotion of student's responsibility towards a greater commitment to the practice of physical exercise. PMID:22379700

  19. Alteration of prolyl oligopeptidase and activated α-2-macroglobulin in multiple sclerosis subtypes and in the clinically isolated syndrome.

    PubMed

    Tenorio-Laranga, Jofre; Peltonen, Iida; Keskitalo, Salla; Duran-Torres, Gilberto; Natarajan, Renuka; Männistö, Pekka T; Nurmi, Antti; Vartiainen, Nina; Airas, Laura; Elovaara, Irina; García-Horsman, J Arturo

    2013-06-15

    Prolyl oligopeptidase (PREP) has been considered as a drug target for the treatment of neurodegenerative diseases. In plasma, PREP has been found altered in several disorders of the central nervous system including multiple sclerosis (MS). Oxidative stress and the levels of an endogenous plasma PREP inhibitor have been proposed to decrease PREP activity in MS. In this work, we measured the circulating levels of PREP in patients suffering of relapsing remitting (RR), secondary progressive (SP), primary progressive (PP) MS, and in subjects with clinically isolated syndrome (CIS). We found a significantly lower PREP activity in plasma of RRMS as well as in PPMS patients and a trend to reduced activity in subjects diagnosed with CIS, compared to controls. No signs of oxidative inactivation of PREP, and no correlation with the endogenous PREP inhibitor, identified as activated α-2-macroglobulin (α2M*), were observed in any of the patients studied. However, a significant decrease of α2M* was recorded in MS. In cell cultures, we found that PREP specifically stimulates immune active cells possibly by modifying the levels of fibrinogen β, thymosin β4, and collagen. Our results open new lines of research on the role of PREP and α2M* in MS, aiming to relate them to the diagnosis and prognosis of this devastating disease. PMID:23643808

  20. Influenza matrix protein 2 alters CFTR expression and function through its ion channel activity

    PubMed Central

    Londino, James D.; Lazrak, Ahmed; Jurkuvenaite, Asta; Collawn, James F.; Noah, James W.

    2013-01-01

    The human cystic fibrosis transmembrane conductance regulator (CFTR) is a cyclic AMP-activated chloride (Cl−) channel in the lung epithelium that helps regulate the thickness and composition of the lung epithelial lining fluid. We investigated whether influenza M2 protein, a pH-activated proton (H+) channel that traffics to the plasma membrane of infected cells, altered CFTR expression and function. M2 decreased CFTR activity in 1) Xenopus oocytes injected with human CFTR, 2) epithelial cells (HEK-293) stably transfected with CFTR, and 3) human bronchial epithelial cells (16HBE14o−) expressing native CFTR. This inhibition was partially reversed by an inhibitor of the ubiquitin-activating enzyme E1. Next we investigated whether the M2 inhibition of CFTR activity was due to an increase of secretory organelle pH by M2. Incubation of Xenopus oocytes expressing CFTR with ammonium chloride or concanamycin A, two agents that alkalinize the secretory pathway, inhibited CFTR activity in a dose-dependent manner. Treatment of M2- and CFTR-expressing oocytes with the M2 ion channel inhibitor amantadine prevented the loss in CFTR expression and activity; in addition, M2 mutants, lacking the ability to transport H+, did not alter CFTR activity in Xenopus oocytes and HEK cells. Expression of an M2 mutant retained in the endoplasmic reticulum also failed to alter CFTR activity. In summary, our data show that M2 decreases CFTR activity by increasing secretory organelle pH, which targets CFTR for destruction by the ubiquitin system. Alteration of CFTR activity has important consequences for fluid regulation and may potentially modify the immune response to viral infection. PMID:23457187

  1. Altered Neural Activity Associated with Mindfulness during Nociception: A Systematic Review of Functional MRI

    PubMed Central

    Bilevicius, Elena; Kolesar, Tiffany A.; Kornelsen, Jennifer

    2016-01-01

    Objective: To assess the neural activity associated with mindfulness-based alterations of pain perception. Methods: The Cochrane Central, EMBASE, Ovid Medline, PsycINFO, Scopus, and Web of Science databases were searched on 2 February 2016. Titles, abstracts, and full-text articles were independently screened by two reviewers. Data were independently extracted from records that included topics of functional neuroimaging, pain, and mindfulness interventions. Results: The literature search produced 946 total records, of which five met the inclusion criteria. Records reported pain in terms of anticipation (n = 2), unpleasantness (n = 5), and intensity (n = 5), and how mindfulness conditions altered the neural activity during noxious stimulation accordingly. Conclusions: Although the studies were inconsistent in relating pain components to neural activity, in general, mindfulness was able to reduce pain anticipation and unpleasantness ratings, as well as alter the corresponding neural activity. The major neural underpinnings of mindfulness-based pain reduction consisted of altered activity in the anterior cingulate cortex, insula, and dorsolateral prefrontal cortex. PMID:27104572

  2. Physical Activity Patterns and Psychological Correlates of Physical Activity among Singaporean Primary, Secondary, and Junior College Students

    ERIC Educational Resources Information Center

    Wang, C. K. John; Koh, K. T.; Biddle, Stuart J. H.; Liu, W. C.; Chye, Stefanie

    2011-01-01

    The purpose of this research was to examine physical activity patterns and psychological correlates of physical activity among primary, secondary, and junior college students in Singapore. A sample of 3,333 school students aged 10 to 18 years took part in the study. Results showed that the younger students had significantly higher physical…

  3. Alternative complement pathway and factor B activities in rats with altered blood levels of thyroid hormone

    PubMed Central

    Bitencourt, C.S.; Duarte, C.G.; Azzolini, A.E.C.S.; Assis-Pandochi, A.I.

    2012-01-01

    Evaluating the activity of the complement system under conditions of altered thyroid hormone levels might help elucidate the role of complement in triggering autoimmune processes. Here, we investigated alternative pathway (AP) activity in male Wistar rats (180 ± 10 g) after altering their thyroid hormone levels by treatment with triiodothyronine (T3), propylthiouracil (PTU) or thyroidectomy. T3 and thyroxine (T4) levels were determined by chemiluminescence assays. Hemolytic assays were performed to evaluate the lytic activity of the AP. Factor B activity was evaluated using factor B-deficient serum. An anti-human factor B antibody was used to measure factor B levels in serum by radial immunodiffusion. T3 measurements in thyroidectomized animals or animals treated with PTU demonstrated a significant reduction in hormone levels compared to control. The results showed a reduction in AP lytic activity in rats treated with increasing amounts of T3 (1, 10, or 50 µg). Factor B activity was also decreased in the sera of hyperthyroid rats treated with 1 to 50 µg T3. Additionally, treating rats with 25 µg T3 significantly increased factor B levels in their sera (P < 0.01). In contrast, increased factor B concentration and activity (32%) were observed in hypothyroid rats. We conclude that alterations in thyroid hormone levels affect the activity of the AP and factor B, which may in turn affect the roles of AP and factor B in antibody production. PMID:22370704

  4. Antifeedant Activity of Ginkgo biloba Secondary Metabolites against Hyphantria cunea Larvae: Mechanisms and Applications.

    PubMed

    Pan, Long; Ren, Lili; Chen, Fang; Feng, Yuqian; Luo, Youqing

    2016-01-01

    Ginkgo biloba is a typical relic plant that rarely suffers from pest hazards. This study analyzed the pattern of G. biloba pest hazards in Beijing; tested the antifeedant activity of G. biloba extracts, including ginkgo flavonoids, ginkgolide, and bilobalide, against Hyphantria cunea larvae; determined the activities of glutathione transferase (GSTs), acetylcholinesterase (AChE), carboxylesterase (CarE) and mixed-functional oxidase (MFO), in larvae after feeding on these G. biloba secondary metabolites; and screened for effective botanical antifeedants in the field. In this study, no indicators of insect infestation were found for any of the examined leaves of G. biloba; all tested secondary metabolites showed significant antifeedant activity and affected the activity of the four larval detoxifying enzymes. Ginkgolide had the highest antifeedant activity and the most significant effect on the detoxifying enzymes (P<0.05). Spraying leaves with G. biloba extracts or ginkgolide both significantly repelled H. cunea larvae in the field (P<0.05), although the former is more economical and practical. This study investigated the antifeedant activity of G. biloba secondary metabolites against H. cunea larvae, and the results provide new insights into the mechanism of G. biloba pest resistance. This study also developed new applications of G. biloba secondary metabolites for effective pest control. PMID:27214257

  5. Antifeedant Activity of Ginkgo biloba Secondary Metabolites against Hyphantria cunea Larvae: Mechanisms and Applications

    PubMed Central

    Ren, Lili; Chen, Fang; Feng, Yuqian

    2016-01-01

    Ginkgo biloba is a typical relic plant that rarely suffers from pest hazards. This study analyzed the pattern of G. biloba pest hazards in Beijing; tested the antifeedant activity of G. biloba extracts, including ginkgo flavonoids, ginkgolide, and bilobalide, against Hyphantria cunea larvae; determined the activities of glutathione transferase (GSTs), acetylcholinesterase (AChE), carboxylesterase (CarE) and mixed-functional oxidase (MFO), in larvae after feeding on these G. biloba secondary metabolites; and screened for effective botanical antifeedants in the field. In this study, no indicators of insect infestation were found for any of the examined leaves of G. biloba; all tested secondary metabolites showed significant antifeedant activity and affected the activity of the four larval detoxifying enzymes. Ginkgolide had the highest antifeedant activity and the most significant effect on the detoxifying enzymes (P<0.05). Spraying leaves with G. biloba extracts or ginkgolide both significantly repelled H. cunea larvae in the field (P<0.05), although the former is more economical and practical. This study investigated the antifeedant activity of G. biloba secondary metabolites against H. cunea larvae, and the results provide new insights into the mechanism of G. biloba pest resistance. This study also developed new applications of G. biloba secondary metabolites for effective pest control. PMID:27214257

  6. SNP array analysis of tyrosine kinase inhibitor-resistant chronic myeloid leukemia identifies heterogeneous secondary genomic alterations

    PubMed Central

    Müschen, Markus; Kato, Motohiro; Kawamata, Norihiko; Meixel, Antonie; Nowak, Verena; Kim, Han S.; Kang, Sharon; Paquette, Ronald; Chang, Mi-Sook; Thoenissen, Nils H.; Mossner, Max; Hofmann, Wolf-Karsten; Kohlmann, Alexander; Weiss, Tamara; Haferlach, Torsten; Haferlach, Claudia; Koeffler, H. Phillip

    2010-01-01

    To elucidate whether tyrosine kinase inhibitor (TKI) resistance in chronic myeloid leukemia is associated with characteristic genomic alterations, we analyzed DNA samples from 45 TKI-resistant chronic myeloid leukemia patients with 250K single nucleotide polymorphism arrays. From 20 patients, matched serial samples of pretreatment and TKI resistance time points were available. Eleven of the 45 TKI-resistant patients had mutations of BCR-ABL1, including 2 T315I mutations. Besides known TKI resistance-associated genomic lesions, such as duplication of the BCR-ABL1 gene (n = 8) and trisomy 8 (n = 3), recurrent submicroscopic alterations, including acquired uniparental disomy, were detectable on chromosomes 1, 8, 9, 17, 19, and 22. On chromosome 22, newly acquired and recurrent deletions of the IGLC1 locus were detected in 3 patients, who had previously presented with lymphoid or myeloid blast crisis. This may support a hypothesis of TKI-induced selection of subclones differentiating into immature B-cell progenitors as a mechanism of disease progression and evasion of TKI sensitivity. PMID:19965645

  7. Maturational alterations in constitutive activity of medial prefrontal cortex kappa-opioid receptors in Wistar rats.

    PubMed

    Sirohi, Sunil; Walker, Brendan M

    2015-11-01

    Opioid receptors can display spontaneous agonist-independent G-protein signaling (basal signaling/constitutive activity). While constitutive κ-opioid receptor (KOR) activity has been documented in vitro, it remains unknown if KORs are constitutively active in native systems. Using [(35) S] guanosine 5'-O-[gamma-thio] triphosphate coupling assay that measures receptor functional state, we identified the presence of medial prefrontal cortex KOR constitutive activity in young rats that declined with age. Furthermore, basal signaling showed an age-related decline and was insensitive to neutral opioid antagonist challenge. Collectively, the present data are first to demonstrate age-dependent alterations in the medial prefrontal cortex KOR constitutive activity in rats and changes in the constitutive activity of KORs can differentially impact KOR ligand efficacy. These data provide novel insights into the functional properties of the KOR system and warrant further consideration of KOR constitutive activity in normal and pathophysiological behavior. Opioid receptors exhibit agonist-independent constitutive activity; however, kappa-opioid receptor (KOR) constitutive activity has not been demonstrated in native systems. Our results confirm KOR constitutive activity in the medial prefrontal cortex (mPFC) that declines with age. With the ability to presynaptically inhibit multiple neurotransmitter systems in the mPFC, maturational or patho-logical alterations in constitutive activity could disrupt corticofugal glutamatergic pyramidal projection neurons mediating executive function. Regulation of KOR constitutive activity could serve as a therapeutic target to treat compromised executive function. PMID:26257334

  8. ALTERATION OF CARDIAC ELECTRICAL ACTIVITY BY WATER-LEACHABLE COMPONENTS OF RESIDUAL OIL FLY ASH (ROFA)

    EPA Science Inventory

    Alteration of cardiac electrical activity by water-leachable components
    of residual oil fly ash (ROFA)

    Desuo Wang, Yuh-Chin T. Huang*, An Xie, Ting Wang

    *Human Studies Division, NHEERL, US EPA
    104 Mason Farm Road, Chapel Hill, NC 27599
    Department of Basic ...

  9. Outcome of Children with Hyperventilation-Induced High-Amplitude Rhythmic Slow Activity with Altered Awareness

    ERIC Educational Resources Information Center

    Barker, Alexander; Ng, Joanne; Rittey, Christopher D. C.; Kandler, Rosalind H.; Mordekar, Santosh R.

    2012-01-01

    Hyperventilation-induced high-amplitude rhythmic slow activity with altered awareness (HIHARS) is increasingly being identified in children and is thought to be an age-related non-epileptic electrographic phenomenon. We retrospectively investigated the clinical outcome in 15 children (six males, nine females) with HIHARS (mean age 7y, SD 1y 11mo;…

  10. Alterations in regional homogeneity of baseline brain activity in pediatric temporal lobe epilepsy.

    PubMed

    Mankinen, Katariina; Long, Xiang-Yu; Paakki, Jyri-Johan; Harila, Marika; Rytky, Seppo; Tervonen, Osmo; Nikkinen, Juha; Starck, Tuomo; Remes, Jukka; Rantala, Heikki; Zang, Yu-Feng; Kiviniemi, Vesa

    2011-02-10

    Recent findings on intracortical EEG measurements show that the synchrony of localized neuronal networks is altered in epileptogenesis, leading to generalized seizure activity via connector hubs in the neuronal networks. Regional homogeneity (ReHo) analysis of blood oxygen level-dependent (BOLD) signals has demonstrated localized signal synchrony and disease-related alterations in a number of instances. We wanted to find out whether the ReHo of resting-state activity can be used to detect regional signal synchrony alterations in children with non-lesional temporal lobe epilepsy (TLE). Twenty-one TLE patients were compared with age and gender-matched healthy controls. Significantly increased ReHo was discovered in the posterior cingulate gyrus and the right medial temporal lobe of the patients, and they also had significantly decreased ReHo in the cerebellum compared with the healthy controls. However, the alterations in ReHo differed between the patients with normal and abnormal interictal EEGs, the latter showing significantly increased ReHo in the right fusiform gyrus and significantly decreased ReHo in the right medial frontal gyrus relative to the controls, while those with normal EEGs had significantly increased ReHo in the right inferior temporal gyrus and the left posterior cingulate gyrus. We conclude that altered BOLD signal synchrony can be detected in the cerebral and cerebellar cortices of children with TLE even in the absence of interictal EEG abnormalities. PMID:21146507

  11. Altered lower leg muscle activation patterns in patients with cerebral palsy during cycling on an ergometer

    PubMed Central

    Alves-Pinto, Ana; Blumenstein, Tobias; Turova, Varvara; Lampe, Renée

    2016-01-01

    Objective Cycling on a recumbent ergometer constitutes one of the most popular rehabilitation exercises in cerebral palsy (CP). However, no control is performed on how muscles are being used during training. Given that patients with CP present altered muscular activity patterns during cycling or walking, it is possible that an incorrect pattern of muscle activation is being promoted during rehabilitation cycling. This study investigated patterns of muscular activation during cycling on a recumbent ergometer in patients with CP and whether those patterns are determined by the degree of spasticity and of mobility. Methods Electromyographic (EMG) recordings of lower leg muscle activation during cycling on a recumbent ergometer were performed in 14 adult patients diagnosed with CP and five adult healthy participants. EMG recordings were done with an eight-channel EMG system built in the laboratory. The activity of the following muscles was recorded: Musculus rectus femoris, Musculus biceps femoris, Musculus tibialis anterior, and Musculus gastrocnemius. The degree of muscle spasticity and mobility was assessed using the Modified Ashworth Scale and the Gross Motor Function Classification System, respectively. Muscle activation patterns were described in terms of onset and duration of activation as well as duration of cocontractions. Results Muscle activation in CP was characterized by earlier onsets, longer periods of activation, a higher occurrence of agonist–antagonist cocontractions, and a more variable cycling tempo in comparison to healthy participants. The degree of altered muscle activation pattern correlated significantly with the degree of spasticity. Conclusion This study confirmed the occurrence of altered lower leg muscle activation patterns in patients with CP during cycling on a recumbent ergometer. There is a need to develop feedback systems that can inform patients and therapists of an incorrect muscle activation during cycling and support the training

  12. Investigation of abiogenic stress-induced alterations in the level of secondary metabolites in poppy plants (Papaver somniferum L.).

    PubMed

    Szabó, Beáta; Lakatos, A; Koszegi, T; Botz, L

    2008-12-01

    We aimed to understand the effects of water stress on the alkaloid production in various developmental stages of poppy plants and the effect of stress on the alkaloids content in the capsules. Three stages of the life cycle of Papaver somniferum L. were selected in our studies: Rosette, Flowering and Lancing developmental stages. Four types of water conditions were examined: Control, Withdrawal of Water, 50% Water Supply and Inundation. The morphological monitoring, results of Relative Water Content and proline content were used as indicators of stress. The result of the measurements in poppy leaves show that the secondary metabolites dramatically respond to these stress conditions. The constant water supply was beneficial for the accumulation of alkaloids in the capsules. PMID:19133499

  13. Altered intrinsic brain activity in patients with paroxysmal kinesigenic dyskinesia by PRRT2 mutation: altered brain activity by PRRT2 mutation.

    PubMed

    Luo, ChunYan; Chen, Yongping; Song, Wei; Chen, Qin; Gong, QiYong; Shang, Hui-Fang

    2013-11-01

    The proline-rich transmembrane protein 2 (PRRT2) gene has been recently identified as a causative gene of paroxysmal kinesigenic dyskinesia (PKD), with an insertion mutation c.649_650insC (p.P217fsX7) reported as the most common mutation. However, the pathogenic mechanism of the mutation of PRRT2 remains largely unknown. Resting-state functional magnetic resonance imaging is a promising approach to assess cerebral function and reveals underlying functional changes. Resting-state functional magnetic resonance imaging was performed in 4 Chinese PKD patients with p.P217fsX7 mutation, 6 Chinese PKD patients without the mutation, and 10 healthy control subjects. Voxel-based analysis was used to characterize alterations in the amplitude of low-frequency fluctuation (ALFF). When compared with the healthy control subjects, both groups of PKD patients showed alterations in spontaneous brain activities within cortical-basal ganglia circuitry. Besides, the group of patients with p.P217fsX7 mutation also exhibited increased ALFF in the right postcenral gyrus and right rolandic operculum area, while the alteration of ALFF in group of patients without the mutation additionally involved the middle orbitofrontal cortex. Direct comparative analysis between these two patient groups revealed significantly increased ALFF in the right postcentral gyrus in the group with p.P217fsX7 mutation. Increased spontaneous brain activity in the cortical-basal ganglia circuitry, especially in the motor preparation areas, is a common pathophysiology in PKD. Differences in the spatial patterns of increased ALFF between patients with and those without the mutation might reflect the distinct pathological mechanism resulting from PRRT2 mutation. PMID:23532549

  14. The alteration of components in the fermented Hwangryunhaedok-tang and its neuroprotective activity

    PubMed Central

    Yang, Hye Jin; Weon, Jin Bae; Lee, Bohyoung; Ma, Choong Je

    2011-01-01

    Background: Hwangryunhaedok-tang is a traditional herbal prescription that has sedative activity, hypotensive and anti-bacterial effects. Objective: In this study, we investigated the alteration of contents of components in Hwangryunhaedok-tang, antioxidant activity and neuroprotective activity by fermentation with Lactobacillus acidophilus KFRI 128. Materials and Methods: Contents of three marker compounds (geniposide, berberine and palmatine) and unknown compounds in the Hwangryunhaedok-tang (HR) and the fermented Hwangryunhaedok-tang (FHR) were measured and compared using the established high-performance liqued chromatograph coupled with a photodiode (HPLC-DAD) method. The antioxidant activity of HR and FHR were determined by DPPH free radical and hydrogen peroxide (H2O2) scavenging assay. Also, the neuroprotective activities of HR and FHR against glutamate-induced oxidative stress in a mouse hippocampal cell line (HT22) were evaluated by MTT assay. Results: The contents of geniposide and palmatine were decreased but the content of berberine was increased in the FHR. And the contents of unknown compounds (1), (2), (3), (4) and (5) in the HR were altered by fermentation. Electron donating activity (EDA, %) value of FHR was higher than HR for DPPH radical scavenging activity and H2O2 scavenging activity, respectively. In the MTT assay, FHR showed more potent neuroprotective activity than HR by 513.90%. Conclusion: The FHR using microorganism could convert compounds in HR and enhance the antioxidant and neuroprotective activity. PMID:21969791

  15. Skeletal muscle plasticity: cellular and molecular responses to altered physical activity paradigms

    NASA Technical Reports Server (NTRS)

    Baldwin, Kenneth M.; Haddad, Fadia

    2002-01-01

    The goal of this article is to examine our current understanding of the chain of events known to be involved in the adaptive process whereby specific genes and their protein products undergo altered expression; specifically, skeletal muscle adaptation in response to altered loading states will be discussed, with a special focus on the regulation of the contractile protein, myosin heavy chain gene expression. This protein, which is both an important structural and regulatory protein comprising the contractile apparatus, can be expressed as different isoforms, thereby having an impact on the functional diversity of the muscle. Because the regulation of the myosin gene family is under the control of a complex set of processes including, but not limited to, activity, hormonal, and metabolic factors, this protein will serve as a cellular "marker" for studies of muscle plasticity in response to various mechanical perturbations in which the quantity and type of myosin isoform, along with other important cellular proteins, are altered in expression.

  16. IIR filtering based adaptive active vibration control methodology with online secondary path modeling using PZT actuators

    NASA Astrophysics Data System (ADS)

    Boz, Utku; Basdogan, Ipek

    2015-12-01

    Structural vibrations is a major cause for noise problems, discomfort and mechanical failures in aerospace, automotive and marine systems, which are mainly composed of plate-like structures. In order to reduce structural vibrations on these structures, active vibration control (AVC) is an effective approach. Adaptive filtering methodologies are preferred in AVC due to their ability to adjust themselves for varying dynamics of the structure during the operation. The filtered-X LMS (FXLMS) algorithm is a simple adaptive filtering algorithm widely implemented in active control applications. Proper implementation of FXLMS requires availability of a reference signal to mimic the disturbance and model of the dynamics between the control actuator and the error sensor, namely the secondary path. However, the controller output could interfere with the reference signal and the secondary path dynamics may change during the operation. This interference problem can be resolved by using an infinite impulse response (IIR) filter which considers feedback of the one or more previous control signals to the controller output and the changing secondary path dynamics can be updated using an online modeling technique. In this paper, IIR filtering based filtered-U LMS (FULMS) controller is combined with online secondary path modeling algorithm to suppress the vibrations of a plate-like structure. The results are validated through numerical and experimental studies. The results show that the FULMS with online secondary path modeling approach has more vibration rejection capabilities with higher convergence rate than the FXLMS counterpart.

  17. A Catalogue of Altered Salivary Proteins Secondary to Invasive Ductal Carcinoma: A Novel In Vivo Paradigm to Assess Breast Cancer Progression

    PubMed Central

    Streckfus, Charles F.; Bigler, Lenora

    2016-01-01

    The objective of this manuscript is to introduce a catalogue of salivary proteins that are altered secondary to carcinoma of the breast. The catalogue of salivary proteins is a compilation of twenty years of research by the authors and consists of 233 high and low abundant proteins which have been identified by LC-MS/MS mass spectrometry, 2D-gel analysis and by enzyme-linked immunosorbent assay. The body of research suggests that saliva is a fluid suffused with solubilized by-products of oncogenic expression and that these proteins may be useful in the study of breast cancer progress, treatment efficacy and the tailoring of individualized patient care. PMID:27477923

  18. Using Computational Chemistry Activities to Promote Learning and Retention in a Secondary School General Chemistry Setting

    ERIC Educational Resources Information Center

    Ochterski, Joseph W.

    2014-01-01

    This article describes the results of using state-of-the-art, research-quality software as a learning tool in a general chemistry secondary school classroom setting. I present three activities designed to introduce fundamental chemical concepts regarding molecular shape and atomic orbitals to students with little background in chemistry, such as…

  19. Guidelines to Assist the Implementation of Differentiated Learning Activities in South African Secondary Schools

    ERIC Educational Resources Information Center

    de Jager, Thelma

    2013-01-01

    Despite previous research and recommendations in South Africa, secondary-school teachers still encounter economic, social and cultural challenges in implementing differentiated learning activities in the classroom. The diversity of learners with learning barriers inevitably leads to an increase in workload for the teachers. This article draws on…

  20. CRITICAL LITERATURE REVIEW AND RESEARCH NEEDED ON ACTIVATED SLUDGE SECONDARY CLARIFIERS

    EPA Science Inventory

    Secondary clarifiers are key to the successful performance of the activated sludge process. They serve to separate out the biological solids and produce a clear effluent and to concentrate the settled solids for return to the aeration basins. Clarifiers have served the purpose fo...

  1. Creative Thinking Development Program for Learning Activity Management of Secondary School Teachers

    ERIC Educational Resources Information Center

    Pukdeewut, Sutinan; Chantarasombat, Chalard; Satapornwong, Pattananusorn

    2013-01-01

    The objectives of this research were: to design a creative thinking development program for learning activity management of secondary school teachers, and to study the program's efficiency and effectiveness of usage. The results of the study were as follows: the program includes the vision, principles, objectives, content, program development…

  2. Living in a Global Age. A Simulation Activity for Upper Elementary and Secondary Level Students.

    ERIC Educational Resources Information Center

    Stanford Univ., CA. Stanford Program on International and Cross Cultural Education.

    Designed to introduce concepts in international trade and global economics to upper elementary and secondary level students, this simulation activity engages students in the group task of assembling flashlights. A variety of topics can be explored, such as energy shortages, international crises, relationships between rich and poor nations, foreign…

  3. Understanding Militant Teacher Union Members' Activities in Secondary Schools

    ERIC Educational Resources Information Center

    Mahlangu, Vimbi P.

    2013-01-01

    This article investigates the activities of teacher unions in some Gauteng secondary schools in South Africa. The methods used in collecting data were questionnaires, interviews and a literature study of appropriate educational and labour law journals, books and newspapers. An interpretive paradigm was used in analysing the data. In this article,…

  4. Somatic Mutations in CCK2R Alter Receptor Activity that Promote Oncogenic Phenotypes

    PubMed Central

    Willard, Melinda D.; Lajiness, Mary E.; Wulur, Isabella H.; Feng, Bo; Swearingen, Michelle L.; Uhlik, Mark T.; Kinzler, Kenneth W.; Velculescu, Victor E.; Sjöblom, Tobias; Markowitz, Sanford D.; Powell, Steven M.; Vogelstein, Bert; Barber, Thomas D.

    2013-01-01

    The roles of cholecystokinin 2 receptor (CCK2R) in numerous physiologic processes in the gastrointestinal tract and central nervous system are ‘well documented. There has been some evidence that CCK2R alterations play a role in cancers, but the functional significance of these alterations for tumorigenesis is unknown. We have identified six mutations in CCK2R among a panel of 140 colorectal cancers and 44 gastric cancers. We show that these mutations increase receptor activity, activate multiple downstream signaling pathways, increase cell migration, and promote angiogenesis. Our findings suggest that somatic mutations in CCK2R may promote tumorigenesis through deregulated receptor activity and highlight the importance of evaluating CCK2R inhibitors to block both the normal and mutant forms of the receptor. PMID:22516348

  5. Evidence for microbial activity at the glass-alteration interface in oceanic basalts

    NASA Astrophysics Data System (ADS)

    Torsvik, Terje; Furnes, Harald; Muehlenbachs, Karlis; Thorseth, Ingunn H.; Tumyr, Ole

    1998-10-01

    A detailed microbiological and geochemical study related to the alteration of basaltic glass of pillow lavas from the oceanic crust recovered from Hole 896A on the Costa Rica Rift (penetrating 290 m into the volcanic basement) has been carried out. A number of independent observations, pointing to the influence of microbes, may be summarized as follows: (1) Alteration textures are reminiscent of microbes in terms of form and shape. (2) Altered material contains appreciable amounts of C, N and K, and the N/C ratios are comparable to those of nitrogen-starved bacteria. (3) Samples stained with a dye (DAPI) that binds specifically to nucleic acids show the presence of DNA in the altered glass. Further, staining with fluorescent labeled oligonucleotide probes that hybridize specifically to 16S-ribosomal RNA of bacteria and archaea demonstrate their presence in the altered part of the glass. (4) Disseminated carbonate in the glassy margin of the majority of pillows shows δ 13C values, significantly lower than that of fresh basalt, also suggests biological activity. The majority of the samples have δ 18O values indicating temperatures of 20-100°C, which is in the range of mesophilic and thermophilic micro-organisms.

  6. A petrographic, geochemical and isotopic (O, H, C and Sr) investigation of secondary minerals in volcaniclastic rocks at Minna Bluff, Antarctica: Petrogenesis of alteration and implications for paleoenvironmental conditions

    NASA Astrophysics Data System (ADS)

    Antibus, J. V.; Panter, K. S.; Wilch, T. I.; Dunbar, N. W.; McIntosh, W. C.; Blusztajn, J.; Tripati, A. K.; Bindeman, I. N.

    2012-12-01

    The alteration of volcanic deposits is a function of eruptive style, environment of deposition and post-depositional processes. In this study we use petrographic and geochemical data on secondary minerals in volcaniclastic deposits at Minna Bluff, a 45-km-long volcanic peninsula in the southern Ross Sea active between 12 and 4 Ma, to unravel their history and study the environmental conditions responsible for their alteration. Glassy volcaniclastic deposits, including lapilli tuff, hyaloclastite breccia and volcanic sediments, have been altered to contain secondary minerals zeolite, carbonate and rare chalcedony and clay (dickite). Carbonates include calcite, Mg-calcite (MgCO3> 4 to <48 mol%), dolomite, magnesite, siderite and rhodochrosite. Zeolites include phillipsite and chabazite and have high and variable alkali contents (Na+K/Ca up to 154) relative to fresh lavas (<15). During the alteration of these deposits, phillipsite formed first followed by chabazite and/or carbonate although carbonates are still thought to be a very early diagenetic precipitate. Compositional zoning in zeolites is poorly developed while carbonates are commonly complex showing changes in Fe, Mn and Sr and Mg/Ca ratios across layers. Carbonate δ18O and δ13C values show wide variations ranging from -0.50 to 21.53‰ and -1.04 to 8.98‰, respectively. Chalcedony δ18O, measured on multiple aliquots from individual vugs and within each vug from one sample, range from 0.68 to 10.37‰ and δD values are light (-187.8 to -220.6‰), matching Antarctic meteoric water. A mean 87Sr/86Sr ratio of 0.70327 ±0.0009 (1σ, n = 12) for carbonates is comparable to values from lavas in this region (Erebus Volcanic Province), indicating that seawater even at low elevations (<40 m asl) was not involved in the alteration of these deposits. Field relationships and laboratory results indicate that alteration and associated mineral precipitation was a result of isolated, ephemeral events involving the

  7. Exposure of Female Macaques to Western-Style Diet With or Without Chronic T In Vivo Alters Secondary Follicle Function During Encapsulated 3-Dimensional Culture

    PubMed Central

    McGee, Whitney K.; Bishop, Cecily V.; Park, Byung S.; Cameron, Judy L.; Zelinski, Mary B.; Stouffer, Richard L.

    2015-01-01

    Increased adiposity and hyperandrogenemia alter reproductive parameters in both animal models and women, but their effects on preantral follicles in the ovary remain unknown. We recently reported that Western-style diet (WSD) consumption over 1 year, with or without chronic exposure to elevated circulating T, increased the body fat percentage, elicited insulin resistance, suppressed estradiol and progesterone production, as well as altered the numbers, size, and dynamics of antral follicles in the ovary during the menstrual cycle in female macaques. Therefore, experiments were designed to compare the WSD and WSD+T effects to age-matched controls on the survival, growth, and function of isolated secondary follicles during 5 weeks of encapsulated 3-dimensional culture. Follicle survival significantly declined in the WSD and WSD+T groups compared with the control (CTRL) group. Although media progesterone levels were comparable among groups, androstenedione and estradiol levels were markedly reduced in the WSD and WSD+T groups compared with the CTRL group at week 5. Anti-Müllerian hormone levels peaked at week 3 and were lower in the WSD+T group compared with the WSD or CTRL group. Vascular endothelial growth factor levels also decreased at week 5 in the WSD+T group compared with the WSD or CTRL group. After human chorionic gonadotropin exposure, only antral follicles developed from the CTRL group yielded metaphase II oocytes. Thus, WSD with or without T exposure affects the cohort of secondary follicles in vivo, suppressing their subsequent survival, production of steroid hormones and local factors, as well as oocyte maturation in vitro. PMID:25545382

  8. Prenatal immune activation alters hippocampal place cell firing characteristics in adult animals.

    PubMed

    Wolff, Amy R; Bilkey, David K

    2015-08-01

    Prenatal maternal immune activation (MIA) is a risk factor for several developmental neuropsychiatric disorders, including autism, bipolar disorder and schizophrenia. Adults with these disorders display alterations in memory function that may result from changes in the structure and function of the hippocampus. In the present study we use an animal model to investigate the effect that a transient prenatal maternal immune activation episode has on the spatially-modulated firing activity of hippocampal neurons in adult animals. MIA was induced in pregnant rat dams with a single injection of the synthetic cytokine inducer polyinosinic:polycytidylic acid (poly I:C) on gestational day 15. Control dams were given a saline equivalent. Firing activity and local field potentials (LFPs) were recorded from the CA1 region of the adult male offspring of these dams as they moved freely in an open arena. Most neurons displayed characteristic spatially-modulated 'place cell' firing activity and while there was no between-group difference in mean firing rate between groups, place cells had smaller place fields in MIA-exposed animals when compared to control-group cells. Cells recorded in MIA-group animals also displayed an altered firing-phase synchrony relationship to simultaneously recorded LFPs. When the floor of the arena was rotated, the place fields of MIA-group cells were more likely to shift in the same direction as the floor rotation, suggesting that local cues may have been more salient for these animals. In contrast, place fields in control group cells were more likely to shift firing position to novel spatial locations suggesting an altered response to contextual cues. These findings show that a single MIA intervention is sufficient to change several important characteristics of hippocampal place cell activity in adult offspring. These changes could contribute to the memory dysfunction that is associated with MIA, by altering the encoding of spatial context and by

  9. Secondary Metabolites Produced by an Endophytic Fungus Pestalotiopsis sydowiana and Their 20S Proteasome Inhibitory Activities.

    PubMed

    Xia, Xuekui; Kim, Soonok; Liu, Changheng; Shim, Sang Hee

    2016-01-01

    Fungal endophytes have attracted attention due to their functional diversity. Secondary metabolites produced by Pestalotiopsis sydowiana from a halophyte, Phragmites communis Trinus, were investigated. Eleven compounds, including four penicillide derivatives (1-4) and seven α-pyrone analogues (5-10) were isolated from cultures of P. sydowiana. The compounds were identified based on spectroscopic data. The inhibitory activities against the 20S proteasome were evaluated. Compounds 1-3, 5, and 9-10 showed modest proteasome inhibition activities, while compound 8 showed strong activity with an IC50 of 1.2 ± 0.3 μM. This is the first study on the secondary metabolites produced by P. sydowiana and their proteasome inhibitory activities. The endophytic fungus P. sydowiana might be a good resource for proteasome inhibitors. PMID:27447600

  10. Quantification of the effects of secondary matrix on the analysis of sandstone composition, and a petrographic-chemical technique for retrieving original framework grain modes of altered sandstones.

    PubMed

    Cox, R; Lowe, D R

    1996-05-01

    Most studies of sandstone provenance involve modal analysis of framework grains using techniques that exclude the fine-grained breakdown products of labile mineral grains and rock fragments, usually termed secondary matrix or pseudomatrix. However, the data presented here demonstrate that, when the proportion of pseudomatrix in a sandstone exceeds 10%, standard petrographic analysis can lead to incorrect provenance interpretation. Petrographic schemes for provenance analysis such as QFL and QFR should not therefore be applied to sandstones containing more than 10% secondary matrix. Pseudomatrix is commonly abundant in sandstones, and this is therefore a problem for provenance analysis. The difficulty can be alleviated by the use of whole-rock chemistry in addition to petrographic analysis. Combination of chemical and point-count data permits the construction of normative compositions that approximate original framework grain compositions. Provenance analysis is also complicated in many cases by fundamental compositional alteration during weathering and transport. Many sandstones, particularly shallow marine deposits, have undergone vigorous reworking, which may destroy unstable mineral grains and rock fragments. In such cases it may not be possible to retrieve provenance information by either petrographic or chemical means. Because of this, pseudomatrix-rich sandstones should be routinely included in chemical-petrological provenance analysis. Because of the many factors, both pre- and post-depositional, that operate to increase the compositional maturity of sandstones, petrologic studies must include a complete inventory of matrix proportions, grain size and sorting parameters, and an assessment of depositional setting. PMID:11539329

  11. OMP gene deletion results in an alteration in odorant-induced mucosal activity patterns.

    PubMed

    Youngentob, S L; Kent, P F; Margolis, F L

    2003-12-01

    Previous behavioral work, using a complex five-odorant identification task, demonstrated that olfactory marker protein (OMP) is critically involved in odor processing to the extent that its loss results in an alteration in odorant quality perception. Exactly how the lack of OMP exerts its influence on the perception of odorant quality is unknown. However, there is considerable neurophysiological evidence that different odorants produce different spatiotemporal patterns of neural activity at the level of the mucosa and that these patterns predict the psychophysically determined perceptual relationship among odorants. In this respect, OMP gene deletion is known to result in a constellation of physiologic defects (i.e., marked reduction in the electroolfactogram (EOG) and altered response and recovery kinetics) that would be expected to alter the odorant-induced spatiotemporal activity patterns that are characteristic of different odorants. This, in turn, would be expected to alter the spatiotemporal patterning of information that results from the mucosal projection onto the bulb, thereby changing odorant quality perception. To test the hypothesis that odorant-induced mucosal activity patterns are altered in mice lacking the gene for OMP, we optically recorded the fluorescent changes in response to odorant stimulation from both the septum and turbinates of both OMP-null and control mice using a voltage-sensitive dye (di-4-ANEPPS Molecular Probes, Eugene, OR) and a Dalsa 120 x 120, 12-bit CCD camera. To maintain continuity with the previous behavioral work, the odorants 2-propanol, citral, carvone, ethylacetoacetate, and propyl acetate were again used. Each odorant was randomly presented to each mucosal surface in a Latin-Square design. The results of this study demonstrated that, for both mouse strains, there do indeed exist different spatiotemporal activity patterns for different odorants. More importantly, however, these patterns significantly differed between OMP

  12. Altered metabolism of gut microbiota contributes to chronic immune activation in HIV-infected individuals.

    PubMed

    Vázquez-Castellanos, J F; Serrano-Villar, S; Latorre, A; Artacho, A; Ferrús, M L; Madrid, N; Vallejo, A; Sainz, T; Martínez-Botas, J; Ferrando-Martínez, S; Vera, M; Dronda, F; Leal, M; Del Romero, J; Moreno, S; Estrada, V; Gosalbes, M J; Moya, A

    2015-07-01

    Altered interplay between gut mucosa and microbiota during treated HIV infection may possibly contribute to increased bacterial translocation and chronic immune activation, both of which are predictors of morbidity and mortality. Although a dysbiotic gut microbiota has recently been reported in HIV+ individuals, the metagenome gene pool associated with HIV infection remains unknown. The aim of this study is to characterize the functional gene content of gut microbiota in HIV+ patients and to define the metabolic pathways of this bacterial community, which is potentially associated with immune dysfunction. We determined systemic markers of innate and adaptive immunity in a cohort of HIV-infected individuals on successful antiretroviral therapy without comorbidities and in healthy non-HIV-infected subjects. Metagenome sequencing revealed an altered functional profile, with enrichment of the genes involved in various pathogenic processes, lipopolysaccharide biosynthesis, bacterial translocation, and other inflammatory pathways. In contrast, we observed depletion of genes involved in amino acid metabolism and energy processes. Bayesian networks showed significant interactions between the bacterial community, their altered metabolic pathways, and systemic markers of immune dysfunction. This study reveals altered metabolic activity of microbiota and provides novel insight into the potential host-microbiota interactions driving the sustained inflammatory state in successfully treated HIV-infected patients. PMID:25407519

  13. Secondary phase formation and the microstructural evolution of surface layers during vapor phase alteration of the French SON 68 nuclear waste glass at 200{degrees}C

    SciTech Connect

    Gong, W.L.; Ewing, R.C.; Wang, L.M.

    1995-12-31

    The SON 68 inactive {open_quotes}R7T7{close_quotes} composition is the French reference glass for the LWR nuclear waste glass. Vapor phase alteration was used to accelerate the reaction progress of glass corrosion and to develop the characteristic suite of secondary, alteration phases. Extensive solid-state characterization (AEM/SEM/HRTEM) was completed on six inactive R7T7 waste glasses which were altered in the presence of saturated water vapor (200{degrees}C) for 91, 241, 908, 1000, 1013, and 1021 days. The AEM samples were examined in cross-section (lattice-fringe imaging, micro-diffraction, and quantitative thin-film EDS analysis). The glass monoliths were invariably covered with a thin altered rind. The layer became thicker with time: 0.5 {mu}m for 22 days; 4 {mu}m for 91 days; 6 {mu}m for 241 days; 10 {mu}m for 908 days; 26 {mu}m for 1013 days; and <35 {mu}m for 1021 days. The composite alteration layer of the SON 68 samples is at least four time less thick than that of the SRL 131 glass composition. Six distinctive zones, based on phase chemistry and microstructure, were distinguished within the well-developed surface layers. Numerous crystalline phases such as analcime, tobermorite, apatite, and weeksite were identified on the surfaces of the reacted glasses as precipitates. Two crystalline phases, Ag{sub 2}TeO{sub 3} and (Ca,Sr)Mo{sub 3}O{sub 9}(OH){sub 2}, were found within the inner zones of surface layers, and they must have nucleated in situ, indicating that Ag, Te, Sr, and Mo can be retained within the surface layer. The majority of the surface layer volume is composed of two morphologically and chemically different structures: one consists of well-crystallized fibrous smectite aggregates occurring along with cavities, the A-domain; and the other consists of poorly-crystallized regions containing needle-like smectite (montmorillonite) crystallites, a silica-rich amorphous matrix, and possibly ZrO{sub 2} particles, the B-domain.

  14. The AngFus3 Mitogen-Activated Protein Kinase Controls Hyphal Differentiation and Secondary Metabolism in Aspergillus niger

    PubMed Central

    Priegnitz, Bert-Ewald; Brandt, Ulrike; Pahirulzaman, Khomaizon A. K.; Dickschat, Jeroen S.

    2015-01-01

    Adaptation to a changing environment is essential for the survival and propagation of sessile organisms, such as plants or fungi. Filamentous fungi commonly respond to a worsening of their growth conditions by differentiation of asexually or sexually produced spores. The formation of these specialized cell types is, however, also triggered as part of the general life cycle by hyphal age or density. Spores typically serve for dispersal and, therefore, translocation but can also act as resting states to endure times of scarcity. Eukaryotic differentiation in response to environmental and self-derived signals is commonly mediated by three-tiered mitogen-activated protein (MAP) kinase signaling cascades. Here, we report that the MAP kinase Fus3 of the black mold Aspergillus niger (AngFus3) and its upstream kinase AngSte7 control vegetative spore formation and secondary metabolism. Mutants lacking these kinases are defective in conidium induction in response to hyphal density but are fully competent in starvation-induced sporulation, indicating that conidiation in A. niger is triggered by various independent signals. In addition, the mutants exhibit an altered profile of volatile metabolites and secrete dark pigments into the growth medium, suggesting a dysregulation of the secondary metabolism. By assigning the AngFus3 MAP kinase pathway to the transduction of a potentially self-derived trigger, this work contributes to the unraveling of the intricate signaling networks controlling fungal differentiation. Moreover, our data further support earlier observations that differentiation and secondary metabolism are tightly linked in filamentous fungi. PMID:25888553

  15. The AngFus3 Mitogen-Activated Protein Kinase Controls Hyphal Differentiation and Secondary Metabolism in Aspergillus niger.

    PubMed

    Priegnitz, Bert-Ewald; Brandt, Ulrike; Pahirulzaman, Khomaizon A K; Dickschat, Jeroen S; Fleißner, André

    2015-06-01

    Adaptation to a changing environment is essential for the survival and propagation of sessile organisms, such as plants or fungi. Filamentous fungi commonly respond to a worsening of their growth conditions by differentiation of asexually or sexually produced spores. The formation of these specialized cell types is, however, also triggered as part of the general life cycle by hyphal age or density. Spores typically serve for dispersal and, therefore, translocation but can also act as resting states to endure times of scarcity. Eukaryotic differentiation in response to environmental and self-derived signals is commonly mediated by three-tiered mitogen-activated protein (MAP) kinase signaling cascades. Here, we report that the MAP kinase Fus3 of the black mold Aspergillus niger (AngFus3) and its upstream kinase AngSte7 control vegetative spore formation and secondary metabolism. Mutants lacking these kinases are defective in conidium induction in response to hyphal density but are fully competent in starvation-induced sporulation, indicating that conidiation in A. niger is triggered by various independent signals. In addition, the mutants exhibit an altered profile of volatile metabolites and secrete dark pigments into the growth medium, suggesting a dysregulation of the secondary metabolism. By assigning the AngFus3 MAP kinase pathway to the transduction of a potentially self-derived trigger, this work contributes to the unraveling of the intricate signaling networks controlling fungal differentiation. Moreover, our data further support earlier observations that differentiation and secondary metabolism are tightly linked in filamentous fungi. PMID:25888553

  16. A semisynthetic strategy leads to alteration of the backbone amidate ligand in the NiSOD active site

    SciTech Connect

    Campeciño, Julius O.; Dudycz, Lech W.; Tumelty, David; Berg, Volker; Cabelli, Diane E.; Maroney, Michael J.

    2015-07-01

    Computational investigations have implicated the amidate ligand in nickel superoxide dismutase (NiSOD) in stabilizing Ni-centered redox catalysis and in preventing cysteine thiolate ligand oxidation. To test these predictions, we have used an experimental approach utilizing a semisynthetic scheme that employs native chemical ligation of a pentapeptide (HCDLP) to recombinant S. coelicolor NiSOD lacking these N-terminal residues, NΔ5-NiSOD. Wild-type enzyme produced in this manner exhibits the characteristic spectral properties of recombinant WT-NiSOD and is as catalytically active. The semisynthetic scheme was also employed to construct a variant where the amidate ligand was converted to a secondary amine, H1*-NiSOD, a novel strategy that retains a backbone N-donor atom. The H1*-NiSOD variant was found to have only ~1% of the catalytic activity of the recombinant wild-type enzyme, and had altered spectroscopic properties. X-ray absorption spectroscopy reveals a four-coordinate planar site with N2S2-donor ligands, consistent with electronic absorption spectroscopic results indicating that the Ni center in H1*-NiSOD is mostly reduced in the as-isolated sample, as opposed to 50:50 Ni(II)/Ni(III) mixture that is typical for the recombinant wild-type enzyme. The EPR spectrum of as-isolated H1*-NiSOD accounts for ~11% of the Ni in the sample and is similar to WT-NiSOD, but more axial, with gz < gx,y. 14N-hyperfine is observed on gzaltered electronic properties and implications for redox catalysis are discussed in light of predictions based on synthetic and computational models.

  17. A Semisynthetic Strategy Leads to Alteration of the Backbone Amidate Ligand in the NiSOD Active Site.

    PubMed

    Campeciño, Julius O; Dudycz, Lech W; Tumelty, David; Berg, Volker; Cabelli, Diane E; Maroney, Michael J

    2015-07-22

    Computational investigations have implicated the amidate ligand in nickel superoxide dismutase (NiSOD) in stabilizing Ni-centered redox catalysis and in preventing cysteine thiolate ligand oxidation. To test these predictions, we have used an experimental approach utilizing a semisynthetic scheme that employs native chemical ligation of a pentapeptide (HCDLP) to recombinant S. coelicolor NiSOD lacking these N-terminal residues, NΔ5-NiSOD. Wild-type enzyme produced in this manner exhibits the characteristic spectral properties of recombinant WT-NiSOD and is as catalytically active. The semisynthetic scheme was also employed to construct a variant where the amidate ligand was converted to a secondary amine, H1*-NiSOD, a novel strategy that retains a backbone N-donor atom. The H1*-NiSOD variant was found to have only ∼1% of the catalytic activity of the recombinant wild-type enzyme, and had altered spectroscopic properties. X-ray absorption spectroscopy reveals a four-coordinate planar site with N2S2-donor ligands, consistent with electronic absorption spectroscopic results indicating that the Ni center in H1*-NiSOD is mostly reduced in the as-isolated sample, as opposed to 50:50 Ni(II)/Ni(III) mixture that is typical for the recombinant wild-type enzyme. The EPR spectrum of as-isolated H1*-NiSOD accounts for ∼11% of the Ni in the sample and is similar to WT-NiSOD, but more axial, with gz < gx,y. (14)N-hyperfine is observed on gz, confirming the addition of the apical histidine ligand in the Ni(III) complex. The altered electronic properties and implications for redox catalysis are discussed in light of predictions based on synthetic and computational models. PMID:26135142

  18. Activated RSC-nucleosome complex and persistently altered form of the nucleosome.

    PubMed

    Lorch, Y; Cairns, B R; Zhang, M; Kornberg, R D

    1998-07-10

    RSC, an abundant, essential chromatin-remodeling complex, related to SWI/SNF complex, binds nucleosomes and naked DNA with comparable affinities, as shown by gel shift analysis. The RSC-nucleosome complex is converted in the presence of ATP to a slower migrating form. This activated complex exhibits greatly increased susceptibility to endo- and exonucleases but retains a full complement of histones. Activation persists in the absence of ATP, and on removal of RSC, the nucleosome is released in an altered form, with a diminished electrophoretic mobility, greater sedimentation rate, and marked instability at elevated ionic strength. The reaction is reversible in the presence of RSC and ATP, with conversion of the altered form back to the nucleosome. PMID:9674424

  19. Altered rest-activity patterns evolve via circadian independent mechanisms in cave adapted balitorid loaches.

    PubMed

    Duboué, Erik R; Borowsky, Richard L

    2012-01-01

    Circadian rhythms and rest homeostasis are independent processes, each regulating important components of rest-activity patterns. Evolutionarily, the two are distinct from one another; total rest time is maintained unaffected even when circadian pacemaker cells are ablated. Throughout the animal kingdom, there exists a huge variation in rest-activity patterns, yet it is unclear how these behaviors have evolved. Here we show that four species of balitorid cavefish have greatly reduced rest times in comparison to rest times of their surface relatives. All four cave species retained biological rhythmicity, and in three of the four there is a pronounced 24-hour rhythm; in the fourth there is an altered rhythmicity of 38-40 hours. Thus, consistent changes in total rest have evolved in these species independent of circadian rhythmicity. Taken together, our data suggest that consistent reduction in total rest times were accomplished evolutionarily through alterations in rest homeostasis. PMID:22348026

  20. Alteration and modulation of protein activity by varying post-translational modification

    SciTech Connect

    Thompson, David N; Reed, David W; Thompson, Vicki S; Lacey, Jeffrey A; Apel, William A

    2015-03-03

    Embodiments of the invention include methods of altering the enzymatic activity or solubility of an extremophilic enzyme or post-translationally modifying a protein of interest via using isolated or partially purified glycosyltransferases and/or post-translational modification proteins, extracts of cells comprising glycosyltransferases and/or post-translational modification proteins, and/or in cells comprising one or more glycosyltransferases and/or post-translational modification proteins.

  1. Alteration and modulation of protein activity by varying post-translational modification

    DOEpatents

    Thompson, David N.; Reed, David W.; Thompson, Vicki S.; Lacey, Jeffrey A.; Apel, William A.

    2016-07-12

    Embodiments of the invention include methods of altering the enzymatic activity or solubility of an extremophilic enzyme or post-translationally modifying a protein of interest via using isolated or partially purified glycosyltransferases and/or post-translational modification proteins, extracts of cells comprising glycosyltransferases and/or post-translational modification proteins, and/or in cells comprising one or more glycosyltransferases and/or post-translational modification proteins.

  2. Alterations in neuronal activity in basal ganglia-thalamocortical circuits in the parkinsonian state

    PubMed Central

    Galvan, Adriana; Devergnas, Annaelle; Wichmann, Thomas

    2015-01-01

    In patients with Parkinson’s disease and in animal models of this disorder, neurons in the basal ganglia and related regions in thalamus and cortex show changes that can be recorded by using electrophysiologic single-cell recording techniques, including altered firing rates and patterns, pathologic oscillatory activity and increased inter-neuronal synchronization. In addition, changes in synaptic potentials or in the joint spiking activities of populations of neurons can be monitored as alterations in local field potentials (LFPs), electroencephalograms (EEGs) or electrocorticograms (ECoGs). Most of the mentioned electrophysiologic changes are probably related to the degeneration of diencephalic dopaminergic neurons, leading to dopamine loss in the striatum and other basal ganglia nuclei, although degeneration of non-dopaminergic cell groups may also have a role. The altered electrical activity of the basal ganglia and associated nuclei may contribute to some of the motor signs of the disease. We here review the current knowledge of the electrophysiologic changes at the single cell level, the level of local populations of neural elements, and the level of the entire basal ganglia-thalamocortical network in parkinsonism, and discuss the possible use of this information to optimize treatment approaches to Parkinson’s disease, such as deep brain stimulation (DBS) therapy. PMID:25698937

  3. Lithium isotopes as an indicator of primary and secondary processes in unequilibrated meteorites: Chondrule cooling and aqueous alteration in CO chondrites

    NASA Astrophysics Data System (ADS)

    Sharrock, J. L.; Harvey, J.; Fehr, M.; James, R. H.; Parkinson, I. J.

    2010-12-01

    Chondrites have escaped planetary scale differentiation and thus represent some of the best examples of early solar system material. However, even the most pristine chondrites have experienced some degree of aqueous alteration and/or metamorphism. Where and when these processes occurred, their nature, duration and extent remains poorly understood (e.g.[1]). During the crystallisation of chondrule phenocrysts, compositional gradients drive the more rapid diffusion of 6Li compared to 7Li, creating distinctive 7Li/6Li profiles [2,3]. This potentially makes Li isotopes a useful tool for the calculation of chondrule cooling rates. Lithium is also highly mobile during the aqueous weathering of silicate material with 7Li preferentially entering the solution, thus fractionating the two isotopes (e.g. [4]); a process already identified in the aqueous alteration of chondritic materials [5]. Lithium isotopes may therefore provide the means to quantify the effects of both primary and secondary processes in chondritic material. We will present new data for intra- and inter-chondrule δ7Li variation, determined by ion microprobe and MC ICP MS, as well as bulk data for Ornans (CO3.3) and Lancé (CO3.4) with the aim to (i) assess the preservation of primary Li isotope diffusion profiles in chondrule phenocrysts (ii) examine the extent and effects of aqueous alteration using the Li isotope systematics of bulk-rock and chondrules, in addition to intra-chondrule δ7Li variations. High Mg# (>0.99) in chondrule cores suggests that primitive geochemical compositions may have been retained. In contrast, lower rim Mg# (≤0.80) suggests diffusive exchange with matrix during cooling or subsequent secondary alteration. As variability in Mg# is also observed close to fractures in the interior of chondrule phenocrysts these variations are unlikely to be primary, suggesting that Li isotope fractionation during chondrule cooling may have been overprinted. Bulk-rock δ7Li values for Ornans (4

  4. Hemin/G-quadruplex structure and activity alteration induced by magnesium cations.

    PubMed

    Kosman, J; Juskowiak, B

    2016-04-01

    The influence of metal cations on G-quadruplex structure and peroxidase-mimicking DNAzyme activity was investigated. Experiments revealed a significant role of magnesium ion, which in the presence of potassium cation influenced DNAzyme activity. This ability has been associated with alteration of G-quadruplex topology and consequently affinity to bind hemin molecule. It has been demonstrated that G-quadruplex based on PS2.M sequence under these conditions formed parallel topology, which exhibited lower activity than that observed in standard potassium-containing solution. On the other hand DNAzyme/magnesium ion system based on telomeric sequence, which did not undergo significant structural changes, exhibited higher peroxidase activity upon magnesium ion addition. In both cases, the stabilization effect of magnesium cations on G-quadruplex structure was observed. The mechanism of DNAzyme activity alteration by magnesium ion can be explained by its influence on the pKa value of DNAzyme. Magnesium ion decreased pKa for PS2.M based system but increased it for telomeric DNAzyme. Magnesium cation effect on G-quadruplex structure as well as DNAzyme activity is particularly important since this ion is one of the most common metal cations in biological samples. PMID:26778160

  5. Alteration of human hepatic drug transporter activity and expression by cigarette smoke condensate.

    PubMed

    Sayyed, Katia; Vee, Marc Le; Abdel-Razzak, Ziad; Jouan, Elodie; Stieger, Bruno; Denizot, Claire; Parmentier, Yannick; Fardel, Olivier

    2016-07-01

    Smoking is well-known to impair pharmacokinetics, through inducing expression of drug metabolizing enzymes. In the present study, we demonstrated that cigarette smoke condensate (CSC) also alters activity and expression of hepatic drug transporters, which are now recognized as major actors of hepatobiliary elimination of drugs. CSC thus directly inhibited activities of sinusoidal transporters such as OATP1B1, OATP1B3, OCT1 and NTCP as well as those of canalicular transporters like P-glycoprotein, MRP2, BCRP and MATE1, in hepatic transporters-overexpressing cells. CSC similarly counteracted constitutive OATP, NTCP and OCT1 activities in human highly-differentiated hepatic HepaRG cells. In parallel, CSC induced expression of BCRP at both mRNA and protein level in HepaRG cells, whereas it concomitantly repressed mRNA expression of various transporters, including OATP1B1, OATP2B1, OAT2, NTCP, OCT1 and BSEP, and enhanced that of MRP4. Such changes in transporter gene expression were found to be highly correlated to those caused by 2,3,7,8-tetrachlorodibenzo-p-dioxin, a reference activator of the aryl hydrocarbon receptor (AhR) pathway, and were counteracted, for some of them, by siRNA-mediated AhR silencing. This suggests that CSC alters hepatic drug transporter levels via activation of the AhR cascade. Importantly, drug transporter expression regulations as well as some transporter activity inhibitions occurred for a range of CSC concentrations similar to those required for inducing drug metabolizing enzymes and may therefore be hypothesized to be relevant for smokers. Taken together, these data established human hepatic transporters as targets of cigarette smoke, which could contribute to known alteration of pharmacokinetics and some liver adverse effects caused by smoking. PMID:27450509

  6. Experimental and analytical study of secondary path variations in active engine mounts

    NASA Astrophysics Data System (ADS)

    Hausberg, Fabian; Scheiblegger, Christian; Pfeffer, Peter; Plöchl, Manfred; Hecker, Simon; Rupp, Markus

    2015-03-01

    Active engine mounts (AEMs) provide an effective solution to further improve the acoustic and vibrational comfort of passenger cars. Typically, adaptive feedforward control algorithms, e.g., the filtered-x-least-mean-squares (FxLMS) algorithm, are applied to cancel disturbing engine vibrations. These algorithms require an accurate estimate of the AEM active dynamic characteristics, also known as the secondary path, in order to guarantee control performance and stability. This paper focuses on the experimental and theoretical study of secondary path variations in AEMs. The impact of three major influences, namely nonlinearity, change of preload and component temperature, on the AEM active dynamic characteristics is experimentally analyzed. The obtained test results are theoretically investigated with a linear AEM model which incorporates an appropriate description for elastomeric components. A special experimental set-up extends the model validation of the active dynamic characteristics to higher frequencies up to 400 Hz. The theoretical and experimental results show that significant secondary path variations are merely observed in the frequency range of the AEM actuator's resonance frequency. These variations mainly result from the change of the component temperature. As the stability of the algorithm is primarily affected by the actuator's resonance frequency, the findings of this paper facilitate the design of AEMs with simpler adaptive feedforward algorithms. From a practical point of view it may further be concluded that algorithmic countermeasures against instability are only necessary in the frequency range of the AEM actuator's resonance frequency.

  7. Melanoma-derived factors alter the maturation and activation of differentiated tissue-resident dendritic cells.

    PubMed

    Hargadon, Kristian M; Bishop, Johnathan D; Brandt, John P; Hand, Zachary C; Ararso, Yonathan T; Forrest, Osric A

    2016-01-01

    Dendritic cells (DCs) are key regulators of host immunity that are capable of inducing either immune tolerance or activation. In addition to their well-characterized role in shaping immune responses to foreign pathogens, DCs are also known to be critical for the induction and maintenance of anti-tumor immune responses. Therefore, it is important to understand how tumors influence the function of DCs and the quality of immune responses they elicit. Although the majority of studies in this field to date have utilized either immortalized DC lines or DC populations that have been generated under artificial conditions from hematopoietic precursors in vitro, we wished to investigate how tumors impact the function of already differentiated, tissue-resident DCs. Therefore, we used both an ex vivo and in vivo model system to assess the influence of melanoma-derived factors on DC maturation and activation. In ex vivo studies with freshly isolated splenic DCs, we demonstrate that the extent to which DC maturation and activation are altered by these factors correlates with melanoma tumorigenicity, and we identify partial roles for tumor-derived transforming growth factor (TGF)β1 and vascular endothelial growth factor (VEGF)-A in the altered functionality of DCs. In vivo studies using a lung metastasis model of melanoma also demonstrate tumorigenicity-dependent alterations to the function of lung-resident DCs, and skewed production of proinflammatory cytokines and chemokines by these tumor-altered cells is associated with recruitment of an immune infiltrate that may ultimately favor tumor immune escape and outgrowth. PMID:26010746

  8. Cutaneous necrosis in pregnancy secondary to activated protein C resistance in hereditary angioedema.

    PubMed

    Perkins, W; Downie, I; Keefe, M; Chisholm, M

    1995-04-01

    A 26-year-old woman with hereditary angineurotic oedema (HAE) presented at 22 weeks gestation with severe cutaneous necrosis similar to that seen in coumarin skin necrosis. Protein S deficiency secondary to HAE and pregnancy was postulated. Treatment with heparin, C1-inhibitor concentrates, systemic steroids and surgical debridement resulted in a successful outcome for both mother and child. Subsequent investigations revealed normal levels of protein C, antithrombin III, total protein S, free protein S but reduced function protein S activity with evidence of activated protein C resistance. Cutaneous necrosis has not been reported in associated with activated protein C resistance previously and the possible mechanisms are discussed. PMID:7745572

  9. The impacts of altered tropical cyclone activity on climate mitigation strategies

    NASA Astrophysics Data System (ADS)

    Fisk, J. P.; Hurtt, G. C.; LePage, Y.; Patel, P.; Chini, L. P.; Thomson, A. M.; Clarke, L.; Calvin, K. V.; Wise, M.; Chambers, J. Q.; Negron Juarez, R. I.

    2012-12-01

    There is growing evidence that anthropogenic climate change may alter patterns of tropical cyclone frequency, intensity and spatial distribution, which in turn will alter the carbon balance of terrestrial systems in the large regions impacted by these storms. Recent studies project up to a doubling of major storms (Saffir-Simpson Scale 3-5) over the next century. Single large storms have been shown to be capable of causing committed carbon emissions equivalent to the annual U.S. carbon sink. These changes have the potential to affect climate mitigation strategies, most of which rely on maintaining or enhancing the terrestrial carbon sink to restrain the accumulation of atmospheric greenhouse gases. Altered patterns of disturbances and the resulting changes to the carbon balance of terrestrial systems could impact the magnitude of emissions to mitigate, the economic value of ecosystem carbon storage, and thus future land-use patterns, food prices and energy technology. Here we investigate the potential consequences of altered tropical cyclone activity on climate mitigation strategies using a fully integrated model (iED) that links advanced ecological and socio-economic models. The model combines the regional integrated assessment algorithms of the Global Change Assessment Model (GCAM), with the climate- sensitive ecosystem and carbon modeling in the Ecosystem Demography (ED) model, and the land-use mapping algorithms of the Global Land-use Model (GLM). We explore a range of scenarios of altered future tropical cyclone frequency, intensity and spatial pattern, the resulting effects on the terrestrial carbon balance, and the coupled effects on the food and energy sector under a range of future climate mitigation goals.

  10. Memory impairment and alterations in prefrontal cortex gamma band activity following methamphetamine sensitization

    PubMed Central

    Linsenbardt, David N.; Lapish, Christopher C.

    2015-01-01

    Rationale Repeated methamphetamine (MA) use leads to increases in the incentive motivational properties of the drug as well as cognitive impairments. These behavioral alterations persist for some time following abstinence, and neuroadaptations in the structure and function of the prefrontal cortex (PFC) are particularly important for their expression. However, there is a weak understanding of the changes in neural firing and oscillatory activity in the PFC evoked by repeated drug use, thus complicating the development of novel treatment strategies for addiction. Objectives The purpose of the current study was to assess changes in cognitive and brain function following MA sensitization. Methods Sensitization was induced in rats, then temporal and recognition memory were assessed after 1 or 30 days of abstinence. Electrophysiological recordings from the medial PFC were also acquired from rats whereupon simultaneous measures of oscillatory and spiking activity were examined. Results Impaired temporal memory was observed after 1 and 30 days of abstinence. However, recognition memory was only impaired after 1 day of abstinence. An injection of MA profoundly decreased neuronal firing rate and the anesthesia-induced slow oscillation (SO) in both sensitized (SENS) and control (CTRL) rats. Strong correlations were observed between the SO and gamma band power, which was altered in SENS animals. A decrease in the number of neurons phase-locked to the gamma oscillation was also observed in SENS animals. Conclusions The changes observed in PFC function may play an integral role in the expression of the altered behavioral phenotype evoked by MA sensitization. PMID:25572530

  11. Repeated episodes of heroin cause enduring alterations of circadian activity in protracted abstinence.

    PubMed

    Stinus, Luis; Cador, Martine; Caille, Stephanie

    2012-01-01

    Opiate withdrawal is followed by a protracted abstinence syndrome consisting of craving and physiological changes. However, few studies have been dedicated to both the characterization and understanding of these long-term alterations in post-dependent subjects. The aim of the present study was to develop an opiate dependence model, which induces long-lasting behavioral changes in abstinent rats. Here, we first compared the effects of several protocols for the induction of opiate dependence (morphine pellets, repeated morphine or heroin injections) on the subsequent response to heroin challenges (0.25 mg/kg) at different time points during abstinence (3, 6, 9 and 18 weeks). In a second set of experiments, rats were exposed to increasing doses of heroin and subsequently monitored for general circadian activity up to 20 weeks of abstinence. Results show that heroin injections rather than the other methods of opiate administration have long-term consequences on rats' sensitivity to heroin with its psychostimulant effects persisting up to 18 weeks of abstinence. Moreover, intermittent episodes of heroin dependence rather than a single exposure produce enduring alteration of the basal circadian activity both upon heroin cessation and protracted abstinence. Altogether, these findings suggest that the induction of heroin dependence through intermittent increasing heroin injections is the optimal method to model long-term behavioral alterations during protracted abstinence in rats. This animal model would be useful in further characterizing long-lasting changes in post-dependent subjects to help understand the prolonged vulnerability to relapse. PMID:24961201

  12. Repeated Episodes of Heroin Cause Enduring Alterations of Circadian Activity in Protracted Abstinence

    PubMed Central

    Stinus, Luis; Cador, Martine; Caille, Stephanie

    2012-01-01

    Opiate withdrawal is followed by a protracted abstinence syndrome consisting of craving and physiological changes. However, few studies have been dedicated to both the characterization and understanding of these long-term alterations in post-dependent subjects. The aim of the present study was to develop an opiate dependence model, which induces long-lasting behavioral changes in abstinent rats. Here, we first compared the effects of several protocols for the induction of opiate dependence (morphine pellets, repeated morphine or heroin injections) on the subsequent response to heroin challenges (0.25 mg/kg) at different time points during abstinence (3, 6, 9 and 18 weeks). In a second set of experiments, rats were exposed to increasing doses of heroin and subsequently monitored for general circadian activity up to 20 weeks of abstinence. Results show that heroin injections rather than the other methods of opiate administration have long-term consequences on rats’ sensitivity to heroin with its psychostimulant effects persisting up to 18 weeks of abstinence. Moreover, intermittent episodes of heroin dependence rather than a single exposure produce enduring alteration of the basal circadian activity both upon heroin cessation and protracted abstinence. Altogether, these findings suggest that the induction of heroin dependence through intermittent increasing heroin injections is the optimal method to model long-term behavioral alterations during protracted abstinence in rats. This animal model would be useful in further characterizing long-lasting changes in post-dependent subjects to help understand the prolonged vulnerability to relapse. PMID:24961201

  13. Physical activity attenuates age-related biomarker alterations in preclinical AD

    PubMed Central

    Schultz, Stephanie A.; Oh, Jennifer M.; Larson, Jordan; Edwards, Dorothy; Cook, Dane; Koscik, Rebecca; Gallagher, Catherine L.; Dowling, N.M.; Carlsson, Cynthia M.; Bendlin, Barbara B.; LaRue, Asenath; Rowley, Howard A.; Christian, Brad T.; Asthana, Sanjay; Hermann, Bruce P.; Johnson, Sterling C.; Sager, Mark A.

    2014-01-01

    Objective: To examine whether engagement in physical activity might favorably alter the age-dependent evolution of Alzheimer disease (AD)-related brain and cognitive changes in a cohort of at-risk, late-middle-aged adults. Methods: Three hundred seventeen enrollees in the Wisconsin Registry for Alzheimer's Prevention underwent T1 MRI; a subset also underwent 11C-Pittsburgh compound B–PET (n = 186) and 18F-fluorodeoxyglucose–PET (n = 152) imaging. Participants' responses on a self-report measure of current physical activity were used to classify them as either physically active or physically inactive based on American Heart Association guidelines. They also completed a comprehensive neuropsychological battery. Covariate-adjusted regression analyses were used to test whether the adverse effect of age on imaging and cognitive biomarkers was modified by physical activity. Results: There were significant age × physical activity interactions for β-amyloid burden (p = 0.014), glucose metabolism (p = 0.015), and hippocampal volume (p = 0.025) such that, with advancing age, physically active individuals exhibited a lesser degree of biomarker alterations compared with the physically inactive. Similar age × physical activity interactions were also observed on cognitive domains of Immediate Memory (p = 0.042) and Visuospatial Ability (p = 0.016). In addition, the physically active group had higher scores on Speed and Flexibility (p = 0.002) compared with the inactive group. Conclusions: In a middle-aged, at-risk cohort, a physically active lifestyle is associated with an attenuation of the deleterious influence of age on key biomarkers of AD pathophysiology. However, because our observational, cross-sectional design cannot establish causality, randomized controlled trials/longitudinal studies will be necessary for determining whether midlife participation in structured physical exercise forestalls the development of AD and related disorders in later life. PMID:25298312

  14. Active Control of Airspring Secondary Suspension for Improving Ride Comfort in Presence of Random Track Irregularity

    NASA Astrophysics Data System (ADS)

    Alfi, Stefano; Bruni, Stefano; Gialleonardo, Egidio Di; Facchinetti, Alan

    The aim of this paper is to explore the possible benefits brought by the use of active control of the airspring secondary suspension for high speed railway vehicles; in this regard, active control is applied to reduce the vertical and pitch carbody oscillations in the low frequency range, according to the concept of skyhook damping. A concept is developed for the active airspring suspension, and a numerical model is derived for the vehicle equipped with the active suspension. The results obtained show that the use of active suspension control offers an important improvement of ride quality, by far larger than that achievable with semi-active suspensions. On the other hand, the issue of air consumption is outlined as a critical point of the proposed concept, requiring further research.

  15. Complete denture base assessments using holograms: dimensional alterations after different activation methods

    NASA Astrophysics Data System (ADS)

    Dughir, Ciprian; Popovschi, Ana Maria; Cojocariu, Andreea Codruta; Topala, Florin Ionel; Negrutiu, Meda Lavinia; Sinescu, Cosmin; de Sabata, Aldo; Duma, Virgil-Florin

    2016-03-01

    Holography is a well-developed method with a large range of applications, including dentistry. This study uses holographic methods for the study of total dental prosthesis. The issue is that the transformation of wax denture base in polymethylacrylate causes dimensional alterations and retractions in the final dental constructs. These could cause the failure of the stability of the complete denture in the oral cavity. Thus, the aim of this study is to determine and to compare using holography, total prosthesis obtained using three different manufacturing methods: pressing, injection, and polymerization. Each of the three types of dentures thus produced were recorded over the previously wax complete base holographic plates. The dimensional alterations that appear after using the different activation methods were thus determined. The most significant modification was remarked in the custom press technology, while the smallest variations were detected in the injection alternative.

  16. A Synonymous Single Nucleotide Polymorphism in ΔF508 CFTR Alters the Secondary Structure of the mRNA and the Expression of the Mutant Protein*

    PubMed Central

    Bartoszewski, Rafal A.; Jablonsky, Michael; Bartoszewska, Sylwia; Stevenson, Lauren; Dai, Qun; Kappes, John; Collawn, James F.; Bebok, Zsuzsa

    2010-01-01

    Recent advances in our understanding of translational dynamics indicate that codon usage and mRNA secondary structure influence translation and protein folding. The most frequent cause of cystic fibrosis (CF) is the deletion of three nucleotides (CTT) from the cystic fibrosis transmembrane conductance regulator (CFTR) gene that includes the last cytosine (C) of isoleucine 507 (Ile507ATC) and the two thymidines (T) of phenylalanine 508 (Phe508TTT) codons. The consequences of the deletion are the loss of phenylalanine at the 508 position of the CFTR protein (ΔF508), a synonymous codon change for isoleucine 507 (Ile507ATT), and protein misfolding. Here we demonstrate that the ΔF508 mutation alters the secondary structure of the CFTR mRNA. Molecular modeling predicts and RNase assays support the presence of two enlarged single stranded loops in the ΔF508 CFTR mRNA in the vicinity of the mutation. The consequence of ΔF508 CFTR mRNA “misfolding” is decreased translational rate. A synonymous single nucleotide variant of the ΔF508 CFTR (Ile507ATC), that could exist naturally if Phe-508 was encoded by TTC, has wild type-like mRNA structure, and enhanced expression levels when compared with native ΔF508 CFTR. Because CFTR folding is predominantly cotranslational, changes in translational dynamics may promote ΔF508 CFTR misfolding. Therefore, we propose that mRNA “misfolding” contributes to ΔF508 CFTR protein misfolding and consequently to the severity of the human ΔF508 phenotype. Our studies suggest that in addition to modifier genes, SNPs may also contribute to the differences observed in the symptoms of various ΔF508 homozygous CF patients. PMID:20628052

  17. Redox activity of urban quasi-ultrafine particles from primary and secondary sources

    NASA Astrophysics Data System (ADS)

    Verma, Vishal; Ning, Zhi; Cho, Arthur K.; Schauer, James J.; Shafer, Martin M.; Sioutas, Constantinos

    2009-12-01

    To characterize the redox activity profiles of atmospheric aerosols from primary (traffic) and secondary photochemical sources, ambient quasi-ultrafine particles were collected near downtown Los Angeles in two different time periods - morning (6:00-9:00 PDT) and afternoon (11:00-14:00 PDT) in the summer of 2008. Detailed chemical analysis of the collected samples, including water-soluble elements, inorganic ions, organic species and water soluble organic carbon (WSOC) was conducted and redox activity of the samples was measured by two different assays: the dithiothreitol (DTT) and the macrophage reactive oxygen species (ROS) assays. Tracers of secondary photochemical reactions, such as sulfate and organic acids were higher (2.1 ± 0.6 times for sulfate, and up to 3 times for the organic acids) in the afternoon period. WSOC was also elevated by 2.5 ± 0.9 times in the afternoon period due to photo-oxidation of primary particles during atmospheric aging. Redox activity measured by the DTT assay was considerably higher for the samples collected during the afternoon; on the other hand, diurnal trends in the ROS-based activity were not consistent between the morning and afternoon periods. A linear regression between redox activity and various PM chemical constituents showed that the DTT assay was highly correlated with WSOC ( R2 = 0.80), while ROS activity was associated mostly with water soluble transition metals (Vanadium, Nickel and Cadmium; R2 > 0.70). The DTT and ROS assays, which are based on the generation of different oxidizing species by chemical PM constituents, provide important information for elucidating the health risks related to PM exposure from different sources. Thus, both primary and secondary particles possess high redox activity; however, photochemical transformations of primary emissions with atmospheric aging enhance the toxicological potency of primary particles in terms of generating oxidative stress and leading to subsequent damage in cells.

  18. Altered Activation of the Tibialis Anterior in Individuals with Pompe Disease: Implications for Motor Unit Dysfunction

    PubMed Central

    Corti, Manuela; Smith, Barbara K; Falk, Darin J; Lawson, Lee Ann; Fuller, David D; Subramony, S.H.; Byrne, Barry J; Christou, Evangelos A

    2014-01-01

    Introduction Pompe disease is a progressive disease that affects skeletal muscles and leads to loss of ambulation. We investigated the activation of the tibialis anterior (TA) in late onset Pompe disease (LOPD) individuals during maximal voluntary contraction (MVC) and evoked involuntary responses. Methods Four LOPD patients and matched control subjects performed MVC of the TA using dorsiflexion and TA evoked responses. Activation of the TA was recorded with surface EMG. Results The Pompe patients exhibited greater power at frequencies below 60 Hz and reduced power above 100 Hz. They exhibited reduced increase in M-wave and prolonged M-wave latency and duration in response to stimulation. Discussion These results provide evidence that LOPD individuals have an altered activation pattern of the TA during maximal contractions. The observed activation pattern may reflect impairments in voluntary command, neuromuscular junction pathology, or compensatory drive due to a reduced number of functional motoneurons. PMID:25186912

  19. Altered gene expression in T-cell receptor signalling in peripheral blood leucocytes in acute coronary syndrome predicts secondary coronary events

    PubMed Central

    Takashima, Shin-ichiro; Usui, Soichiro; Kurokawa, Keisuke; Kitano, Teppei; Kato, Takeshi; Murai, Hisayoshi; Furusho, Hiroshi; Oda, Hiroyuki; Maruyama, Michiro; Nagata, Yoshiki; Usuda, Kazuo; Kubota, Koji; Takeshita, Yumie; Sakai, Yoshio; Honda, Masao; Kaneko, Shuichi; Takamura, Masayuki

    2016-01-01

    Objective Comprehensive profiling of gene expression in peripheral blood leucocytes (PBLs) in patients with acute coronary syndrome (ACS) as a prognosticator is needed. We explored the specific profile of gene expression in PBLs in ACS for long-term risk stratification. Methods 30 patients with ACS who underwent primary percutaneous coronary intervention (PCI) and 15 age-matched adults who participated in medical check-ups were enrolled from three centres. Peripheral blood samples were collected to extract RNA for microarray analyses. Results During the 5-year follow-up, 36% of this cohort developed the expected non-fatal coronary events (NFEs) of target lesion revascularisation (TLR) and PCI for a de novo lesion. Class comparison analysis (p<0.005) demonstrated that 83 genes among 7785 prefiltered genes (41 upregulated vs 42 downregulated genes) were extracted to classify the patients according to the occurrence of NFE. Pathway analysis based on gene ontology revealed that the NFEs were associated with altered gene expression regarding the T-cell receptor signalling pathway in ACS. Univariate t test showed that the expression level of death-associated protein kinase1 (DAPK1), known to regulate inflammation, was the most significantly negatively regulated gene in the event group (0.61-fold, p<0.0005). Kaplan-Meier curve analysis and multivariate analysis adjusted for baseline characteristics or clinical biomarkers demonstrated that lower DAPK1 expression in PBL emerged as an independent risk factor for the NFEs (HR: 8.73; CI 1.05 to 72.8, p=0.045). Conclusions Altered gene expression in T-cell receptor signalling in PBL in ACS could be a prognosticator for secondary coronary events. Trial registration number UMIN000001932; Results. PMID:27403330

  20. C3 exoenzyme impairs cell proliferation and apoptosis by altering the activity of transcription factors.

    PubMed

    von Elsner, Leonie; Hagemann, Sandra; Just, Ingo; Rohrbeck, Astrid

    2016-09-01

    C3 exoenzyme from C. botulinum is an ADP-ribosyltransferase that inactivates selectively RhoA, B, and C by coupling an ADP-ribose moiety. Rho-GTPases are involved in various cellular processes, such as regulation of actin cytoskeleton, cell proliferation, and apoptosis. Previous studies of our group with the murine hippocampal cell line HT22 revealed a C3-mediated inhibition of cell proliferation after 48 h and a prevention of serum-starved cells from apoptosis. For both effects, alterations of various signaling pathways are already known, including also changes on the transcriptional level. Investigations on the transcriptional activity in HT22 cells treated with C3 for 48 h identified five out of 48 transcription factors namely Sp1, ATF2, E2F-1, CBF, and Stat6 with a significantly regulated activity. For validation of identified transcription factors, studies on the protein level of certain target genes were performed. Western blot analyses exhibited an enhanced abundance of Sp1 target genes p21 and COX-2 as well as an increase in phosphorylation of c-Jun. In contrast, the level of p53 and apoptosis-inducing GADD153, a target gene of ATF2, was decreased. Our results reveal that C3 regulates the transcriptional activity of Sp1 and ATF2 resulting downstream in an altered protein abundance of various target genes. As the affected proteins are involved in the regulation of cell proliferation and apoptosis, thus the C3-mediated anti-proliferative and anti-apoptotic effects are consequences of the Rho-dependent alterations of the activity of certain transcriptional factors. PMID:27351882

  1. Altered cognition-related brain activity and interactions with acute pain in migraine.

    PubMed

    Mathur, Vani A; Khan, Shariq A; Keaser, Michael L; Hubbard, Catherine S; Goyal, Madhav; Seminowicz, David A

    2015-01-01

    Little is known about the effect of migraine on neural cognitive networks. However, cognitive dysfunction is increasingly being recognized as a comorbidity of chronic pain. Pain appears to affect cognitive ability and the function of cognitive networks over time, and decrements in cognitive function can exacerbate affective and sensory components of pain. We investigated differences in cognitive processing and pain-cognition interactions between 14 migraine patients and 14 matched healthy controls using an fMRI block-design with two levels of task difficulty and concurrent heat (painful and not painful) stimuli. Across groups, cognitive networks were recruited in response to a difficult cognitive task, and a pain-task interaction was found in the right (contralateral to pain stimulus) posterior insula (pINS), such that activity was modulated by decreasing the thermal pain stimulus or by engaging the difficult cognitive task. Migraine patients had less task-related deactivation within the left dorsolateral prefrontal cortex (DLPFC) and left dorsal anterior midcingulate cortex (aMCC) compared to controls. These regions have been reported to have decreased cortical thickness and cognitive-related deactivation within other pain populations, and are also associated with pain regulation, suggesting that the current findings may reflect altered cognitive function and top-down regulation of pain. During pain conditions, patients had decreased task-related activity, but more widespread task-related reductions in pain-related activity, compared to controls, suggesting cognitive resources may be diverted from task-related to pain-reduction-related processes in migraine. Overall, these findings suggest that migraine is associated with altered cognitive-related neural activity, which may reflect altered pain regulatory processes as well as broader functional restructuring. PMID:25610798

  2. Age-related alterations in cyclic nucleotide phosphodiesterase activity in dystrophic mouse leg muscle.

    PubMed

    Bloom, Timothy J

    2005-11-01

    Previous reports have described both increased and decreased cyclic nucleotide phosphodiesterase (PDE) activity in dystrophic muscle. Total PDE activity was measured in hind leg muscle from a mouse model of Duchenne muscular dystrophy (mdx) and a genetic control strain at 5, 8, 10, and 15 weeks of age. Total PDE activity declined in fractions isolated from mdx muscle over this time period, but was stable in fractions from control mice. Compared with age-matched controls, younger mdx muscle had higher cAMP and cGMP PDE activity. However, at 15 weeks, fractions from both strains had similar cGMP PDE activity and mdx fractions had lower cAMP PDE activity than controls. Particulate fractions from mdx muscle showed an age-related decline in sensitivity to the PDE4 inhibitor RO 20-1724. A similar loss of sensitivity to the PDE2 inhibitor erythro-9-(2-hydroxyl-3-nonyl)-adenine (EHNA) was seen in a particulate fraction from mdx muscle and to a lesser degree in control muscle. These results suggest that the earlier disagreement regarding altered cyclic nucleotide metabolism in dystrophic muscle may be due to changes with age in PDE activity of dystrophic tissue. The age-related decline in particulate PDE activity seen in dystrophic muscle appears to be isozyme-specific and not due to a generalized decrease in total PDE activity. PMID:16391714

  3. Alterations in plasminogen activation correlate with epithelial cell dysplasia grading in colorectal adenomas.

    PubMed Central

    Protiva, P.; Sordat, I.; Chaubert, P.; Saraga, E.; Trân-Thang, C.; Sordat, B.; Blum, A. L.; Dorta, G.

    1998-01-01

    Proteases are important for neoplastic invasion but a specific role for the plasminogen activator system in the progression of colorectal epithelial dysplasia to adenomatous lesions remains unclear. Consecutive tissue cryosections of 51 adenomas, 49 distant mucosa samples and five mucosa samples from control subjects were histopathologically analysed for dysplasia grade and tissue type, urokinase plasminogen activator levels and plasminogen activator inhibitor type 1 (PAI-1) using immunosorbent methods. Plasminogen activation and urokinase-mediated proteolytic activity levels were assessed using in situ zymography. Plasminogen activation and tissue-type activator levels were lower in adenomas than in mucosae (P < 0.001). PAI-1 concentration and urokinase levels were higher in adenomas than in mucosae (P < 0.001 and P < 0.001 respectively). In adenomas, urokinase concentration increased in parallel with PAI-1, but only the urokinase levels correlated with the dysplasia grade (P < 0.01). Thus, the alterations in plasminogen activation correlated with epithelial cell dysplasia grading. In the mucosa to adenoma transition, a marked decrease in tissue-type plasminogen activator occurred. In adenomas, this decrease was accompanied by a concomitant increase in urokinase and PAI-1. The urokinase level only continued to rise in parallel with the dysplasia grade. Resulting protease-antiprotease imbalance in high-grade dysplasia may represent the phenotypic change associated with malignant transformation and invasive behaviour. Images Figure 2 PMID:9461001

  4. Diabetes-induced myelin abnormalities are associated with an altered lipid pattern: protective effects of LXR activation[S

    PubMed Central

    Cermenati, Gaia; Abbiati, Federico; Cermenati, Solei; Brioschi, Elisabetta; Volonterio, Alessandro; Cavaletti, Guido; Saez, Enrique; De Fabiani, Emma; Crestani, Maurizio; Garcia-Segura, Luis M.; Melcangi, Roberto C.; Caruso, Donatella; Mitro, Nico

    2012-01-01

    Diabetic peripheral neuropathy (DPN) is characterized by myelin abnormalities; however, the molecular mechanisms underlying such deficits remain obscure. To uncover the effects of diabetes on myelin alterations, we have analyzed myelin composition. In a streptozotocin-treated rat model of diabetic neuropathy, analysis of sciatic nerve myelin lipids revealed that diabetes alters myelin's phospholipid, FA, and cholesterol content in a pattern that can modify membrane fluidity. Reduced expression of relevant genes in the FA biosynthetic pathway and decreased levels of the transcriptionally active form of the lipogenic factor sterol-regulatory element binding factor-1c (SREBF-1c) were found in diabetic sciatic nerve. Expression of myelin's major protein, myelin protein zero (P0), was also suppressed by diabetes. In addition, we confirmed that diabetes induces sciatic nerve myelin abnormalities, primarily infoldings that have previously been associated with altered membrane fluidity. In a diabetic setting, synthetic activator of the nuclear receptor liver X receptor (LXR) increased SREBF-1c function and restored myelin lipid species and P0 expression levels to normal. These LXR-modulated improvements were associated with restored myelin structure in sciatic nerve and enhanced performance in functional tests such as thermal nociceptive threshold and nerve conduction velocity. These findings demonstrate an important role for the LXR-SREBF-1c axis in protection from diabetes-induced myelin abnormalities. PMID:22158827

  5. Parental Involvement, Student Active Engagement and the "Secondary Slump" Phenomenon--Evidence from a Three-Year Study in a Barbadian Secondary School

    ERIC Educational Resources Information Center

    Marshall, Ian A.; Jackman, Grace-Anne

    2015-01-01

    This study examined the relationship between parental involvement and a proximal student academic outcome-active engagement, for a cohort of 160 students on their transition to secondary school and at three subsequent time periods. The student-reported measures were assessed using the Hoover-Dempsey and Sandler (2005) instrument. Results provide…

  6. Antimicrobial activity of secondary metabolites from Streptomyces sp. K15, an endophyte in Houttuynia cordata Thunb.

    PubMed

    Chen, Huabao; Yang, Chunping; Ke, Tao; Zhou, Miaomiao; Li, Zhaojun; Zhang, Min; Gong, Guoshu; Hou, Taiping

    2015-01-01

    We isolated Streptomyces sp. K15 from the root tissue of Houttuynia cordata Thunb and found that some of its secondary metabolites exhibited significant antimicrobial activity against Botrytis cinerea. Moreover, we separated, purified and identified the major active ingredient to be 2-pyrrol formic acid by using silica gel column chromatography, high-performance liquid chromatography and NMR analysis of the spectral data. 2-Pyrrol formic acid critically inhibited the growth of some phytopathogenic bacteria. Therefore, it has potential value in agricultural applications. PMID:25675117

  7. Mutations in the Catalytic Loop HRD Motif Alter the Activity and Function of Drosophila Src64

    PubMed Central

    Strong, Taylor C.; Kaur, Gurvinder; Thomas, Jeffrey H.

    2011-01-01

    The catalytic loop HRD motif is found in most protein kinases and these amino acids are predicted to perform functions in catalysis, transition to, and stabilization of the active conformation of the kinase domain. We have identified mutations in a Drosophila src gene, src64, that alter the three HRD amino acids. We have analyzed the mutants for both biochemical activity and biological function during development. Mutation of the aspartate to asparagine eliminates biological function in cytoskeletal processes and severely reduces fertility, supporting the amino acid's critical role in enzymatic activity. The arginine to cysteine mutation has little to no effect on kinase activity or cytoskeletal reorganization, suggesting that the HRD arginine may not be critical for coordinating phosphotyrosine in the active conformation. The histidine to leucine mutant retains some kinase activity and biological function, suggesting that this amino acid may have a biochemical function in the active kinase that is independent of its side chain hydrogen bonding interactions in the active site. We also describe the phenotypic effects of other mutations in the SH2 and tyrosine kinase domains of src64, and we compare them to the phenotypic effects of the src64 null allele. PMID:22132220

  8. Prolonged activation of NMDA receptors promotes dephosphorylation and alters postendocytic sorting of GABAB receptors

    PubMed Central

    Terunuma, Miho; Vargas, Karina J.; Wilkins, Megan E.; Ramírez, Omar A.; Jaureguiberry-Bravo, Matías; Pangalos, Menelas N.; Smart, Trevor G.; Moss, Stephen J.; Couve, Andrés

    2010-01-01

    Slow and persistent synaptic inhibition is mediated by metabotropic GABAB receptors (GABABRs). GABABRs are responsible for the modulation of neurotransmitter release from presynaptic terminals and for hyperpolarization at postsynaptic sites. Postsynaptic GABABRs are predominantly found on dendritic spines, adjacent to excitatory synapses, but the control of their plasma membrane availability is still controversial. Here, we explore the role of glutamate receptor activation in regulating the function and surface availability of GABABRs in central neurons. We demonstrate that prolonged activation of NMDA receptors (NMDA-Rs) leads to endocytosis, a diversion from a recycling route, and subsequent lysosomal degradation of GABABRs. These sorting events are paralleled by a reduction in GABABR-dependent activation of inwardly rectifying K+ channel currents. Postendocytic sorting is critically dependent on phosphorylation of serine 783 (S783) within the GABABR2 subunit, an established substrate of AMP-dependent protein kinase (AMPK). NMDA-R activation leads to a rapid increase in phosphorylation of S783, followed by a slower dephosphorylation, which results from the activity of AMPK and protein phosphatase 2A, respectively. Agonist activation of GABABRs counters the effects of NMDA. Thus, NMDA-R activation alters the phosphorylation state of S783 and acts as a molecular switch to decrease the abundance of GABABRs at the neuronal plasma membrane. Such a mechanism may be of significance during synaptic plasticity or pathological conditions, such as ischemia or epilepsy, which lead to prolonged activation of glutamate receptors. PMID:20643948

  9. The Role of the Secondary Coordination Sphere in Metal-Mediated Dioxygen Activation

    PubMed Central

    Shook, Ryan L.

    2012-01-01

    Alfred Werner proposed nearly 100 years ago that the secondary coordination sphere has a role in determining physical properties of transition metal complexes. We now know that the secondary coordination sphere impacts nearly all aspects of transition metal chemistry, including the reactivity and selectivity in metal-mediated processes. These features are highlighted in the binding and activation of dioxygen by transition metal complexes. There are clear connections between the control of the secondary coordination sphere and the ability of metal complexes to 1) reversibly bind dioxygen or 2) bind and activate dioxygen to form highly reactive M–oxo complexes. In this forum article, several biological and synthetic examples are presented and discussed in terms of structure-function relationships. Particular emphasis is given to systems with defined non-covalent interactions, such as intramolecular hydrogen bonds involving dioxygen-derived ligands. To further illustrate these effects, the homolytic cleavage of C–H bonds by M–oxo complexes with basic oxo ligands is described. PMID:20380466

  10. Mutation of Gly721 Alters DNA Topoisomerase I Active Site Architecture and Sensitivity to Camptothecin*

    PubMed Central

    van der Merwe, Marie; Bjornsti, Mary-Ann

    2015-01-01

    DNA topoisomerase I (Top1p) catalyzes the relaxation of supercoiled DNA via a concerted mechanism of DNA strand cleavage and religation. Top1p is the cellular target of the anticancer drug camptothecin (CPT), which reversibly stabilizes a covalent enzyme-DNA intermediate. Top1p clamps around duplex DNA, wherein the core and C-terminal domains are connected by extended α-helices (linker domain), which position the active site Tyr of the C-terminal domain within the catalytic pocket. The physical connection of the linker with the Top1p clamp as well as linker flexibility affect enzyme sensitivity to CPT. Crystallographic data reveal that a conserved Gly residue (located at the juncture between the linker and C-terminal domains) is at one end of a short α-helix, which extends to the active site Tyr covalently linked to the DNA. In the presence of drug, the linker is rigid and this α-helix extends to include Gly and the preceding Leu. We report that mutation of this conserved Gly in yeast Top1p alters enzyme sensitivity to CPT. Mutating Gly to Asp, Glu, Asn, Gln, Leu, or Ala enhanced enzyme CPT sensitivity, with the acidic residues inducing the greatest increase in drug sensitivity in vivo and in vitro. By contrast, Val or Phe substituents rendered the enzyme CPT-resistant. Mutation-induced alterations in enzyme architecture preceding the active site Tyr suggest these structural transitions modulate enzyme sensitivity to CPT, while enhancing the rate of DNA cleavage. We postulate that this conserved Gly residue provides a flexible hinge within the Top1p catalytic pocket to facilitate linker dynamics and the structural alterations that accompany drug binding of the covalent enzyme-DNA intermediate. PMID:18056711

  11. Altered Theta Oscillations and Aberrant Cortical Excitatory Activity in the 5XFAD Model of Alzheimer's Disease

    PubMed Central

    Siwek, Magdalena Elisabeth; Müller, Ralf; Henseler, Christina; Trog, Astrid; Lundt, Andreas; Wormuth, Carola; Broich, Karl; Weiergräber, Marco; Papazoglou, Anna

    2015-01-01

    Alzheimer's disease (AD) is an age-related neurodegenerative disorder characterized by impairment of memory function. The 5XFAD mouse model was analyzed and compared with wild-type (WT) controls for aberrant cortical excitability and hippocampal theta oscillations by using simultaneous video-electroencephalogram (EEG) monitoring. Seizure staging revealed that 5XFAD mice exhibited cortical hyperexcitability whereas controls did not. In addition, 5XFAD mice displayed a significant increase in hippocampal theta activity from the light to dark phase during nonmotor activity. We also observed a reduction in mean theta frequency in 5XFAD mice compared to controls that was again most prominent during nonmotor activity. Transcriptome analysis of hippocampal probes and subsequent qPCR validation revealed an upregulation of Plcd4 that might be indicative of enhanced muscarinic signalling. Our results suggest that 5XFAD mice exhibit altered cortical excitability, hippocampal dysrhythmicity, and potential changes in muscarinic signaling. PMID:25922768

  12. Plant adaptation to extreme environments: the example of Cistus salviifolius of an active geothermal alteration field.

    PubMed

    Bartoli, Giacomo; Bottega, Stefania; Forino, Laura M C; Ciccarelli, Daniela; Spanò, Carmelina

    2014-02-01

    Cistus salviifolius is able to colonise one of the most extreme active geothermal alteration fields in terms of both soil acidity and hot temperatures. The analyses of morpho-functional and physiological characters, investigated in leaves of plants growing around fumaroles (G leaves) and in leaves developed by the same plants after transfer into growth chamber under controlled conditions (C leaves) evidenced the main adaptive traits developed by this pioneer plant in a stressful environment. These traits involved leaf shape and thickness, mesophyll compactness, stomatal and trichome densities, chloroplast size. Changes of functional and physiological traits concerned dry matter content, peroxide and lipid peroxidation, leaf area, relative water and pigment contents. A higher reducing power and antioxidant enzymatic activity were typical of G leaves. Though the high levels of stress parameters, G leaves showed stress-induced specific morphogenic and physiological responses putatively involved in their surviving in active geothermal habitats. PMID:24581804

  13. Alterations in the heart rate and activity rhythms of three orbital astronauts on a space mission.

    PubMed

    Liu, Zhizhen; Wan, Yufeng; Zhang, Lin; Tian, Yu; Lv, Ke; Li, Yinghui; Wang, Chunhui; Chen, Xiaoping; Chen, Shanguang; Guo, Jinhu

    2015-01-01

    Environmental factors in space are dramatically different from those on Earth. The spaceflight environment has been known to influence human physiology and behavior on orbital missions. In this study, we investigated alterations in the diurnal rhythms of activity and heart rate of three Chinese astronauts on a space mission. An analysis of the heart rate data showed a significant decrease in heart rate amplitudes during flight in all three subjects. The heart rate amplitudes of all the three astronauts were significantly dampened during flight, and the minimum as well as the maximum value of heart rate increased after flight. A phase shift in heart rate was observed in one of the three astronauts after flight. These results demonstrate the influence of spaceflight on heart physiology and function. In addition, a significant decrease in body trunk activity and rhythmicity occurred during flight, demonstrating that the spaceflight environment disturbs motion adaptation and diurnal activity rhythms. PMID:26177621

  14. SGIP1 alters internalization and modulates signaling of activated cannabinoid receptor 1 in a biased manner.

    PubMed

    Hájková, Alena; Techlovská, Šárka; Dvořáková, Michaela; Chambers, Jayne Nicole; Kumpošt, Jiří; Hubálková, Pavla; Prezeau, Laurent; Blahos, Jaroslav

    2016-08-01

    Many diseases of the nervous system are accompanied by alterations in synaptic functions. Synaptic plasticity mediated by the endogenous cannabinoid system involves the activation of the cannabinoid receptor 1 (CB1R). The principles of CB1R signaling must be understood in detail for its therapeutic exploration. We detected the Src homology 3-domain growth factor receptor-bound 2-like (endophilin) interacting protein 1 (SGIP1) as a novel CB1R partner. SGIP1 is functionally linked to clathrin-mediated endocytosis and its overexpression in animals leads to an energy regulation imbalance resulting in obesity. We report that SGIP1 prevents the endocytosis of activated CB1R and that it alters signaling via the CB1R in a biased manner. CB1R mediated G-protein activation is selectively influenced by SGIP1, β-arrestin associated signaling is changed profoundly, most likely as a consequence of the prevention of the receptor's internalization elicited by SGIP1. PMID:26970018

  15. Anabolic steroids alter the physiological activity of aggression circuits in the lateral anterior hypothalamus.

    PubMed

    Morrison, T R; Sikes, R W; Melloni, R H

    2016-02-19

    Syrian hamsters exposed to anabolic/androgenic steroids (AAS) during adolescence consistently show increased aggressive behavior across studies. Although the behavioral and anatomical profiles of AAS-induced alterations have been well characterized, there is a lack of data describing physiological changes that accompany these alterations. For instance, behavioral pharmacology and neuroanatomical studies show that AAS-induced changes in the vasopressin (AVP) neural system within the latero-anterior hypothalamus (LAH) interact with the serotonin (5HT) and dopamine (DA) systems to modulate aggression. To characterize the electrophysiological profile of the AAS aggression circuit, we recorded LAH neurons in adolescent male hamsters in vivo and microiontophoretically applied agonists and antagonists of aggressive behavior. The interspike interval (ISI) of neurons from AAS-treated animals correlated positively with aggressive behaviors, and adolescent AAS exposure altered parameters of activity in regular firing neurons while also changing the proportion of neuron types (i.e., bursting, regular, irregular). AAS-treated animals had more responsive neurons that were excited by AVP application, while cells from control animals showed the opposite effect and were predominantly inhibited by AVP. Both DA D2 antagonists and 5HT increased the firing frequency of AVP-responsive cells from AAS animals and dual application of AVP and D2 antagonists doubled the excitatory effect of AVP or D2 antagonist administration alone. These data suggest that multiple DA circuits in the LAH modulate AAS-induced aggressive responding. More broadly, these data show that multiple neurochemical interactions at the neurophysiological level are altered by adolescent AAS exposure. PMID:26691962

  16. The crowded sea: incorporating multiple marine activities in conservation plans can significantly alter spatial priorities.

    PubMed

    Mazor, Tessa; Possingham, Hugh P; Edelist, Dori; Brokovich, Eran; Kark, Salit

    2014-01-01

    Successful implementation of marine conservation plans is largely inhibited by inadequate consideration of the broader social and economic context within which conservation operates. Marine waters and their biodiversity are shared by a host of stakeholders, such as commercial fishers, recreational users and offshore developers. Hence, to improve implementation success of conservation plans, we must incorporate other marine activities while explicitly examining trade-offs that may be required. In this study, we test how the inclusion of multiple marine activities can shape conservation plans. We used the entire Mediterranean territorial waters of Israel as a case study to compare four planning scenarios with increasing levels of complexity, where additional zones, threats and activities were added (e.g., commercial fisheries, hydrocarbon exploration interests, aquaculture, and shipping lanes). We applied the marine zoning decision support tool Marxan to each planning scenario and tested a) the ability of each scenario to reach biodiversity targets, b) the change in opportunity cost and c) the alteration of spatial conservation priorities. We found that by including increasing numbers of marine activities and zones in the planning process, greater compromises are required to reach conservation objectives. Complex plans with more activities incurred greater opportunity cost and did not reach biodiversity targets as easily as simplified plans with less marine activities. We discovered that including hydrocarbon data in the planning process significantly alters spatial priorities. For the territorial waters of Israel we found that in order to protect at least 10% of the range of 166 marine biodiversity features there would be a loss of ∼15% of annual commercial fishery revenue and ∼5% of prospective hydrocarbon revenue. This case study follows an illustrated framework for adopting a transparent systematic process to balance biodiversity goals and economic

  17. The Crowded Sea: Incorporating Multiple Marine Activities in Conservation Plans Can Significantly Alter Spatial Priorities

    PubMed Central

    Mazor, Tessa; Possingham, Hugh P.; Edelist, Dori; Brokovich, Eran; Kark, Salit

    2014-01-01

    Successful implementation of marine conservation plans is largely inhibited by inadequate consideration of the broader social and economic context within which conservation operates. Marine waters and their biodiversity are shared by a host of stakeholders, such as commercial fishers, recreational users and offshore developers. Hence, to improve implementation success of conservation plans, we must incorporate other marine activities while explicitly examining trade-offs that may be required. In this study, we test how the inclusion of multiple marine activities can shape conservation plans. We used the entire Mediterranean territorial waters of Israel as a case study to compare four planning scenarios with increasing levels of complexity, where additional zones, threats and activities were added (e.g., commercial fisheries, hydrocarbon exploration interests, aquaculture, and shipping lanes). We applied the marine zoning decision support tool Marxan to each planning scenario and tested a) the ability of each scenario to reach biodiversity targets, b) the change in opportunity cost and c) the alteration of spatial conservation priorities. We found that by including increasing numbers of marine activities and zones in the planning process, greater compromises are required to reach conservation objectives. Complex plans with more activities incurred greater opportunity cost and did not reach biodiversity targets as easily as simplified plans with less marine activities. We discovered that including hydrocarbon data in the planning process significantly alters spatial priorities. For the territorial waters of Israel we found that in order to protect at least 10% of the range of 166 marine biodiversity features there would be a loss of ∼15% of annual commercial fishery revenue and ∼5% of prospective hydrocarbon revenue. This case study follows an illustrated framework for adopting a transparent systematic process to balance biodiversity goals and economic

  18. Magnetic activity of red secondaries: clues from the outburst cycle variations of dwarf novae

    NASA Astrophysics Data System (ADS)

    Chinarova, L. L.

    Photometric variations of 6 dwarf novae stars are studied based on the photographic observations from the Odessa, Moscow and Sonneberg plate collections and published visual monitoring data from the AFOEV database (Schweitzer E.: 1993, Bull. AFOEV, 64, 14). The moments of maxima are determined by using the "running parabola" fit (Andronov I.L., 1990, Kinematika Fizika Nebesn. Tel., v.6,,N 6, 87) with automatically determined filter half-width (Andronov I.L., 1997, As.Ap. Suppl., in press). All investigated stars exhibit significant changes not only from cycle-to-cycle, but from season-to-season as well. Secondary decade-scale cycles of smooth variations (Bianchini A., 1990, AJ 99, 1941) and abrupt switchings (Andronov I.L., Shakun L.I., 1990, ASS 169, 237) were interpreted by a solar-type activity of the red dwarf secondary in a binary system and may argue for existence of two different subgroups of the dwarf novae.

  19. Non-prenylatable, cytosolic Rac1 alters neurite outgrowth while retaining the ability to be activated.

    PubMed

    Reddy, Jairus M; Samuel, Filsy G; McConnell, Jordan A; Reddy, Cristina P; Beck, Brian W; Hynds, DiAnna L

    2015-03-01

    Rac1 is an important regulator of axon extension, cell migration and actin reorganization. Like all Rho guanine triphosphatases (GTPases), Rac1 is targeted to the membrane by the addition of a geranylgeranyl moiety, an action thought to result in Rac1 guanosine triphosphate (GTP) binding. However, the role that Rac1 localization plays in its activation (GTP loading) and subsequent activation of effectors is not completely clear. To address this, we developed a non-prenylatable emerald green fluorescent protein (EmGFP)-Rac1 fusion protein (EmGFP-Rac1(C189A)) and assessed how expressing this construct affected neurite outgrowth, Rac1 localization and activation in neuroblastoma cells. Expression of EmGFP-Rac1(C189A) increased localization to the cytosol and induced cell clustering while increasing neurite initiation. EmGFP-Rac1(C189A) expression also increased Rac1 activation in the cytosol, compared to cells expressing wild-type Rac1 (EmGFP-Rac1). These results suggest that activation of Rac1 may not require plasma membrane localization, potentially leading to differential activation of cytosolic signaling pathways that alter cell morphology. Understanding the consequences of differential localization and activation of Rho GTPases, including Rac1, could lead to new therapeutic targets for treating neurological disorders. PMID:25479592

  20. Alterations in Daytime and Nighttime Activity in Piglets after Focal and Diffuse Brain Injury.

    PubMed

    Olson, Emily; Badder, Carlie; Sullivan, Sarah; Smith, Colin; Propert, Kathleen; Margulies, Susan S

    2016-04-15

    We have developed and implemented a noninvasive, objective neurofunctional assessment for evaluating the sustained effects of traumatic brain injury (TBI) in piglets with both diffuse and focal injury types. Derived from commercial actigraphy methods in humans, this assessment continuously monitors the day/night activity of piglets using close-fitting jackets equipped with tri-axial accelerometers to monitor movements of the thorax. Acceleration metrics were correlated (N = 7 naïve piglets) with video images to define values associated with a range of activities, from recumbancy (rest) to running. Both focal (N = 8) and diffuse brain injury (N = 9) produced alterations in activity that were significant 4 days post-TBI. Compared to shams (N = 6) who acclimated to the animal facility 4 days after an anesthesia experience by blurring the distinction between day and night activity, post-TBI time-matched animals had larger fractions of inactive periods during the daytime than nighttime, and larger fractions of active time in the night were spent in high activity (e.g., constant walking, intermittent running) than during the day. These persistent disturbances in rest and activity are similar to those observed in human adults and children post-TBI, establishing actigraphy as a translational metric, used in both humans and large animals, for assessment of injury severity, progressions, and intervention. PMID:26414329

  1. MYB58 and MYB63 are transcriptional activators of the lignin biosynthetic pathway during secondary cell wall formation in Arabidopsis.

    PubMed

    Zhou, Jianli; Lee, Chanhui; Zhong, Ruiqin; Ye, Zheng-Hua

    2009-01-01

    It has previously been shown that SECONDARY WALL-ASSOCIATED NAC DOMAIN PROTEIN1 (SND1) is a key transcription factor regulating secondary cell wall formation, including the biosynthesis of cellulose, xylan, and lignin. In this study, we show that two closely related SND1-regulated MYB transcription factors, MYB58 and MYB63, are transcriptional regulators specifically activating lignin biosynthetic genes during secondary wall formation in Arabidopsis thaliana. MYB58 and MYB63 are phylogenetically distinct from previously characterized MYBs shown to be associated with secondary wall formation or phenylpropanoid metabolism. Expression studies showed that MYB58 and MYB63 are specifically expressed in fibers and vessels undergoing secondary wall thickening. Dominant repression of their functions led to a reduction in secondary wall thickening and lignin content. Overexpression of MYB58 and MYB63 resulted in specific activation of lignin biosynthetic genes and concomitant ectopic deposition of lignin in cells that are normally unlignified. MYB58 was able to activate directly the expression of lignin biosynthetic genes and a secondary wall-associated laccase (LAC4) gene. Furthermore, the expression of MYB58 and MYB63 was shown to be regulated by the SND1 close homologs NST1, NST2, VND6, and VND7 and their downstream target MYB46. Together, our results indicate that MYB58 and MYB63 are specific transcriptional activators of lignin biosynthesis in the SND1-mediated transcriptional network regulating secondary wall formation. PMID:19122102

  2. Endophytic Streptomyces in the traditional medicinal plant Arnica montana L.: secondary metabolites and biological activity.

    PubMed

    Wardecki, Tina; Brötz, Elke; De Ford, Christian; von Loewenich, Friederike D; Rebets, Yuriy; Tokovenko, Bogdan; Luzhetskyy, Andriy; Merfort, Irmgard

    2015-08-01

    Arnica montana L. is a medical plant of the Asteraceae family and grows preferably on nutrient poor soils in mountainous environments. Such surroundings are known to make plants dependent on symbiosis with other organisms. Up to now only arbuscular mycorrhizal fungi were found to act as endophytic symbiosis partners for A. montana. Here we identified five Streptomyces strains, microorganisms also known to occur as endophytes in plants and to produce a huge variety of active secondary metabolites, as inhabitants of A. montana. The secondary metabolite spectrum of these strains does not contain sesquiterpene lactones, but consists of the glutarimide antibiotics cycloheximide and actiphenol as well as the diketopiperazines cyclo-prolyl-valyl, cyclo-prolyl-isoleucyl, cyclo-prolyl-leucyl and cyclo-prolyl-phenylalanyl. Notably, genome analysis of one strain was performed and indicated a huge genome size with a high number of natural products gene clusters among which genes for cycloheximide production were detected. Only weak activity against the Gram-positive bacterium Staphylococcus aureus was revealed, but the extracts showed a marked cytotoxic activity as well as an antifungal activity against Candida parapsilosis and Fusarium verticillioides. Altogether, our results provide evidence that A. montana and its endophytic Streptomyces benefit from each other by completing their protection against competitors and pathogens and by exchanging plant growth promoting signals with nutrients. PMID:26036671

  3. Progressive development of cardiomyopathy following altered autonomic activity in status epilepticus.

    PubMed

    Read, Morgayn I; McCann, Dominic M; Millen, Rebecca N; Harrison, Joanne C; Kerr, D Steven; Sammut, Ivan A

    2015-11-01

    Seizures are associated with altered autonomic activity, which has been implicated in the development of cardiac dysfunction and structural damage. This study aimed to investigate the involvement of the autonomic nervous system in seizure-induced cardiomyopathy. Male Sprague-Dawley rats (320-350 g) were implanted with EEG/ECG electrodes to allow simultaneous telemetric recordings during seizures induced by intrahippocampal (2 nmol, 1 μl/min) kainic acid and monitored for 7 days. Seizure activity occurred in conjunction with increased heart rate (20%), blood pressure (25%), and QTc prolongation (15%). This increased sympathetic activity was confirmed by the presence of raised plasma noradrenaline levels at 3 h post-seizure induction. By 48 h post-seizure induction, sympathovagal balance was shifted in favor of sympathetic dominance, as indicated by both heart rate variability (LF/HF ratio of 3.5 ± 1.0) and pharmacological autonomic blockade. Functional cardiac deficits were evident at 7 and 28 days, as demonstrated by echocardiography showing a decreased ejection fraction (14% compared with control, P < 0.05) and dilated cardiomyopathy present at 28 days following seizure induction. Histological changes, including cardiomyocyte vacuolization, cardiac fibrosis, and inflammatory cell infiltration, were evident within 48 h of seizure induction and remained present for up to 28 days. These structural changes most probably contributed to an increased susceptibility to aconitine-induced arrhythmias. This study confirms that prolonged seizure activity results in acute and chronic alterations in cardiovascular control, leading to a deterioration in cardiac structure and function. This study further supports the need for modulation of sympathetic activity as a promising therapeutic approach in seizure-induced cardiomyopathy. PMID:26342065

  4. Altered differentiation and paracrine stimulation of mammary epithelial cell proliferation by conditionally activated Smoothened

    PubMed Central

    Visbal, Adriana P.; LaMarca, Heather L.; Villanueva, Hugo; Toneff, Michael J.; Li, Yi; Rosen, Jeffrey M.; Lewis, Michael T.

    2011-01-01

    The Hedgehog (Hh) signaling network is critical for patterning and organogenesis in mammals, and has been implicated in a variety of cancers. Smoothened (Smo), the gene encoding the principal signal transducer, is overexpressed frequently in breast cancer, and constitutive activation in MMTV-SmoM2 transgenic mice caused alterations in mammary gland morphology, increased proliferation, and changes in stem/progenitor cell number. Both in transgenic mice and in clinical specimens, proliferative cells did not usually express detectable Smo, suggesting the hypothesis that Smo functioned in a non-cell autonomous manner to stimulate proliferation. Here, we employed a genetically tagged mouse model carrying a Cre-recombinase-dependent conditional allele of constitutively active Smo (SmoM2) to test this hypothesis. MMTV-Cre- or adenoviral-Cre-mediated SmoM2 expression in the luminal epithelium, but not in the myoepithelium, was required for the hyper-proliferative phenotypes. High levels of proliferation were observed in cells adjacent or in close-proximity to Smo expressing cells demonstrating that SmoM2 expressing cells were stimulating proliferation via a paracrine or juxtacrine mechanism. In contrast, Smo expression altered luminal cell differentiation in a cell-autonomous manner. SmoM2 expressing cells, purified by fluorescence activated cell sorting (FACS) via the genetic fluorescent tag, expressed high levels of Ptch2, Gli1, Gli2, Jag2 and Dll-1, and lower levels of Notch4 and Hes6, in comparison to wildtype cells. These studies provide insight into the mechanism of Smo activation in the mammary gland and its possible roles in breast tumorigenesis. In addition, these results also have potential implications for the interpretation of proliferative phenotypes commonly observed in other organs as a consequence of hedgehog signaling activation. PMID:21276786

  5. Altered activity of the medial prefrontal cortex and amygdala during acquisition and extinction of an active avoidance task

    PubMed Central

    Jiao, Xilu; Beck, Kevin D.; Myers, Catherine E.; Servatius, Richard J.; Pang, Kevin C. H.

    2015-01-01

    Altered medial prefrontal cortex (mPFC) and amygdala function is associated with anxiety-related disorders. While the mPFC-amygdala pathway has a clear role in fear conditioning, these structures are also involved in active avoidance. Given that avoidance perseveration represents a core symptom of anxiety disorders, the neural substrate of avoidance, especially its extinction, requires better understanding. The present study was designed to investigate the activity, particularly, inhibitory neuronal activity in mPFC and amygdala during acquisition and extinction of lever-press avoidance in rats. Neural activity was examined in the mPFC, intercalated cell clusters (ITCs) lateral (LA), basal (BA) and central (CeA) amygdala, at various time points during acquisition and extinction, using induction of the immediate early gene product, c-Fos. Neural activity was greater in the mPFC, LA, BA, and ITC during the extinction phase as compared to the acquisition phase. In contrast, the CeA was the only region that was more activated during acquisition than during extinction. Our results indicate inhibitory neurons are more activated during late phase of acquisition and extinction in the mPFC and LA, suggesting the dynamic involvement of inhibitory circuits in the development and extinction of avoidance response. Together, these data start to identify the key brain regions important in active avoidance behavior, areas that could be associated with avoidance perseveration in anxiety disorders. PMID:26441578

  6. Antimicrobial and antiprotozoal activities of secondary metabolites from the fungus Eurotium repens

    PubMed Central

    Gao, Jiangtao; Radwan, Mohamed M.; León, Francisco; Wang, Xiaoning; Jacob, Melissa R.; Tekwani, Babu L.; Khan, Shabana I.; Lupien, Shari; Hill, Robert A.; Dugan, Frank M.; Cutler, Horace G.

    2011-01-01

    In this study, we examined in vitro antibacterial, antifungal, antimalarial, and antileishmanial activities of secondary metabolites (1–8) isolated from the fungus Eurotium repens. All compounds showed mild to moderate antibacterial or antifungal or both activities except 7. The activity of compound 6 was the best of the group tested. The in vitro antimalarial evaluation of these compounds revealed that compounds 1–3, 5, and 6 showed antimalarial activities against both chloroquine-sensitive and chloroquine-resistant strains of Plasmodium falciparum with IC50 values in the range of 1.1–3.0 μg/ml without showing any cytotoxicity to the mammalian cells. Compound 5 displayed the highest antimalarial activity. Antileishmanial activity against Leishmania donovani promastigotes was observed for compounds 1–6 with IC50 values ranging from 6.2 to 23 μg/ml. Antileishmanial activity of compounds 5 and 6 (IC50 values of 7.5 and 6.2 μg/ml, respectively) was more potent than 1–4 (IC50 values ranging from 19–23 μg/ml). Compounds 7 and 8 did not show any antiprotozoal effect. Preliminary structure and activity relationship studies indicated that antibacterial, antifungal, antimalarial, and antileishmanial activities associated with phenol derivates (1–6) seem to be dependent on the number of double bonds in the side chain, which would be important for lead optimization in the future. PMID:23024574

  7. Simulated microgravity alters multipotential differentiation of rat mesenchymal stem cells in association with reduced telomerase activity

    NASA Astrophysics Data System (ADS)

    Sun, Lianwen; Gan, Bo; Fan, Yubo; Xie, Tian; Hu, Qinghua; Zhuang, Fengyuan

    Microgravity is one of the most important characteristics in space flight. Exposure to microgravity results in extensive physiological changes in humans. Bone loss is one of the changes with serious consequences; however, the mechanism retains unclear. As the origin of osteoprogenitors, mesenchymal stem cells (MSCs) may play an important role in it. After cultured under simulated microgravity (in a rotary cell culture system, RCCS), MSCs were stained using oil red O to identify adipocytes. The mRNA level of bone morphogenetic protein (BMP)-2 and peroxisome proliferators-activated receptor (PPAR) γ2 was determined by RT-PCR. Otherwise, MSCs were induced to osteogenic differentiation after microgravity culture, and then the activity of alkaline phosphatase (ALP) was determined by PNPP and the content of osteocalcin (OC) by ELISA. Furthermore, the telomerase activity in MSCs was measured by TRAP. The results showed that simulated microgravity inhibited osteoblastic differentiation and induced adipogenic differentiation accompanied by the change of gene expression of BMP-2 and PPARγ2 in MSCs. Meanwhile, the telomerase activity decreased significantly in MSCs under simulated microgravity. The reduced bone formation in space flight may partly be due to the altered potential differentiation of MSCs associated with telomerase activity which plays a key role in regulating the lifespan of cell proliferation and differentiation. Therefore, telomerase activation/replacement may act as a potential countermeasure for microgravity-induced bone loss.

  8. Maternal caffeine exposure alters neuromotor development and hippocampus acetylcholinesterase activity in rat offspring.

    PubMed

    Souza, Ana Claudia; Souza, Andressa; Medeiros, Liciane Fernandes; De Oliveira, Carla; Scarabelot, Vanessa Leal; Da Silva, Rosane Souza; Bogo, Mauricio Reis; Capiotti, Katiucia Marques; Kist, Luiza Wilges; Bonan, Carla D; Caumo, Wolnei; Torres, Iraci L S

    2015-01-21

    The objective of this study was to evaluate the effects of maternal caffeine intake on the neuromotor development of rat offspring and on acetylcholine degradation and acetylcholinesterase (AChE) expression in the hippocampus of 14-day-old infant rats. Rat dams were treated with caffeine (0.3g/L) throughout gestation and lactation until the pups were 14 days old. The pups were divided into three groups: (1) control, (2) caffeine, and (3) washout caffeine. The washout group received a caffeine solution until the seventh postnatal day (P7). Righting reflex (RR) and negative geotaxis (NG) were assessed to evaluate postural parameters as an index of neuromotor reflexes. An open-field (OF) test was conducted to assess locomotor and exploratory activities as well as anxiety-like behaviors. Caffeine treatment increased both RR and NG latency times. In the OF test, the caffeine group had fewer outer crossings and reduced locomotion compared to control, while the washout group showed increased inner crossings in relation to the other groups and fewer rearings only in comparison to the control group. We found decreased AChE activity in the caffeine group compared to the other groups, with no alteration in AChE transcriptional regulation. Chronic maternal exposure to caffeine promotes important alterations in neuromotor development. These results highlight the ability of maternal caffeine intake to interfere with cholinergic neurotransmission during brain development. PMID:25451122

  9. Altered Brain Activities Associated with Neural Repetition Effects in Mild Cognitive Impairment Patients.

    PubMed

    Yu, Jing; Li, Rui; Jiang, Yang; Broster, Lucas S; Li, Juan

    2016-05-11

    Older adults with mild cognitive impairment (MCI) manifest impaired explicit memory. However, studies on implicit memory such as repetition effects in persons with MCI have been limited. In the present study, 17 MCI patients and 16 healthy normal controls (NC) completed a modified delayed-match-to-sample task while undergoing functional magnetic resonance imaging. We aim to examine the neural basis of repetition; specifically, to elucidate whether and how repetition-related brain responses are altered in participants with MCI. When repeatedly rejecting distracters, both NC and MCI showed similar behavioral repetition effects; however, in both whole-brain and region-of-interest analyses of functional data, persons with MCI showed reduced repetition-driven suppression in the middle occipital and middle frontal gyrus. Further, individual difference analysis found that activation in the left middle occipital gyrus was positively correlated with rejecting reaction time and negatively correlated with accuracy rate, suggesting a predictor of repetition behavioral performance. These findings provide new evidence to support the view that neural mechanisms of repetition effect are altered in MCI who manifests compensatory repetition-related brain activities along with their neuropathology. PMID:27176074

  10. Epigenetic alteration to activate Bmp2-Smad signaling in Raf-induced senescence

    PubMed Central

    Fujimoto, Mai; Mano, Yasunobu; Anai, Motonobu; Yamamoto, Shogo; Fukuyo, Masaki; Aburatani, Hiroyuki; Kaneda, Atsushi

    2016-01-01

    AIM: To investigate epigenomic and gene expression alterations during cellular senescence induced by oncogenic Raf. METHODS: Cellular senescence was induced into mouse embryonic fibroblasts (MEFs) by infecting retrovirus to express oncogenic Raf (RafV600E). RNA was collected from RafV600E cells as well as MEFs without infection and MEFs with mock infection, and a genome-wide gene expression analysis was performed using microarray. The epigenomic status for active H3K4me3 and repressive H3K27me3 histone marks was analyzed by chromatin immunoprecipitation-sequencing for RafV600E cells on day 7 and for MEFs without infection. These data for Raf-induced senescence were compared with data for Ras-induced senescence that were obtained in our previous study. Gene knockdown and overexpression were done by retrovirus infection. RESULTS: Although the expression of some genes including secreted factors was specifically altered in either Ras- or Raf-induced senescence, many genes showed similar alteration pattern in Raf- and Ras-induced senescence. A total of 841 commonly upregulated 841 genes and 573 commonly downregulated genes showed a significant enrichment of genes related to signal and secreted proteins, suggesting the importance of alterations in secreted factors. Bmp2, a secreted protein to activate Bmp2-Smad signaling, was highly upregulated with gain of H3K4me3 and loss of H3K27me3 during Raf-induced senescence, as previously detected in Ras-induced senescence, and the knockdown of Bmp2 by shRNA lead to escape from Raf-induced senescence. Bmp2-Smad inhibitor Smad6 was strongly repressed with H3K4me3 loss in Raf-induced senescence, as detected in Ras-induced senescence, and senescence was also bypassed by Smad6 induction in Raf-activated cells. Different from Ras-induced senescence, however, gain of H3K27me3 did not occur in the Smad6 promoter region during Raf-induced senescence. When comparing genome-wide alteration between Ras- and Raf-induced senescence, genes

  11. A bifunctional enzyme from Rhodococcus erythropolis exhibiting secondary alcohol dehydrogenase-catalase activities.

    PubMed

    Martinez-Rojas, Enriqueta; Kurt, Tutku; Schmidt, Udo; Meyer, Vera; Garbe, Leif-Alexander

    2014-11-01

    Alcohol dehydrogenases have long been recognized as potential biocatalyst for production of chiral fine and bulk chemicals. They are relevant for industry in enantiospecific production of chiral compounds. In this study, we identified and purified a nicotinamide adenine dinucleotide (NAD)-dependent secondary alcohol dehydrogenase (SdcA) from Rhodococcus erythropolis oxidizing γ-lactols into γ-lactones. SdcA showed broad substrate specificity on γ-lactols; secondary aliphatic alcohols with 8 and 10 carbon atoms were also substrates and oxidized with (2S)-stereospecificity. The enzyme exhibited moderate stability with a half-life of 5 h at 40 °C and 20 days at 4 °C. Mass spectrometric identification revealed high sequence coverage of SdcA amino acid sequence to a highly conserved catalase from R. erythropolis. The corresponding encoding gene was isolated from genomic DNA and subsequently overexpressed in Escherichia coli BL21 DE3 cells. In addition, the recombinant SdcA was purified and characterized in order to confirm that the secondary alcohol dehydrogenase and catalase activity correspond to the same enzyme. PMID:24846734

  12. A semisynthetic strategy leads to alteration of the backbone amidate ligand in the NiSOD active site

    DOE PAGESBeta

    Campeciño, Julius O.; Dudycz, Lech W.; Tumelty, David; Berg, Volker; Cabelli, Diane E.; Maroney, Michael J.

    2015-07-01

    Computational investigations have implicated the amidate ligand in nickel superoxide dismutase (NiSOD) in stabilizing Ni-centered redox catalysis and in preventing cysteine thiolate ligand oxidation. To test these predictions, we have used an experimental approach utilizing a semisynthetic scheme that employs native chemical ligation of a pentapeptide (HCDLP) to recombinant S. coelicolor NiSOD lacking these N-terminal residues, NΔ5-NiSOD. Wild-type enzyme produced in this manner exhibits the characteristic spectral properties of recombinant WT-NiSOD and is as catalytically active. The semisynthetic scheme was also employed to construct a variant where the amidate ligand was converted to a secondary amine, H1*-NiSOD, a novel strategymore » that retains a backbone N-donor atom. The H1*-NiSOD variant was found to have only ~1% of the catalytic activity of the recombinant wild-type enzyme, and had altered spectroscopic properties. X-ray absorption spectroscopy reveals a four-coordinate planar site with N2S2-donor ligands, consistent with electronic absorption spectroscopic results indicating that the Ni center in H1*-NiSOD is mostly reduced in the as-isolated sample, as opposed to 50:50 Ni(II)/Ni(III) mixture that is typical for the recombinant wild-type enzyme. The EPR spectrum of as-isolated H1*-NiSOD accounts for ~11% of the Ni in the sample and is similar to WT-NiSOD, but more axial, with gz < gx,y. 14N-hyperfine is observed on gz« less

  13. Altered temporal variance and neural synchronization of spontaneous brain activity in anesthesia.

    PubMed

    Huang, Zirui; Wang, Zhiyao; Zhang, Jianfeng; Dai, Rui; Wu, Jinsong; Li, Yuan; Liang, Weimin; Mao, Ying; Yang, Zhong; Holland, Giles; Zhang, Jun; Northoff, Georg

    2014-11-01

    Recent studies at the cellular and regional levels have pointed out the multifaceted importance of neural synchronization and temporal variance of neural activity. For example, neural synchronization and temporal variance has been shown by us to be altered in patients in the vegetative state (VS). This finding nonetheless leaves open the question of whether these abnormalities are specific to VS or rather more generally related to the absence of consciousness. The aim of our study was to investigate the changes of inter- and intra-regional neural synchronization and temporal variance of resting state activity in anesthetic-induced unconsciousness state. Applying an intra-subject design, we compared resting state activity in functional magnetic resonance imaging (fMRI) between awake versus anesthetized states in the same subjects. Replicating previous studies, we observed reduced functional connectivity within the default mode network (DMN) and thalamocortical network in the anesthetized state. Importantly, intra-regional synchronization as measured by regional homogeneity (ReHo) and temporal variance as measured by standard deviation (SD) of the BOLD signal were significantly reduced in especially the cortical midline regions, while increased in the lateral cortical areas in the anesthetized state. We further found significant frequency-dependent effects of SD in the thalamus, which showed abnormally high SD in Slow-5 (0.01-0.027 Hz) in the anesthetized state. Our results show for the first time of altered temporal variance of resting state activity in anesthesia. Combined with our findings in the vegetative state, these findings suggest a close relationship between temporal variance, neural synchronization and consciousness. PMID:24867379

  14. Primary centers and secondary concentrations of tectonic activity through time in the western hemisphere of Mars

    USGS Publications Warehouse

    Anderson, R.C.; Dohm, J.M.; Golombek, M.P.; Haldemann, A.F.C.; Franklin, B.J.; Tanaka, K.L.; Lias, J.; Peer, B.

    2001-01-01

    Five main stages of radial and concentric structures formed around Tharsis from the Noachian through the Amazonian as determined by geologic mapping of 24,452 structures within the stratigraphic framework of Mars and by testing their radial and concentric orientations. Tectonic activity peaked in the Noachian (stage 1) around the largest center, Claritas, an elongate center extending more than 20?? in latitude and defined by about half of the total grabens which are concentrated in the Syria Planum, Thaumasia, and Tempe Terra regions. During the Late Noachian and Early Hesperian (stage 2), extensional structures formed along the length of present-day Valles Marineris and in Thaumasia (with a secondary concentration near Warrego Vallis) radial to a region just to the south of the central margin of Valles Marineris. Early Hesperian (stage 3) radial grabens in Pavonis, Syria, Ulysses, and Tempe Terra and somewhat concentric wrinkle ridges in Lunae and Solis Plana and in Thaumasia, Sirenum, Memnonia, and Amazonis are centered northwest of Syria with secondary centers at Thaumasia, Tempe Terra, Ulysses Fossae, and western Valles Marineris. Late Hesperian/Early Amazonian (stage 4) structures around Alba Patera, the northeast trending alignment of Tharsis Montes, and Olympus Mons appears centered on Alba Patera. Stage 5 structures (Middle-Late Amazonian) represent the last pulse of Tharsis-related activity and are found around the large shield volcanoes and are centered near Pavonis Mons. Tectonic activity around Tharsis began in the Noachian and generally decreased through geologic time to the Amazonian. Statistically significant radial distributions of structures formed during each stage, centered at different locations within the higher elevations of Tharsis. Secondary centers of radial structures during many of the stages appear related to previously identified local magmatic centers that formed at different times and locations throughout Tharsis. Copyright 2001 by

  15. Vitamin D3 alters microglia immune activation by an IL-10 dependent SOCS3 mechanism.

    PubMed

    Boontanrart, Mandy; Hall, Samuel D; Spanier, Justin A; Hayes, Colleen E; Olson, Julie K

    2016-03-15

    Microglia become activated immune cells during infection or disease in the central nervous system (CNS). However, the mechanisms that downregulate activated microglia to prevent immune-mediated damage are not completely understood. Vitamin D3 has been suggested to have immunomodulatory affects, and high levels of vitamin D3 have been correlated with a decreased risk for developing some neurological diseases. Recent studies have demonstrated the synthesis of active vitamin D3, 1,25-dihydroxyvitamin D3, within the CNS, but its cellular source and neuroprotective actions remain unknown. Therefore, we wanted to determine whether microglia can respond to vitamin D3 and whether vitamin D3 alters immune activation of microglia. We have previously shown that microglia become activated by IFNγ or LPS or by infection with virus to express pro-inflammatory cytokines, chemokines, and effector molecules. In this study, activated microglia increased the expression of the vitamin D receptor and Cyp27b1, which encodes the enzyme for converting vitamin D3 into its active form, thereby enhancing their responsiveness to vitamin D3. Most importantly, the activated microglia exposed to vitamin D3 had reduced expression of pro-inflammatory cytokines, IL-6, IL-12, and TNFα, and increased expression of IL-10. The reduction in pro-inflammatory cytokines was dependent on IL-10 induction of suppressor of cytokine signaling-3 (SOCS3). Therefore, vitamin D3 increases the expression of IL-10 creating a feedback loop via SOCS3 that downregulates the pro-inflammatory immune response by activated microglia which would likewise prevent immune mediated damage in the CNS. PMID:26943970

  16. Modeling Secondary Organic Aerosols over Europe: Impact of Activity Coefficients and Viscosity

    NASA Astrophysics Data System (ADS)

    Kim, Y.; Sartelet, K.; Couvidat, F.

    2014-12-01

    Semi-volatile organic species (SVOC) can condense on suspended particulate materials (PM) in the atmosphere. The modeling of condensation/evaporation of SVOC often assumes that gas-phase and particle-phase concentrations are at equilibrium. However, recent studies show that secondary organic aerosols (SOA) may not be accurately represented by an equilibrium approach between the gas and particle phases, because organic aerosols in the particle phase may be very viscous. The condensation in the viscous liquid phase is limited by the diffusion from the surface of PM to its core. Using a surrogate approach to represent SVOC, depending on the user's choice, the secondary organic aerosol processor (SOAP) may assume equilibrium or model dynamically the condensation/evaporation between the gas and particle phases to take into account the viscosity of organic aerosols. The model is implemented in the three-dimensional chemistry-transport model of POLYPHEMUS. In SOAP, activity coefficients for organic mixtures can be computed using UNIFAC for short-range interactions between molecules and AIOMFAC to also take into account the effect of inorganic species on activity coefficients. Simulations over Europe are performed and POLYPHEMUS/SOAP is compared to POLYPHEMUS/H2O, which was previously used to model SOA using the equilibrium approach with activity coefficients from UNIFAC. Impacts of the dynamic approach on modeling SOA over Europe are evaluated. The concentrations of SOA using the dynamic approach are compared with those using the equilibrium approach. The increase of computational cost is also evaluated.

  17. Chronic social stress in puberty alters appetitive male sexual behavior and neural metabolic activity.

    PubMed

    Bastida, Christel C; Puga, Frank; Gonzalez-Lima, Francisco; Jennings, Kimberly J; Wommack, Joel C; Delville, Yvon

    2014-07-01

    Repeated social subjugation in early puberty lowers testosterone levels. We used hamsters to investigate the effects of social subjugation on male sexual behavior and metabolic activity within neural systems controlling social and motivational behaviors. Subjugated animals were exposed daily to aggressive adult males in early puberty for postnatal days 28 to 42, while control animals were placed in empty clean cages. On postnatal day 45, they were tested for male sexual behavior in the presence of receptive female. Alternatively, they were tested for mate choice after placement at the base of a Y-maze containing a sexually receptive female in one tip of the maze and an ovariectomized one on the other. Social subjugation did not affect the capacity to mate with receptive females. Although control animals were fast to approach females and preferred ovariectomized individuals, subjugated animals stayed away from them and showed no preference. Cytochrome oxidase activity was reduced within the preoptic area and ventral tegmental area in subjugated hamsters. In addition, the correlation of metabolic activity of these areas with the bed nucleus of the stria terminalis and anterior parietal cortex changed significantly from positive in controls to negative in subjugated animals. These data show that at mid-puberty, while male hamsters are capable of mating, their appetitive sexual behavior is not fully mature and this aspect of male sexual behavior is responsive to social subjugation. Furthermore, metabolic activity and coordination of activity in brain areas related to sexual behavior and motivation were altered by social subjugation. PMID:24852486

  18. Chronic Social Stress in Puberty Alters Appetitive Male Sexual Behavior and Neural Metabolic Activity

    PubMed Central

    Bastida, Christel C.; Puga, Frank; Gonzalez-Lima, Francisco; Jennings, Kimberly J.; Wommack, Joel C.; Delville, Yvon

    2014-01-01

    Repeated social subjugation in early puberty lowers testosterone levels. We used hamsters to investigate the effects of social subjugation on male sexual behavior and metabolic activity within neural systems controlling social and motivational behaviors. Subjugated animals were exposed daily to aggressive adult males in early puberty for postnatal days 28 to 42, while control animals were placed in empty clean cages. On postnatal day 45, they were tested for male sexual behavior in the presence of receptive female. Alternatively, they were tested for mate choice after placement at the base of a Y-maze containing a sexually receptive female in one tip of the maze and an ovariectomized one on the other. Social subjugation did not affect the capacity to mate with receptive females. Although control animals were fast to approach females and preferred ovariectomized individuals, subjugated animals stayed away from them and showed no preference. Cytochrome oxidase activity was reduced within the preoptic area and ventral tegmental area in subjugated hamsters. In addition, the correlation of metabolic activity of these areas with the bed nucleus of the stria terminalis and anterior parietal cortex changed significantly from positive in controls to negative in subjugated animals. These data show that at mid-puberty, while male hamsters are capable of mating, their appetitive sexual behavior is not fully mature and this aspect of male sexual behavior is responsive to social subjugation. Furthermore, metabolic activity and coordination of activity in brain areas related to sexual behavior and motivation was altered by social subjugation. PMID:24852486

  19. Regulation and activity of secretory leukoprotease inhibitor (SLPI) is altered in smokers.

    PubMed

    Meyer, Megan; Bauer, Rebecca N; Letang, Blanche D; Brighton, Luisa; Thompson, Elizabeth; Simmen, Rosalia C M; Bonner, James; Jaspers, Ilona

    2014-02-01

    A hallmark of cigarette smoking is a shift in the protease/antiprotease balance, in favor of protease activity. However, it has recently been shown that smokers have increased expression of a key antiprotease, secretory leukoprotease inhibitor (SLPI), yet the mechanisms involved in SLPI transcriptional regulation and functional activity of SLPI remain unclear. We examined SLPI mRNA and protein secretion in differentiated nasal epithelial cells (NECs) and nasal lavage fluid (NLF) from nonsmokers and smokers and demonstrated that SLPI expression is increased in NECs and NLF from smokers. Transcriptional regulation of SLPI expression was confirmed using SLPI promoter reporter assays followed by chromatin immunoprecipitation. The role of STAT1 in regulating SLPI expression was further elucidated using WT and stat1(-/-) mice. Our data demonstrate that STAT1 regulates SLPI transcription in epithelial cells and slpi protein in the lungs of mice. Additionally, we reveal that NECs from smokers have increased STAT1 mRNA/protein expression. Finally, we demonstrate that SLPI contained in the nasal mucosa of smokers is proteolytically cleaved but retains functional activity against neutrophil elastase. These results demonstrate that smoking enhances expression of SLPI in NECs in vitro and in vivo, and that this response is regulated by STAT1. In addition, despite posttranslational cleavage of SLPI, antiprotease activity against neutrophil elastase is enhanced in smokers. Together, our findings show that SLPI regulation and activity is altered in the nasal mucosa of smokers, which could have broad implications in the context of respiratory inflammation and infection. PMID:24285265

  20. Altered resting-state functional activity in posttraumatic stress disorder: A quantitative meta-analysis

    PubMed Central

    Wang, Ting; Liu, Jia; Zhang, Junran; Zhan, Wang; Li, Lei; Wu, Min; Huang, Hua; Zhu, Hongyan; Kemp, Graham J.; Gong, Qiyong

    2016-01-01

    Many functional neuroimaging studies have reported differential patterns of spontaneous brain activity in posttraumatic stress disorder (PTSD), but the findings are inconsistent and have not so far been quantitatively reviewed. The present study set out to determine consistent, specific regional brain activity alterations in PTSD, using the Effect Size Signed Differential Mapping technique to conduct a quantitative meta-analysis of resting-state functional neuroimaging studies of PTSD that used either a non-trauma (NTC) or a trauma-exposed (TEC) comparison control group. Fifteen functional neuroimaging studies were included, comparing 286 PTSDs, 203 TECs and 155 NTCs. Compared with NTC, PTSD patients showed hyperactivity in the right anterior insula and bilateral cerebellum, and hypoactivity in the dorsal medial prefrontal cortex (mPFC); compared with TEC, PTSD showed hyperactivity in the ventral mPFC. The pooled meta-analysis showed hypoactivity in the posterior insula, superior temporal, and Heschl’s gyrus in PTSD. Additionally, subgroup meta-analysis (non-medicated subjects vs. NTC) identified abnormal activation in the prefrontal-limbic system. In meta-regression analyses, mean illness duration was positively associated with activity in the right cerebellum (PTSD vs. NTC), and illness severity was negatively associated with activity in the right lingual gyrus (PTSD vs. TEC). PMID:27251865

  1. Altered resting-state functional activity in posttraumatic stress disorder: A quantitative meta-analysis.

    PubMed

    Wang, Ting; Liu, Jia; Zhang, Junran; Zhan, Wang; Li, Lei; Wu, Min; Huang, Hua; Zhu, Hongyan; Kemp, Graham J; Gong, Qiyong

    2016-01-01

    Many functional neuroimaging studies have reported differential patterns of spontaneous brain activity in posttraumatic stress disorder (PTSD), but the findings are inconsistent and have not so far been quantitatively reviewed. The present study set out to determine consistent, specific regional brain activity alterations in PTSD, using the Effect Size Signed Differential Mapping technique to conduct a quantitative meta-analysis of resting-state functional neuroimaging studies of PTSD that used either a non-trauma (NTC) or a trauma-exposed (TEC) comparison control group. Fifteen functional neuroimaging studies were included, comparing 286 PTSDs, 203 TECs and 155 NTCs. Compared with NTC, PTSD patients showed hyperactivity in the right anterior insula and bilateral cerebellum, and hypoactivity in the dorsal medial prefrontal cortex (mPFC); compared with TEC, PTSD showed hyperactivity in the ventral mPFC. The pooled meta-analysis showed hypoactivity in the posterior insula, superior temporal, and Heschl's gyrus in PTSD. Additionally, subgroup meta-analysis (non-medicated subjects vs. NTC) identified abnormal activation in the prefrontal-limbic system. In meta-regression analyses, mean illness duration was positively associated with activity in the right cerebellum (PTSD vs. NTC), and illness severity was negatively associated with activity in the right lingual gyrus (PTSD vs. TEC). PMID:27251865

  2. Nrf2 Activation Promotes Keratinocyte Survival during Early Skin Carcinogenesis via Metabolic Alterations.

    PubMed

    Rolfs, Frank; Huber, Marcel; Kuehne, Andreas; Kramer, Stefan; Haertel, Eric; Muzumdar, Sukalp; Wagner, Johanna; Tanner, Yasmine; Böhm, Friederike; Smola, Sigrun; Zamboni, Nicola; Levesque, Mitchell P; Dummer, Reinhard; Beer, Hans-Dietmar; Hohl, Daniel; Werner, Sabine; Schäfer, Matthias

    2015-11-15

    Pharmacologic activation of the transcription factor NRF2 has been suggested to offer a strategy for cancer prevention. In this study, we present evidence from murine tumorigenesis experiments suggesting there may be limitations to this possibility, based on tumorigenic effects of Nrf2 in murine keratinocytes that have not been described previously. In this setting, Nrf2 expression conferred metabolic alterations in keratinocytes that were protumorigenic in nature, affecting enzymes involved in glutathione biosynthesis or in the oxidative pentose phosphate pathway and other NADPH-producing enzymes. Under stress conditions, coordinate increases in NADPH, purine, and glutathione levels promoted the survival of keratinocytes harboring oncogenic mutations, thereby promoting tumor development. The protumorigenic activity of Nrf2 in keratinocytes was particularly significant in a mouse model of skin tumorigenesis that did not rely upon chemical carcinogenesis. In exploring the clinical relevance of our findings, we confirm that NRF2 and protumorigenic NRF2 target genes were activated in some actinic keratoses, the major precancerous lesion in human skin. Overall, our results reveal an unexpected tumor-promoting activity of activated NRF2 during early phases of skin tumorigenesis. PMID:26530903

  3. Evaluation of Potential Clinical Surrogate Markers of a Trauma Induced Alteration of Clotting Factor Activities

    PubMed Central

    Payas, Arzu; Schoeneberg, Carsten; Wegner, Alexander; Kauther, Max Daniel; Lendemans, Sven

    2016-01-01

    Objective. The aim of this study was to identify routinely available clinical surrogate markers for potential clotting factor alterations following multiple trauma. Methods. In 68 patients admitted directly from the scene of the accident, all soluble clotting factors were analyzed and clinical data was collected prospectively. Ten healthy subjects served as control group. Results. Patients showed reduced activities of clotting factors II, V, VII, and X and calcium levels (all P < 0.0001 to 0.01). Levels of hemoglobin and base deficit correlated moderately to highly with the activities of a number of clotting factors. Nonsurvivors and patients who needed preclinical intubation or hemostatic therapy showed significantly reduced factor activities at admission. In contrast, factor VIII activity was markedly elevated after injury in general (P < 0.0001), but reduced in nonsurvivors (P < 0.05). Conclusions. Multiple trauma causes an early reduction of the activities of nearly all soluble clotting factors in general. Initial hemoglobin and, with certain qualifications, base deficit levels demonstrated a potential value in detecting those underlying clotting factor deficiencies. Nevertheless, their role as triggers of a hemostatic therapy as well as the observed response of factor VIII to multiple trauma and also its potential prognostic value needs further evaluation. PMID:27433474

  4. Tics are caused by alterations in prefrontal areas, thalamus and putamen, while changes in the cingulate gyrus reflect secondary compensatory mechanisms

    PubMed Central

    2014-01-01

    Background Despite strong evidence that the pathophysiology of Tourette syndrome (TS) involves structural and functional disturbances of the basal ganglia and cortical frontal areas, findings from in vivo imaging studies have provided conflicting results. In this study we used whole brain diffusion tensor imaging (DTI) to investigate the microstructural integrity of white matter pathways and brain tissue in 19 unmedicated, adult, male patients with TS “only” (without comorbid psychiatric disorders) and 20 age- and sex-matched control subjects. Results Compared to normal controls, TS patients showed a decrease in the fractional anisotropy index (FA) bilaterally in the medial frontal gyrus, the pars opercularis of the left inferior frontal gyrus, the middle occipital gyrus, the right cingulate gyrus, and the medial premotor cortex. Increased apparent diffusion coefficient (ADC) maps were detected in the left cingulate gyrus, prefrontal areas, left precentral gyrus, and left putamen. There was a negative correlation between tic severity and FA values in the left superior frontal gyrus, medial frontal gyrus bilaterally, cingulate gyrus bilaterally, and ventral posterior lateral nucleus of the right thalamus, and a positive correlation in the body of the corpus callosum, left thalamus, right superior temporal gyrus, and left parahippocampal gyrus. There was also a positive correlation between regional ADC values and tic severity in the left cingulate gyrus, putamen bilaterally, medial frontal gyrus bilaterally, left precentral gyrus, and ventral anterior nucleus of the left thalamus. Conclusions Our results confirm prior studies suggesting that tics are caused by alterations in prefrontal areas, thalamus and putamen, while changes in the cingulate gyrus seem to reflect secondary compensatory mechanisms. Due to the study design, influences from comorbidities, gender, medication and age can be excluded. PMID:24397347

  5. Activation of the oncogenic potential of the avian cellular src protein by specific structural alteration of the carboxy terminus.

    PubMed Central

    Reynolds, A B; Vila, J; Lansing, T J; Potts, W M; Weber, M J; Parsons, J T

    1987-01-01

    The role of tyrosine phosphorylation in the regulation of tyrosine protein kinase activity was investigated using site-directed mutagenesis to alter the structure and environment of the three tyrosine residues present in the C terminus of avian pp60c-src. Mutations that change Tyr 527 to Phe or Ser activate in vivo tyrosine protein kinase activity and induce cellular transformation of chicken cells in culture. In contrast, alterations of tyrosine residues present at positions 511 or 519 in c-src do not induce transformation or in vivo tyrosine protein kinase activity. Amber mutations, which alter the structure of the pp60c-src C terminus by inducing premature termination of the c-src protein at either residue 518 or 523 also induce morphological transformation and increase in vivo tyrosine phosphorylation, whereas removal of the last four residues of c-src by chain termination at residue 530 does not alter the kinase activity or the biological activity of the resultant c-src protein. We conclude from these studies that C-terminal alterations which either remove or replace Tyr 527 serve to activate the c-src protein resulting in cellular transformation and increased in vivo tyrosine protein kinase activity. Images Fig. 2. Fig. 3. Fig. 4. PMID:2822389

  6. Leptin in nucleus of the solitary tract alters the cardiovascular responses to aortic baroreceptor activation.

    PubMed

    Ciriello, John

    2013-06-01

    Recent data suggests that neurons expressing the long form of the leptin receptor form at least two distinct groups within the caudal nucleus of the solitary tract (NTS): a group within the lateral NTS (Slt) and one within the medial (Sm) and gelantinosa (Sg) NTS. Discrete injections of leptin into Sm and Sg, a region that receives chemoreceptor input, elicit increases in arterial pressure (AP) and renal sympathetic nerve activity (RSNA). However, the effect of microinjections of leptin into Slt, a region that receives baroreceptor input is unknown. Experiments were done in the urethane-chloralose anesthetized, paralyzed and artificially ventilated Wistar or Zucker obese rat to determine leptin's effect in Slt on heart rate (HR), AP and RSNA during electrical stimulation of the aortic depressor nerve (ADN). Depressor sites within Slt were first identified by the microinjection of l-glutamate (Glu; 0.25M; 10nl) followed by leptin microinjections. In the Wistar rat leptin microinjection (50ng; 20nl) into depressor sites within the lateral Slt elicited increases in HR and RSNA, but no changes in AP. Additionally, leptin injections into Slt prior to Glu injections at the same site or to stimulation of the ADN were found to attenuate the decreases in HR, AP and RSNA to both the Glu injection and ADN stimulation. In Zucker obese rats, leptin injections into NTS depressor sites did not elicit cardiovascular responses, nor altered the cardiovascular responses elicited by stimulation of ADN. Those data suggest that leptin acts at the level of NTS to alter the activity of neurons that mediate the cardiovascular responses to activation of the aortic baroreceptor reflex. PMID:23535030

  7. Altered Skeletal Muscle Lipase Expression and Activity Contribute to Insulin Resistance in Humans

    PubMed Central

    Badin, Pierre-Marie; Louche, Katie; Mairal, Aline; Liebisch, Gerhard; Schmitz, Gerd; Rustan, Arild C.; Smith, Steven R.; Langin, Dominique; Moro, Cedric

    2011-01-01

    OBJECTIVE Insulin resistance is associated with elevated content of skeletal muscle lipids, including triacylglycerols (TAGs) and diacylglycerols (DAGs). DAGs are by-products of lipolysis consecutive to TAG hydrolysis by adipose triglyceride lipase (ATGL) and are subsequently hydrolyzed by hormone-sensitive lipase (HSL). We hypothesized that an imbalance of ATGL relative to HSL (expression or activity) may contribute to DAG accumulation and insulin resistance. RESEARCH DESIGN AND METHODS We first measured lipase expression in vastus lateralis biopsies of young lean (n = 9), young obese (n = 9), and obese-matched type 2 diabetic (n = 8) subjects. We next investigated in vitro in human primary myotubes the impact of altered lipase expression/activity on lipid content and insulin signaling. RESULTS Muscle ATGL protein was negatively associated with whole-body insulin sensitivity in our population (r = −0.55, P = 0.005), whereas muscle HSL protein was reduced in obese subjects. We next showed that adenovirus-mediated ATGL overexpression in human primary myotubes induced DAG and ceramide accumulation. ATGL overexpression reduced insulin-stimulated glycogen synthesis (−30%, P < 0.05) and disrupted insulin signaling at Ser1101 of the insulin receptor substrate-1 and downstream Akt activation at Ser473. These defects were fully rescued by nonselective protein kinase C inhibition or concomitant HSL overexpression to restore a proper lipolytic balance. We show that selective HSL inhibition induces DAG accumulation and insulin resistance. CONCLUSIONS Altogether, the data indicate that altered ATGL and HSL expression in skeletal muscle could promote DAG accumulation and disrupt insulin signaling and action. Targeting skeletal muscle lipases may constitute an interesting strategy to improve insulin sensitivity in obesity and type 2 diabetes. PMID:21498783

  8. Inhibiting activator protein-1 activity alters cocaine-induced gene expression and potentiates sensitization.

    PubMed

    Paletzki, R F; Myakishev, M V; Polesskaya, O; Orosz, A; Hyman, S E; Vinson, C

    2008-04-01

    We have expressed A-FOS, an inhibitor of activator protein-1 (AP-1) DNA binding, in adult mouse striatal neurons. We observed normal behavior including locomotion and exploratory activities. Following a single injection of cocaine, locomotion increased similarly in both the A-FOS expressing and littermate controls. However, following repeated injections of cocaine, the A-FOS expressing mice showed increased locomotion relative to littermate controls, an increase that persisted following a week of withdrawal and subsequent cocaine administration. These results indicate that AP-1 suppresses this behavioral response to cocaine. We analyzed mRNA from the striatum before and 4 and 24 h after a single cocaine injection in both A-FOS and control striata using Affymetrix microarrays (430 2.0 Array) to identify genes mis-regulated by A-FOS that may mediate the increased locomotor sensitization to cocaine. A-FOS expression did not change gene expression in the basal state or 4 h following cocaine treatment relative to controls. However, 24 h after an acute cocaine treatment, 84 genes were identified that were differentially expressed between the A-FOS and control mice. Fifty-six genes are down-regulated while 28 genes are up-regulated including previously identified candidates for addiction including brain-derived neurotrophic factor and period homolog 1. Using a random sample of identified genes, quantitative PCR was used to verify the microarray studies. The chromosomal location of these 84 genes was compared with human genome scans of addiction to identify potential genes in humans that are involved in addiction. PMID:18355967

  9. Alterations in cardiac sarcolemmal Ca/sup 2 +/ pump activity during diabetes mellitus

    SciTech Connect

    Heyliger, C.E.; Prakash, A.; McNeill, J.

    1987-03-01

    Diabetes mellitus is frequently associated with a primary cardiomyopathy. The mechanisms responsible for this heart disease are not clear, but an alteration in myocardial Ca/sup 2 +/ transport is believed to be involved in its development. Even though sarcolemma plays a crucial role in cellular Ca/sup 2 +/ transport, little appears to be known about its Ca/sup 2 +/ transporting capability in the diabetic myocardium. In this regard, the authors have examined the status of the cardiac sarcolemmal Ca/sup 2 +/ pump during diabetes mellitus. Purified sarcolemmal membranes were isolated from male Wistar diabetic rat hearts 8 wk after streptozotocin injection. Ca/sup 2 +/ pump activity assessed by measuring its Ca/sup 2 +/-stimulated adenosine triphosphatase and Ca/sup 2 +/-uptake ability in the absence and presence of calmodulin was significantly depressed in the diabetic myocardium relative to controls. These results did not appear to have been influenced by the minimal sarcoplasmic reticular and mitochondrial contamination of this membrane preparation. Hence, it appears that the sarcolemmal Ca/sup 2 +/ pump is defective in the diabetic myocardium and may be involved in the altered Ca/sup 2 +/ transport of the heart during diabetes mellitus.

  10. Leukemia-associated activating mutation of Flt3 expands dendritic cells and alters T cell responses.

    PubMed

    Lau, Colleen M; Nish, Simone A; Yogev, Nir; Waisman, Ari; Reiner, Steven L; Reizis, Boris

    2016-03-01

    A common genetic alteration in acute myeloid leukemia is the internal tandem duplication (ITD) in FLT3, the receptor for cytokine FLT3 ligand (FLT3L). Constitutively active FLT3-ITD promotes the expansion of transformed progenitors, but also has pleiotropic effects on hematopoiesis. We analyzed the effect of FLT3-ITD on dendritic cells (DCs), which express FLT3 and can be expanded by FLT3L administration. Pre-leukemic mice with the Flt3(ITD) knock-in allele manifested an expansion of classical DCs (cDCs) and plasmacytoid DCs. The expansion originated in DC progenitors, was cell intrinsic, and was further enhanced in Flt3(ITD/ITD) mice. The mutation caused the down-regulation of Flt3 on the surface of DCs and reduced their responsiveness to Flt3L. Both canonical Batf3-dependent CD8(+) cDCs and noncanonical CD8(+) cDCs were expanded and showed specific alterations in their expression profiles. Flt3(ITD) mice showed enhanced capacity to support T cell proliferation, including a cell-extrinsic expansion of regulatory T (T reg) cells. Accordingly, these mice restricted alloreactive T cell responses during graft-versus-host reaction, but failed to control autoimmunity without T reg cells. Thus, the FLT3-ITD mutation directly affects DC development, indirectly modulating T cell homeostasis and supporting T reg cell expansion. We hypothesize that this effect of FLT3-ITD might subvert immunosurveillance and promote leukemogenesis in a cell-extrinsic manner. PMID:26903243

  11. Altered patterns of cortical activation in ALS patients during attention and cognitive response inhibition tasks.

    PubMed

    Goldstein, L H; Newsom-Davis, I C; Bryant, V; Brammer, M; Leigh, P N; Simmons, A

    2011-12-01

    Since amyotrophic lateral sclerosis (ALS) can be accompanied by executive dysfunction, it is hypothesised that ALS patients will have impaired performance on tests of cognitive inhibition. We predicted that ALS patients would show patterns of abnormal activation in extramotor regions when performing tests requiring the inhibition of prepotent responses (the Stroop effect) and the inhibition of prior negatively primed responses (the negative priming effect) when compared to healthy controls. Functional magnetic resonance imaging was used to measure activation during a sparse sequence block design paradigm investigating the Stroop and negative priming effects in 14 ALS patients and 8 healthy age- and IQ-matched controls. Behavioural measures of performance were collected. Both groups' reaction times (RTs) reflected the Stroop effect during scanning. The ALS and control groups did not differ significantly for any of the behavioural measures but did show significant differences in cerebral activation during both tasks. The ALS group showed increased activation predominantly in the left middle temporal gyrus (BA 20/21), left superior temporal gyrus (BA 22) and left anterior cingulate gyrus (BA 32). Neither group's RT data showed clear evidence of a negative priming effect. However the ALS group showed decreased activation, relative to controls, particularly in the left cingulate gyrus (BA 23/24), left precentral gyrus (BA 4/6) and left medial frontal gyrus (BA 6). Greater cerebral activation in the ALS group accompanying the performance of the Stroop effect and areas of decreased activation during the negative priming comparison suggest altered inhibitory processing in ALS, consistent with other evidence of executive dysfunction in ALS. The current findings require further exploration in a larger study. PMID:21556876

  12. Childhood maltreatment is associated with altered frontolimbic neurobiological activity during wakefulness in adulthood

    PubMed Central

    Insana, Salvatore P.; Banihashemi, Layla; Herringa, Ryan J.; Kolko, David J.; Germain, Anne

    2015-01-01

    Childhood maltreatment can disturb brain development, and subsequently lead to adverse socioemotional and mental health problems across the lifespan. The long-term association between childhood maltreatment and resting-wake brain activity during adulthood is unknown and was examined in the current study. Forty one medically stable and medication-free military veterans (M=29.31±6.01 years, 78% male) completed a battery of clinical assessments and had [18F]-fluorodeoxyglucose positron emission tomography neuroimaging scans during quiet wakefulness. After statistically adjusting for later-life trauma and mental health problems, childhood maltreatment was negatively associated with brain activity within a-priori defined regions that included the left orbital frontal cortex and left hippocampus. Childhood maltreatment was significantly associated with increased and decreased brain activity within six additional whole-brain clusters that included frontal, parietal-temporal, cerebellar, limbic, and midbrain regions. Childhood maltreatment is associated with altered neural activity in adulthood within regions that are involved in executive functioning and cognitive control, socioemotional processes, autonomic functions, and sleep/wake regulation. This study provides support for taking a lifespan developmental approach to understanding the effects of early-life maltreatment on later-life neurobiology, socioemotional functioning, and mental health. PMID:26198818

  13. Chronic methylphenidate alters locomotor activity and dopamine transporters differently from cocaine.

    PubMed

    Izenwasser, S; Coy, A E; Ladenheim, B; Loeloff, R J; Cadet, J L; French, D

    1999-06-01

    Continuous infusion of cocaine produces partial behavioral tolerance to its locomotor activating effects, while daily injections produce sensitization. Methylphenidate binds with a similar affinity to cocaine at the dopamine transporter, but has a much lower affinity for the serotonin transporter than does cocaine. This study was done to compare the effects of chronic methylphenidate with chronic cocaine. The pattern of locomotor activity over a 7 day treatment period was significantly different from cocaine. Methylphenidate elevated activity on each day, compared to saline, yet neither tolerance to a continuous infusion of the drug, nor sensitization to repeated daily injections was produced. We have previously shown that neither of these treatments with cocaine produces significant alterations in dopamine transporter density 1 day after the end of treatment. In contrast, methylphenidate injections significantly decreased dopamine transporters in rostral caudate putamen, with no change in nucleus accumbens. Continuous infusion of methylphenidate had no effect on dopamine transporters in either brain region. These findings provide further evidence that different classes of dopamine uptake inhibitors may interact with the dopamine transporter in qualitatively different manners. Furthermore, it is possible that the inhibition of serotonin uptake by cocaine may contribute to the adaptations in behavioral activity that are seen during chronic treatment. PMID:10414438

  14. Functional insights into modulation of BKCa channel activity to alter myometrial contractility

    PubMed Central

    Lorca, Ramón A.; Prabagaran, Monali; England, Sarah K.

    2014-01-01

    The large-conductance voltage- and Ca2+-activated K+ channel (BKCa) is an important regulator of membrane excitability in a wide variety of cells and tissues. In myometrial smooth muscle, activation of BKCa plays essential roles in buffering contractility to maintain uterine quiescence during pregnancy and in the transition to a more contractile state at the onset of labor. Multiple mechanisms of modulation have been described to alter BKCa channel activity, expression, and cellular localization. In the myometrium, BKCa is regulated by alternative splicing, protein targeting to the plasma membrane, compartmentation in membrane microdomains, and posttranslational modifications. In addition, interaction with auxiliary proteins (i.e., β1- and β2-subunits), association with G-protein coupled receptor signaling pathways, such as those activated by adrenergic and oxytocin receptors, and hormonal regulation provide further mechanisms of variable modulation of BKCa channel function in myometrial smooth muscle. Here, we provide an overview of these mechanisms of BKCa channel modulation and provide a context for them in relation to myometrial function. PMID:25132821

  15. Neonatal exposure to amphetamine alters social affiliation and central dopamine activity in adult male prairie voles.

    PubMed

    Fukushiro, D F; Olivera, A; Liu, Y; Wang, Z

    2015-10-29

    The prairie vole (Microtus ochrogaster) is a socially monogamous rodent species that forms pair bonds after mating. Recent data have shown that amphetamine (AMPH) is rewarding to prairie voles as it induces conditioned place preferences. Further, repeated treatment with AMPH impairs social bonding in adult prairie voles through a central dopamine (DA)-dependent mechanism. The present study examined the effects of neonatal exposure to AMPH on behavior and central DA activity in adult male prairie voles. Our data show that neonatal exposure to AMPH makes voles less social in an affiliation test during adulthood, but does not affect animals' locomotor activity and anxiety-like behavior. Neonatal exposure to AMPH also increases the levels of tyrosine hydroxylase (TH) and DA transporter (DAT) mRNA expression in the ventral tegmental area (VTA) in the brain, indicating an increase in central DA activity. As DA has been implicated in AMPH effects on behavioral and cognitive functions, altered DA activity in the vole brain may contribute to the observed changes in social behavior. PMID:26321240

  16. Responses of Electromyogram Activity in Adductor Longus Muscle of Rats to the Altered Gravity Levels

    NASA Astrophysics Data System (ADS)

    Ohira, Takashi; Wang, Xiao Dong; Terada, Masahiro; Kawano, Fuminori; Higo, Yoko; Nakai, Naoya; Ochiai, Toshimasa; Gyotoku, Jyunichirou; Nishimoto, Norihiro; Ogura, Akihiko; Ohira, Yoshinobu

    2008-06-01

    Responses of electromyogram (EMG) activities in the rostral and caudal regions of adductor longus (AL) muscle to altered gravity levels during parabolic flight of a jet airplane, as well as hindlimb suspension, were investigated in adult rats. Tonic EMGs in both regions were noted when the rats were exposed to hyper-G, as well as 1-G. The hip joints were adducted and the sedental quadrupedal position was maintained at these G levels. However, the EMG activities in these regions decreased and became phasic, when the hip joints were abducted and extended backward in μ-G environment. Such changes of joint angles caused passive shortening of sarcomeres only in the caudal region of AL. Atrophy and shift toward fast-twitch type were noted in fibers of the caudal region after 16-day unloading. Although fiber transformation was also induced in the rostral region, no atrophy was seen in fast-twitch fibers. The data may suggest that the atrophy and shift of phenotype caused by gravitational unloading in fibers of the caudal region may be related to the decrease in the neural and mechanical activities. Fiber type transformation toward fast-twitch type may be also related to the change of muscle activity from tonic to phasic patterns, which are the typical characteristics of fast-twitch muscle. However, the responses to unloading in fibers of rostral region were not related to the reduction of mechanical load.

  17. Diverse clinical compounds alter the quaternary structure and inhibit the activity of an essential enzyme

    PubMed Central

    Lawrence, Sarah H.; Selwood, Trevor; Jaffe, Eileen K.

    2011-01-01

    An in vitro evaluation of the Johns Hopkins Clinical Compound Library demonstrates that certain drugs can alter the quaternary structure of an essential human protein. Human porphobilinogen synthase (HsPBGS) is an essential enzyme involved in heme biosynthesis; it exists as an equilibrium of high activity octamers, low activity hexamers, and alternate dimer configurations that dictate the stoichiometry and architecture of further assembly. Reduced HsPBGS activity is implicated in toxicities associated with lead poisoning and ALAD porphyria, the latter of which involves hexamer-favoring HsPBGS variants. A medium-throughput native PAGE mobility shift screen, coupled with evaluation of hits as HsPBGS inhibitors, revealed twelve drugs that stabilize the HsPBGS hexamer and inhibit HsPBGS activity in vitro. A detailed characterization of these effects is presented. Drug inhibition of HsPBGS in vivo by inducing hexamer formation would constitute an unprecedented mechanism for side effects. We suggest that small molecule perturbation of quaternary structure equilibria be considered as a general mechanism for drug action and side effects. PMID:21506274

  18. Surface Alteration of Activated Carbon for Detoxification of Copper (ii) from Industrial Effluents

    NASA Astrophysics Data System (ADS)

    Bhutto, Sadaf; Khan, M. Nasiruddin

    2013-04-01

    The low-cost modified activated carbons were prepared from Thar and Lakhra (Pakistan) coals by activation with sulfuric acid and further modified with citric, tartaric and acetic acids for the selective adsorption of Cu(II) from aqueous solution. The original carbon obtained from activated Thar and Lakhra coals at pH 3.0 displayed significant adsorption capacity for lead and insignificant capacity values (0.880 and 0.830 mgṡg-1) for copper. However, after modification with citric, tartaric and acetic acid the copper adsorption capacities enhanced in the range of 5.56-21.85 and 6.05-44.61 times, respectively. The Langmuir, Freundlich and Temkin adsorption isotherms were used to elucidate the observed sorption phenomena. The isotherm equilibrium data was well fitted by the Langmuir and sufficiently fitted to the Freundlich models. The calculated thermodynamic parameters such as change in Gibbs free energy (ΔG°), enthalpy (ΔH°) and entropy (ΔS°) inferred that the investigated adsorption was spontaneous and endothermic in nature. Based on the results, it was concluded that the surface alteration with citric and tartaric acid, Thar and Lakhra activated carbons had significant potential for selective removal of copper(II) from industrial wastewater.

  19. Altered Spontaneous Brain Activity in Patients with Hemifacial Spasm: A Resting-State Functional MRI Study

    PubMed Central

    Tu, Ye; Wei, Yongxu; Sun, Kun; Zhao, Weiguo; Yu, Buwei

    2015-01-01

    Resting-state functional magnetic resonance imaging (fMRI) has been used to detect the alterations of spontaneous neuronal activity in various neurological and neuropsychiatric diseases, but rarely in hemifacial spasm (HFS), a nervous system disorder. We used resting-state fMRI with regional homogeneity (ReHo) analysis to investigate changes in spontaneous brain activity of patients with HFS and to determine the relationship of these functional changes with clinical features. Thirty patients with HFS and 33 age-, sex-, and education-matched healthy controls were included in this study. Compared with controls, HFS patients had significantly decreased ReHo values in left middle frontal gyrus (MFG), left medial cingulate cortex (MCC), left lingual gyrus, right superior temporal gyrus (STG) and right precuneus; and increased ReHo values in left precentral gyrus, anterior cingulate cortex (ACC), right brainstem, and right cerebellum. Furthermore, the mean ReHo value in brainstem showed a positive correlation with the spasm severity (r = 0.404, p = 0.027), and the mean ReHo value in MFG was inversely related with spasm severity in HFS group (r = -0.398, p = 0.028). This study reveals that HFS is associated with abnormal spontaneous brain activity in brain regions most involved in motor control and blinking movement. The disturbances of spontaneous brain activity reflected by ReHo measurements may provide insights into the neurological pathophysiology of HFS. PMID:25603126

  20. PRENATAL ALCOHOL EXPOSURE ALTERS STEADY-STATE AND ACTIVATED GENE EXPRESSION IN THE ADULT RAT BRAIN

    PubMed Central

    Stepien, Katarzyna A.; Lussier, Alexandre A.; Neumann, Sarah M.; Pavlidis, Paul; Kobor, Michael S.; Weinberg, Joanne

    2016-01-01

    Background Prenatal alcohol exposure (PAE) is associated with alterations in numerous physiological systems, including the stress and immune systems . We have previously shown that PAE increases the course and severity of arthritis in an adjuvant-induced arthritis (AA) model. While the molecular mechanisms underlying these effects are not fully known, changes in neural gene expression are emerging as important factors in the etiology of PAE effects. As the prefrontal cortex (PFC) and hippocampus (HPC) play key roles in neuroimmune function, PAE-induced alterations to their transcriptome may underlie abnormal steady-state functions and responses to immune challenge. The current study examined brains from adult PAE and control females from our recent AA study to determine whether PAE causes long-term alterations in gene expression and whether these mediate the altered severity and course of arthritis in PAE females Methods Adult females from PAE, pair-fed [PF], and ad libitum-fed control [C]) groups were injected with either saline or complete Freund’s adjuvant. Animals were terminated at the peak of inflammation or during resolution (days 16 and 39 post-injection, respectively); cohorts of saline-injected PAE, PF and C females were terminated in parallel. Gene expression was analyzed in the PFC and HPC using whole genome mRNA expression microarrays. Results Significant changes in gene expression in both the PFC and HPC were found in PAE compared to controls in response to ethanol exposure alone (saline-injected females), including genes involved in neurodevelopment, apoptosis, and energy metabolism. Moreover, in response to inflammation (adjuvant-injected females), PAE animals showed unique expression patterns, while failing to exhibit the activation of genes and regulators involved in the immune response observed in control and pair-fed animals. Conclusions These results support the hypothesis that PAE affects neuroimmune function at the level of gene expression

  1. Effect alteration of methamphetamine by amino acids or their salts on ambulatory activity in mice.

    PubMed

    Kuribara, H; Tadokoro, S

    1983-02-01

    Effect alterations of methamphetamine by pretreatment of amino acids or their salts on ambulatory activity in mice were investigated to confirm a fact that certain amino acids, particularly monosodium L-glutamate, are added to methamphetamine by the street users, and that the amino acids augment the effect of methamphetamine. The ambulatory activity of mouse was measured by a tilting-type round activity cage of 25 cm in diameter. The amino acids or their salts tested were monosodium L-glutamate, monosodium L-aspartate, gamma-amino-butyric acid, L-alanine, L-lysine hydrochloride and L-arginine hydrochloride. A single administration of each chemical at doses of 1 and 2 g/kg i.p. did not induce a marked change in the ambulatory activity in mice. Methamphetamine 2 mg/kg s.c. induced an increase in the ambulatory activity with a peak at 40 min after the administration, and the increased ambulatory activity persisted for 3 hr. The ambulation-increasing effect of methamphetamine was augmented by the pretreatment of monosodium L-glutamate and monosodium L-aspartate at 30 min before the methamphetamine administration, while attenuated by the pretreatment of L-lysine hydrochloride and L-arginine hydrochloride in a dose-dependent manner. Gamma-aminobutyric acid and L-alanine did not affect the effect of methamphetamine. Similar augmentation and attenuation in the ambulation-increasing effect of methamphetamine were induced by the pretreatment of sodium bicarbonate 0.9 g/kg i.p. (urinary alkalizer) and ammonium chloride 0.07 g/kg i.p. (urinary acidifier), respectively. The urinary pH level was elevated by the administration of monosodium L-glutamate, monosodium L-aspartate and sodium bicarbonate, and decreased by L-lysine hydrochloride, L-arginine hydrochloride and ammonium chloride. Gamma-aminobutyric acid and L-alanine did not elicit a marked change in the urinary pH level. The present experiment confirms the fact in human that monosodium L-glutamate augments the effect of

  2. Albinism-Causing Mutations in Recombinant Human Tyrosinase Alter Intrinsic Enzymatic Activity

    PubMed Central

    Dolinska, Monika B.; Kovaleva, Elena; Backlund, Peter; Wingfield, Paul T.; Brooks, Brian P.; Sergeev, Yuri V.

    2014-01-01

    Background Tyrosinase (TYR) catalyzes the rate-limiting, first step in melanin production and its gene (TYR) is mutated in many cases of oculocutaneous albinism (OCA1), an autosomal recessive cause of childhood blindness. Patients with reduced TYR activity are classified as OCA1B; some OCA1B mutations are temperature-sensitive. Therapeutic research for OCA1 has been hampered, in part, by the absence of purified, active, recombinant wild-type and mutant human enzymes. Methodology/Principal Findings The intra-melanosomal domain of human tyrosinase (residues 19–469) and two OCA1B related temperature-sensitive mutants, R422Q and R422W were expressed in insect cells and produced in T. ni larvae. The short trans-membrane fragment was deleted to avoid potential protein insolubility, while preserving all other functional features of the enzymes. Purified tyrosinase was obtained with a yield of >1 mg per 10 g of larval biomass. The protein was a monomeric glycoenzyme with maximum enzyme activity at 37°C and neutral pH. The two purified mutants when compared to the wild-type protein were less active and temperature sensitive. These differences are associated with conformational perturbations in secondary structure. Conclusions/Significance The intramelanosomal domains of recombinant wild-type and mutant human tyrosinases are soluble monomeric glycoproteins with activities which mirror their in vivo function. This advance allows for the structure – function analyses of different mutant TYR proteins and correlation with their corresponding human phenotypes; it also provides an important tool to discover drugs that may improve tyrosinase activity and treat OCA1. PMID:24392141

  3. Lab-on-a-chip workshop activities for secondary school students.

    PubMed

    Esfahani, Mohammad M N; Tarn, Mark D; Choudhury, Tahmina A; Hewitt, Laura C; Mayo, Ashley J; Rubin, Theodore A; Waller, Mathew R; Christensen, Martin G; Dawson, Amy; Pamme, Nicole

    2016-01-01

    The ability to engage and inspire younger generations in novel areas of science is important for bringing new researchers into a burgeoning field, such as lab-on-a-chip. We recently held a lab-on-a-chip workshop for secondary school students, for which we developed a number of hands-on activities that explained various aspects of microfluidic technology, including fabrication (milling and moulding of microfluidic devices, and wax printing of microfluidic paper-based analytical devices, so-called μPADs), flow regimes (gradient formation via diffusive mixing), and applications (tissue analysis and μPADs). Questionnaires completed by the students indicated that they found the workshop both interesting and informative, with all activities proving successful, while providing feedback that could be incorporated into later iterations of the event. PMID:26865902

  4. Secondary metabolites of plants from the genus chloranthus: chemistry and biological activities.

    PubMed

    Wang, An-Ran; Song, Hong-Chuan; An, Hong-Mei; Huang, Qian; Luo, Xie; Dong, Jin-Yan

    2015-04-01

    Chloranthus, a genus of the family Chloranthaceae, which is mainly distributed in eastern and southern Asia, has been used in Chinese folk medicine due to its antitumor, antifungal, and anti-inflammatory activities. This review compiles the research on isolation, structure elucidation, structural diversity, and bioactivities of Chloranthus secondary metabolites reported between 2007 and 2013. The metabolites listed encompass 82 sesquiterpenoids, 50 dimeric sesquiterpenoids, 15 diterpenoids, one coumarin, and five other compounds. Among them, dimeric sesquiterpenoids, the characteristic components of plants from the genus Chloranthus, have attracted considerable attention due to their complex structures and significant biological features, e.g., antitumor, antibacterial, antifungal, anti-inflammatory, and hepatoprotective activities, and potent and selective inhibition of the delayed rectifier (IK) K(+) current and tyrosinase. PMID:25879494

  5. Lab-on-a-chip workshop activities for secondary school students

    PubMed Central

    Esfahani, Mohammad M. N.; Tarn, Mark D.; Choudhury, Tahmina A.; Hewitt, Laura C.; Mayo, Ashley J.; Rubin, Theodore A.; Waller, Mathew R.; Christensen, Martin G.; Dawson, Amy; Pamme, Nicole

    2016-01-01

    The ability to engage and inspire younger generations in novel areas of science is important for bringing new researchers into a burgeoning field, such as lab-on-a-chip. We recently held a lab-on-a-chip workshop for secondary school students, for which we developed a number of hands-on activities that explained various aspects of microfluidic technology, including fabrication (milling and moulding of microfluidic devices, and wax printing of microfluidic paper-based analytical devices, so-called μPADs), flow regimes (gradient formation via diffusive mixing), and applications (tissue analysis and μPADs). Questionnaires completed by the students indicated that they found the workshop both interesting and informative, with all activities proving successful, while providing feedback that could be incorporated into later iterations of the event. PMID:26865902

  6. Whole Blood Activation Results in Altered T Cell and Monocyte Cytokine Production Profiles by Flow Cytometry

    NASA Technical Reports Server (NTRS)

    Crucian, Brian E.; Sams, Clarence F.

    2001-01-01

    An excellent monitor of the immune balance of peripheral circulating cells is to determine their cytokine production patterns in response to stimuli. Using flow cytometry, a positive identification of cytokine producing cells in a mixed culture may be achieved. Recently, the ability to assess cytokine production following a whole-blood activation culture has been described. In this study, whole blood activation was compared to traditional PBMC activation and the individual cytokine secretion patterns for both T cells, T cell subsets and monocytes was determined by flow cytometry. RESULTS: For T cell cytokine assessment (IFNg/IL-10 and IL-21/L-4) following PMA +ionomycin activation: (1) a Significantly greater percentages of T cells producing IFNgamma and IL-2 were observed following whole-blood culture and (2) altered T cell cytokine production kinetics were observed by varying whole blood culture times. Four-color analysiS was used to allow assessment of cytokine production by specific T cell subsets. It was found that IFNgamma production was significantly elevated in the CD3+/CD8+ T cell population as compared to the CD3+/CD8- population following five hours of whole blood activation. Conversely, IL-2 and IL-10 production were Significantly elevated in the CD3+/CD8- T cell population as compared to the CD3+/CD8+ population. Monocyte cytokine production was assessed in both culture systems following LPS activation for 24 hours. A three-color flow cytometric was used to assess two cytokines (IL-1a/IL-12 and TNFa/IL-10) in conjunction with CD14. Nearly all monocytes were stimulated to produce IL-1a, IL-12 and TNFa. equally well in both culture systems, however monocyte production of IL-10 was significantly elevated in whole blood culture as compared to PBMC culture. IL-12 producing monocytes appeared to be a distinct subpopulation of the IL-1a producing set, whereas IL-10 and TNFa producing monocytes were largely mutually exclusive. IL-10 and TNFa producing

  7. Irradiation- and cyclophosphamide-induced alterations in Syrian hamster T-cell population activity

    SciTech Connect

    Bagasra, O.; Tabor, D.

    1986-02-01

    The treatment of hamsters with either irradiation (IR) or cyclophosphamide (CYP) markedly alters select aspects of their cellular immune functions in a dose-related manner. One mechanism that may be responsible for this activity appears to be the dimunition of a T-lymphocyte subpopulation that exerts suppressive influence upon the B-lymphocyte reactivity toward antigens. This study shows that in the hamster, immune susceptibility is affected by the magnitude and orientation of these agents (ie, IR, CYP) as they temporally relate to immunization and/or challenge with the antigen. Moreover, there is evidence that T-independent as well as T-dependent responses are affected by these treatments. Therefore, cyclophosphamide and irradiation modalities can be employed to modify the cellular immune responses in the hamster.

  8. Alterations in primary and secondary metabolism in Vitis vinifera 'Malvasía de Banyalbufar' upon infection with Grapevine leafroll-associated virus 3.

    PubMed

    Montero, Rafael; Pérez-Bueno, María Luisa; Barón, Matilde; Florez-Sarasa, Igor; Tohge, Takayuki; Fernie, Alisdair Robert; Ouad, Hanan El Aou; Flexas, Jaume; Bota, Josefina

    2016-08-01

    Plant defense mechanisms against pathogens result in differential regulation of various processes of primary and secondary metabolism. Imaging techniques, such as fluorescence imaging and thermography, are very valuable tools providing spatial and temporal information about these processes. In this study, effects of Grapevine leafroll-associated virus 3 (GLRaV-3) on grapevine physiology were analyzed in pot-grown asymptomatic plants of the white cultivar Malvasía de Banyalbufar. The virus triggered changes in the activity of photosynthesis and secondary metabolism. There was a decrease in the photorespiratory intermediates glycine and serine in infected plants, possibly as a defense response against the infection. The content of malate, which plays an important role in plant metabolism, also decreased. These results correlate with the increased non-photochemical quenching found in infected plants. On the other hand, the concentration of flavonols (represented by myricetin, kaempferol and quercetin derivatives) and hydroxycinnamic acids (which include derivatives of caffeic acid) increased following infection by the virus. These compounds could be responsible for the increase in multicolor fluorescence F440 (blue fluorescence) and F520 (green fluorescence) on the leaves, and changes in the fluorescence parameters F440/F680, F440/F740, F520/F680, F520/F740 and F680/F740. The combined analysis of chlorophyll fluorescence kinetics and blue-green fluorescence emitted by phenolics could constitute disease signatures allowing the discrimination between GLRaV-3 infected and non-infected plants at very early stage of infection, prior to the development of symptoms. PMID:26926417

  9. Altered Insula Activity during Visceral Interoception in Weight-Restored Patients with Anorexia Nervosa.

    PubMed

    Kerr, Kara L; Moseman, Scott E; Avery, Jason A; Bodurka, Jerzy; Zucker, Nancy L; Simmons, W Kyle

    2016-01-01

    Anorexia nervosa (AN) is a devastating psychiatric illness that is associated with significant morbidity and mortality. Aberrant visceral interoceptive processing within the insula has been hypothesized to be an important mechanism in AN's pathophysiology due to the theoretical link between interoception and emotional experience. We therefore utilized functional magnetic resonance imaging (fMRI) to examine whether altered insula functioning underlies visceral interoception in AN. Fifteen females with restricting-type AN and 15 healthy control females underwent fMRI while performing an interoceptive attention task during which they focused on sensations in their heart, stomach, and bladder. Participants also performed an anxious rumination task while in the scanner. AN participants were weight-restored and free of psychotropic medications. Two distinct regions of the insula-anterior insula and dorsal mid-insula-exhibited a significant (p<0.05) interaction between group and interoceptive modality. The post hoc analyses revealed that in the dorsal mid-insula the interaction was driven by group differences during stomach interoception (p=0.002, Bonferroni corrected), whereas in the anterior insula the interaction was driven by group differences during heart interoception (p=0.03, Bonferroni corrected). In addition, individuals with AN displayed increased activation during anxious rumination in the dorsal mid-insula, and activation in this region during stomach interoception was correlated with measures of anxiety and psychopathology. This relationship between altered visceral interoception and clinical symptoms in AN suggests an important mechanism for the disorder. Additional research is needed to examine whether interventions targeting visceral interoception may increase the efficacy of treatments for AN. PMID:26084229

  10. Zinc oxide nanoparticles alter hatching and larval locomotor activity in zebrafish (Danio rerio).

    PubMed

    Chen, Te-Hao; Lin, Chia-Chi; Meng, Pei-Jie

    2014-07-30

    Zinc oxide nanoparticles (ZnO NP) are extensively used in various consumer products such as sunscreens and cosmetics, with high potential of being released into aquatic environments. In this study, fertilized zebrafish (Danio rerio) eggs were exposed to various concentrations of ZnO NP suspensions (control, 0.1, 0.5, 1, 5, and 10mg/L) or their respective centrifuged supernatants (0.03, 0.01, 0.08, 0.17, 0.75, and 1.21mg/L dissolved Zn ions measured) until reaching free swimming stage. Exposure to ZnO NP suspensions and their respective centrifuged supernatants caused similar hatching delay, but did not cause larval mortality or malformation. Larval activity level, mean velocity, and maximum velocity were altered in the groups exposed to high concentrations of ZnO NP (5-10mg/L) but not in the larvae exposed to the supernatants. To evaluate possible mechanism of observed effects caused by ZnO NP, we also manipulated the antioxidant environment by co-exposure to an antioxidant compound (N-acetylcysteine, NAC) or an antioxidant molecule suppressor (buthionine sulfoximine, BSO) with 5mg/L ZnO NP. Co-exposure to NAC did not alter the effects of ZnO NP on hatchability, but co-exposure to BSO caused further hatching delay. For larval locomotor activity, co-exposure to NAC rescued the behavioral effect caused by ZnO NP, but co-exposure to BSO did not exacerbate the effect. Our data indicated that toxicity of ZnO NP cannot be solely explained by dissolved Zn ions, and oxidative stress may involve in ZnO NP toxicity. PMID:24424259

  11. Prenatal stress is a vulnerability factor for altered morphology and biological activity of microglia cells.

    PubMed

    Ślusarczyk, Joanna; Trojan, Ewa; Głombik, Katarzyna; Budziszewska, Bogusława; Kubera, Marta; Lasoń, Władysław; Popiołek-Barczyk, Katarzyna; Mika, Joanna; Wędzony, Krzysztof; Basta-Kaim, Agnieszka

    2015-01-01

    Several lines of evidence suggest that the dysregulation of the immune system is an important factor in the development of depression. Microglia are the resident macrophages of the central nervous system and a key player in innate immunity of the brain. We hypothesized that prenatal stress (an animal model of depression) as a priming factor could affect microglial cells and might lead to depressive-like disturbances in adult male rat offspring. We investigated the behavioral changes (sucrose preference test, Porsolt test), the expression of C1q and CD40 mRNA and the level of microglia (Iba1 positive) in 3-month-old control and prenatally stressed male offspring rats. In addition, we characterized the morphological and biochemical parameters of potentially harmful (NO, iNOS, IL-1β, IL-18, IL-6, TNF-α, CCL2, CXCL12, CCR2, CXCR4) and beneficial (insulin-like growth factor-1 (IGF-1), brain derived neurotrophic factor (BDNF)) phenotypes in cultures of microglia obtained from the cortices of 1-2 days old control and prenatally stressed pups. The adult prenatally stressed rats showed behavioral (anhedonic- and depression-like) disturbances, enhanced expression of microglial activation markers and an increased number of Iba1-immunopositive cells in the hippocampus and frontal cortex. The morphology of glia was altered in cultures from prenatally stressed rats, as demonstrated by immunofluorescence microscopy. Moreover, in these cultures, we observed enhanced expression of CD40 and MHC II and release of pro-inflammatory cytokines, including IL-1β, IL-18, TNF-α and IL-6. Prenatal stress significantly up-regulated levels of the chemokines CCL2, CXCL12 and altered expression of their receptors, CCR2 and CXCR4 while IGF-1 production was suppressed in cultures of microglia from prenatally stressed rats. Our results suggest that prenatal stress may lead to excessive microglia activation and contribute to the behavioral changes observed in depression in adulthood. PMID

  12. Multiple conductance states of the light-activated channel of Limulus ventral photoreceptors. Alteration of conductance state during light

    PubMed Central

    1991-01-01

    The properties of light-dependent channels in Limulus ventral photoreceptors have been studied in cell-attached patches. Two sizes of single-channel events are seen during illumination. Previous work has characterized the large (40 pS) events; the goal of the current work was to characterize the small (15 pS) events and determine their relationship to the large events. The small events are activated by light rather than as a secondary result of the change in membrane voltage during light. The mean open time of the small events is 1.34 +/- 0.49 ms (mean +/- SD, n = 15), approximately 50% of that of the large events. The large and small events have the same reversal potential and a similar dependence of open-state probability on voltage. Evidence that these events are due to different conductance states of the same channel comes from analysis of relatively infrequent events showing a direct transition between the 15 and 40-pS levels. Furthermore, large and small events do not superpose, even at positive voltages when the probability of being open is very high, as would be predicted if the two-sized events were due to independent channels. Expression of the different conductance states is not random; during steady illumination there are alternating periods of several hundred milliseconds in which there are consecutive, sequential large events followed by periods in which there are consecutive, sequential small events. At early times during the response to a step of light, the large conductance state is preferentially expressed. At later times, there is an increase in the relative contribution of the low conductance state. These findings indicate that there is a process that changes the preferred conductance state of the channel. This alteration has functional importance in the process of light adaptation. PMID:1875187

  13. Altered Intrinsic Regional Activity and Interregional Functional Connectivity in Post-stroke Aphasia

    PubMed Central

    Yang, Mi; Li, Jiao; Li, Yibo; Li, Rong; Pang, Yajing; Yao, Dezhong; Liao, Wei; Chen, Huafu

    2016-01-01

    Several neuroimaging studies have examined cerebral function in patients who suffer from aphasia, but the mechanism underlying this disorder remains poorly understood. In this study, we examined alterations in the local regional and remote interregional network cerebral functions in aphasia combined with amplitude of low-frequency fluctuations and interregional functional connectivity (FC) using resting-state functional magnetic resonance imaging. A total of 17 post-stroke aphasic patients, all having suffered a stroke in the left hemisphere, as well as 20 age- and sex-matched healthy controls, were enrolled in this study. The aphasic patients showed significantly increased intrinsic regional activity mainly in the contralesional mesial temporal (hippocampus/parahippocampus, [HIP/ParaHIP]) and lateral temporal cortices. In addition, intrinsic regional activity in the contralesional HIP/ParaHIP was negatively correlated with construction score. Aphasic patients showed increased remote interregional FC between the contralesional HIP/ParaHIP and fusiform gyrus, but reduced FC in the ipsilesional occipital and parietal cortices. These findings suggested that the intrinsic regional brain dysfunctions in aphasia were related to interregional functional connectivity. Changes in the intrinsic regional brain activity and associated remote functional connectivity pattern would provide valuable information to enhance the understanding of the pathophysiological mechanisms of aphasia. PMID:27091494

  14. Altered invertase activities of symptomatic tissues on Beet severe curly top virus (BSCTV) infected Arabidopsis thaliana.

    PubMed

    Park, Jungan; Kim, Soyeon; Choi, Eunseok; Auh, Chung-Kyun; Park, Jong-Bum; Kim, Dong-Giun; Chung, Young-Jae; Lee, Taek-Kyun; Lee, Sukchan

    2013-09-01

    Arabidopsis thaliana infected with Beet severe curly top virus (BSCTV) exhibits systemic symptoms such as stunting of plant growth, callus induction on shoot tips, and curling of leaves and shoot tips. The regulation of sucrose metabolism is essential for obtaining the energy required for viral replication and the development of symptoms in BSCTV-infected A. thaliana. We evaluated the changed transcript level and enzyme activity of invertases in the inflorescence stems of BSCTV-infected A. thaliana. These results were consistent with the increased pattern of ribulose-1,5-bisphosphate carboxylase/oxygenase activity and photosynthetic pigment concentration in virus-infected plants to supply more energy for BSCTV multiplication. The altered gene expression of invertases during symptom development was functionally correlated with the differential expression patterns of D-type cyclins, E2F isoforms, and invertase-related genes. Taken together, our results indicate that sucrose sensing by BSCTV infection may regulate the expression of sucrose metabolism and result in the subsequent development of viral symptoms in relation with activation of cell cycle regulation. PMID:23589148

  15. Spaceflight alters expression of microRNA during T-cell activation.

    PubMed

    Hughes-Fulford, Millie; Chang, Tammy T; Martinez, Emily M; Li, Chai-Fei

    2015-12-01

    Altered immune function has been demonstrated in astronauts during spaceflights dating back to Apollo and Skylab; this could be a major barrier to long-term space exploration. We tested the hypothesis that spaceflight causes changes in microRNA (miRNA) expression. Human leukocytes were stimulated with mitogens on board the International Space Station using an onboard normal gravity control. Bioinformatics showed that miR-21 was significantly up-regulated 2-fold during early T-cell activation in normal gravity, and gene expression was suppressed under microgravity. This was confirmed using quantitative real-time PCR (n = 4). This is the first report that spaceflight regulates miRNA expression. Global microarray analysis showed significant (P < 0.05) suppression of 85 genes under microgravity conditions compared to normal gravity samples. EGR3, FASLG, BTG2, SPRY2, and TAGAP are biologically confirmed targets and are co-up-regulated with miR-21. These genes share common promoter regions with pre-mir-21; as the miR-21 matures and accumulates, it most likely will inhibit translation of its target genes and limit the immune response. These data suggest that gravity regulates T-cell activation not only by transcription promotion but also by blocking translation via noncoding RNA mechanisms. Moreover, this study suggests that T-cell activation itself may induce a sequence of gene expressions that is self-limited by miR-21. PMID:26276131

  16. Interleukin-15 Modulates Adipose Tissue by Altering Mitochondrial Mass and Activity

    PubMed Central

    Barra, Nicole G.; Palanivel, Rengasamy; Denou, Emmanuel; Chew, Marianne V.; Gillgrass, Amy; Walker, Tina D.; Kong, Josh; Richards, Carl D.; Jordana, Manel; Collins, Stephen M.; Trigatti, Bernardo L.; Holloway, Alison C.; Raha, Sandeep; Steinberg, Gregory R.; Ashkar, Ali A.

    2014-01-01

    Interleukin-15 (IL-15) is an immunomodulatory cytokine that affects body mass regulation independent of lymphocytes; however, the underlying mechanism(s) involved remains unknown. In an effort to investigate these mechanisms, we performed metabolic cage studies, assessed intestinal bacterial diversity and macronutrient absorption, and examined adipose mitochondrial activity in cultured adipocytes and in lean IL-15 transgenic (IL-15tg), overweight IL-15 deficient (IL-15−/−), and control C57Bl/6 (B6) mice. Here we show that differences in body weight are not the result of differential activity level, food intake, or respiratory exchange ratio. Although intestinal microbiota differences between obese and lean individuals are known to impact macronutrient absorption, differing gut bacteria profiles in these murine strains does not translate to differences in body weight in colonized germ free animals and macronutrient absorption. Due to its contribution to body weight variation, we examined mitochondrial factors and found that IL-15 treatment in cultured adipocytes resulted in increased mitochondrial membrane potential and decreased lipid deposition. Lastly, IL-15tg mice have significantly elevated mitochondrial activity and mass in adipose tissue compared to B6 and IL-15−/− mice. Altogether, these results suggest that IL-15 is involved in adipose tissue regulation and linked to altered mitochondrial function. PMID:25517731

  17. Kinetics of exercise-induced neural activation; interpretive dilemma of altered cerebral perfusion.

    PubMed

    Miyazawa, Taiki; Horiuchi, Masahiro; Ichikawa, Daisuke; Sato, Kohei; Tanaka, Naoki; Bailey, Damian M; Ogoh, Shigehiko

    2012-02-01

    Neural activation decreases cerebral deoxyhaemoglobin (HHb(C)) and increases oxyhaemoglobin concentration (O(2)Hb(C)). In contrast, patients who present with restricted cerebral blood flow, such as those suffering from cerebral ischaemia or Alzheimer's disease, and during the course of ageing the converse occurs, in that HHb(C) increases and O(2)Hb(C) decreases during neural activation. In the present study, we examined the interpretive implications of altered exercise-induced cerebral blood flow for cortical oxygenation in healthy subjects. Both O(2)Hb(C) and HHb(C) (prefrontal cortex) were determined in 11 healthy men using near-infrared spectroscopy (NIRS). Middle cerebral artery mean blood velocity (MCA V(mean)) was determined via transcranial Doppler ultrasonography. Measurements were performed during contralateral hand-grip exercise during suprasystolic bilateral thigh-cuff occlusion (Cuff+) and within 2 s of cuff release (Cuff-) for the acute manipulation of cerebral perfusion. During Cuff+, both MCA V(mean) and O(2)Hb(C) increased during exercise, whereas HHb(C) decreased. In contrast, the opposite occurred during the Cuff- manipulation. These findings highlight the inverse relationship between cerebral blood flow and cerebral oxygenation as determined by NIRS, which has interpretive implications for the kinetics underlying exercise-induced neural activation. PMID:22041980

  18. Altered error-related brain activity in youth with major depression.

    PubMed

    Ladouceur, Cecile D; Slifka, John S; Dahl, Ronald E; Birmaher, Boris; Axelson, David A; Ryan, Neal D

    2012-07-01

    Depression is associated with impairments in cognitive control including action monitoring processes, which involve the detection and processing of erroneous responses in order to adjust behavior. Although numerous studies have reported altered error-related brain activity in depressed adults, relatively little is known about age-related changes in error-related brain activity in depressed youth. This study focuses on the error-related negativity (ERN), a negative deflection in the event-related potential (ERP) that is maximal approximately 50ms following errors. High-density ERPs were examined following responses on a flanker task in 24 youth diagnosed with MDD and 14 low-risk healthy controls (HC). Results indicate that compared to HC, MDD youth had significantly smaller ERN amplitudes and did not exhibit the normative increases in ERN amplitudes as a function of age. Also, ERN amplitudes were similar in depressed youth with and without comorbid anxiety. These results suggest that depressed youth exhibit different age-related changes in brain activity associated with action monitoring processes. Findings are discussed in terms of existing work on the neural correlates of action monitoring and depression and the need for longitudinal research studies investigating the development of neural systems underlying action monitoring in youth diagnosed with and at risk for depression. PMID:22669036

  19. Inhibitory Interneuron Deficit Links Altered Network Activity and Cognitive Dysfunction in Alzheimer Model

    PubMed Central

    Verret, Laure; Mann, Edward O.; Hang, Giao B.; Barth, Albert M. I.; Cobos, Inma; Ho, Kaitlyn; Devidze, Nino; Masliah, Eliezer; Kreitzer, Anatol C.; Mody, Istvan; Mucke, Lennart; Palop, Jorge J.

    2012-01-01

    SUMMARY Alzheimer's disease (AD) results in cognitive decline and altered network activity, but the mechanisms are unknown. To identify such mechanisms, we studied human amyloid precursor protein (hAPP) transgenic mice, which simulate key aspects of AD. Electroencephalographic recordings in hAPP mice revealed spontaneous epileptiform discharges, indicating network hypersynchrony, primarily during reduced gamma oscillatory activity. Because this oscillatory rhythm is generated by inhibitory parvalbumin (PV) cells, network dysfunction in hAPP mice might arise from impaired PV cells. Supporting this hypothesis, hAPP mice and AD patients had decreased levels of the interneuron-specific and PV cell–predominant voltage-gated sodium channel subunit Nav1.1. Restoring Nav1.1 levels in hAPP mice by Nav1.1-BAC expression increased inhibitory synaptic activity and gamma oscillations and reduced hypersynchrony, memory deficits, and premature mortality. We conclude that reduced Nav1.1 levels and PV cell dysfunction critically contribute to abnormalities in oscillatory rhythms, network synchrony, and memory in hAPP mice and possibly in AD. PMID:22541439

  20. Moderate differences in circulating corticosterone alter receptor-mediated regulation of 5-hydroxytryptamine neuronal activity.

    PubMed

    Judge, Sarah J; Ingram, Colin D; Gartside, Sarah E

    2004-12-01

    Circulating glucocorticoid levels vary with stress and psychiatric illness and play a potentially important role in regulating transmitter systems that regulate mood. To determine whether chronic variation in corticosterone levels within the normal diurnal range altered the control of 5-hydroxytryptamine (5-HT) neuronal activity, male rats were adrenalectomized and implanted with either a 2% or 70% corticosterone/cholesterol pellet (100 mg). Two weeks later, the regulation of 5-HT neuronal activity in the dorsal raphe nucleus was studied by in vitro electrophysiology. At this time, serum corticosterone levels approximated the low-point (2%) and mid-point (70%) of the diurnal range. The excitatory response of 5-HT neurones to the alpha1-adrenoceptor agonist phenylephrine (1-11 microM) was significantly greater in the 2% group compared to the 70% group. By contrast, the inhibitory response to 5-HT (10-50 microM) was significantly lower in the 2% group compared to the 70% group. Thus, chronic variation in circulating corticosterone over a narrow part of the normal diurnal range causes a shift in the balance of positive and negative regulation of 5-HT neurones, with increased alpha 1-adrenoceptor-mediated excitation and reduced 5-HT-mediated autoinhibition at lower corticosterone levels. This shift would have a major impact on control of 5-HT neuronal activity. PMID:15582914

  1. Field Trip Guide to Serpentinite, Silica-Carbonate Alteration, and Related Hydrothermal Activity in the Clear Lake Region, California

    SciTech Connect

    Fraser Goff; George Guthrie

    1999-06-01

    This guide is designed to familiarize scientists with the geology, structure, alteration, and fluids typical of California serpentinites for purposes of carbon dioxide sequestration (Lackner et al., 1995). Goff et al. (1997) and Goff and Lackner (1998) describe the geology and geochemistry of some of the serpentinites from this area. Mechanisms of silica-carbonate alteration were outlined by Barnes et al. (1973). Donnelly-Nolan et al. (1993) most recently reviewed relations between regional hydrothermal alteration and Quarternary volcanic activity. Stanley et al. (1998) summarized geophysical characteristics of the region.

  2. Spatiotemporal relations of primary sensorimotor and secondary motor activation patterns mapped by NIR imaging

    PubMed Central

    Khan, Bilal; Chand, Pankaj; Alexandrakis, George

    2011-01-01

    Functional near infrared (fNIR) imaging was used to identify spatiotemporal relations between spatially distinct cortical regions activated during various hand and arm motion protocols. Imaging was performed over a field of view (FOV, 12 x 8.4 cm) including the secondary motor, primary sensorimotor, and the posterior parietal cortices over a single brain hemisphere. This is a more extended FOV than typically used in current fNIR studies. Three subjects performed four motor tasks that induced activation over this extended FOV. The tasks included card flipping (pronation and supination) that, to our knowledge, has not been performed in previous functional magnetic resonance imaging (fMRI) or fNIR studies. An earlier rise and a longer duration of the hemodynamic activation response were found in tasks requiring increased physical or mental effort. Additionally, analysis of activation images by cluster component analysis (CCA) demonstrated that cortical regions can be grouped into clusters, which can be adjacent or distant from each other, that have similar temporal activation patterns depending on whether the performed motor task is guided by visual or tactile feedback. These analyses highlight the future potential of fNIR imaging to tackle clinically relevant questions regarding the spatiotemporal relations between different sensorimotor cortex regions, e.g. ones involved in the rehabilitation response to motor impairments. PMID:22162826

  3. Alignment of Hands-on STEM Engagement Activities with Positive STEM Dispositions in Secondary School Students

    NASA Astrophysics Data System (ADS)

    Christensen, Rhonda; Knezek, Gerald; Tyler-Wood, Tandra

    2015-12-01

    This study examines positive dispositions reported by middle school and high school students participating in programs that feature STEM-related activities. Middle school students participating in school-to-home hands-on energy monitoring activities are compared to middle school and high school students in a different project taking part in activities such as an after-school robotics program. Both groups are compared and contrasted with a third group of high school students admitted at the eleventh grade to an academy of mathematics and science. All students were assessed using the same science, technology, engineering and mathematics (STEM) dispositions instrument. Findings indicate that the after-school group whose participants self-selected STEM engagement activities, and the self-selected academy of mathematics and science group, each had highly positive STEM dispositions comparable to those of STEM professionals, while a subset of the middle school whole-classroom energy monitoring group that reported high interest in STEM as a career, also possessed highly positive STEM dispositions comparable to the STEM Professionals group. The authors conclude that several different kinds of hands-on STEM engagement activities are likely to foster or maintain positive STEM dispositions at the middle school and high school levels, and that these highly positive levels of dispositions can be viewed as a target toward which projects seeking to interest mainstream secondary students in STEM majors in college and STEM careers, can hope to aspire. Gender findings regarding STEM dispositions are also reported for these groups.

  4. Scapular Bracing and Alteration of Posture and Muscle Activity in Overhead Athletes With Poor Posture

    PubMed Central

    Cole, Ashley K; McGrath, Melanie L; Harrington, Shana E; Padua, Darin A; Rucinski, Terri J; Prentice, William E

    2013-01-01

    Context Overhead athletes commonly have poor posture. Commercial braces are used to improve posture and function, but few researchers have examined the effects of shoulder or scapular bracing on posture and scapular muscle activity. Objective To examine whether a scapular stabilization brace acutely alters posture and scapular muscle activity in healthy overhead athletes with forward-head, rounded-shoulder posture (FHRSP). Design Randomized controlled clinical trial. Setting Applied biomechanics laboratory. Patients or Other Participants Thirty-eight healthy overhead athletes with FHRSP. Intervention(s) Participants were assigned randomly to 2 groups: compression shirt with no strap tension (S) and compression shirt with the straps fully tensioned (S + T). Posture was measured using lateral-view photography with retroreflective markers. Electromyography (EMG) of the upper trapezius (UT), middle trapezius (MT), lower trapezius (LT), and serratus anterior (SA) in the dominant upper extremity was measured during 4 exercises (scapular punches, W's, Y's, T's) and 2 glenohumeral motions (forward flexion, shoulder extension). Posture and exercise EMG measurements were taken with and without the brace applied. Main Outcome Measure(s) Head and shoulder angles were measured from lateral-view digital photographs. Normalized surface EMG was used to assess mean muscle activation of the UT, MT, LT, and SA. Results Application of the brace decreased forward shoulder angle in the S + T condition. Brace application also caused a small increase in LT EMG during forward flexion and Y's and a small decrease in UT and MT EMG during shoulder extension. Brace application in the S + T group decreased UT EMG during W's, whereas UT EMG increased during W's in the S group. Conclusions Application of the scapular brace improved shoulder posture and scapular muscle activity, but EMG changes were highly variable. Use of a scapular brace might improve shoulder posture and muscle activity in

  5. Altered left ventricular performance in aging physically active mice with an ankle sprain injury.

    PubMed

    Turner, Michael J; Guderian, Sophie; Wikstrom, Erik A; Huot, Joshua R; Peck, Bailey D; Arthur, Susan T; Marino, Joseph S; Hubbard-Turner, Tricia

    2016-02-01

    We assessed the impact of differing physical activity levels throughout the lifespan, using a musculoskeletal injury model, on the age-related changes in left ventricular (LV) parameters in active mice. Forty male mice (CBA/J) were randomly placed into one of three running wheel groups (transected CFL group, transected ATFL/CFL group, SHAM group) or a SHAM Sedentary group (SHAMSED). Before surgery and every 6 weeks after surgery, LV parameters were measured under 2.5 % isoflurane inhalation. Group effects for daily distance run was significantly greater for the SHAM and lesser for the ATLF/CFL mice (p = 0.013) with distance run decreasing with age for all mice (p < 0.0001). Beginning at 6 months of age, interaction (group × age) was noted with LV posterior wall thickness-to-radius ratios (h/r) where h/r increased with age in the ATFL/CFL and SHAMSED mice while the SHAM and CFL mice exhibited decreased h/r with age (p = 0.0002). Passive filling velocity (E wave) was significantly greater in the SHAM mice and lowest for the ATFL/CFL and SHAMSED mice (p < 0.0001) beginning at 9 months of age. Active filling velocity (A wave) was not different between groups (p = 0.10). Passive-to-active filling velocity ratio (E/A ratio) was different between groups (p < 0.0001), with higher ratios for the SHAM mice and lower ratios for the ATFL/CFL and SHAMSED mice in response to physical activity beginning at 9 months of age. Passive-to-active filling velocity ratio decreased with age (p < 0.0001). Regular physical activity throughout the lifespan improved LV structure, passive filling velocity, and E/A ratio by 6 to 9 months of age and attenuated any negative alterations throughout the second half of life. The diastolic filling differences were found to be significantly related to the amount of activity performed by 9 months and at the end of the lifespan. PMID:26803818

  6. Antiproliferative, Antibacterial and Antifungal Activity of the Lichen Xanthoria parietina and Its Secondary Metabolite Parietin

    PubMed Central

    Basile, Adriana; Rigano, Daniela; Loppi, Stefano; Di Santi, Annalisa; Nebbioso, Angela; Sorbo, Sergio; Conte, Barbara; Paoli, Luca; De Ruberto, Francesca; Molinari, Anna Maria; Altucci, Lucia; Bontempo, Paola

    2015-01-01

    Lichens are valuable natural resources used for centuries throughout the world as medicine, food, fodder, perfume, spices and dyes, as well as for other miscellaneous purposes. This study investigates the antiproliferative, antibacterial and antifungal activity of the acetone extract of the lichen Xanthoria parietina (Linnaeus) Theodor Fries and its major secondary metabolite, parietin. The extract and parietin were tested for antimicrobial activity against nine American Type Culture Collection standard and clinically isolated bacterial strains, and three fungal strains. Both showed strong antibacterial activity against all bacterial strains and matched clinical isolates, particularly against Staphylococcus aureus from standard and clinical sources. Among the fungi tested, Rhizoctonia solani was the most sensitive. The antiproliferative effects of the extract and parietin were also investigated in human breast cancer cells. The extract inhibited proliferation and induced apoptosis, both effects being accompanied by modulation of expression of cell cycle regulating genes such as p16, p27, cyclin D1 and cyclin A. It also mediated apoptosis by activating extrinsic and intrinsic cell death pathways, modulating Tumor Necrosis Factor-related apoptosis-inducing ligand (TRAIL) and B-cell lymphoma 2 (Bcl-2), and inducing Bcl-2-associated agonist of cell death (BAD) phosphorylation. Our results indicate that Xanthoria parietina is a major potential source of antimicrobial and anticancer substances. PMID:25860944

  7. Antiproliferative, antibacterial and antifungal activity of the lichen Xanthoria parietina and its secondary metabolite parietin.

    PubMed

    Basile, Adriana; Rigano, Daniela; Loppi, Stefano; Di Santi, Annalisa; Nebbioso, Angela; Sorbo, Sergio; Conte, Barbara; Paoli, Luca; De Ruberto, Francesca; Molinari, Anna Maria; Altucci, Lucia; Bontempo, Paola

    2015-01-01

    Lichens are valuable natural resources used for centuries throughout the world as medicine, food, fodder, perfume, spices and dyes, as well as for other miscellaneous purposes. This study investigates the antiproliferative, antibacterial and antifungal activity of the acetone extract of the lichen Xanthoria parietina (Linnaeus) Theodor Fries and its major secondary metabolite, parietin. The extract and parietin were tested for antimicrobial activity against nine American Type Culture Collection standard and clinically isolated bacterial strains, and three fungal strains. Both showed strong antibacterial activity against all bacterial strains and matched clinical isolates, particularly against Staphylococcus aureus from standard and clinical sources. Among the fungi tested, Rhizoctonia solani was the most sensitive. The antiproliferative effects of the extract and parietin were also investigated in human breast cancer cells. The extract inhibited proliferation and induced apoptosis, both effects being accompanied by modulation of expression of cell cycle regulating genes such as p16, p27, cyclin D1 and cyclin A. It also mediated apoptosis by activating extrinsic and intrinsic cell death pathways, modulating Tumor Necrosis Factor-related apoptosis-inducing ligand (TRAIL) and B-cell lymphoma 2 (Bcl-2), and inducing Bcl-2-associated agonist of cell death (BAD) phosphorylation. Our results indicate that Xanthoria parietina is a major potential source of antimicrobial and anticancer substances. PMID:25860944

  8. CCN activity and volatility of β-caryophyllene secondary organic aerosol

    NASA Astrophysics Data System (ADS)

    Frosch, M.; Bilde, M.; Nenes, A.; Praplan, A. P.; Jurányi, Z.; Dommen, J.; Gysel, M.; Weingartner, E.; Baltensperger, U.

    2012-08-01

    In a series of smog chamber experiments, the Cloud Condensation Nuclei (CCN) activity of Secondary Organic Aerosol (SOA) generated from ozonolysis of β-caryophyllene was characterized by determining the CCN derived hygroscopicity parameter, κCCN, from experimental data. Two types of CCN counters, operating at different temperatures, were used. The effect of semi-volatile organic compounds on the CCN activity of SOA was studied using a thermodenuder. Overall, SOA was only slightly CCN active (with κCCN in the range 0.001-0.16), and in dark experiments with no OH scavenger present, κCCN decreased when particles were sent through the thermodenuder (with a temperature up to 50 °C). SOA was generated under different experimental conditions: in some experiments, an OH scavenger (2-butanol) was added. SOA from these experiments was less CCN active than SOA produced in experiments without an OH scavenger (i.e. where OH was produced during ozonolysis). In other experiments, lights were turned on, either without or with the addition of HONO (OH source). This led to the formation of more CCN active SOA. SOA was aged up to 30 h through exposure to ozone and (in experiments with no OH scavenger present) to OH. In all experiments, the derived κCCN consistently increased with time after initial injection of β-caryophyllene, showing that chemical ageing increases the CCN activity of β-caryophyllene SOA. κCCN was also observed to depend on supersaturation, which was explained either as an evaporation artifact from semi-volatile SOA (only observed in experiments lacking light exposure) or, alternatively, by effects related to chemical composition depending on dry particle size. Using the method of Threshold Droplet Growth Analysis it was also concluded that the activation kinetics of the SOA do not differ significantly from calibration ammonium sulphate aerosol.

  9. CCN activity and volatility of β-caryophyllene secondary organic aerosol

    NASA Astrophysics Data System (ADS)

    Frosch, M.; Bilde, M.; Nenes, A.; Praplan, A. P.; Jurányi, Z.; Dommen, J.; Gysel, M.; Weingartner, E.; Baltensperger, U.

    2013-02-01

    In a series of smog chamber experiments, the cloud condensation nuclei (CCN) activity of secondary organic aerosol (SOA) generated from ozonolysis of β-caryophyllene was characterized by determining the CCN derived hygroscopicity parameter, κCCN, from experimental data. Two types of CCN counters, operating at different temperatures, were used. The effect of semi-volatile organic compounds on the CCN activity of SOA was studied using a thermodenuder. Overall, SOA was only slightly CCN active (with κCCN in the range 0.001-0.16), and in dark experiments with no OH scavenger present, κCCN decreased when particles were sent through the thermodenuder (with a temperature up to 50 °C). SOA was generated under different experimental conditions: In some experiments, an OH scavenger (2-butanol) was added. SOA from these experiments was less CCN active than SOA produced in experiments without an OH scavenger (i.e. where OH was produced during ozonolysis). In other experiments, lights were turned on, either without or with the addition of HONO (OH source). This led to the formation of more CCN active SOA. SOA was aged up to 30 h through exposure to ozone and (in experiments with no OH scavenger present) to OH. In all experiments, the derived κCCN consistently increased with time after initial injection of β-caryophyllene, showing that chemical ageing increases the CCN activity of β-caryophyllene SOA. κCCN was also observed to depend on supersaturation, which was explained either as an evaporation artifact from semi-volatile SOA (only observed in experiments lacking light exposure) or, alternatively, by effects related to chemical composition depending on dry particle size. Using the method of Threshold Droplet Growth Analysis it was also concluded that the activation kinetics of the SOA do not differ significantly from calibration ammonium sulphate aerosol for particles aged for several hours.

  10. Alterations of estrous activity in the ewe by circadian-based manipulation of the endogenous pacemaker.

    PubMed

    Guerin, M V; Matthews, C D

    1998-02-01

    The timing of reproductive activity in the seasonal breeding Romney Marsh ewe depends on the measurement of photoperiodic time. In this experiment, artificial light and dark signals are provided in a measured sequence at an inappropriate time of year to induce breeding out of phase with environmental photoperiod. The endogenous circadian responses and reproductive effects are documented. One group (Group A, control) of 6 Romney Marsh ewes was held in natural photoperiod throughout the experiment. For 8 weeks centered about the winter solstice (Stage 1), an additional 18 animals (Groups B, C, and D) were exposed to an artificial earlier dawn. Measurements of endogenous melatonin performed under acutely extended darkness confirmed a phase advance of the endogenous circadian pacemaker of the suprachiasmatic nucleus compared to control animals. In Stage 2, to the summer solstice (21 December), Group B animals were returned to natural photoperiod, Group C animals were subjected to an earlier artificial dusk, and Group D animals were subjected to an artificial delayed dawn. Melatonin measurements during Stage 2 confirmed that onset and offset times for Group C were earlier and that onset and offset times for Group D were delayed compared to corresponding times for Group B animals. Ovarian activity was monitored throughout. During Stage 2, Groups C and D commenced reproductive activity in mid-spring, and this continued until the experimental conditions changed. Groups A and B commenced reproductive activity at the normal timing in the subsequent autumn. Although not exclusive, these results are consistent with a coincidence model to explain the timing of seasonal breeding in this species with a dusk-located phase of the endogenous pacemaker sensitive to both light and melatonin. The temporal relationship between circadian alterations and the environmental photoperiod warrants further investigation as an explanation for seasonal breeding. PMID:9486844

  11. Lingual Muscle Activity Across Sleep–Wake States in Rats with Surgically Altered Upper Airway

    PubMed Central

    Rukhadze, Irma; Kalter, Julie; Stettner, Georg M.; Kubin, Leszek

    2014-01-01

    Obstructive sleep apnea (OSA) patients have increased upper airway muscle activity, including such lingual muscles as the genioglossus (GG), geniohyoid (GH), and hyoglossus (HG). This adaptation partially protects their upper airway against obstructions. Rodents are used to study the central neural control of sleep and breathing but they do not naturally exhibit OSA. We investigated whether, in chronically instrumented, behaving rats, disconnecting the GH and HG muscles from the hyoid (H) apparatus would result in a compensatory increase of other upper airway muscle activity (electromyogram, EMG) and/or other signs of upper airway instability. We first determined that, in intact rats, lingual (GG and intrinsic) muscles maintained stable activity levels when quantified based on 2 h-long recordings conducted on days 6 through 22 after instrumentation. We then studied five rats in which the tendons connecting the GH and HG muscles to the H apparatus were experimentally severed. When quantified across all recording days, lingual EMG during slow-wave sleep (SWS) was modestly but significantly increased in rats with surgically altered upper airway [8.6 ± 0.7% (SE) vs. 6.1 ± 0.7% of the mean during wakefulness; p = 0.012]. Respiratory modulation of lingual EMG occurred mainly during SWS and was similarly infrequent in both groups, and the incidence of sighs and central apneas also was similar. Thus, a weakened action of selected lingual muscles did not produce sleep-disordered breathing but resulted in a relatively elevated activity in other lingual muscles during SWS. These results encourage more extensive surgical manipulations with the aim to obtain a rodent model with collapsible upper airway. PMID:24803913

  12. Activation of 5-HT3 receptors leads to altered responses 6 months after MDMA treatment.

    PubMed

    Gyongyosi, Norbert; Balogh, Brigitta; Katai, Zita; Molnar, Eszter; Laufer, Rudolf; Tekes, Kornelia; Bagdy, Gyorgy

    2010-03-01

    The recreational drug "Ecstasy" [3,4-methylenedioxymethamphetamine (MDMA)] has a well-characterised neurotoxic effect on the 5-hydroxytryptamine (5-HT) neurons in animals. Despite intensive studies, the long-term functional consequencies of the 5-HT neurodegeneration remains elusive. The aim of this study was to investigate whether any alteration of 5-hydroxytryptamine-3 (5-HT(3)) receptor functions on the sleep-wake cycle, motor activity, and quantitative EEG could be detected 6 months after a single dose of 15 mg/kg of MDMA. The selective 5-HT(3) receptor agonist m-chlorophenylbiguanide (mCPBG; 1 mg/kg, i.p.) or vehicle was administered to freely moving rats pre-treated with MDMA (15 mg/kg, i.p.) or vehicle 6 months earlier. Polysomnographic and motor activity recordings were performed. Active wake (AW), passive wake (PW), light slow wave sleep (SWS-1), deep slow wave sleep (SWS-2), and paradoxical sleep were classified. In addition, EEG power spectra were calculated for the second hour after mCPBG treatment for each stage. AW increased and SWS-1 decreased in the second hour after mCPBG treatment in control animals. mCPBG caused significant changes in the EEG power in states with cortical activation (AW, PW, paradoxical sleep). In addition, mCPBG had a biphasic effect on hippocampal theta power in AW with a decrease in 7 Hz and a stage-selective increase in the upper range (8-9 Hz). Effects of mCPBG on the time spent in AW and SWS-1 were eliminated or reduced in MDMA-treated animals. In addition, mCPBG did not increase the upper theta power of AW in rats pre-treated with MDMA. These data suggest long-term changes in 5-HT(3) receptor function after MDMA. PMID:20052506

  13. Altered relationships between age and functional brain activation in adolescents at clinical high risk for psychosis.

    PubMed

    Karlsgodt, Katherine H; van Erp, Theo G M; Bearden, Carrie E; Cannon, Tyrone D

    2014-01-30

    Schizophrenia is considered a neurodevelopmental disorder, but whether the adolescent period, proximal to onset, is associated with aberrant development in individuals at clinical high risk (CHR) for psychosis is incompletely understood. While abnormal gray and white matter development has been observed, alterations in functional neuroimaging (fMRI) parameters during adolescence as related to conversion to psychosis have not yet been investigated. Twenty CHR individuals and 19 typically developing controls (TDC), (ages 14-21), were recruited from the Center for Assessment and Prevention of Prodromal States (CAPPS) at UCLA. Participants performed a Sternberg-style verbal working memory (WMem) task during fMRI and data were analyzed using a cross-sectional design to test the hypothesis that there is a deviant developmental trajectory in WMem associated neural circuitry in those at risk for psychosis. Eight of the CHR adolescents converted to psychosis within 2 years of initial assessment. A voxel-wise regression examining the relationship between age and activation revealed a significant group-by-age interaction. TDC showed a negative association between age and functional activation in the WMem circuitry while CHR adolescents showed a positive association. Moreover, CHR patients who later converted to overt psychosis showed a distinct pattern of abnormal age-associated activation in the frontal cortex relative to controls, while non-converters showed a more diffuse posterior pattern. Finding that age related variation in baseline patterns of neural activity differentiate individuals who subsequently convert to psychosis from healthy subjects suggests that these differences are likely to be clinically relevant. PMID:24144510

  14. Altered polymorphonuclear leukocyte Fc gamma R expression contributes to decreased candicidal activity during intraabdominal sepsis

    SciTech Connect

    Simms, H.H.; D'Amico, R.; Monfils, P.; Burchard, K.W. )

    1991-03-01

    We investigated the effects of untreated intraabdominal sepsis on polymorphonuclear leukocyte (PMN) candicidal activity. Two groups of swine were studied. Group I (n=6) underwent sham laparotomy, group II (n=7) underwent cecal ligation and incision. Untreated intraabdominal sepsis resulted in a progressive decrease in PMN candicidal activity. Concomitant rosetting and phagocytosis assays demonstrated a decrease in both the attachment and phagocytosis of Candida albicans opsonized with both normal and septic swine serum by PMNs in group II. Iodine 125-labeled swine immunoglobulin G (IgG) and fluorescein isothioalanate (FITC)-labeled swine IgG were used to investigate Fc gamma receptor ligand interactions. Scatchard analyses demonstrated a progressive decline in both the binding affinity constant and number of IgG molecules bound per PMN. Stimulation of the oxidative burst markedly reduced 125I-labeled IgG binding in both group I and group II, with a greater decrement being seen in animals with intraabdominal sepsis. Further, in group II, PMN recycling of the Fc gamma receptor to the cell surface after generation of the oxidative burst was reduced by postoperative day 4. Binding of monoclonal antibodies to Fc gamma receptor II, but not Fc gamma receptor I/III markedly reduced intracellular candicidal activity. Immunofluorescence studies revealed a homogeneous pattern of FITC-IgG uptake by nearly all group I PMNs, whereas by postoperative day 8 a substantial number of PMNs from group II failed to internalize the FITC-IgG. These studies suggest that untreated intraabdominal sepsis reduces PMN candicidal activity and that this is due, in part, to altered PMN Fc gamma receptor ligand interactions.

  15. Altered Regional and Circuit Resting-State Activity Associated with Unilateral Hearing Loss

    PubMed Central

    Zhao, Fu; Wang, Zhenmin; Ge, Jianqiao; Zhang, Kai; Gao, Zhixian; Gao, Jia-Hong; Yang, Yihong; Fan, Jin; Zou, Qihong; Liu, Pinan

    2014-01-01

    The deprivation of sensory input after hearing damage results in functional reorganization of the brain including cross-modal plasticity in the sensory cortex and changes in cognitive processing. However, it remains unclear whether partial deprivation from unilateral auditory loss (UHL) would similarly affect the neural circuitry of cognitive processes in addition to the functional organization of sensory cortex. Here, we used resting-state functional magnetic resonance imaging to investigate intrinsic activity in 34 participants with UHL from acoustic neuroma in comparison with 22 matched normal controls. In sensory regions, we found decreased regional homogeneity (ReHo) in the bilateral calcarine cortices in UHL. However, there was an increase of ReHo in the right anterior insular cortex (rAI), the key node of cognitive control network (CCN) and multimodal sensory integration, as well as in the left parahippocampal cortex (lPHC), a key node in the default mode network (DMN). Moreover, seed-based resting–state functional connectivity analysis showed an enhanced relationship between rAI and several key regions of the DMN. Meanwhile, lPHC showed more negative relationship with components in the CCN and greater positive relationship in the DMN. Such reorganizations of functional connectivity within the DMN and between the DMN and CCN were confirmed by a graph theory analysis. These results suggest that unilateral sensory input damage not only alters the activity of the sensory areas but also reshapes the regional and circuit functional organization of the cognitive control network. PMID:24788317

  16. Basic Mechanisms of RNA Polymerase II Activity and Alteration of Gene Expression in Saccharomyces cerevisiae

    PubMed Central

    Kaplan, Craig D.

    2014-01-01

    Transcription by RNA Polymerase II (Pol II), and all RNA polymerases for that matter, may be understood as comprising two cycles. The first cycle relates to the basic mechanism of the transcription process wherein Pol II must select the appropriate nucleoside triphosphate (NTP) substrate complementary to the DNA template, catalyze phosphodiester bond formation, and translocate to the next position on the DNA template. Performing this cycle in an iterative fashion allows the synthesis of RNA chains that can be over one million nucleotides in length in some larger eukaryotes. Overlaid upon this enzymatic cycle, transcription may be divided into another cycle of three phases: initiation, elongation, and termination. Each of these phases has a large number of associated transcription factors that function to promote or regulate the gene expression process. Complicating matters, each phase of the latter transcription cycle are coincident with cotranscriptional RNA processing events. Additionally, transcription takes place within a highly dynamic and regulated chromatin environment. This chromatin environment is radically impacted by active transcription and associated chromatin modifications and remodeling, while also functioning as a major platform for Pol II regulation. This review will focus on our basic knowledge of the Pol II transcription mechanism, and how altered Pol II activity impacts gene expression in vivo in the model eukaryote Saccharomyces cerevisiae. PMID:23022618

  17. Theory of mind network activity is altered in subjects with familial liability for schizophrenia.

    PubMed

    Mohnke, Sebastian; Erk, Susanne; Schnell, Knut; Romanczuk-Seiferth, Nina; Schmierer, Phöbe; Romund, Lydia; Garbusow, Maria; Wackerhagen, Carolin; Ripke, Stephan; Grimm, Oliver; Haller, Leila; Witt, Stephanie H; Degenhardt, Franziska; Tost, Heike; Heinz, Andreas; Meyer-Lindenberg, Andreas; Walter, Henrik

    2016-02-01

    As evidenced by a multitude of studies, abnormalities in Theory of Mind (ToM) and its neural processing might constitute an intermediate phenotype of schizophrenia. If so, neural alterations during ToM should be observable in unaffected relatives of patients as well, since they share a considerable amount of genetic risk. While behaviorally, impaired ToM function is confirmed meta-analytically in relatives, evidence on aberrant function of the neural ToM network is sparse and inconclusive. The present study therefore aimed to further explore the neural correlates of ToM in relatives of schizophrenia. About 297 controls and 63 unaffected first-degree relatives of patients with schizophrenia performed a ToM task during functional magnetic resonance imaging. Consistent with the literature relatives exhibited decreased activity of the medial prefrontal cortex. Additionally, increased recruitment of the right middle temporal gyrus and posterior cingulate cortex was found, which was related to subclinical paranoid symptoms in relatives. These results further support decreased medial prefrontal activation during ToM as an intermediate phenotype of genetic risk for schizophrenia. Enhanced recruitment of posterior ToM areas in relatives might indicate inefficiency mechanisms in the presence of genetic risk. PMID:26341902

  18. The impact of initiation: Early onset marijuana smokers demonstrate altered Stroop performance and brain activation.

    PubMed

    Sagar, K A; Dahlgren, M K; Gönenç, A; Racine, M T; Dreman, M W; Gruber, S A

    2015-12-01

    Marijuana (MJ) use is on the rise, particularly among teens and emerging adults. This poses serious public health concern, given the potential deleterious effects of MJ on the developing brain. We examined 50 chronic MJ smokers divided into early onset (regular MJ use prior to age 16; n=24) and late onset (age 16 or later; n=26), and 34 healthy control participants (HCs). All completed a modified Stroop Color Word Test during fMRI. Results demonstrated that MJ smokers exhibited significantly poorer performance on the Interference subtest of the Stroop, as well as altered patterns of activation in the cingulate cortex relative to HCs. Further, early onset MJ smokers exhibited significantly poorer performance relative to both HCs and late onset smokers. Additionally, earlier age of MJ onset as well as increased frequency and magnitude (grams/week) of MJ use were predictive of poorer Stroop performance. fMRI results revealed that while late onset smokers demonstrated a more similar pattern of activation to the control group, a different pattern was evident in the early onset group. These findings underscore the importance of assessing age of onset and patterns of MJ use and support the need for widespread education and intervention efforts among youth. PMID:25936584

  19. Alterations in locomotor activity induced by radioprotective doses of 16,16-dimethyl prostaglandin E2

    SciTech Connect

    Landauer, M.R.; Walden, T.L.; Davis, H.D.; Dominitz, J.A.

    1987-01-01

    16,16-Dimethyl prostaglandin E2 (DiPGE2) is an effective radioprotectant when administered before irradiation. A notable side effect of this compound is sedation. In separate experiments, the dose-response determinations of the time course of locomotor activity and 30-day survival after 10 Gy gamma irradiation (LD100) were made. Adult male CD2F1 mice were injected subcutaneously with vehicle or DiPGE2 in doses ranging from 0.01 to 40 micrograms per mouse. A dose of 0.01 micrograms did not result in alterations in locomotor behaviour or enhance survival. Doses greater than 1 microgram produced ataxia and enhanced radiation survival in a dose-dependent fashion. Full recovery of locomotor activity did not occur until 6 and 30 hr after injection for the 10 microgram and 40 microgram groups, respectively. Radioprotection was observed when DiPGE2 was administered preirradiation but not postirradiation. Doses of 1 and 10 micrograms were maximally effective as a radioprotectant if injected 5 min prior to irradiation (80%-90% survival). A dose of 40 micrograms resulted in 100% survival when injected 5-30 min before irradiation. Therefore, increasing doses of DiPGE2 resulted in an enhanced effectiveness as a radioprotectant. However, the doses that were the most radioprotective were also the most debilitating to the animal.

  20. Altered Hemodynamic Activity in Conduct Disorder: A Resting-State fMRI Investigation

    PubMed Central

    Zhou, Jiansong; Yao, Nailin; Fairchild, Graeme; Zhang, Yingdong; Wang, Xiaoping

    2015-01-01

    Background Youth with conduct disorder (CD) not only inflict serious physical and psychological harm on others, but are also at greatly increased risk of sustaining injuries, developing depression or substance abuse, and engaging in criminal behaviors. The underlying neurobiological basis of CD remains unclear. Objective The present study investigated whether participants with CD have altered hemodynamic activity under resting-state conditions. Methods Eighteen medication-naïve boys with CD and 18 age- and sex- matched typically developing (TD) controls underwent functional magnetic resonance imaging (MRI) scans in the resting state. The amplitude of low-frequency fluctuations (ALFF) was measured and compared between the CD and TD groups. Results Compared with the TD participants, the CD participants showed lower ALFF in the bilateral amygdala/parahippocampus, right lingual gyrus, left cuneus and right insula. Higher ALFF was observed in the right fusiform gyrus and right thalamus in the CD participants compared to the TD group. Conclusions Youth with CD displayed widespread functional abnormalities in emotion-related and visual cortical regions in the resting state. These results suggest that deficits in the intrinsic activity of resting state networks may contribute to the etiology of CD. PMID:25816069

  1. High fat diet induced alterations of atrial electrical activities in mice

    PubMed Central

    Zhang, Fan; Hartnett, Sigurd; Sample, Alex; Schnack, Sabrina; Li, Yifan

    2016-01-01

    Obesity is a well-known risk factor for various cardiovascular diseases. Recent clinical data showed that overweight and obese patients have higher incidence of atrial fibrillation (AF) compared with individuals with normal body weights, but the underlying mechanisms remain to be elucidated. In this study, we investigated the effects of a high fat diet on atrial activities in mice. ICR male mice were fed a regular diet (RD) or a high fat diet (HFD) for 8 weeks. Mice fed HFD showed significantly greater body weight gains and visceral fat accumulation compared with RD mice. Under anesthetic condition, baseline arterial blood pressure and heart rate were not significantly different between RD and HFD groups. Although no spontaneous or atrial stimulation-induced atrial fibrillation was observed, this study revealed several alterations in the activities and protein levels in the atria in HFD mice. Surface electrocardiogram (ECG) revealed significantly shortened PR interval in HFD mice. In the atrial stimulation experiments, the sinoatrial (SA) node recovery time was significantly prolonged whereas the atrial effective refractory period was significantly reduced in HFD mice as compared with RD mice. Western blot showed protein levels of two major potassium channels, Kv1.5 and Kv4.2/3, were significantly increased in atria of HFD mice. These data indicate that HFD induces atrial electrophysiological remodeling in mice, which may be a potential mechanism underlying the increased risk for atrial arrhythmias in obesity and metabolic disorders. PMID:27073731

  2. Basic mechanisms of RNA polymerase II activity and alteration of gene expression in Saccharomyces cerevisiae.

    PubMed

    Kaplan, Craig D

    2013-01-01

    Transcription by RNA polymerase II (Pol II), and all RNA polymerases for that matter, may be understood as comprising two cycles. The first cycle relates to the basic mechanism of the transcription process wherein Pol II must select the appropriate nucleoside triphosphate (NTP) substrate complementary to the DNA template, catalyze phosphodiester bond formation, and translocate to the next position on the DNA template. Performing this cycle in an iterative fashion allows the synthesis of RNA chains that can be over one million nucleotides in length in some larger eukaryotes. Overlaid upon this enzymatic cycle, transcription may be divided into another cycle of three phases: initiation, elongation, and termination. Each of these phases has a large number of associated transcription factors that function to promote or regulate the gene expression process. Complicating matters, each phase of the latter transcription cycle are coincident with cotranscriptional RNA processing events. Additionally, transcription takes place within a highly dynamic and regulated chromatin environment. This chromatin environment is radically impacted by active transcription and associated chromatin modifications and remodeling, while also functioning as a major platform for Pol II regulation. This review will focus on our basic knowledge of the Pol II transcription mechanism, and how altered Pol II activity impacts gene expression in vivo in the model eukaryote Saccharomyces cerevisiae. This article is part of a Special Issue entitled: RNA Polymerase II Transcript Elongation. PMID:23022618

  3. Ethanol alters cellular activation and CD14 partitioning in lipid rafts

    SciTech Connect

    Dai Qun; Zhang Jun; Pruett, Stephen B. . E-mail: spruet@lsuhsc.edu

    2005-06-24

    Alcohol consumption interferes with innate immunity. In vivo EtOH administration suppresses cytokine responses induced through Toll-like receptor 4 (TLR4) and inhibits TLR4 signaling. Actually, EtOH exhibits a generalized suppressive effect on signaling and cytokine responses induced by through most TLRs. However, the underlying mechanism remains unknown. RAW264.7 cells were treated with LPS or co-treated with EtOH or with lipid raft-disrupting drugs. TNF-{alpha} production, IRAK-1 activation, and CD14 partition were evaluated. EtOH or nystatin, a lipid raft-disrupting drug, suppressed LPS-induced production of TNF-{alpha}. The suppressive effect of EtOH on LPS-induced TNF-{alpha} production was additive with that of methyl-{beta}-cyclodextrin (MCD), another lipid raft-disrupting drug. EtOH interfered with IRAK-1 activation, an early TLR4 intracellular signaling event. Cell fractionation analyses show that acute EtOH altered LPS-related partition of CD14, a critical component of the LPS receptor complex. These results suggest a novel mechanism of EtOH action that involves interference with lipid raft clustering induced by LPS. This membrane action of EtOH might be one of the mechanisms by which EtOH acts as a generalized suppressor for TLR signaling.

  4. Altering the interfacial activation mechanism of a lipase by solid-phase selective chemical modification.

    PubMed

    López-Gallego, Fernando; Abian, Olga; Guisán, Jose Manuel

    2012-09-01

    This study presents a combined protein immobilization, directed mutagenesis, and site-selective chemical modification approach, which was used to create a hyperactivated semisynthetic variant of BTL2. Various alkane chains were tethered at three different positions in order to mimic the lipase interfacial activation exogenously triggered by detergents. Optimum results were obtained when a dodecane chain was introduced at position 320 by solid-phase site-selective chemical modification. The resulting semisynthetic variant showed a 2.5-fold higher activity than the wild-type nonmodified variant in aqueous conditions. Remarkably, this is the maximum hyperactivation ever observed for BTL2 in the presence of detergents such as Triton X-100. We present evidence to suggest that the endogenous dodecane chain hyperactivates the enzyme in a similar fashion as an exogenous detergent molecule. In this way, we also observe a faster irreversible enzyme inhibition and an altered detergent sensitivity profile promoted by the site-selective chemical modification. These findings are also supported by fluorescence studies, which reveal that the structural conformation changes of the semisynthetic variant are different to those of the wild type, an effect that is more pronounced in the presence of detergent. Finally, the optimal immobilized semisynthetic variant was successfully applied to the selective synthesis of oxiran-2-yl butyrate. Significantly, this biocatalyst is 12-fold more efficient than the immobilized wild-type enzyme, producing the S-enantiomer with higher enantiospecificity (ee = 92%). PMID:22876885

  5. The role of hydroxyl group acidity on the activity of silica-supported secondary amines for the self-condensation of n-butanal.

    PubMed

    Shylesh, Sankaranarayanapillai; Hanna, David; Gomes, Joseph; Canlas, Christian G; Head-Gordon, Martin; Bell, Alexis T

    2015-02-01

    The catalytic activity of secondary amines supported on mesoporous silica for the self-condensation of n-butanal to 2-ethylhexenal can be altered significantly by controlling the Brønsted acidity of M--OH species present on the surface of the support. In this study, M--OH (M=Sn, Zr, Ti, and Al) groups were doped onto the surface of SBA-15, a mesoporous silica, prior to grafting secondary propyl amine groups on to the support surface. The catalytic activity was found to depend critically on the synthesis procedure, the nature and amount of metal species introduced and the spatial separation between the acidic sites and amine groups. DFT analysis of the reaction pathway indicates that, for weak Brønsted acid groups, such as Si--OH, the rate-limiting step is C--C bond formation, whereas for stronger Brønsted acid groups, such as Ti and Al, hydrolysis of iminium species produced upon C--C bond formation is the rate-limiting step. Theoretical analysis shows further that the apparent activation energy decreases with increasing Brønsted acidity of the M--OH groups, consistent with experimental observation. PMID:25314616

  6. Effect of External Electric Field on Substrate Transport of a Secondary Active Transporter.

    PubMed

    Zhang, Ji-Long; Zheng, Qing-Chuan; Yu, Li-Ying; Li, Zheng-Qiang; Zhang, Hong-Xing

    2016-08-22

    Substrate transport across a membrane accomplished by a secondary active transporter (SAT) is essential to the normal physiological function of living cells. In the present research, a series of all-atom molecular dynamics (MD) simulations under different electric field (EF) strengths was performed to investigate the effect of an external EF on the substrate transport of an SAT. The results show that EF both affects the interaction between substrate and related protein's residues by changing their conformations and tunes the timeline of the transport event, which collectively reduces the height of energy barrier for substrate transport and results in the appearance of two intermediate conformations under the existence of an external EF. Our work spotlights the crucial influence of external EFs on the substrate transport of SATs and could provide a more penetrating understanding of the substrate transport mechanism of SATs. PMID:27472561

  7. Design of secondary optics for IRED in active night vision systems.

    PubMed

    Xin, Di; Liu, Hua; Jing, Lei; Wang, Yao; Xu, Wenbin; Lu, Zhenwu

    2013-01-14

    An effective optical design method is proposed to solve the problem of adjustable view angle for infrared illuminator in active night vision systems. A novel total internal reflection (TIR) lens with three segments of the side surface is designed as the secondary optics of infrared emitting diode (IRED). It can provide three modes with different view angles to achieve a complete coverage of the monitored area. As an example, a novel TIR lens is designed for SONY FCB-EX 480CP camera. Optical performance of the novel TIR lens is investigated by both numerical simulation and experiments. The results demonstrate that it can meet the requirements of different irradiation distances quit well with view angles of 7.5°, 22° and 50°. The mean optical efficiency is improved from 62% to 75% and the mean irradiance uniformity is improved from 65% to 85% compared with the traditional structure. PMID:23389004

  8. Alterations in some lipid components and Ca2+ ATPase activity in brain of rats fed an atherogenic diet.

    PubMed

    Oner, P; Bekpinar, S; Oz, B

    1991-06-01

    Male Wistar rats were fed an atherogenic diet for four months to investigate possible diet-induced lipid alterations and brain Ca2+ ATPase activity. Total cholesterol and triglyceride levels were found to be increased significantly in both serum and brain while the phospholipid level was decreased in both. The distribution of serum cholesterol between high-density and low-density lipoproteins was altered when compared to control rats with a decrement in HDL-cholesterol and a pronounced increment in LDL-cholesterol. The atherogenic diet resulted in about 50% depression in brain Ca2+ ATPase activity. It is concluded that alterations in ion transport and neurotransmitter release may be expected due to pronounced inhibition of brain Ca2+ ATPase activity in rats fed an atherogenic diet. PMID:1835114

  9. Large-Scale In-situ Experiments to Determine Geochemical Alterations and Microbial Activities at the Geological Repository

    NASA Astrophysics Data System (ADS)

    Choung, S.; Francis, A. J.; Um, W.; Choi, S.; Kim, S.; Park, J.; Kim, S.

    2013-12-01

    The countries that have generated nuclear power have facing problems on the disposal of accumulated radioactive wastes. Geological disposal method has been chosen in many countries including Korea. A safety issue after the closure of geological repository has been raised, because microbial activities lead overpressure in the underground facilities through gas production. In particular, biodegradable organic materials derived from low- and intermediate-level radioactive wastes play important role on microbial activities in the geological repository. This study performed large scale in-situ experiments using organic wastes and groundwater, and investigated geochemical alteration and microbial activities at early stage (~63 days) as representative of the period, after closure of the geological repository. The geochemical alteration controlled significantly the microorganism types and populations. Database of the biogeochemical alteration facilitates prediction of radionuclides' mobility and establishment of remedial strategy against unpredictable accidents and hazards at early stage right after closure of the geological repository.

  10. The Mountain West and the World: International Connections and Alternative Futures. A Handbook of 15 Activities for Secondary Classrooms.

    ERIC Educational Resources Information Center

    Smith, Gary R.; Bienstock, Eric M.

    Activities to supplement secondary school global or future studies courses in the 10 state Mountain West region are presented in this teacher handbook. Material is divided into 3 sections. Section 1, an introduction to international connectedness, contains 7 activities focusing on the Mountain West's interdependence with the rest of the world. A…

  11. Employment and Post-Secondary Educational Activities for Young Adults with Autism Spectrum Disorders during the Transition to Adulthood

    ERIC Educational Resources Information Center

    Taylor, Julie Lounds; Seltzer, Marsha Mailick

    2011-01-01

    This report describes the post-high school educational and occupational activities for 66 young adults with autism spectrum disorders who had recently exited the secondary school system. Analyses indicated low rates of employment in the community, with the majority of young adults (56%) spending time in sheltered workshops or day activity centers.…

  12. An Analysis of Writing Activities in the Student Workbooks of a Secondary-Level Turkish Language Course

    ERIC Educational Resources Information Center

    Çerçi, Arif

    2016-01-01

    The purpose of this study is to analyze writing activities in the student workbooks of a secondary-level Turkish language course (grades 5 to 8) according to the principles of progressive writing. The study is descriptive and employs content analysis as a qualitative research paradigm. The writing activities of the books in this study all…

  13. Alterations in lower limb multimuscle activation patterns during stair climbing in female total knee arthroplasty patients.

    PubMed

    Kuntze, G; von Tscharner, V; Hutchison, C; Ronsky, J L

    2015-11-01

    Total knee arthroplasty (TKA) patients commonly experience neuromuscular adaptations that may affect stair climbing competence. This study identified multimuscle pattern (MMP) changes in postoperative female TKA patients during stair climbing with a support vector machine (SVM). It was hypothesized that TKA patients adopt temporal and spectral muscle activation characteristics indicative of muscle atrophy and cocontraction strategies. Nineteen female subjects [10 unilateral sex-specific TKAs, 62.2 ± 8.6 yr, body mass index (BMI) 28.2 ± 5.4 kg/m(2); 9 healthy control subjects, 61.4 ± 7.4 yr, BMI 25.6 ± 2.4 kg/m(2)] were recruited. Surface electromyograms (EMGs) were obtained for seven lower limb muscles of the affected limb of TKA subjects and a randomly assigned limb for control subjects during stair climbing. Stance phase (±30%) EMG data were wavelet transformed and normalized to total power. Data across all muscles were combined to form MMPs and analyzed with a SVM. Statistical analysis was performed with binomial tests, independent group t-tests, or independent group Mann-Whitney U-tests in SPSS (P < 0.05). SVM results indicated significantly altered muscle activation patterns in the TKA group for biceps femoris (recognition rate 84.2%), semitendinosus (recognition rate 73.7%), gastrocnemius (recognition rate 68.4%), and tibialis anterior (recognition rate 68.4%). Further analysis identified no significant differences in spectral activation characteristics between groups. Temporal adaptations, indicative of cocontraction strategies, were, however, evident in TKA MMPs. This approach may provide a valuable tool for clinical neuromuscular function assessment and rehabilitation monitoring. PMID:26354313

  14. Benzene's metabolites alter c-MYB activity via reactive oxygen species in HD3 cells

    SciTech Connect

    Wan, Joanne; Winn, Louise M. . E-mail: winnl@queensu.ca

    2007-07-15

    Benzene is a known leukemogen that is metabolized to form reactive intermediates and reactive oxygen species (ROS). The c-Myb oncoprotein is a transcription factor that has a critical role in hematopoiesis. c-Myb transcript and protein have been overexpressed in a number of leukemias and cancers. Given c-Myb's role in hematopoiesis and leukemias, it is hypothesized that benzene interferes with the c-Myb signaling pathway and that this involves ROS. To investigate our hypothesis, we evaluated whether benzene, 1,4-benzoquinone, hydroquinone, phenol, and catechol generated ROS in chicken erythroblast HD3 cells, as measured by 5-(and-6)-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate (DCFDA) and dihydrorhodamine-123 (DHR-123), and whether the addition of 100 U/ml of the antioxidating enzyme superoxide dismutase (SOD) could prevent ROS generation. Reduced to oxidized glutathione ratios (GSH:GSSG) were also assessed as well as hydroquinone and benzoquinone's effects on c-Myb protein levels and activation of a transiently transfected reporter construct. Finally we attempted to abrogate benzene metabolite mediated increases in c-Myb activity with the use of SOD. We found that benzoquinone, hydroquinone, and catechol increased DCFDA fluorescence, increased DHR-123 fluorescence, decreased GSH:GSSG ratios, and increased reporter construct expression after 24 h of exposure. SOD was able to prevent DCFDA fluorescence and c-Myb activity caused by benzoquinone and hydroquinone only. These results are consistent with other studies, which suggest metabolite differences in benzene-mediated toxicity. More importantly, this study supports the hypothesis that benzene may mediate its toxicity through ROS-mediated alterations in the c-Myb signaling pathway.

  15. Post-Spaceflight (STS-135) Mouse Splenocytes Demonstrate Altered Activation Properties and Surface Molecule Expression

    PubMed Central

    Crucian, Brian; Sams, Clarence

    2015-01-01

    Alterations in immune function have been documented during or post-spaceflight and in ground based models of microgravity. Identification of immune parameters that are dysregulated during spaceflight is an important step in mitigating crew health risks during deep space missions. The in vitro analysis of leukocyte activity post-spaceflight in both human and animal species is primarily focused on lymphocytic function. This report completes a broader spectrum analysis of mouse lymphocyte and monocyte changes post 13 days orbital flight (mission STS-135). Analysis includes an examination in surface markers for cell activation, and antigen presentation and co-stimulatory molecules. Cytokine production was measured after stimulation with T-cell mitogen or TLR-2, TLR-4, or TLR-5 agonists. Splenocyte surface marker analysis immediate post-spaceflight and after in vitro culture demonstrated unique changes in phenotypic populations between the flight mice and matched treatment ground controls. Post-spaceflight splenocytes (flight splenocytes) had lower expression intensity of CD4+CD25+ and CD8+CD25+ cells, lower percentage of CD11c+MHC II+ cells, and higher percentage of CD11c+MHC I+ populations compared to ground controls. The flight splenocytes demonstrated an increase in phagocytic activity. Stimulation with ConA led to decrease in CD4+ population but increased CD4+CD25+ cells compared to ground controls. Culturing with TLR agonists led to a decrease in CD11c+ population in splenocytes isolated from flight mice compared to ground controls. Consequently, flight splenocytes with or without TLR-agonist stimulation showed a decrease in CD11c+MHC I+, CD11c+MHC II+, and CD11c+CD86+ cells compared to ground controls. Production of IFN-γ was decreased and IL-2 was increased from ConA stimulated flight splenocytes. This study demonstrated that expression of surface molecules can be affected by conditions of spaceflight and impaired responsiveness persists under culture

  16. Spatiotemporal alterations of cortical network activity by selective loss of NOS-expressing interneurons.

    PubMed

    Shlosberg, Dan; Buskila, Yossi; Abu-Ghanem, Yasmin; Amitai, Yael

    2012-01-01

    Deciphering the role of GABAergic neurons in large neuronal networks such as the neocortex forms a particularly complex task as they comprise a highly diverse population. The neuronal isoform of the enzyme nitric oxide synthase (nNOS) is expressed in the neocortex by specific subsets of GABAergic neurons. These neurons can be identified in live brain slices by the nitric oxide (NO) fluorescent indicator diaminofluorescein-2 diacetate (DAF-2DA). However, this indicator was found to be highly toxic to the stained neurons. We used this feature to induce acute phototoxic damage to NO-producing neurons in cortical slices, and measured subsequent alterations in parameters of cellular and network activity. Neocortical slices were briefly incubated in DAF-2DA and then illuminated through the 4× objective. Histochemistry for NADPH-diaphorase (NADPH-d), a marker for nNOS activity, revealed elimination of staining in the illuminated areas following treatment. Whole cell recordings from several neuronal types before, during, and after illumination confirmed the selective damage to non-fast-spiking (FS) interneurons. Treated slices displayed mild disinhibition. The reversal potential of compound synaptic events on pyramidal neurons became more positive, and their decay time constant was elongated, substantiating the removal of an inhibitory conductance. The horizontal decay of local field potentials (LFPs) was significantly reduced at distances of 300-400 μm from the stimulation, but not when inhibition was non-selectively weakened with the GABA(A) blocker picrotoxin. Finally, whereas the depression of LFPs along short trains of 40 Hz stimuli was linearly reduced with distance or initial amplitude in control slices, this ordered relationship was disrupted in DAF-treated slices. These results reveal that NO-producing interneurons in the neocortex convey lateral inhibition to neighboring columns, and shape the spatiotemporal dynamics of the network's activity. PMID:22347168

  17. Identifying candidate causal variants responsible for altered activity of the ABCB1 multidrug resistance gene.

    PubMed

    Soranzo, Nicole; Cavalleri, Gianpiero L; Weale, Michael E; Wood, Nicholas W; Depondt, Chantal; Marguerie, Richard; Sisodiya, Sanjay M; Goldstein, David B

    2004-07-01

    The difficulty of fine localizing the polymorphisms responsible for genotype-phenotype correlations is emerging as an important constraint in the implementation and interpretation of genetic association studies, and calls for the definition of protocols for the follow-up of associated variants. One recent example is the 3435C>T polymorphism in the multidrug transporter gene ABCB1, associated with protein expression and activity, and with several clinical conditions. Available data suggest that 3435C>T may not directly cause altered transport activity, but may be associated with one or more causal variants in the poorly characterized stretch of linkage disequilibrium (LD) surrounding it. Here we describe a strategy for the follow-up of reported associations, including a Bayesian formalization of the associated interval concept previously described by Goldstein. We focus on the region of high LD around 3435C>T to compile an exhaustive list of variants by (1) using a relatively coarse set of marker typings to assess the pattern of LD, and (2) resequencing derived and ancestral chromosomes at 3435C>T through the associated interval. We identified three intronic sites that are strongly associated with the 3435C>T polymorphism. One of them is associated with multidrug resistance in patients with epilepsy (chi2 = 3.78, P = 0.052), and sits within a stretch of significant evolutionary conservation. We argue that these variants represent additional candidates for influencing multidrug resistance due to P-glycoprotein activity, with the IVS 26+80 T>C being the best candidate among the three intronic sites. Finally, we describe a set of six haplotype tagging single-nucleotide polymorphisms that represent common ABCB1 variation surrounding 3435C>T in Europeans. PMID:15197162

  18. Altered neural activity in the `when' pathway during temporal processing in fragile X premutation carriers

    PubMed Central

    Kim, So-Yeon; Tassone, Flora; Simon, Tony J.; Rivera, Susan M.

    2016-01-01

    Mutations of the fragile X mental retardation 1 (FMR1) gene are the genetic cause of fragile X syndrome (FXS). Large expansions of the CGG repeat (>200 repeats) consequently result in transcriptional silencing of the FMR1 gene and deficiency/absence of the FMR1 protein (FMRP). Carriers with a premutation allele (55–200 of CGG repeats) are often associated with mildly reduced levels of FMRP and/or elevated levels of FMR1 mRNA. Recent studies have shown that infants with FXS exhibit severely reduced resolution of temporal attention, whereas spatial resolution of attention is not impaired. Following from these findings in the full mutation, the current study used fMRI to examine whether premutation carriers would exhibit atypical temporal processing at behavioral and/or neural levels. Using spatial and temporal working memory (SWM and TWM) tasks, separately tagging spatial and temporal processing, we demonstrated that neurotypical adults showed greater activation in the `when pathway' (i.e., the right temporoparietal junction: TPJ) during TWM retrieval than SWM retrieval. However, premutation carriers failed to show this increased involvement of the right TPJ during retrieval of temporal information. Further, multiple regression analyses on right TPJ activation and FMR1 gene expression (i.e., CGG repeat size and FMR1 mRNA) suggests that elevated FMR1 mRNA level is a powerful predictor accounting for reduced right TPJ activation associated with temporal processing in premutation carriers. In conclusion, the current study provides the first evidence on altered neural correlates of temporal processing in adults with the premutation, explained by their FMR1 gene expression. PMID:24398265

  19. The time course of altered brain activity during 7-day simulated microgravity.

    PubMed

    Liao, Yang; Lei, Meiying; Huang, Haibo; Wang, Chuang; Duan, Jiaobo; Li, Hongzheng; Liu, Xufeng

    2015-01-01

    Microgravity causes multiple changes in physical and mental levels in humans, which can induce performance deficiency among astronauts. Studying the variations in brain activity that occur during microgravity would help astronauts to deal with these changes. In the current study, resting-state functional magnetic resonance imaging (rs-fMRI) was used to observe the variations in brain activity during a 7-day head down tilt (HDT) bed rest, which is a common and reliable model for simulated microgravity. The amplitudes of low frequency fluctuation (ALFF) of twenty subjects were recorded pre-head down tilt (pre-HDT), during a bed rest period (HDT0), and then each day in the HDT period (HDT1-HDT7). One-way analysis of variance (ANOVA) of the ALFF values over these 8 days was used to test the variation across time period (p < 0.05, corrected). Compared to HDT0, subjects presented lower ALFF values in the posterior cingulate cortex (PCC) and higher ALFF values in the anterior cingulate cortex (ACC) during the HDT period, which may partially account for the lack of cognitive flexibility and alterations in autonomic nervous system seen among astronauts in microgravity. Additionally, the observed improvement in function in CPL during the HDT period may play a compensatory role to the functional decline in the paracentral lobule to sustain normal levels of fine motor control for astronauts in a microgravity environment. Above all, those floating brain activities during 7 days of simulated microgravity may indicate that the brain self-adapts to help astronauts adjust to the multiple negative stressors encountered in a microgravity environment. PMID:26029071

  20. The time course of altered brain activity during 7-day simulated microgravity

    PubMed Central

    Liao, Yang; Lei, Meiying; Huang, Haibo; Wang, Chuang; Duan, Jiaobo; Li, Hongzheng; Liu, Xufeng

    2015-01-01

    Microgravity causes multiple changes in physical and mental levels in humans, which can induce performance deficiency among astronauts. Studying the variations in brain activity that occur during microgravity would help astronauts to deal with these changes. In the current study, resting-state functional magnetic resonance imaging (rs-fMRI) was used to observe the variations in brain activity during a 7-day head down tilt (HDT) bed rest, which is a common and reliable model for simulated microgravity. The amplitudes of low frequency fluctuation (ALFF) of twenty subjects were recorded pre-head down tilt (pre-HDT), during a bed rest period (HDT0), and then each day in the HDT period (HDT1–HDT7). One-way analysis of variance (ANOVA) of the ALFF values over these 8 days was used to test the variation across time period (p < 0.05, corrected). Compared to HDT0, subjects presented lower ALFF values in the posterior cingulate cortex (PCC) and higher ALFF values in the anterior cingulate cortex (ACC) during the HDT period, which may partially account for the lack of cognitive flexibility and alterations in autonomic nervous system seen among astronauts in microgravity. Additionally, the observed improvement in function in CPL during the HDT period may play a compensatory role to the functional decline in the paracentral lobule to sustain normal levels of fine motor control for astronauts in a microgravity environment. Above all, those floating brain activities during 7 days of simulated microgravity may indicate that the brain self-adapts to help astronauts adjust to the multiple negative stressors encountered in a microgravity environment. PMID:26029071

  1. Altered neural activity in the 'when' pathway during temporal processing in fragile X premutation carriers.

    PubMed

    Kim, So-Yeon; Tassone, Flora; Simon, Tony J; Rivera, Susan M

    2014-03-15

    Mutations of the fragile X mental retardation 1 (FMR1) gene are the genetic cause of fragile X syndrome (FXS). Large expansions of the CGG repeat (>200 repeats) consequently result in transcriptional silencing of the FMR1 gene and deficiency/absence of the FMR1 protein (FMRP). Carriers with a premutation allele (55-200 of CGG repeats) are often associated with mildly reduced levels of FMRP and/or elevated levels of FMR1 mRNA. Recent studies have shown that infants with FXS exhibit severely reduced resolution of temporal attention, whereas spatial resolution of attention is not impaired. Following from these findings in the full mutation, the current study used fMRI to examine whether premutation carriers would exhibit atypical temporal processing at behavioral and/or neural levels. Using spatial and temporal working memory (SWM and TWM) tasks, separately tagging spatial and temporal processing, we demonstrated that neurotypical adults showed greater activation in the 'when pathway' (i.e., the right temporoparietal junction: TPJ) during TWM retrieval than SWM retrieval. However, premutation carriers failed to show this increased involvement of the right TPJ during retrieval of temporal information. Further, multiple regression analyses on right TPJ activation and FMR1 gene expression (i.e., CGG repeat size and FMR1 mRNA) suggests that elevated FMR1 mRNA level is a powerful predictor accounting for reduced right TPJ activation associated with temporal processing in premutation carriers. In conclusion, the current study provides the first evidence on altered neural correlates of temporal processing in adults with the premutation, explained by their FMR1 gene expression. PMID:24398265

  2. Secondary cell with orthorhombic alkali metal/manganese oxide phase active cathode material

    DOEpatents

    Doeff, M.M.; Peng, M.Y.; Ma, Y.; Visco, S.J.; DeJonghe, L.C.

    1996-09-24

    An alkali metal manganese oxide secondary cell is disclosed which can provide a high rate of discharge, good cycling capabilities, good stability of the cathode material, high specific energy (energy per unit of weight) and high energy density (energy per unit volume). The active material in the anode is an alkali metal and the active material in the cathode comprises an orthorhombic alkali metal manganese oxide which undergoes intercalation and deintercalation without a change in phase, resulting in a substantially linear change in voltage with change in the state of charge of the cell. The active material in the cathode is an orthorhombic structure having the formula M{sub x}Z{sub y}Mn{sub (1{minus}y)}O{sub 2}, where M is an alkali metal; Z is a metal capable of substituting for manganese in the orthorhombic structure such as iron, cobalt or titanium; x ranges from about 0.2 in the fully charged state to about 0.75 in the fully discharged state, and y ranges from 0 to 60 atomic %. Preferably, the cell is constructed with a solid electrolyte, but a liquid or gelatinous electrolyte may also be used in the cell. 11 figs.

  3. Secondary cell with orthorhombic alkali metal/manganese oxide phase active cathode material

    DOEpatents

    Doeff, Marca M.; Peng, Marcus Y.; Ma, Yanping; Visco, Steven J.; DeJonghe, Lutgard C.

    1996-01-01

    An alkali metal manganese oxide secondary cell is disclosed which can provide a high rate of discharge, good cycling capabilities, good stability of the cathode material, high specific energy (energy per unit of weight) and high energy density (energy per unit volume). The active material in the anode is an alkali metal and the active material in the cathode comprises an orthorhombic alkali metal manganese oxide which undergoes intercalation and deintercalation without a change in phase, resulting in a substantially linear change in voltage with change in the state of charge of the cell. The active material in the cathode is an orthorhombic structure having the formula M.sub.x Z.sub.y Mn.sub.(1-y) O.sub.2, where M is an alkali metal; Z is a metal capable of substituting for manganese in the orthorhombic structure such as iron, cobalt or titanium; x ranges from about 0.2 in the fully charged state to about 0.75 in the fully discharged state, and y ranges from 0 to 60 atomic %. Preferably, the cell is constructed with a solid electrolyte, but a liquid or gelatinous electrolyte may also be used in the cell.

  4. On the achievable performance using variable geometry active secondary suspension systems in commercial vehicles

    NASA Astrophysics Data System (ADS)

    Evers, Willem-Jan; Besselink, Igo; Teerhuis, Arjan; Nijmeijer, Henk

    2011-10-01

    There is a need to further improve driver comfort in commercial vehicles. The variable geometry active suspension offers an interesting option to achieve this in an energy efficient way. However, the optimal control strategy and the overal performance potential remains unclear. The aim of this paper is to quantify the level of performance improvement that can theoretically be obtained by replacing a conventional air sprung cabin suspension design with a variable geometry active suspension. Furthermore, the difference between the use of a linear quadratic (LQ) optimal controller and a classic skyhook controller is investigated. Hereto, an elementary variable geometry actuator model and experimentally validated four degrees of freedom quarter truck model are adopted. The results show that the classic skyhook controller gives a relatively poor performance while a comfort increase of 17-28% can be obtained with the LQ optimal controller, depending on the chosen energy weighting. Furthermore, an additional 75% comfort increase and 77% energy cost reduction can be obtained, with respect to the fixed gain energy optimal controller, using condition-dependent control gains. So, it is concluded that the performance potential using condition-dependent controllers is huge, and that the use of the classic skyhook control strategy should, in general, be avoided when designing active secondary suspensions for commercial vehicles.

  5. Altered expression of urokinase-type plasminogen activator and plasminogen activator inhibitor in high-risk soft tissue sarcomas.

    PubMed

    Benassi, M S; Ponticelli, F; Azzoni, E; Gamberi, G; Pazzaglia, L; Chiechi, A; Conti, A; Spessotto, P; Scapolan, M; Pignotti, E; Bacchini, P; Picci, P

    2007-09-01

    In recent years, classification of soft-tissue sarcomas (STS) has improved with cytogenetic analyses, but their clinical behavior is still not easily predictable. The aim of this study was to detect alterations in the urokinase-type plasminogen system, involved in tumor growth and invasion, by comparing mRNA levels of its components with those of paired normal tissues, and relating them with patient clinical course. Real-time PCR was performed on human STS cell lines and tissues from highly malignant STS, including leiomyosarcomas and malignant fibrous histiocytomas, to evaluate the expression of urokinase-type plasminogen activator (uPA), uPA receptor (uPAR) and plasminogen activator inhibitor-1 (PAI-1). Immunohistochemistry of gene products was also performed. Median mRNA values of all genes studied were higher in tumors than in paired normal tissues. In agreement with data on STS cell lines, significant up-regulation for uPA and PAI-1 genes compared to reference values was seen. Moreover, different levels of expression were related to histotype and metastatic phenotype. There was accordance between uPA mRNA and protein expression, while immunodetection of PAI-1 product was weak and scattered. Clearly, the controversial role of PAI-1 protein requires further biological analyses, but evident involvement of uPA/PAI-1 gene overexpression in STS malignancy may highlight a molecular defect useful in discriminating STS high-risk patients. PMID:17523079

  6. Field validation of listings of food stores and commercial physical activity establishments from secondary data

    PubMed Central

    Paquet, Catherine; Daniel, Mark; Kestens, Yan; Léger, Karine; Gauvin, Lise

    2008-01-01

    Background Food- and activity-related establishments are increasingly viewed as neighbourhood resources that potentially condition health-related behaviour. The primary objective of the current study was to establish, using ground truthing (on-site verification), the validity of measures of availability of food stores and physical activity establishments that were obtained from commercial database and Internet searches. A secondary objective was to examine differences in validity results according to neighbourhood characteristics and commercial establishment categories. Methods Lists of food stores and physical activity-related establishments in 12 census tracts within the Montreal metropolitan region were compiled using a commercial database (n = 171 establishments) and Internet search engines (n = 123 establishments). Ground truthing through field observations was performed to assess the presence of listed establishments and identify those absent. Percentage agreement, sensitivity (proportion of establishments found in the field that were listed), and positive predictive value (proportion of listed establishments found in the field) were calculated and contrasted according to data sources, census tracts characteristics, and establishment categories. Results Agreement with field observations was good (0.73) for the commercial list, and moderate (0.60) for the Internet-based list. The commercial list was superior to the Internet-based list for correctly listing establishments present in the field (sensitivity), but slightly inferior in terms of the likelihood that a listed establishment was present in the field (positive predictive value). Agreement was higher for food stores than for activity-related establishments. Conclusion Commercial data sources may provide a valid alternative to field observations and could prove a valuable tool in the evaluation of commercial environments relevant to eating behaviour. In contrast, this study did not find strong evidence in

  7. Activity and High-Order Effective Connectivity Alterations in Sanfilippo C Patient-Specific Neuronal Networks

    PubMed Central

    Canals, Isaac; Soriano, Jordi; Orlandi, Javier G.; Torrent, Roger; Richaud-Patin, Yvonne; Jiménez-Delgado, Senda; Merlin, Simone; Follenzi, Antonia; Consiglio, Antonella; Vilageliu, Lluïsa; Grinberg, Daniel; Raya, Angel

    2015-01-01

    Summary Induced pluripotent stem cell (iPSC) technology has been successfully used to recapitulate phenotypic traits of several human diseases in vitro. Patient-specific iPSC-based disease models are also expected to reveal early functional phenotypes, although this remains to be proved. Here, we generated iPSC lines from two patients with Sanfilippo type C syndrome, a lysosomal storage disorder with inheritable progressive neurodegeneration. Mature neurons obtained from patient-specific iPSC lines recapitulated the main known phenotypes of the disease, not present in genetically corrected patient-specific iPSC-derived cultures. Moreover, neuronal networks organized in vitro from mature patient-derived neurons showed early defects in neuronal activity, network-wide degradation, and altered effective connectivity. Our findings establish the importance of iPSC-based technology to identify early functional phenotypes, which can in turn shed light on the pathological mechanisms occurring in Sanfilippo syndrome. This technology also has the potential to provide valuable readouts to screen compounds, which can prevent the onset of neurodegeneration. PMID:26411903

  8. Altered regional activity and inter-regional functional connectivity in psychogenic non-epileptic seizures.

    PubMed

    Li, Rong; Li, Yibo; An, Dongmei; Gong, Qiyong; Zhou, Dong; Chen, Huafu

    2015-01-01

    Although various imaging studies have focused on detecting the cerebral function underlying psychogenic non-epileptic seizures (PNES), the nature of PNES remains poorly understood. In this study, we combined the resting state fMRI with fractional amplitude of low-frequency fluctuations (fALFF) and functional connectivity based on the seed voxel linear correlation approach to examine the alterations of regional and inter-regional network cerebral functions in PNES. A total of 20 healthy controls and 18 patients were enrolled. The PNES patients showed significantly increased fALFF mainly in the dorsolateral prefrontal cortex (DLPFC), parietal cortices, and motor areas, as well as decreased fALFF in the triangular inferior frontal gyrus. Thus, our results add to literature suggesting abnormalities of neural synchrony in PNES. Moreover, PNES exhibited widespread inter-regional neural network deficits, including increased (DLPFC, sensorimotor, and limbic system) and decreased (ventrolateral prefrontal cortex) connectivity, indicating that changes in the regional cerebral function are related to remote inter-regional network deficits. Correlation analysis results revealed that the connectivity between supplementary motor area and anterior cingulate cortex correlated with the PNES frequency, further suggesting the skewed integration of synchronous activity could predispose to the occurrence of PNES. Our findings provided novel evidence to investigate the pathophysiological mechanisms of PNES. PMID:26109123

  9. Loss of UCP2 attenuates mitochondrial dysfunction without altering ROS production and uncoupling activity.

    PubMed

    Kukat, Alexandra; Dogan, Sukru Anil; Edgar, Daniel; Mourier, Arnaud; Jacoby, Christoph; Maiti, Priyanka; Mauer, Jan; Becker, Christina; Senft, Katharina; Wibom, Rolf; Kudin, Alexei P; Hultenby, Kjell; Flögel, Ulrich; Rosenkranz, Stephan; Ricquier, Daniel; Kunz, Wolfram S; Trifunovic, Aleksandra

    2014-06-01

    Although mitochondrial dysfunction is often accompanied by excessive reactive oxygen species (ROS) production, we previously showed that an increase in random somatic mtDNA mutations does not result in increased oxidative stress. Normal levels of ROS and oxidative stress could also be a result of an active compensatory mechanism such as a mild increase in proton leak. Uncoupling protein 2 (UCP2) was proposed to play such a role in many physiological situations. However, we show that upregulation of UCP2 in mtDNA mutator mice is not associated with altered proton leak kinetics or ROS production, challenging the current view on the role of UCP2 in energy metabolism. Instead, our results argue that high UCP2 levels allow better utilization of fatty acid oxidation resulting in a beneficial effect on mitochondrial function in heart, postponing systemic lactic acidosis and resulting in longer lifespan in these mice. This study proposes a novel mechanism for an adaptive response to mitochondrial cardiomyopathy that links changes in metabolism to amelioration of respiratory chain deficiency and longer lifespan. PMID:24945157

  10. Loss of UCP2 Attenuates Mitochondrial Dysfunction without Altering ROS Production and Uncoupling Activity

    PubMed Central

    Kukat, Alexandra; Dogan, Sukru Anil; Edgar, Daniel; Mourier, Arnaud; Jacoby, Christoph; Maiti, Priyanka; Mauer, Jan; Becker, Christina; Senft, Katharina; Wibom, Rolf; Kudin, Alexei P.; Hultenby, Kjell; Flögel, Ulrich; Rosenkranz, Stephan; Ricquier, Daniel; Kunz, Wolfram S.; Trifunovic, Aleksandra

    2014-01-01

    Although mitochondrial dysfunction is often accompanied by excessive reactive oxygen species (ROS) production, we previously showed that an increase in random somatic mtDNA mutations does not result in increased oxidative stress. Normal levels of ROS and oxidative stress could also be a result of an active compensatory mechanism such as a mild increase in proton leak. Uncoupling protein 2 (UCP2) was proposed to play such a role in many physiological situations. However, we show that upregulation of UCP2 in mtDNA mutator mice is not associated with altered proton leak kinetics or ROS production, challenging the current view on the role of UCP2 in energy metabolism. Instead, our results argue that high UCP2 levels allow better utilization of fatty acid oxidation resulting in a beneficial effect on mitochondrial function in heart, postponing systemic lactic acidosis and resulting in longer lifespan in these mice. This study proposes a novel mechanism for an adaptive response to mitochondrial cardiomyopathy that links changes in metabolism to amelioration of respiratory chain deficiency and longer lifespan. PMID:24945157

  11. NF-Y activates genes of metabolic pathways altered in cancer cells

    PubMed Central

    Benatti, Paolo; Chiaramonte, Maria Luisa; Lorenzo, Mariangela; Hartley, John A.; Hochhauser, Daniel; Gnesutta, Nerina; Mantovani, Roberto; Imbriano, Carol; Dolfini, Diletta

    2016-01-01

    The trimeric transcription factor NF-Y binds to the CCAAT box, an element enriched in promoters of genes overexpressed in tumors. Previous studies on the NF-Y regulome identified the general term metabolism as significantly enriched. We dissect here in detail the targeting of metabolic genes by integrating analysis of NF-Y genomic binding and profilings after inactivation of NF-Y subunits in different cell types. NF-Y controls de novo biosynthetic pathways of lipids, teaming up with the master SREBPs regulators. It activates glycolytic genes, but, surprisingly, is neutral or represses mitochondrial respiratory genes. NF-Y targets the SOCG (Serine, One Carbon, Glycine) and Glutamine pathways, as well as genes involved in the biosynthesis of polyamines and purines. Specific cancer-driving nodes are generally under NF-Y control. Altogether, these data delineate a coherent strategy to promote expression of metabolic genes fuelling anaerobic energy production and other anabolic pathways commonly altered in cancer cells. PMID:26646448

  12. Mild blast events alter anxiety, memory, and neural activity patterns in the anterior cingulate cortex.

    PubMed

    Xie, Kun; Kuang, Hui; Tsien, Joe Z

    2013-01-01

    There is a general interest in understanding of whether and how exposure to emotionally traumatizing events can alter memory function and anxiety behaviors. Here we have developed a novel laboratory-version of mild blast exposure comprised of high decibel bomb explosion sound coupled with strong air blast to mice. This model allows us to isolate the effects of emotionally fearful components from those of traumatic brain injury or bodily injury typical associated with bomb blasts. We demonstrate that this mild blast exposure is capable of impairing object recognition memory, increasing anxiety in elevated O-maze test, and resulting contextual generalization. Our in vivo neural ensemble recording reveal that such mild blast exposures produced diverse firing changes in the anterior cingulate cortex, a region processing emotional memory and inhibitory control. Moreover, we show that these real-time neural ensemble patterns underwent post-event reverberations, indicating rapid consolidation of those fearful experiences. Identification of blast-induced neural activity changes in the frontal brain may allow us to better understand how mild blast experiences result in abnormal changes in memory functions and excessive fear generalization related to post-traumatic stress disorder. PMID:23741416

  13. Mild Blast Events Alter Anxiety, Memory, and Neural Activity Patterns in the Anterior Cingulate Cortex

    PubMed Central

    Xie, Kun; Kuang, Hui; Tsien, Joe Z.

    2013-01-01

    There is a general interest in understanding of whether and how exposure to emotionally traumatizing events can alter memory function and anxiety behaviors. Here we have developed a novel laboratory-version of mild blast exposure comprised of high decibel bomb explosion sound coupled with strong air blast to mice. This model allows us to isolate the effects of emotionally fearful components from those of traumatic brain injury or bodily injury typical associated with bomb blasts. We demonstrate that this mild blast exposure is capable of impairing object recognition memory, increasing anxiety in elevated O-maze test, and resulting contextual generalization. Our in vivo neural ensemble recording reveal that such mild blast exposures produced diverse firing changes in the anterior cingulate cortex, a region processing emotional memory and inhibitory control. Moreover, we show that these real-time neural ensemble patterns underwent post-event reverberations, indicating rapid consolidation of those fearful experiences. Identification of blast-induced neural activity changes in the frontal brain may allow us to better understand how mild blast experiences result in abnormal changes in memory functions and excessive fear generalization related to post-traumatic stress disorder. PMID:23741416

  14. Cumulative industrial activity alters lotic fish assemblages in two boreal forest watersheds of Alberta, Canada.

    PubMed

    Scrimgeour, Garry J; Hvenegaard, Paul J; Tchir, John

    2008-12-01

    We evaluated the cumulative effects of land use disturbance resulting from forest harvesting, and exploration and extraction of oil and gas resources on the occurrence and structure of stream fish assemblages in the Kakwa and Simonette watersheds in Alberta, Canada. Logistic regression models showed that the occurrence of numerically dominant species in both watersheds was related to two metrics defining industrial activity (i.e., percent disturbance and road density), in addition to stream wetted width, elevation, reach slope, and percent fines. Occurrences of bull trout, slimy sculpin, and white sucker were negatively related to percent disturbance and that of Arctic grayling, and mountain whitefish were positively related to percent disturbance and road density. Assessments of individual sites showed that 76% of the 74 and 46 test sites in the Kakwa and Simonette watersheds were possibly impaired or impaired. Impaired sites in the Kakwa Watershed supported lower densities of bull trout, mountain whitefish, and rainbow trout, but higher densities of Arctic grayling compared to appropriate reference sites. Impaired sites in the Simonette Watershed supported lower densities of bull trout, but higher densities of lake chub compared to reference sites. Our data suggest that current levels of land use disturbance alters the occurrence and structure of stream fish assemblages. PMID:18815827

  15. Cumulative Industrial Activity Alters Lotic Fish Assemblages in Two Boreal Forest Watersheds of Alberta, Canada

    NASA Astrophysics Data System (ADS)

    Scrimgeour, Garry J.; Hvenegaard, Paul J.; Tchir, John

    2008-12-01

    We evaluated the cumulative effects of land use disturbance resulting from forest harvesting, and exploration and extraction of oil and gas resources on the occurrence and structure of stream fish assemblages in the Kakwa and Simonette watersheds in Alberta, Canada. Logistic regression models showed that the occurrence of numerically dominant species in both watersheds was related to two metrics defining industrial activity (i.e., percent disturbance and road density), in addition to stream wetted width, elevation, reach slope, and percent fines. Occurrences of bull trout, slimy sculpin, and white sucker were negatively related to percent disturbance and that of Arctic grayling, and mountain whitefish were positively related to percent disturbance and road density. Assessments of individual sites showed that 76% of the 74 and 46 test sites in the Kakwa and Simonette watersheds were possibly impaired or impaired. Impaired sites in the Kakwa Watershed supported lower densities of bull trout, mountain whitefish, and rainbow trout, but higher densities of Arctic grayling compared to appropriate reference sites. Impaired sites in the Simonette Watershed supported lower densities of bull trout, but higher densities of lake chub compared to reference sites. Our data suggest that current levels of land use disturbance alters the occurrence and structure of stream fish assemblages.

  16. Stress-induced alterations of left-right electrodermal activity coupling indexed by pointwise transinformation.

    PubMed

    Světlák, M; Bob, P; Roman, R; Ježek, S; Damborská, A; Chládek, J; Shaw, D J; Kukleta, M

    2013-01-01

    In this study, we tested the hypothesis that experimental stress induces a specific change of left-right electrodermal activity (EDA) coupling pattern, as indexed by pointwise transinformation (PTI). Further, we hypothesized that this change is associated with scores on psychometric measures of the chronic stress-related psychopathology. Ninety-nine university students underwent bilateral measurement of EDA during rest and stress-inducing Stroop test and completed a battery of self-report measures of chronic stress-related psychopathology. A significant decrease in the mean PTI value was the prevalent response to the stress conditions. No association between chronic stress and PTI was found. Raw scores of psychometric measures of stress-related psychopathology had no effect on either the resting levels of PTI or the amount of stress-induced PTI change. In summary, acute stress alters the level of coupling pattern of cortico-autonomic influences on the left and right sympathetic pathways to the palmar sweat glands. Different results obtained using the PTI, EDA laterality coefficient, and skin conductance level also show that the PTI algorithm represents a new analytical approach to EDA asymmetry description. PMID:24359433

  17. Alteration of transcriptional networks in the entorhinal cortex after maternal immune activation and adolescent cannabinoid exposure.

    PubMed

    Hollins, Sharon L; Zavitsanou, Katerina; Walker, Frederick Rohan; Cairns, Murray J

    2016-08-01

    Maternal immune activation (MIA) and adolescent cannabinoid exposure (ACE) have both been identified as major environmental risk factors for schizophrenia. We examined the effects of these two risk factors alone, and in combination, on gene expression during late adolescence. Pregnant rats were exposed to the viral infection mimic polyriboinosinic-polyribocytidylic acid (poly I:C) on gestational day (GD) 15. Adolescent offspring received daily injections of the cannabinoid HU210 for 14days starting on postnatal day (PND) 35. Gene expression was examined in the left entorhinal cortex (EC) using mRNA microarrays. We found prenatal treatment with poly I:C alone, or HU210 alone, produced relatively minor changes in gene expression. However, following combined treatments, offspring displayed significant changes in transcription. This dramatic and persistent alteration of transcriptional networks enriched with genes involved in neurotransmission, cellular signalling and schizophrenia, was associated with a corresponding perturbation in the expression of small non-coding microRNA (miRNA). These results suggest that a combination of environmental exposures during development leads to significant genomic remodeling that disrupts maturation of the EC and its associated circuitry with important implications as the potential antecedents of memory and learning deficits in schizophrenia and other neuropsychiatric disorders. PMID:26923065

  18. Influence of altered precipitation pattern on greenhouse gas emissions and soil enzyme activities in Pannonian soils

    NASA Astrophysics Data System (ADS)

    Forstner, Stefan Johannes; Michel, Kerstin; Berthold, Helene; Baumgarten, Andreas; Wanek, Wolfgang; Zechmeister-Boltenstern, Sophie; Kitzler, Barbara

    2013-04-01

    Precipitation patterns are likely to be altered due to climate change. Recent models predict a reduction of mean precipitation during summer accompanied by a change in short-term precipitation variability for central Europe. Correspondingly, the risk for summer drought is likely to increase. This may especially be valid for regions which already have the potential for rare, but strong precipitation events like eastern Austria. Given that these projections hold true, soils in this area will receive water irregularly in few, heavy rainfall events and be subjected to long-lasting dry periods in between. This pattern of drying/rewetting can alter soil greenhouse gas fluxes, creating a potential feedback mechanism for climate change. Microorganisms are the key players in most soil carbon (C) and nitrogen (N) transformation processes including greenhouse gas exchange. A conceptual model proposed by Schimel and colleagues (2007) links microbial stress-response physiology to ecosystem-scale biogeochemical processes: In order to cope with decreasing soil water potential, microbes modify resource allocation patterns from growth to survival. However, it remains unclear how microbial resource acquisition via extracellular enzymes and microbial-controlled greenhouse gas fluxes respond to water stress induced by soil drying/rewetting. We designed a laboratory experiment to test for effects of multiple drying/rewetting cycles on soil greenhouse gas fluxes (CO2, CH4, N2O, NO), microbial biomass and extracellular enzyme activity. Three soils representing the main soil types of eastern Austria were collected in June 2012 at the Lysimeter Research Station of the Austrian Agency for Health and Food Safety (AGES) in Vienna. Soils were sieved to 2mm, filled in steel cylinders and equilibrated for one week at 50% water holding capacity (WHC) for each soil. Then soils were separated into two groups: One group received water several times per week (C=control), the other group received

  19. Tissue Plasminogen Activator Use in Cardiac Arrest Secondary to Fulminant Pulmonary Embolism

    PubMed Central

    Yousuf, Tariq; Brinton, Taylor; Ahmed, Khansa; Iskander, Joy; Woznicka, Daniel; Kramer, Jason; Kopiec, Adam; Chadaga, Amar R.; Ortiz, Kathia

    2016-01-01

    Background Tissue plasminogen activator (tPA) is used emergently to dissolve thrombi in the treatment of fulminant pulmonary embolism. Currently, there is a relative contraindication to tPA in the setting of traumatic or prolonged cardiopulmonary resuscitation > 10 minutes because of the risk of massive hemorrhage. Methods Our single-center, retrospective study investigated patients experiencing cardiac arrest (CA) secondary to pulmonary embolus. We compared the effectiveness of advanced cardiac life support with the administration of tPA vs. the standard of care consisting of advanced cardiac life support without thrombolysis. The primary endpoint was survival to discharge. Secondary endpoints were return of spontaneous circulation (ROSC), major bleeding, and minor bleeding. Results We analyzed 42 patients, of whom 19 received tPA during CA. Patients who received tPA were not associated with a statistically significant increase in survival to discharge (10.5% vs. 8.7%, P = 1.00) or ROSC (47.4% vs. 47.8%, P = 0.98) compared to the control group. We observed no statistically significant difference between the groups in major bleeding events (5.3% in the tPA group vs. 4.3% in the control group, P = 1.00) and minor bleeding events (10.5% in the tPA group vs. 0.0% in the control group, P = 0.11). Conclusion This study did not find a statistically significant difference in survival to discharge or in ROSC in patients treated with tPA during CA compared to patients treated with standard therapy. However, because no significant difference was found in major or minor bleeding, we suggest that the potential therapeutic benefits of this medication should not be limited by the potential for massive hemorrhage. Larger prospective studies are warranted to define the efficacy and safety profile of thrombolytic use in this population. PMID:26858790

  20. Alterations in enterocyte mitochondrial respiratory function and enzyme activities in gastrointestinal dysfunction following brain injury

    PubMed Central

    Zhu, Ke-Jun; Huang, Hong; Chu, Hui; Yu, Hang; Zhang, Shi-Ming

    2014-01-01

    AIM: To determine the alterations in rat enterocyte mitochondrial respiratory function and enzyme activities following traumatic brain injury (TBI). METHODS: Fifty-six male SD rats were randomly divided into seven groups (8 rats in each group): a control group (rats with sham operation) and traumatic brain injury groups at 6, 12, 24 h, days 2, 3, and 7 after operation. TBI models were induced by Feendy’s free-falling method. Mitochondrial respiratory function (respiratory control ratio and ADP/O ratio) was measured with a Clark oxygen electrode. The activities of respiratory chain complex I-IV and related enzymes were determined by spectrophotometry. RESULTS: Compared with the control group, the mitochondrial respiratory control ratio (RCR) declined at 6 h and remained at a low level until day 7 after TBI (control, 5.42 ± 0.46; 6 h, 5.20 ± 0.18; 12 h, 4.55 ± 0.35; 24 h, 3.75 ± 0.22; 2 d, 4.12 ± 0.53; 3 d, 3.45 ± 0.41; 7 d, 5.23 ± 0.24, P < 0.01). The value of phosphate-to-oxygen (P/O) significantly decreased at 12, 24 h, day 2 and day 3, respectively (12 h, 3.30 ± 0.10; 24 h, 2.61 ± 0.21; 2 d, 2.95 ± 0.18; 3 d, 2.76 ± 0.09, P < 0.01) compared with the control group (3.46 ± 0.12). Two troughs of mitochondrial respiratory function were seen at 24 h and day 3 after TBI. The activities of mitochondrial complex I (6 h: 110 ± 10, 12 h: 115 ± 12, 24 h: 85 ± 9, day 2: 80 ± 15, day 3: 65 ± 16, P < 0.01) and complex II (6 h: 105 ± 8, 12 h: 110 ± 92, 24 h: 80 ± 10, day 2: 76 ± 8, day 3: 68 ± 12, P < 0.01) were increased at 6 h and 12 h following TBI, and then significantly decreased at 24 h, day 2 and day 3, respectively. However, there were no differences in complex I and II activities between the control and TBI groups. Furthermore, pyruvate dehydrogenase (PDH) activity was significantly decreased at 6 h and continued up to 7 d after TBI compared with the control group (6 h: 90 ± 8, 12 h: 85 ± 10, 24 h: 65 ± 12, day 2: 60 ± 9, day 3: 55

  1. Alteration mineralogy of Home Plate and Columbia Hills—Formation conditions in context to impact, volcanism, and fluvial activity

    NASA Astrophysics Data System (ADS)

    Filiberto, Justin; Schwenzer, Susanne P.

    2013-10-01

    The Mars Exploration Rover Spirit investigated the igneous and alteration mineralogy and chemistry of Home Plate and its surrounding deposits. Here, we focus on using thermochemical modeling to understand the secondary alteration mineralogy at the Home Plate outcrop and surrounding Columbia Hills region in Gusev crater. At high temperatures (300 °C), magnetite occurs at very high W/R ratios, but the alteration assemblage is dominated by chlorite and serpentine over most of the W/R range. Quartz, epidote, and typical high-T phases such as feldspar, pyroxene, and garnet occur at low W/R. At epithermal temperatures (150 °C), hematite occurs at very high W/R. A range of phyllosilicates, including kaolinite, nontronite, chlorite, and serpentine are precipitated at specific W/R. Amphibole, with garnet, feldspar, and pyroxene occur at low W/R. If the CO2 content of the system is high, the assemblage is dominated by carbonate with increasing amounts of an SiO2-phase, kaolinite, carpholite, and chlorite with lower W/R. At temperatures of hydrous weathering (13 °C), the oxide phase is goethite, silicates are chlorite, nontronite, and talc, plus an SiO2-phase. In the presence of CO2, the mineral assemblage at high W/R remains the same, and only at low W/R, i.e., with increasing salinity, carbonate precipitates. The geochemical gradients observed at Home Plate are attributed to short-lived, initially high (300 °C) temperature, but fast cooling events, which are in agreement with our models and our interpretation of a multistage alteration scenario of Home Plate and Gusev in general. Alteration at various temperatures and during different geological processes within Gusev crater has two effects, both of which increase the habitability of the local environment: precipitation of hydrous sheet silicates, and formation of a brine, which might contain elements essential for life in diluted, easily accessible form.

  2. Familial Alzheimer's disease-associated presenilin-1 alters cerebellar activity and calcium homeostasis.

    PubMed

    Sepulveda-Falla, Diego; Barrera-Ocampo, Alvaro; Hagel, Christian; Korwitz, Anne; Vinueza-Veloz, Maria Fernanda; Zhou, Kuikui; Schonewille, Martijn; Zhou, Haibo; Velazquez-Perez, Luis; Rodriguez-Labrada, Roberto; Villegas, Andres; Ferrer, Isidro; Lopera, Francisco; Langer, Thomas; De Zeeuw, Chris I; Glatzel, Markus

    2014-04-01

    Familial Alzheimer's disease (FAD) is characterized by autosomal dominant heritability and early disease onset. Mutations in the gene encoding presenilin-1 (PS1) are found in approximately 80% of cases of FAD, with some of these patients presenting cerebellar damage with amyloid plaques and ataxia with unclear pathophysiology. A Colombian kindred carrying the PS1-E280A mutation is the largest known cohort of PS1-FAD patients. Here, we investigated PS1-E280A-associated cerebellar dysfunction and found that it occurs early in PS1-E208A carriers, while cerebellar signs are highly prevalent in patients with dementia. Postmortem analysis of cerebella of PS1-E280A carrier revealed greater Purkinje cell (PC) loss and more abnormal mitochondria compared with controls. In PS1-E280A tissue, ER/mitochondria tethering was impaired, Ca2+ channels IP3Rs and CACNA1A were downregulated, and Ca2+-dependent mitochondrial transport proteins MIRO1 and KIF5C were reduced. Accordingly, expression of PS1-E280A in a neuronal cell line altered ER/mitochondria tethering and transport compared with that in cells expressing wild-type PS1. In a murine model of PS1-FAD, animals exhibited mild ataxia and reduced PC simple spike activity prior to cerebellar β-amyloid deposition. Our data suggest that impaired calcium homeostasis and mitochondrial dysfunction in PS1-FAD PCs reduces their activity and contributes to motor coordination deficits prior to Aβ aggregation and dementia. We propose that PS1-E280A affects both Ca2+ homeostasis and Aβ precursor processing, leading to FAD and neurodegeneration. PMID:24569455

  3. The effect of NGATHA altered activity on auxin signaling pathways within the Arabidopsis gynoecium.

    PubMed

    Martínez-Fernández, Irene; Sanchís, Sofía; Marini, Naciele; Balanzá, Vicente; Ballester, Patricia; Navarrete-Gómez, Marisa; Oliveira, Antonio C; Colombo, Lucia; Ferrándiz, Cristina

    2014-01-01

    The four NGATHA genes (NGA) form a small subfamily within the large family of B3-domain transcription factors of Arabidopsis thaliana. NGA genes act redundantly to direct the development of the apical tissues of the gynoecium, the style, and the stigma. Previous studies indicate that NGA genes could exert this function at least partially by directing the synthesis of auxin at the distal end of the developing gynoecium through the upregulation of two different YUCCA genes, which encode flavin monooxygenases involved in auxin biosynthesis. We have compared three developing pistil transcriptome data sets from wildtype, nga quadruple mutants, and a 35S::NGA3 line. The differentially expressed genes showed a significant enrichment for auxin-related genes, supporting the idea of NGA genes as major regulators of auxin accumulation and distribution within the developing gynoecium. We have introduced reporter lines for several of these differentially expressed genes involved in synthesis, transport and response to auxin in NGA gain- and loss-of-function backgrounds. We present here a detailed map of the response of these reporters to NGA misregulation that could help to clarify the role of NGA in auxin-mediated gynoecium morphogenesis. Our data point to a very reduced auxin synthesis in the developing apical gynoecium of nga mutants, likely responsible for the lack of DR5rev::GFP reporter activity observed in these mutants. In addition, NGA altered activity affects the expression of protein kinases that regulate the cellular localization of auxin efflux regulators, and thus likely impact auxin transport. Finally, protein accumulation in pistils of several ARFs was differentially affected by nga mutations or NGA overexpression, suggesting that these accumulation patterns depend not only on auxin distribution but could be also regulated by transcriptional networks involving NGA factors. PMID:24904608

  4. First demonstration that brain CYP2D-mediated opiate metabolic activation alters analgesia in vivo.

    PubMed

    Zhou, Kaidi; Khokhar, Jibran Y; Zhao, Bin; Tyndale, Rachel F

    2013-06-15

    The response to centrally acting drugs is highly variable between individuals and does not always correlate with plasma drug levels. Drug-metabolizing CYP enzymes in the brain may contribute to this variability by affecting local drug and metabolite concentrations. CYP2D metabolizes codeine to the active morphine metabolite. We investigated the effect of inhibiting brain, and not liver, CYP2D activity on codeine-induced analgesia. Rats received intracerebroventricular injections of CYP2D inhibitors (20 μg propranolol or 40 μg propafenone) or vehicle controls. Compared to vehicle-pretreated rats, inhibitor-pretreated rats had: (a) lower analgesia in the tail-flick test (p<0.05) and lower areas under the analgesia-time curve (p<0.02) within the first hour after 30 mg/kg subcutaneous codeine, (b) lower morphine concentrations and morphine to codeine ratios in the brain (p<0.02 and p<0.05, respectively), but not in plasma (p>0.6 and p>0.7, respectively), tested at 30 min after 30 mg/kg subcutaneous codeine, and (c) lower morphine formation from codeine ex vivo by brain membranes (p<0.04), but not by liver microsomes (p>0.9). Analgesia trended toward a correlation with brain morphine concentrations (p=0.07) and correlated with brain morphine to codeine ratios (p<0.005), but not with plasma morphine concentrations (p>0.8) or plasma morphine to codeine ratios (p>0.8). Our findings suggest that brain CYP2D affects brain morphine levels after peripheral codeine administration, and may thereby alter codeine's therapeutic efficacy, side-effect profile and abuse liability. Brain CYPs are highly variable due to genetics, environmental factors and age, and may therefore contribute to interindividual variation in the response to centrally acting drugs. PMID:23623752

  5. Familial Alzheimer’s disease–associated presenilin-1 alters cerebellar activity and calcium homeostasis

    PubMed Central

    Sepulveda-Falla, Diego; Barrera-Ocampo, Alvaro; Hagel, Christian; Korwitz, Anne; Vinueza-Veloz, Maria Fernanda; Zhou, Kuikui; Schonewille, Martijn; Zhou, Haibo; Velazquez-Perez, Luis; Rodriguez-Labrada, Roberto; Villegas, Andres; Ferrer, Isidro; Lopera, Francisco; Langer, Thomas; De Zeeuw, Chris I.; Glatzel, Markus

    2014-01-01

    Familial Alzheimer’s disease (FAD) is characterized by autosomal dominant heritability and early disease onset. Mutations in the gene encoding presenilin-1 (PS1) are found in approximately 80% of cases of FAD, with some of these patients presenting cerebellar damage with amyloid plaques and ataxia with unclear pathophysiology. A Colombian kindred carrying the PS1-E280A mutation is the largest known cohort of PS1-FAD patients. Here, we investigated PS1-E280A–associated cerebellar dysfunction and found that it occurs early in PS1-E208A carriers, while cerebellar signs are highly prevalent in patients with dementia. Postmortem analysis of cerebella of PS1-E280A carrier revealed greater Purkinje cell (PC) loss and more abnormal mitochondria compared with controls. In PS1-E280A tissue, ER/mitochondria tethering was impaired, Ca2+ channels IP3Rs and CACNA1A were downregulated, and Ca2+-dependent mitochondrial transport proteins MIRO1 and KIF5C were reduced. Accordingly, expression of PS1-E280A in a neuronal cell line altered ER/mitochondria tethering and transport compared with that in cells expressing wild-type PS1. In a murine model of PS1-FAD, animals exhibited mild ataxia and reduced PC simple spike activity prior to cerebellar β-amyloid deposition. Our data suggest that impaired calcium homeostasis and mitochondrial dysfunction in PS1-FAD PCs reduces their activity and contributes to motor coordination deficits prior to Aβ aggregation and dementia. We propose that PS1-E280A affects both Ca2+ homeostasis and Aβ precursor processing, leading to FAD and neurodegeneration. PMID:24569455

  6. Maternal Immune Activation Alters Nonspatial Information Processing in the Hippocampus of the Adult Offspring

    PubMed Central

    Ito, Hiroshi T.; Smith, Stephen E. P.; Hsiao, Elaine; Patterson, Paul H.

    2010-01-01

    The observation that maternal infection increases the risk for schizophrenia in the offspring suggests that the maternal immune system plays a key role in the etiology of schizophrenia. In a mouse model, maternal immune activation (MIA) by injection of poly(I:C) yields adult offspring that display abnormalities in a variety of behaviors relevant to schizophrenia. As abnormalities in the hippocampus are a consistent observation in schizophrenia patients, we examined synaptic properties in hippocampal slices prepared from the offspring of poly(I:C)- and saline-treated mothers. Compared to controls, CA1 pyramidal neurons from adult offspring of MIA mothers display reduced frequency and increased amplitude of miniature excitatory postsynaptic currents. In addition, the specific component of the temporoammonic pathway that mediates object-related information displays increased sensitivity to dopamine. To assess hippocampal network function in vivo, we used expression of the immediate early gene, c-Fos, as a surrogate measure of neuronal activity. Compared to controls, the offspring of poly(I:C)-treated mothers display a distinct c-Fos expression pattern in area CA1 following novel object, but not novel location, exposure. Thus, the offspring of MIA mothers may have an abnormality in modality-specific information processing. Indeed, the MIA offspring display enhanced discrimination in a novel object recognition, but not in an object location, task. Thus, analysis of object and spatial information processing at both synaptic and behavioral levels reveals a largely selective abnormality in object information processing in this mouse model. Our results suggest that altered processing of object-related information may be part of the pathogenesis of schizophrenia-like cognitive behaviors. PMID:20227486

  7. [Cerebral hemodynamics in children of 8-12 years old with alterations of the motor activity of central origin].

    PubMed

    Holovchenko, I V; Haĭdaĭ, M I

    2013-01-01

    In children with altered physical activity there is a lack of brain blood supply, which is the most pronounced in the system of the vertebral arteries right hemisphere, and a low volume speed of blood flow in the internal carotid artery and in the system of the vertebral arteries. Children of the main group have a decreased venous outflow from the cavity of the skull, which is accompanied by altered venous circulation in the sinuses of the brain. It is established that in the system of the vertebral arteries a hemispheric asymmetry of growth in the right hemisphere is observed, in contrast to the left hemisphere, indicators of vascular tone of arterial and venous type of small caliber. Children with altered physical activity have higher values of indicators of venous outflow, than the children of the control group, and they have better venous outflow from the carotid system and a slightly worse with vertebro-basilar. PMID:24400562

  8. Tanshinone-1 induces tumor cell killing, enhanced by inhibition of secondary activation of signaling networks

    PubMed Central

    Xu, L; Feng, J-M; Li, J-X; Zhu, J-M; Song, S-S; Tong, L-J; Chen, Y; Yang, X-Y; Shen, Y-Y; Lian, F-L; Li, Y-P; Lin, D-H; Ding, J; Miao, Z-H

    2013-01-01

    Tumor multidrug resistance (MDR) can result from overexpression of drug transporters and deregulation of cellular signaling transduction. New agents and strategies are required for overcoming MDR. Here, we report that tanshinone-1, a bioactive ingredient in traditional Chinese medicine, directly killed MDR tumor cells and their corresponding parental cells, which was potentiated by inhibition of secondary activation of signaling networks. Tanshinone-1 was slightly more potent at inducing cytotoxicity and apoptosis in MDR cells than in corresponding parental cells. Tanshinone-1-induced MDR cell killing was independent of the function and expression of drug transporters but was partially correlated with the phosphatase-dependent reduction of phospho-705-Stat3, which secondarily activated p38-, AKT-, and ERK-involved signaling networks. Cotreatments with p38, AKT, and ERK inhibitors potentiated the anti-MDR effects of tanshinone-1. Our study presents a model for MDR cell killing using a compound of natural origin. This model could lead to new therapeutic strategies for targeting signaling network(s) in MDR cancers as well as new strategies for multitarget design. PMID:24201804

  9. Microbial communication leading to the activation of silent fungal secondary metabolite gene clusters

    PubMed Central

    Netzker, Tina; Fischer, Juliane; Weber, Jakob; Mattern, Derek J.; König, Claudia C.; Valiante, Vito; Schroeckh, Volker; Brakhage, Axel A.

    2015-01-01

    Microorganisms form diverse multispecies communities in various ecosystems. The high abundance of fungal and bacterial species in these consortia results in specific communication between the microorganisms. A key role in this communication is played by secondary metabolites (SMs), which are also called natural products. Recently, it was shown that interspecies “talk” between microorganisms represents a physiological trigger to activate silent gene clusters leading to the formation of novel SMs by the involved species. This review focuses on mixed microbial cultivation, mainly between bacteria and fungi, with a special emphasis on the induced formation of fungal SMs in co-cultures. In addition, the role of chromatin remodeling in the induction is examined, and methodical perspectives for the analysis of natural products are presented. As an example for an intermicrobial interaction elucidated at the molecular level, we discuss the specific interaction between the filamentous fungi Aspergillus nidulans and Aspergillus fumigatus with the soil bacterium Streptomyces rapamycinicus, which provides an excellent model system to enlighten molecular concepts behind regulatory mechanisms and will pave the way to a novel avenue of drug discovery through targeted activation of silent SM gene clusters through co-cultivations of microorganisms. PMID:25941517

  10. Human cellular retinaldehyde-binding protein has secondary thermal 9-cis-retinal isomerase activity.

    PubMed

    Bolze, Christin S; Helbling, Rachel E; Owen, Robin L; Pearson, Arwen R; Pompidor, Guillaume; Dworkowski, Florian; Fuchs, Martin R; Furrer, Julien; Golczak, Marcin; Palczewski, Krzysztof; Cascella, Michele; Stocker, Achim

    2014-01-01

    Cellular retinaldehyde-binding protein (CRALBP) chaperones 11-cis-retinal to convert opsin receptor molecules into photosensitive retinoid pigments of the eye. We report a thermal secondary isomerase activity of CRALBP when bound to 9-cis-retinal. UV/vis and (1)H NMR spectroscopy were used to characterize the product as 9,13-dicis-retinal. The X-ray structure of the CRALBP mutant R234W:9-cis-retinal complex at 1.9 Å resolution revealed a niche in the binding pocket for 9-cis-aldehyde different from that reported for 11-cis-retinal. Combined computational, kinetic, and structural data lead us to propose an isomerization mechanism catalyzed by a network of buried waters. Our findings highlight a specific role of water molecules in both CRALBP-assisted specificity toward 9-cis-retinal and its thermal isomerase activity yielding 9,13-dicis-retinal. Kinetic data from two point mutants of CRALBP support an essential role of Glu202 as the initial proton donor in this isomerization reaction. PMID:24328211

  11. Differential Reovirus-Specific and Herpesvirus-Specific Activator Protein 1 Activation of Secretogranin II Leads to Altered Virus Secretion

    PubMed Central

    Berard, Alicia R.; Severini, Alberto

    2015-01-01

    ABSTRACT Viruses utilize host cell machinery for propagation and manage to evade cellular host defense mechanisms in the process. Much remains unknown regarding how the host responds to viral infection. We recently performed global proteomic screens of mammalian reovirus TIL- and T3D-infected and herpesvirus (herpes simplex virus 1 [HSV-1])-infected HEK293 cells. The nonenveloped RNA reoviruses caused an upregulation, whereas the enveloped DNA HSV-1 caused a downregulation, of cellular secretogranin II (SCG2). SCG2, a member of the granin family that functions in hormonal peptide sorting into secretory vesicles, has not been linked to virus infections previously. We confirmed SCG2 upregulation and found SCG2 phosphorylation by 18 h postinfection (hpi) in reovirus-infected cells. We also found a decrease in the amount of reovirus secretion from SCG2 knockdown cells. Similar analyses of cells infected with HSV-1 showed an increase in the amount of secreted virus. Analysis of the stress-activated protein kinase (SAPK)/Jun N-terminal protein kinase (JNK) pathway indicated that each virus activates different pathways leading to activator protein 1 (AP-1) activation, which is the known SCG2 transcription activator. We conclude from these experiments that the negative correlation between SCG2 quantity and virus secretion for both viruses indicates a virus-specific role for SCG2 during infection. IMPORTANCE Mammalian reoviruses affect the gastrointestinal system or cause respiratory infections in humans. Recent work has shown that all mammalian reovirus strains (most specifically T3D) may be useful oncolytic agents. The ubiquitous herpes simplex viruses cause common sores in mucosal areas of their host and have coevolved with hosts over many years. Both of these virus species are prototypical representatives of their viral families, and investigation of these viruses can lead to further knowledge of how they and the other more pathogenic members of their respective

  12. Manipulating the Behavior-Altering Effect of the Motivating Operation: Examination of the Influence on Challenging Behavior during Leisure Activities

    ERIC Educational Resources Information Center

    O'Reilly, Mark F.; Sigafoos, Jeff; Lancioni, Giulio; Rispoli, Mandy; Lang, Russell; Chan, Jeff; Machalicek, Wendy; Langthorne, Paul

    2008-01-01

    We examined the behavior-altering effect of the motivating operation on challenging behavior during leisure activities for three individuals with severe disabilities. Prior functional analyses indicated that challenging behavior was maintained by positive reinforcement in the form of attention or tangible items for all participants. During leisure…

  13. Targeting mitochondrial alterations to prevent type 2 diabetes--evidence from studies of dietary redox-active compounds.

    PubMed

    Cheng, Zhiyong; Schmelz, Eva M; Liu, Dongmin; Hulver, Matthew W

    2014-08-01

    As a growing epidemic, type 2 diabetes mellitus (T2DM) has significantly affected the individual's quality of life and economy of the society. Understanding the mechanisms of the disease and discovery of new therapeutic options has become more urgent than ever before. Mitochondrial alterations (e.g. functional alterations, and impaired biogenesis and dynamics) are strongly associated with the development of T2DM. Accumulation of reactive oxygen species or intermediates of incomplete fatty acid oxidation due to mitochondrial deficiency activates stress kinases and dampens insulin signaling. Redox-active compounds such as resveratrol, pyrroloquinoline quinone, and hydroxytyrosol can potently counteract reactive oxygen species, and improve mitochondrial function and biogenesis. Therefore, targeting the mitochondrial alterations with these redox-active compounds may lead to new therapeutic or preventive options for T2DM. In this article, we review the molecular mechanisms of mitochondrial alterations in T2DM, and the action of redox-active compounds to reverse mitochondrial changes and oxidative stress in T2DM. In addition, the current challenges and future directions are discussed and prospected. PMID:24668725

  14. CCN activation and hygroscopic growth measurements of secondary organic aerosols from tree emissions

    NASA Astrophysics Data System (ADS)

    Buchholz, Angela; Mentel, Thomas F.; Kiendler-Scharr, Astrid; Spindler, Christian; Tillmann, Ralf; Kleist, Einhard; Wildt, Juergen

    2010-05-01

    Plant emitted volatile organic compounds (VOCs) are a major precursor of secondary organic aerosols (SOA), an important constituent of atmospheric aerosols. We used the Juelich Plant Atmosphere Chamber (JPAC) at the Research Center Juelich to investigate the microphysical properties of aerosols. SOA particles were produced from the ozonolysis and reaction of OH radicals with the complex VOC mixture emitted from trees typical for the boreal forest. Hygroscopic growth factors (GF) were determined with a humidity tandem differential mobility analyzer (HTDMA) for different particle sizes at RH = 2 - 97%. Cloud condensation nuclei (CCN) activation was measured with a continuous flow CCN counter (DMT). Additionally, the chemical composition, size distribution and number concentration of the particles were measured. The gas phase was monitored with GC-MS and PTR-MS. Changing the emission pattern of the trees changed the measured GF and the diameter of the dry particles that were activated (Dcrit). However, below 80% RH the GF changes are within the range of the measurement error. The GF (RH = 95%) are between 1.11 and 1.19 and the Dcrit(SS = 0.4%) in a range of 93 - 100nm. Koehler theory was applied to achieve closure between CCN activation and GF measurements. The κ parameter according to Petters and Kreidenweis (2007) was calculated for all SS (κ(CCN)) and RH (κ(GF)). The κ(GF) decrease with increasing RH but levels off at RH > 95%. Assuming the surface tension of pure water, κ(GF, RH>95%) would be by a factor of 2 lower than κ(CCN). Closure between the HTDMA and CCN measurement requires the use of either a lower surface tension or a limited solubility of the organic material. Reference: Petters, M. D. and Kreidenweis, S. M. (2007). Atmos. Chem. Phys., 7, 1961-1971.

  15. Altered cardiovascular autonomic regulation in overweight children engaged in regular physical activity.

    PubMed

    Lucini, Daniela; de Giacomi, Gaia; Tosi, Fabio; Malacarne, Mara; Respizzi, Stefano; Pagani, Massimo

    2013-03-01

    Overweight (OW) and obesity in children are important forerunners of cardiovascular risk, possibly through autonomic nervous system (ANS) dysregulation, while physical exercise exerts a beneficial influence. In this observational study we hypothesise that OW might influence ANS profile even in a population performing high volume of supervised exercise. We study 103 young soccer players, homogeneous in terms of gender (all male), cultural background, school, age (11.2 ± 1 years) and exercise routine, since they all belong to the same soccer club, thus guaranteeing equality of supervised training and similar levels of competitiveness. ANS is evaluated by autoregressive spectral analysis of heart rate and systolic arterial pressure (SAP) variabilities. We estimate also the accumulated weekly Metabolic Equivalents and time spent in sedentary activities. We subdivide the entire population in two subgroups (normal weight and OW) based on the International Obesity Task Force criteria. In OW soccer players (10.7% of total group) we observe an altered profile of autonomic cardiovascular regulation, characterised by higher values of SAP (113 ± 4 vs 100 ± 1 mm Hg, 39.7 ± 3 vs 66.2 ± 10%), higher Low Frequency variability power of SAP (an index of vasomotor sympathetic regulation) (12 ± 3 vs 4.5 mm Hg(2)) and smaller spontaneous baroreflex gain (an index of cardiac vagal regulation) (19 ± 3 vs 33 ± 3 ms/mm Hg) (all (p < 0.02)). Moreover Correlation analysis on the entire study population shows a significant link between anthropometric and autonomic indices. These data show that OW is associated to a clear autonomic impairment even in children subjected to an intense aerobic training. PMID:23086975

  16. Stoichiometry of altered hERG1 channel gating by small molecule activators.

    PubMed

    Wu, Wei; Sachse, Frank B; Gardner, Alison; Sanguinetti, Michael C

    2014-04-01

    Voltage-gated K(+) channels are tetramers formed by coassembly of four identical or highly related subunits. All four subunits contribute to formation of the selectivity filter, the narrowest region of the channel pore which determines K(+) selective conductance. In some K(+) channels, the selectivity filter can undergo a conformational change to reduce K(+) flux by a mechanism called C-type inactivation. In human ether-a-go-go-related gene 1 (hERG1) K(+) channels, C-type inactivation is allosterically inhibited by ICA-105574, a substituted benzamide. PD-118057, a 2-(phenylamino) benzoic acid, alters selectivity filter gating to enhance open probability of channels. Both compounds bind to a hydrophobic pocket located between adjacent hERG1 subunits. Accordingly, a homotetrameric channel contains four identical activator binding sites. Here we determine the number of binding sites required for maximal drug effect and determine the role of subunit interactions in the modulation of hERG1 gating by these compounds. Concatenated tetramers were constructed to contain a variable number (zero to four) of wild-type and mutant hERG1 subunits, either L646E to inhibit PD-118057 binding or F557L to inhibit ICA-105574 binding. Enhancement of hERG1 channel current magnitude by PD-118057 and attenuated inactivation by ICA-105574 were mediated by cooperative subunit interactions. Maximal effects of the both compounds required the presence of all four binding sites. Understanding how hERG1 agonists allosterically modify channel gating may facilitate mechanism-based drug design of novel agents for treatment of long QT syndrome. PMID:24638994

  17. Stoichiometry of altered hERG1 channel gating by small molecule activators

    PubMed Central

    Wu, Wei; Sachse, Frank B.; Gardner, Alison

    2014-01-01

    Voltage-gated K+ channels are tetramers formed by coassembly of four identical or highly related subunits. All four subunits contribute to formation of the selectivity filter, the narrowest region of the channel pore which determines K+ selective conductance. In some K+ channels, the selectivity filter can undergo a conformational change to reduce K+ flux by a mechanism called C-type inactivation. In human ether-a-go-go–related gene 1 (hERG1) K+ channels, C-type inactivation is allosterically inhibited by ICA-105574, a substituted benzamide. PD-118057, a 2-(phenylamino) benzoic acid, alters selectivity filter gating to enhance open probability of channels. Both compounds bind to a hydrophobic pocket located between adjacent hERG1 subunits. Accordingly, a homotetrameric channel contains four identical activator binding sites. Here we determine the number of binding sites required for maximal drug effect and determine the role of subunit interactions in the modulation of hERG1 gating by these compounds. Concatenated tetramers were constructed to contain a variable number (zero to four) of wild-type and mutant hERG1 subunits, either L646E to inhibit PD-118057 binding or F557L to inhibit ICA-105574 binding. Enhancement of hERG1 channel current magnitude by PD-118057 and attenuated inactivation by ICA-105574 were mediated by cooperative subunit interactions. Maximal effects of the both compounds required the presence of all four binding sites. Understanding how hERG1 agonists allosterically modify channel gating may facilitate mechanism-based drug design of novel agents for treatment of long QT syndrome. PMID:24638994

  18. Altered Vision-Related Resting-State Activity in Pituitary Adenoma Patients with Visual Damage

    PubMed Central

    Qian, Haiyan; Wang, Xingchao; Wang, Zhongyan; Wang, Zhenmin; Liu, Pinan

    2016-01-01

    Objective To investigate changes of vision-related resting-state activity in pituitary adenoma (PA) patients with visual damage through comparison to healthy controls (HCs). Methods 25 PA patients with visual damage and 25 age- and sex-matched corrected-to-normal-vision HCs underwent a complete neuro-ophthalmologic evaluation, including automated perimetry, fundus examinations, and a magnetic resonance imaging (MRI) protocol, including structural and resting-state fMRI (RS-fMRI) sequences. The regional homogeneity (ReHo) of the vision-related cortex and the functional connectivity (FC) of 6 seeds within the visual cortex (the primary visual cortex (V1), the secondary visual cortex (V2), and the middle temporal visual cortex (MT+)) were evaluated. Two-sample t-tests were conducted to identify the differences between the two groups. Results Compared with the HCs, the PA group exhibited reduced ReHo in the bilateral V1, V2, V3, fusiform, MT+, BA37, thalamus, postcentral gyrus and left precentral gyrus and increased ReHo in the precuneus, prefrontal cortex, posterior cingulate cortex (PCC), anterior cingulate cortex (ACC), insula, supramarginal gyrus (SMG), and putamen. Compared with the HCs, V1, V2, and MT+ in the PAs exhibited decreased FC with the V1, V2, MT+, fusiform, BA37, and increased FC primarily in the bilateral temporal lobe (especially BA20,21,22), prefrontal cortex, PCC, insular, angular gyrus, ACC, pre-SMA, SMG, hippocampal formation, caudate and putamen. It is worth mentioning that compared with HCs, V1 in PAs exhibited decreased or similar FC with the thalamus, whereas V2 and MT+ exhibited increased FCs with the thalamus, especially pulvinar. Conclusions In our study, we identified significant neural reorganization in the vision-related cortex of PA patients with visual damage compared with HCs. Most subareas within the visual cortex exhibited remarkable neural dysfunction. Some subareas, including the MT+ and V2, exhibited enhanced FC with the thalamic

  19. Identification of activation-tag Arabidopsis mutants with altered production of germination stimulants for Phelipanche ramosa (L.)

    PubMed Central

    Kirilova, Ina; Denev, Iliya D.; Bineva, Rumyana; Gevezova, Maria; Alexandrova, Milena; Kostov, Kaloyan; Batchvarova, Rossitza

    2014-01-01

    Germination of seeds of root parasites like broomrapes (Orobanchaceae) is tightly regulated by chemical products exuded from the roots of the host plant, known as germination stimulants (GSs). Changes in the levels of synthesis and emission of GS can allow the development of practical measures for control of the crops-harming parasitic species. However, the genes encoding enzymes responsible for GS biosynthesis are still unknown. We performed a large-scale screening of 62,000 Arabidopsis activation-tag mutants for alteration in susceptibility to Phelipanche ramosa and to identify lines with altered GS production among them. After five successive screenings we identified 36 lines with altered susceptibility to P. ramosa. Seven of them displayed altered levels of GS production. By using a combination of Southern blot and thermal asymmetric interlaced polymerase chain reaction (TAIL-PCR), we pinpointed the location of activation-tag constructs in these lines. A combination of differential display and quantitative real-time PCR (qRT-PCR) allowed us to identify several affected genes. Two of them are directly involved in isoprenoid biosynthetic pathway in chloroplasts, and we believe that their activation led to increased levels of GS production. We believe that these genes are responsible for increased GS production in five of the Arabidopsis lines resistant to P. ramosa. PMID:26740753

  20. Mechanisms of simultaneous hydrogen production and estrogenic activity removal from secondary effluent though solar photocatalysis.

    PubMed

    Zhang, Wenlong; Li, Yi; Wang, Chao; Wang, Peifang; Wang, Qing; Wang, Dawei

    2013-06-01

    The mechanisms of simultaneous photocatalytic hydrogen production and estrogenic activity (EA) removal from secondary effluent were investigated by evaluating the effects of initial dissolved oxygen (DO), organic matter, and inorganic ions on the process. The photocatalytic process was enhanced and can be divided into two phases according to the availability of DO. In aerobic phase, the humic/fulvic-like compounds in hydrophilic substances fraction were preferentially decomposed by aerobic photo-formed reactive oxygen species (i.e. O2(-), h(+), and OH) with generation of electron donors (i.e. formaldehyde, acetaldehyde, acetate, and formate). Approximately 41% of dissolved organic carbon and 90% of EA were reduced in the aerobic phase. In the following anoxic phase, the hydrogen production was significantly improved (apparent photonic efficiency 3.04 × 10(-3)) by the generated electron donors and accompanied with completely EA removal by the anoxic photo-formed OH. Hydrogen production was enhanced with the presence of low concentrations of HPO4(2-) (below 0.1 mmol/L) and HCO(3-) (below 0.2 mmol/L) through accelerating electrons accumulation while it was inhibited at high concentrations since the formed ion-radicals could not decompose humic/fulvic-like compounds. EA removal was inhibited by HPO4(2-) and HCO(3-) through scavenging h(+)/$OH. The presence of NO(3-) (below 1 mmol/L) only resulted in minor impacts since NO(3-) was almost unreactive toward electronor OH in neutral conditions. PMID:23562501

  1. The role of cysteine in the alteration of bovine liver dihydrodiol dehydrogenase 3 activity.

    PubMed Central

    Nanjo, H; Adachi, H; Aketa, M; Mizoguchi, T; Nishihara, T; Terada, T

    1995-01-01

    Bovine liver NADP(+)-dependent dihydrodiol dehydrogenase (DD3) is extremely sensitive to SH reagents such as N-ethylmaleimide (NEM) and 5,5'-dithiobis(2-nitrobenzoic acid). NEM produced time- and concentration-dependent inactivation of DD3 in a pseudo-first-order reaction manner. This inactivation was prevented by NADP+, 3-acetylpyridine-adenine dinucleotide phosphate, 2',5'-ADP and 2'-AMP but not by substrates, NAD+, nicotinamide mononucleotide or 5'-ADP.DD3 was absorbed by an affinity column of thiopropyl-Sepharose 6B, but enzyme incubated with both NEM and NADP+ was not. Moreover, one [14C]NEM molecule was incorporated into a cysteine of DD3 in the presence, and two cysteines of DD3 in the absence, of NADP+. These results suggested that two cysteine residues were modified per enzyme molecule by NEM, one was protected by NADP+ and the other had no significant function for the enzyme activity. Two radiolabelled peptides (P1 and P2) produced by the digestion with lysyl endopeptidase of [14C]NEM-modified DD3 could be separated by reverse-phase HPLC. P1, which was radiolabelled by [14C]NEM only in the absence of NADP+, showed the following sequence; H2N-Tyr-Lys-Pro-Val-Xaa-Asn-Gln-Val-Glu- NEM.Cys-His-Pro-Tyr-Phe-Asn-Gln-Ser-Lys-COOH (Xaa indicates a possible cysteine residue). This sequence was very similar to that of rat liver 3 alpha-hydroxysteroid/dihydrodiol dehydrogenase (3 alpha-HSD/DD) (residues 184 to 201) and was also highly conserved in the aldo-keto reductase superfamily. The sequence of P2, which had radioactivity in both the absence and presence of NADP+, also contained an NEM-modified cysteine and was similar in sequence to the regions located in loop A of rat 3 alpha-HSD/DD. The present study suggests that P1, which may have a cysteine residue corresponding to Cys-193 of rat 3 alpha-HSD/DD, functions in the alteration of DD3 activity depending on the modulation of NADP(+)-binding ability through a thiol/disulphide exchange reaction similar to that of

  2. Activity Theory as a Tool to Address the Problem of Chemistry's Lack of Relevance in Secondary School Chemical Education

    ERIC Educational Resources Information Center

    Van Aalsvoort, Joke

    2004-01-01

    In a previous article, the problem of chemistry's lack of relevance in secondary chemical education was analysed using logical positivism as a tool. This article starts with the hypothesis that the problem can be addressed by means of activity theory, one of the important theories within the sociocultural school. The reason for this expectation is…

  3. Physical Education Teacher Education Students' Knowledge, Perceptions and Experiences of Promoting Healthy, Active Lifestyles in Secondary Schools

    ERIC Educational Resources Information Center

    Harris, Jo

    2014-01-01

    Background: Physical education teacher education (PETE) offers a context for students to learn about the promotion of active lifestyles in secondary schools through their interactions and experiences during the teacher education process. However, previous studies have found low levels of health-related fitness knowledge amongst PETE students,…

  4. Evaluation of in vitro antiprotozoal activity of Ajuga laxmannii and its secondary metabolites.

    PubMed

    Atay, Irem; Kirmizibekmez, Hasan; Kaiser, Marcel; Akaydin, Galip; Yesilada, Erdem; Tasdemir, Deniz

    2016-09-01

    Context Some Ajuga L. (Lamiaceae) species are traditionally used for the treatment of malaria, as well as fever, which is a common symptom of many parasitic diseases. Objective In the continuation of our studies on the identification of antiprotozoal secondary metabolites of Turkish Lamiaceae species, we have investigated the aerial parts of Ajuga laxmannii. Materials and methods The aerial parts of A. laxmannii were extracted with MeOH. The H2O subextract was subjected to polyamide, C18-MPLC and SiO2 CCs to yield eight metabolites. The structures of the isolates were elucidated by NMR spectroscopy and MS analyses. The extract, subextracts as well as the isolates were tested for their in vitro antiprotozoal activities against Plasmodium falciparum, Trypanasoma brucei rhodesiense, T. cruzi and Leishmania donovani at concentrations of 90-0.123 μg/mL. Results Two iridoid glycosides harpagide (1) and 8-O-acetylharpagide (2), three o-coumaric acid derivatives cis-melilotoside (3), trans-melilotoside (4) and dihydromelilotoside (5), two phenylethanoid glycosides verbascoside (6) and galactosylmartynoside (7) and a flavone-C-glycoside, isoorientin (8) were isolated. Many compounds showed moderate to good antiparasitic activity, with isoorientin (8) displaying the most significant antimalarial potential (an IC50 value of 9.7 μg/mL). Discussion and conclusion This is the first report on the antiprotozoal evaluation of A. laxmannii extracts and isolates. Furthermore, isoorientin and dihydromelilotoside are being reported for the first time from the genus Ajuga. PMID:26734766

  5. Altered neural activation during prepotent response inhibition in breast cancer survivors treated with chemotherapy: an fMRI study.

    PubMed

    Kam, Julia W Y; Boyd, Lara A; Hsu, Chun L; Liu-Ambrose, Teresa; Handy, Todd C; Lim, Howard J; Hayden, Sherri; Campbell, Kristin L

    2016-09-01

    While impairments in executive functions have been reported in breast cancer survivors (BCS) who have undergone adjuvant chemotherapy, only a limited number of functional neuroimaging studies have associated alterations in cerebral activity with executive functions deficits in BCS. Using fMRI, the current study assessed the neural basis underlying a specific facet of executive function, namely prepotent response inhibition. 12 BCS who self-reported cognitive problems up to 3 years following cancer treatment and 12 female healthy comparisons (HC) performed the Stroop task. We compared their neural activation between the incongruent and neutral experimental conditions. Relative to the HC group, BCS showed lower blood-oxygen level dependent signal in several frontal regions, including the anterior cingulate cortex, a region critical for response inhibition. Our data indicates reduced neural activation in BCS during a prepotent response inhibition task, providing support for the prevailing notion of neural alterations observed in BCS treated with chemotherapy. PMID:26489975

  6. XPC silencing in normal human keratinocytes triggers metabolic alterations through NOX-1 activation-mediated reactive oxygen species

    PubMed Central

    Rezvani, Hamid Reza; Rossignol, Rodrigue; Ali, Nsrein; Benard, Giovanni; Tang, Xiuwei; Yang, Hee Seung; Jouary, Thomas; de Verneuil, Hubert; Taïeb, Alain; Kim, Arianna L.; Mazurier, Frédéric

    2011-01-01

    Summary Cancer cells utilize complex mechanisms to remodel their bioenergetic properties. We exploited the intrinsic genomic stability of xeroderma pigmentosum C (XPC) to understand the interrelationships between genomic instability, reactive oxygen species (ROS) generation, and metabolic alterations during neoplastic transformation. We showed that knockdown of XPC (XPCKD) in normal human keratinocytes results in metabolism remodeling through NADPH oxidase-1 (NOX-1) activation, which in turn leads to increased ROS levels. While enforcing antioxidant defenses by overexpressing catalase, CuZnSOD, or MnSOD could not block the metabolism remodeling, impaired NOX-1 activation abrogates both alteration in ROS levels and modifications of energy metabolism. As NOX-1 activation is observed in human squamous cell carcinomas (SCCs), the blockade of NOX-1 could be a target for the prevention and the treatment of skin cancers. PMID:21167810

  7. Methoxychlor induces atresia by altering Bcl2 factors and inducing caspase activity in mouse ovarian antral follicles in vitro

    PubMed Central

    Basavarajappa, Mallikarjuna S.; Karman, Bethany N.; Wang, Wei; Gupta, Rupesh K.; Flaws, Jodi A.

    2012-01-01

    Methoxychlor (MXC) is an organochlorine pesticide widely used in many countries against various species of insects that attack crops and domestic animals. MXC reduces fertility by increasing atresia (death) of antral follicles in vivo. MXC also induces atresia of antral follicles after 96 h in vitro. The current work tested the hypothesis that MXC induces morphological atresia at early time points (24 and 48 h) by altering pro-apoptotic (Bax, Bok, Casp3, and caspase activity) and anti-apoptotic (Bcl2 and Bcl-xL) factors in the follicles. The results indicate that at 24 h, MXC increased Bcl-xL and Bax mRNA levels and increased the ratio of Bax/Bcl2. At 48–96 h, MXC induced morphological atresia. At 24–96 h, MXC increased caspase activities. These data suggest that MXC may induce atresia by altering Bcl2 factors and inducing caspase activities in antral follicles. PMID:23000595

  8. Glycosaminoglycans from aged human hippocampus have altered capacities to regulate trophic factors activities but not Aβ42 peptide toxicity.

    PubMed

    Huynh, Minh Bao; Villares, Joao; Díaz, Julia Elisa Sepúlveda; Christiaans, Stephy; Carpentier, Gilles; Ouidja, Mohand Ouidir; Sissoeff, Ludmilla; Raisman-Vozari, Rita; Papy-Garcia, Dulce

    2012-05-01

    Glycosaminoglycans (GAGs) are major extracellular matrix components known to tightly regulate cell behavior by interacting with tissue effectors as trophic factors and other heparin binding proteins. Alterations of GAGs structures might thus modify the nature and extent of these interactions and alter tissue integrity. Here, we studied levels and composition of GAGs isolated from adult and aged human hippocampus and investigated if their changes can influence the function of important trophic factors and the Aβ42 peptide toxicity. Biochemical analyses showed that heparan sulfates are increased in the aged hippocampus. Moreover, GAGs from aged hippocampus showed altered capacities to regulate trophic factor activities without changing their capacities to protect cells from Aβ42 toxicity, compared to adult hippocampus GAGs. Structural alterations in GAGs from elderly were suggested by differential transcripts levels of key biosynthetic enzymes. C5-epimerase and 2-OST expressions were decreased while NDST-2 and 3-OST-4 were increased; in contrast, heparanase expression was unchanged. Results suggest that alteration of GAGs in hippocampus of aged subjects could participate to tissue impairment during aging. PMID:22035591

  9. Transcriptomes reveal alterations in gravity impact circadian clocks and activate mechanotransduction pathways with adaptation through epigenetic change.

    PubMed

    Casey, Theresa; Patel, Osman V; Plaut, Karen

    2015-04-01

    Few studies have investigated the impact of alterations in gravity on mammalian transcriptomes. Here, we describe the impact of spaceflight on mammary transcriptome of late pregnant rats and the effect of hypergravity exposure on mammary, liver, and adipose transcriptomes in late pregnancy and at the onset of lactation. RNA was isolated from mammary collected on pregnancy day 20 from rats exposed to spaceflight from days 11 to 20 of gestation. To measure the impact of hypergravity on mammary, liver, and adipose transcriptomes we isolated RNA from tissues collected on P20 and lactation day 1 from rats exposed to hypergravity beginning on pregnancy day 9. Gene expression was measured with Affymetrix GeneChips. Microarray analysis of variance revealed alterations in gravity affected the expression of genes that regulate circadian clocks and activate mechanotransduction pathways. Changes in these systems may explain global gene expression changes in immune response, metabolism, and cell proliferation. Expression of genes that modify chromatin structure and methylation was affected, suggesting adaptation to gravity alterations may proceed through epigenetic change. Altered gravity experiments offer insights into the role of forces omnipresent on Earth that shape genomes in heritable ways. Our study is the first to analyze the impact of alterations in gravity on transcriptomes of pregnant and lactating mammals. Findings provide insight into systems that sense gravity and the way in which they affect phenotype, as well as the possibility of sustaining life beyond Earth's orbit. PMID:25649141

  10. Scapular and rotator cuff muscle activity during arm elevation: A review of normal function and alterations with shoulder impingement

    PubMed Central

    Phadke, V; Camargo, PR; Ludewig, PM

    2009-01-01

    Objective The purpose of this manuscript is to review current knowledge of how muscle activation and force production contribute to shoulder kinematics in healthy subjects and persons with shoulder impingement. Results The middle and lower serratus anterior muscles produce scapular upward rotation, posterior tilting, and external rotation. Upper trapezius produces clavicular elevation and retraction. The middle trapezius is primarily a medial stabilizer of the scapula. The lower trapezius assists in medial stabilization and upward rotation of the scapula. The pectoralis minor is aligned to resist normal rotations of the scapula during arm elevation. The rotator cuff is critical to stabilization and prevention of excess superior translation of the humeral head, as well as production of glenohumeral external rotation during arm elevation. Alterations in activation amplitude or timing have been identified across various investigations of subjects with shoulder impingement as compared to healthy controls. These include decreased activation of the middle or lower serratus anterior and rotator cuff, delayed activation of middle and lower trapezius, and increased activation of the upper trapezius and middle deltoid in impingement subjects. In addition, subjects with a short resting length of the pectoralis minor exhibit altered scapular kinematic patterns similar to those found in persons with shoulder impingement. Conclusion These normal muscle functional capabilities and alterations in patient populations should be considered when planning exercise approaches for the rehabilitation of these patients. PMID:20411160

  11. Nogo-A-deficient Transgenic Rats Show Deficits in Higher Cognitive Functions, Decreased Anxiety, and Altered Circadian Activity Patterns

    PubMed Central

    Petrasek, Tomas; Prokopova, Iva; Sladek, Martin; Weissova, Kamila; Vojtechova, Iveta; Bahnik, Stepan; Zemanova, Anna; Schönig, Kai; Berger, Stefan; Tews, Björn; Bartsch, Dusan; Schwab, Martin E.; Sumova, Alena; Stuchlik, Ales

    2014-01-01

    Decreased levels of Nogo-A-dependent signaling have been shown to affect behavior and cognitive functions. In Nogo-A knockout and knockdown laboratory rodents, behavioral alterations were observed, possibly corresponding with human neuropsychiatric diseases of neurodevelopmental origin, particularly schizophrenia. This study offers further insight into behavioral manifestations of Nogo-A knockdown in laboratory rats, focusing on spatial and non-spatial cognition, anxiety levels, circadian rhythmicity, and activity patterns. Demonstrated is an impairment of cognitive functions and behavioral flexibility in a spatial active avoidance task, while non-spatial memory in a step-through avoidance task was spared. No signs of anhedonia, typical for schizophrenic patients, were observed in the animals. Some measures indicated lower anxiety levels in the Nogo-A-deficient group. Circadian rhythmicity in locomotor activity was preserved in the Nogo-A knockout rats and their circadian period (tau) did not differ from controls. However, daily activity patterns were slightly altered in the knockdown animals. We conclude that a reduction of Nogo-A levels induces changes in CNS development, manifested as subtle alterations in cognitive functions, emotionality, and activity patterns. PMID:24672453

  12. Sperm surface protein PH-20 is bifunctional: one activity is a hyaluronidase and a second, distinct activity is required in secondary sperm-zona binding.

    PubMed

    Hunnicutt, G R; Primakoff, P; Myles, D G

    1996-07-01

    In previous studies, we have found that the sperm membrane protein PH-20 acts during two different stages of fertilization. On acrosome-intact sperm, PH-20 has a hyaluronidase activity that is required for sperm penetration through the cumulus cell layer that surrounds the oocyte. On acrosome-reacted sperm, PH-20 has a required function in sperm-zona binding (secondary binding). Because hyaluronic acid (HA) has been detected in the zona pellucida, secondary sperm-zona adhesion could depend on repetitive binding and hydrolysis of HA by PH-20 acting as a hyaluronidase. Alternatively, PH-20 may be bifunctional and have a second, different activity required for secondary binding. To distinguish between these two possibilities, in this study we used reagents that inhibit either PH-20's function in sperm-zona binding or its hyaluronidase activity. We found that an anti-PH-20 monoclonal antibody that inhibited sperm-zona binding (approximately 90%) had no effect on hyaluronidase activity. Conversely, apigenin, a hyaluronidase inhibitor, blocked PH-20 hyaluronidase activity 93% without inhibiting sperm-zona binding. Similarly, another anti-PH-20 monoclonal antibody that inhibited hyaluronidase activity 95% only partially inhibited sperm-zona binding (approximately 45%). We also extensively pretreated oocytes with hyaluronidase to remove all accessible HA on or in the zona pellucida and found little or no effect on secondary sperm-zona binding. Our results suggest that PH-20 is bifunctional and has two activities: a hyaluronidase activity and a second, separate activity required for secondary sperm-zona binding. PMID:8793062

  13. Effect of Hydrothermal Alteration on Rock Properties in Active Geothermal Setting

    NASA Astrophysics Data System (ADS)

    Mikisek, P.; Bignall, G.; Sepulveda, F.; Sass, I.

    2012-04-01

    Hydrothermal alteration records the physical-chemical changes of rock and mineral phases caused by the interaction of hot fluids and wall rock, which can impact effective permeability, porosity, thermal parameters, rock strength and other rock properties. In this project, an experimental approach has been used to investigate the effects of hydrothermal alteration on rock properties. A rock property database of contrastingly altered rock types and intensities has been established. The database details horizontal and vertical permeability, porosity, density, thermal conductivity and thermal heat capacity for ~300 drill core samples from wells THM12, THM13, THM14, THM17, THM18, THM22 and TH18 in the Wairakei-Tauhara geothermal system (New Zealand), which has been compared with observed hydrothermal alteration type, rank and intensity obtained from XRD analysis and optical microscopy. Samples were selected from clay-altered tuff and intercalated siltstones of the Huka Falls Formation, which acts as a cap rock at Wairakei-Tauhara, and tuffaceous sandstones of the Waiora Formation, which is a primary reservoir-hosting unit for lateral and vertical fluid flows in the geothermal system. The Huka Falls Formation exhibits argillic-type alteration of varying intensity, while underlying Waiora Formations exhibits argillic- and propylithic-type alteration. We plan to use a tempered triaxial test cell at hydrothermal temperatures (up to 200°C) and pressures typical of geothermal conditions, to simulate hot (thermal) fluid percolation through the rock matrix of an inferred "reservoir". Compressibility data will be obtained under a range of operating (simulation reservoir) conditions, in a series of multiple week to month-long experiments that will monitor change in permeability and rock strength accompanying advancing hydrothermal alteration intensity caused by the hot brine interacting with the rock matrix. We suggest, our work will provide new baseline information concerning

  14. Effects of activated carbon ageing in three PCB contaminated sediments: Sorption efficiency and secondary effects on Lumbriculus variegatus.

    PubMed

    Nybom, Inna; Waissi-Leinonen, Greta; Mäenpää, Kimmo; Leppänen, Matti T; Kukkonen, Jussi V K; Werner, David; Akkanen, Jarkko

    2015-11-15

    The sorption efficiency and possible secondary effects of activated carbon (AC) (ø 63-200 μm) was studied with Lumbriculus variegatus in three PCB contaminated sediments applying long AC-sediment contact time (3 years). AC amendment efficiently reduced PCB bioavailability as determined with both, L. variegatus bioaccumulation test and passive samplers. However, dose related secondary effects of AC on egestion rate and biomass were observed (applied doses 0.25% and 2.5% sediment dry weight). The sorption capacity and secondary effects remained similar when the experiments were repeated after three years of AC-sediment contact time. Further, transmission electron microscopy (TEM) samples revealed morphological changes in the L. variegatus gut wall microvilli layer. Sediment properties affected both sorption efficiency and secondary effects, but 2.5% AC addition had significant effects regardless of the sediment. In, conclusion, AC is an efficient and stable sorbent to decrease the bioavailability of PCBs. However, sediment dwelling organisms, such as Oligochaete worms in this study, may be sensitive to the carbon amendments. The secondary effects and possible morphological changes in benthic organisms should not be overlooked as in many cases they form the basis of the aquatic food webs. PMID:26364225

  15. Flexibility in the site of exon junction complex deposition revealed by functional group and RNA secondary structure alterations in the splicing substrate

    PubMed Central

    Mishler, Dennis M.; Christ, Alexander B.; Steitz, Joan A.

    2008-01-01

    The exon junction complex (EJC) is critical for mammalian nonsense-mediated mRNA decay and translational regulation, but the mechanism of its stable deposition on mRNA is unknown. To examine requirements for EJC deposition, we created splicing substrates containing either DNA nucleotides or RNA secondary structure in the 5′ exon. Using RNase H protection, toeprinting, and coimmunoprecipitation assays, we found that EJC location shifts upstream when a stretch of DNA or RNA secondary structure appears at the canonical deposition site. These upstream shifts occur prior to exon ligation and are often accompanied by decreases in deposition efficiency. Although the EJC core protein eIF4AIII contacts four ribose 2′OH groups in crystal structures, we demonstrate that three 2′OH groups are sufficient for deposition. Thus, the site of EJC deposition is more flexible than previously appreciated and efficient deposition appears spatially limited. PMID:18952819

  16. Antinociceptive activity of extracts and secondary metabolites from wild growing and micropropagated plants of Renealmia alpinia

    PubMed Central

    Gómez-Betancur, Isabel; Cortés, Natalie; Benjumea, Dora; Osorio, Edison; León, Francisco; Cutler, Stephen J.

    2015-01-01

    Ethnopharmacological relevance Renealmia alpinia is native to the American continent and can be found from Mexico to Brazil, and in the Caribbean islands. It is known as “matandrea” in Colombia, and it has been commonly used in traditional medicine to treat painful diseases and ailments. Based on its traditional uses, it is of interest to evaluate the pharmacologic effects of this plant and its secondary metabolites. Materials and methods Methanol and aqueous extracts of wild and micropropagated R. alpinia (leaves) were obtained and chemically compared by High Performance Thin Layer Chromatography (HPTLC). The antinociceptive activity of these extracts was examined using an in vivo assay (Siegmund test). Additionally, the dichloromethane extract of R. alpinia was fractionated and pure compounds were isolated by chromatographic methods. The structure elucidation of isolated compounds was performed by NMR experiments and spectroscopic techniques and comparison with the literature data. Purified compounds were evaluated for their in vitro binding affinity for opioids and cannabinoids receptors. Results The dichloromethane extract of the plant’s aerial part afforded sinostrobin (1), naringenin 7,4′-dimethyl ether (2), 2′,6′-dihydroxy-4′-methoxychalcone (3), 4-methoxy-6-(2-phenylethenyl)-2H-pyran-2-one (4), naringenin 7-methyl ether (5) and 3,5-heptanediol, 1,7-diphenyl (6), which were isolated using chromatographic methods. Their chemical structures were established by physical and spectroscopic techniques. The antinociceptive effects observed in mice by extracts of wild and micropropagated plants were similar. The compounds isolated from R. alpinia do not show affinity to opioid or cannabinoid receptors. Conclusion Aqueous and methanol extracts of R. alpinia provide antinociceptive and analgesic effects in an in vivo model. These results contribute additional insight as to why this plant is traditionally used for pain management. Also, this is the first

  17. Element redistribution during hydrothermal alteration of rhyolite in an active geothermal system: Yellowstone drill cores Y-7 and Y-8

    NASA Astrophysics Data System (ADS)

    Sturchio, Neil C.; Muehlenbachs, Karlis; Seitz, Martin G.

    1986-08-01

    Hydrothermal alteration of the 0.54 Ma Biscuit Basin rhyolite flow in Yellowstone drill cores Y-7 and Y-8 has involved significant changes in Ti-normalized whole rock concentrations of Li, Mg, Ca, Na, K, Mn, Rb, Sr, Sb, Cs, Ba, and U, whereas such changes have generally not occurred for Al, Fe, Sc, Co, Y, Zr, REE, Hf, Ta, and Th. The relatively mobile elements have been redistributed over distances from 2-5 cm to more than 10-100 m, and are associated mainly with zeolites and clays, in thoroughly altered samples; average whole rock changes in Ti-normalized mass range from about 0.5-17 g/Kg (9-49%) for major elements and 0.1-280 mg/Kg (19-4260%) for minor and trace elements. Compositional changes correlate with hydrothermal mineralogy. The relatively immobile elements have been redistributed over a distance of at least 10-100 μm but less than 2-5 cm, and are associated mainly with clays, in thoroughly altered samples. Addition of SiO 2 ranges from 110-890 g/Kg in samples where porosity has been thoroughly sealed by silica deposition. Thermal water is not in oxygen isotopic equilibrium with any primary or secondary phases analyzed except calcite. Modest depletions of 18O (1-2%) due to exchange with thermal water apparently have occurred in Y-8 plagioclase and obsidian. Oxygen isotope ratios in obsidian-replacing smectite and in veinlet celadonite and β-cristobalite suggest that these phases precipitated from water locally enriched in 18O (up to ~8% heavier than present thermal water). The minimum integrated water/rock mass ratio in Y-7 and Y-8 is 10 3-10 4 (assuming advective transport).

  18. Arsenic alters vascular smooth muscle cell focal adhesion complexes leading to activation of FAK-src mediated pathways

    SciTech Connect

    Pysher, Michele D. Chen, Qin M.; Vaillancourt, Richard R.

    2008-09-01

    Chronic exposure to arsenic has been linked to tumorigenesis, cardiovascular disease, hypertension, atherosclerosis, and peripheral vascular disease; however, the molecular mechanisms underlying its pathological effects remain elusive. In this study, we investigated arsenic-induced alteration of focal adhesion protein complexes in normal, primary vascular smooth muscle cells. We demonstrate that exposure to environmentally relevant concentrations of arsenic (50 ppb As{sup 3+}) can alter focal adhesion protein co-association leading to activation of downstream pathways. Co-associated proteins were identified and quantitated via co-immunoprecipitation, SDS-PAGE, and Western blot analysis followed by scanning densitometry. Activation of MAPK pathways in total cell lysates was evaluated using phosphor-specific antibodies. In our model, arsenic treatment caused a sustained increase in FAK-src association and activation, and induced the formation of unique signaling complexes (beginning after 3-hour As{sup 3+} exposure and continuing throughout the 12-hour time course studied). The effects of these alterations were manifested as chronic stimulation of downstream PAK, ERK and JNK pathways. Past studies have demonstrated that these pathways are involved in cellular survival, growth, proliferation, and migration in VSMCs.

  19. Regulation of WT1 by phosphorylation: inhibition of DNA binding, alteration of transcriptional activity and cellular translocation.

    PubMed Central

    Ye, Y; Raychaudhuri, B; Gurney, A; Campbell, C E; Williams, B R

    1996-01-01

    Phosphorylation is one of the major post-translational mechanisms by which the activity of transcription factors is regulated. We have investigated the role of phosphorylation in the regulation of nucleic acid binding activity and the nuclear translocation of WT1. Two recombinant WT1 proteins containing the DNA binding domain with or without a three amino acid (KTS) insertion (WT1ZF + KTS and WT1ZF - KTS) were strongly phosphorylated by protein kinase A (PKA) and protein kinase C (PKC) in vitro. Both PKA and PKC phosphorylation inhibited the ability of WT1ZF + KTS or WT1ZF - KTS to bind to a sequence derived from the WT1 promoter region in gel mobility shift assays. The binding of WT1ZF - KTS to an EGR1 consensus binding site was also inhibited by prior PKA and PKC phosphorylation. We also demonstrate the RNA binding activity of WT1, but this was not altered by phosphorylation. PKA activation by dibutyryl cAMP in WT1-transfected cells resulted in the reversal of WT1 suppression of a reporter construct. Although WT1 protein is predominantly localized to the nucleus, this expression pattern is altered upon PKA activation, resulting in the cytoplasmic retention of WT1. Accordingly, phosphorylation may play a role in modulating the transcriptional regulatory activity of WT1 through interference with nuclear translocation, as well as by inhibition of WT1 DNA binding. Images PMID:8896454

  20. Altered Spontaneous Brain Activity in Betel Quid Dependence: A Resting-state Functional Magnetic Resonance Imaging Study.

    PubMed

    Liu, Tao; Li, Jian-Jun; Zhao, Zhong-Yan; Yang, Guo-Shuai; Pan, Meng-Jie; Li, Chang-Qing; Pan, Su-Yue; Chen, Feng

    2016-02-01

    It has been suggested by the first voxel-based morphometry investigation that betel quid dependence (BQD) individuals are presented with brain structural changes in previous reports, and there may be a neurobiological basis for BQD individuals related to an increased risk of executive dysfunction and disinhibition, subjected to the reward system, cognitive system, and emotion system. However, the effects of BQD on neural activity remain largely unknown. Individuals with impaired cognitive control of behavior often reveal altered spontaneous cerebral activity in resting-state functional magnetic resonance imaging and those changes are usually earlier than structural alteration.Here, we examined BQD individuals (n = 33) and age-, sex-, and education-matched healthy control participants (n = 32) in an resting-state functional magnetic resonance imaging study to observe brain function alterations associated with the severity of BQD. Amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) values were both evaluated to stand for spontaneous cerebral activity. Gray matter volumes of these participants were also calculated for covariate.In comparison with healthy controls, BQD individuals demonstrated dramatically decreased ALFF and ReHo values in the prefrontal gurus along with left fusiform, and increased ALFF and ReHo values in the primary motor cortex area, temporal lobe as well as some regions of occipital lobe. The betel quid dependence scores (BQDS) were negatively related to decreased activity in the right anterior cingulate.The abnormal spontaneous cerebral activity revealed by ALFF and ReHo calculation excluding the structural differences in patients with BQD may help us probe into the neurological pathophysiology underlying BQD-related executive dysfunction and disinhibition. Diminished spontaneous brain activity in the right anterior cingulate cortex may, therefore, represent a biomarker of BQD individuals. PMID:26844480

  1. Central Muscarinic Cholinergic Activation Alters Interaction between Splenic Dendritic Cell and CD4+CD25- T Cells in Experimental Colitis

    PubMed Central

    Pavlov, Valentin A.; Tracey, Kevin J.; Khafipour, Ehsan; Ghia, Jean-Eric

    2014-01-01

    Background The cholinergic anti-inflammatory pathway (CAP) is based on vagus nerve (VN) activity that regulates macrophage and dendritic cell responses in the spleen through alpha-7 nicotinic acetylcholine receptor (a7nAChR) signaling. Inflammatory bowel disease (IBD) patients present dysautonomia with decreased vagus nerve activity, dendritic cell and T cell over-activation. The aim of this study was to investigate whether central activation of the CAP alters the function of dendritic cells (DCs) and sequential CD4+/CD25−T cell activation in the context of experimental colitis. Methods The dinitrobenzene sulfonic acid model of experimental colitis in C57BL/6 mice was used. Central, intracerebroventricular infusion of the M1 muscarinic acetylcholine receptor agonist McN-A-343 was used to activate CAP and vagus nerve and/or splenic nerve transection were performed. In addition, the role of α7nAChR signaling and the NF-kB pathway was studied. Serum amyloid protein (SAP)-A, colonic tissue cytokines, IL-12p70 and IL-23 in isolated splenic DCs, and cytokines levels in DC-CD4+CD25−T cell co-culture were determined. Results McN-A-343 treatment reduced colonic inflammation associated with decreased pro-inflammatory Th1/Th17 colonic and splenic cytokine secretion. Splenic DCs cytokine release was modulated through α7nAChR and the NF-kB signaling pathways. Cholinergic activation resulted in decreased CD4+CD25−T cell priming. The anti-inflammatory efficacy of central cholinergic activation was abolished in mice with vagotomy or splenic neurectomy. Conclusions Suppression of splenic immune cell activation and altered interaction between DCs and T cells are important aspects of the beneficial effect of brain activation of the CAP in experimental colitis. These findings may lead to improved therapeutic strategies in the treatment of IBD. PMID:25295619

  2. Impurities analysis of polycrystalline silicon substrates: Neutronic Activation Analysis (NAA) and Secondary Ion Mass Spectrometry (SIMS)

    NASA Astrophysics Data System (ADS)

    Lounis, A.; Lenouar, K.; Gritly, Y.; Abbad, B.; Azzaz, M.; Taïbi, K.

    2010-01-01

    In this study we have determined the concentration of some impurities such as carbon, iron, copper, titanium, nickel of the flat product (polycrystalline silicon). These impurities generate a yield decrease in the photovoltaic components. The material (polycrystalline silicon) used in this work is manufactured by the Unit of Silicon Technology Development (UDTS Algiers, Algeria). The 80 kg ingot has been cutted into 16 briquettes in order to have plates (flat product) of 100 mm×100 mm dimensions. Each briquette is divided into three parts top (T), middle (M) and bottom (B). For this purpose, the following instrumental analysis techniques have been employed: neutronic analysis (neutronic activation analysis) and secondary ion mass spectrometry (SIMS). Masses of 80 mg are sampled and form of discs 18 mm in diameter, then exposed to a flux of neutron of 2.1012neutron cm-2 s-1 during 15 min. The energetic profile of incidental flux is constituted of fast neutrons (ΦR = 3.1012n.cm-2 s-1; E = 2 Mev), thermal neutrons (ΦTH = 1013n.cm-2 s-1; E = 0.025 ev) and epithermal neutrons (Φepi = 7.1011 n cm-2 s-1; E>4.9 ev), irradiation time 15 mn, after 20 mn of decrement, acquisitions of 300 s are carried out. The results are expressed by disintegration per second which does not exceed the 9000 Bq, 500 Bq and 2600 Bq, respectively for copper, titanium and nickel. It is observed that the impurities concentrations in the medium are higher. The impurities in the bottom of the ingots originate from the crucible. The impurities in the top originate from impurities dissolved in the liquid silicon, which have segregated to the top layer of the ingot and after solidification diffuse. Silicon corresponds to a mixture of three isotopes 28Si, 29Si and 30Si. These elements clearly appear on the mass spectrum (SIMS). The presence of iron and the one of nickel has been noticed.

  3. CCN Activity, Hygroscopicity, and Droplet Activation Kinetics of Secondary Organic Aerosol Resulting from the 2010 Gulf Oil Spill

    NASA Astrophysics Data System (ADS)

    Moore, R.; Lathem, T. L.; Cerully, K.; Bahreini, R.; Brock, C. A.; Langridge, J. M.; Middlebrook, A. M.; Nenes, A.; Calnex Science Team

    2010-12-01

    hygroscopicity (κ ~ 0.05-0.1). It has been previously established for secondary organic aerosol that hygroscopicity increases with increasing oxidation (as characterized by the organic oxygen:carbon ratio) [3], and vice versa, and this dataset is used to evaluate this empirical finding. Particles measured in plumes downwind of the DWH site were seen to exhibit slow activation kinetics, consistent with a tenfold decrease in the mass transfer coefficient as compared to that of pure, ammonium sulfate. Observations of similar kinetic effects have been previously observed by Ruehl et al. in the California marine boundary layer and by Lathem and Nenes in fresh Canadian biomass burning plumes [2,4]. This study provides additional information about aerosol kinetic effects in this unique environment. [1] Moore, R. H. and A. Nenes. Aerosol Sci. Technol., 2009. [2] Lathem, T. L. and A. Nenes, in preparation. [3] Jimenez, J. L., et al. Science, 2010. [4] Ruehl, C., et al., Geophys. Res. Lett., 2009.

  4. Clinical, cognitive, and functional connectivity correlations of resting-state intrinsic brain activity alterations in unmedicated depression

    PubMed Central

    Tadayonnejad, Reza; Yang, Shaolin; Kumar, Anand; Ajilore, Olusola

    2014-01-01

    The pervasive and persistent nature of depressive symptoms has made resting-state functional magnetic resonance imaging (rs-fMRI) an appropriate approach for understanding the underlying mechanisms of major depressive disorder. The majority of rs-fMRI research has focused on depression-related alterations in the interregional coordination of brain baseline low frequency oscillations (LFOs). However, alteration of the regional amplitude of LFOs in depression, particularly its clinical, cognitive and network implications have not been examined comprehensively yet. rs-fMRI amplitudes of low-frequency fluctuation (ALFF/fALFF) mediated by two LFOs bands of 0.01-0.08 Hz (LF-ALFF/fALFF) and 0.1-0.25 Hz (HF-ALFF/fALFF) were measured in unmedicated subjects with major depressive disorder (n=20) and a healthy control group (n=25). A novel method of “ALFF-based functional connectivity” analysis was developed to test regional/network interaction abnormalities in depression. Our results revealed abnormal alterations in ALFF for both lower and higher frequency bands of LFOs in regions that participate in affective networks, corticostriatal circuits and motor/somatosensory networks. A strong positive correlation was detected between depressive symptom severity and fALFF in the anterior cingulate cortex. Functional connectivity of the thalamus and postcentral area with altered ALFF were found to be decreased with other interacting regions of their involved networks. Major depressive disorder relates to the alterations of regional properties of intrinsic neural activity with meaningful clinical and cognitive correlations. This study also proposes an integrating regional/network dysfunction in MDD. PMID:25451423

  5. Decreased glutathione S-transferase expression and activity and altered sex steroids in Lake Apopka brown bullheads (Ameriurus nebulosus)

    USGS Publications Warehouse

    Gallagher, E.P.; Gross, T.S.; Sheehy, K.M.

    2001-01-01

    A number of freshwater lakes and reclaimed agricultural sites in Central Florida have been the receiving waters for agrochemical and municipal runoff. One of these sites, Lake Apopka, is also a eutrophic system that has been the focus of several case studies reporting altered reproductive activity linked to bioaccumulation of persistent organochlorine chemicals in aquatic species. The present study was initiated to determine if brown bullheads (Ameriurus nebulosus) from the north marsh of Lake Apopka (Lake Apopka Marsh) exhibit an altered capacity to detoxify environmental chemicals through hepatic glutathione S-transferase (GST)-mediated conjugation as compared with bullheads from a nearby reference site (Lake Woodruff). We also compared plasma sex hormone concentrations (testosterone, 17-?? estradiol, and 11 keto-testosterone) in bullheads from the two sites. Female bullheads from Lake Apopka had 40% lower initial rate GST conjugative activity toward 1-chloro-2,4-dinitrobenzene (CDNB), 50% lower activity towards p-nitrobutyl chloride (NBC), 33% lower activity toward ethacrynic acid (ECA), and 43% lower activity toward ??5-androstene-3,17-dione (??5-ADI), as compared with female bullheads from Lake Woodruff. Enzyme kinetic analyses demonstrated that female bullheads from Lake Apopka had lower GST-catalyzed CDNB clearance than did female Lake Woodruff bullheads. Western blotting studies of bullhead liver cytosolic proteins demonstrated that the reduced GST catalytic activities in female Lake Apopka bullheads were accompanied by lower expression of hepatic GST protein. No site differences were observed with respect to GST activities or GST protein expression in male bullheads. Female Lake Apopka bullheads also had elevated concentrations of plasma androgens (testosterone and 11-ketotestosterone) as compared with females from Lake Woodruff. In contrast, male Lake Apopka bullheads had elevated levels of plasma estrogen but similar levels of androgens as compared with

  6. Active binary R Arae revisited: Bringing the secondary component to light and physical modelling of the circumstellar material

    NASA Astrophysics Data System (ADS)

    Bakış, H.; Bakış, V.; Eker, Z.; Demircan, O.

    2016-05-01

    The spectral lines of the secondary component of the active binary system R Ara were uncovered for the first time, which allowed directly to determine the parameters of the spectroscopic orbit. The mass ratio of the system is updated to a new observational value of M2/M1 = 0.305 ± 0.005 which is ˜20 per cent smaller than the literature value (M2/M1 = 0.39). Modelling the reconstructed component spectra yielded the equatorial rotational velocities of the components as vrot1 = 202 km s-1 and vrot2 = 73 km s-1 indicating a very fast rotation (˜5 times faster than the synchronous rotation velocity) for the primary and synchronous rotation for the secondary component. The circumstellar material in the system was investigated using the Hipparcossatellite data and the high-resolution (R ˜ 41 000) spectral data. According to our model, there is always material transferring from the secondary component on to the primary causing a hot region on its surface. The structural difference between the spectra taken at the same orbital phase but at different epochs proved that the density and the velocity of the transferring material are variable. There are three main trends in the light curve and spectral line variations suggesting the activity cycles for the system, namely quiescent, moderate and, active cycles. It was estimated that the circumstellar material around could be extended to large distances up to 40 R⊙ from the system.

  7. Nitric oxide is involved in methyl jasmonate-induced defense responses and secondary metabolism activities of Taxus cells.

    PubMed

    Wang, Jian Wen; Wu, Jian Yong

    2005-06-01

    Methyl jasmonate (MeJA), a methyl ester of jasmonic acid (JA), is a well-established signal molecule in plant defense responses and an effective inducer of secondary metabolite accumulation in plant cell cultures such as the valuable anticancer diterpenoid taxol (paclitaxel) in Taxus spp. This work examines the involvement of nitric oxide (NO) in MeJA-induced plant defense responses and secondary metabolism in Taxus chinensis cell cultures. Exogenously supplied MeJA at 100 microM induced rapid production of NO in the Taxus cell cultures, reaching a maximum within 6 h of MeJA supply. Several other responses occurred concomitantly, including the production of hydrogen peroxide (H2O2), and the increases in intracellular malondialdehyde (MDA) content, lipoxygenase (LOX) and phenylalanine ammonium-lyase (PAL) activities. The MeJA-induced H2O2 production was suppressed by an NO donor, sodium nitroprusside (SNP), but enhanced by NO inhibitors, N (omega)-nitro-L-arginine (L-NNA) and 2-phenyl-4,4,5,5-tetramethyl-imidazoline-1-oxyl-3-oxide (PTIO). In contrast, the MeJA-induced MDA, LOX and PAL were all enhanced by the NO donor but suppressed by the NO inhibitors. The NO inhibitors also suppressed MeJA-induced taxol accumulation. These results are suggestive of a role for NO as a signal element for activating the MeJA-induced defense responses and secondary metabolism activities of plant cells. PMID:15829512

  8. Health/Home Economics Classroom Activities for Secondary Schools. Schools in an Aging Society.

    ERIC Educational Resources Information Center

    Connecticut State Dept. of Education, Hartford.

    As the fastest-growing segment of society, older adults can be valuable resources for schools. The intent of this guide is to promote education for, with, and about older adults; to confront stereotypic images; and to present an accurate and balanced view of aging. The manual consists of 21 lesson plans for secondary teachers of health and home…

  9. The "Marinated" Classroom. A Sourcebook of Aquatic Activities for the Secondary Classroom.

    ERIC Educational Resources Information Center

    Rakow, Steven J.

    This handbook is designed to meet the aquatic education needs of Minnesota secondary teachers and students (aquatic education referring to the study of freshwater systems). The handbook is divided into three parts. Part 1 (an introduction) provides an overview of aquatic education, a description of the use of the handbook, and two indices to…

  10. Effect of Competition on the Production and Activity of Secondary Metabolites in Aspergillus species

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Secondary metabolites are of intense interest to humans due to their pharmaceutical and/or toxic properties. Aspergillus species secrete these metabolites by themselves and in the presence of other fungal species. Here, we have performed co-cultivation competition assays among different Aspergillu...

  11. Exploring Secondary Students' Understanding of Chemical Kinetics through Inquiry-Based Learning Activities

    ERIC Educational Resources Information Center

    Chairam, Sanoe; Klahan, Nutsuda; Coll, Richard K.

    2015-01-01

    This research is trying to evaluate the feedback of Thai secondary school students to inquiry-based teaching and learning methods, exemplified by the study of chemical kinetics. This work used the multiple-choice questions, scientifically practical diagram and questionnaire to assess students' understanding of chemical kinetics. The findings…

  12. The Occupational Identity of In-Service Secondary Music Educators: Formative Interpersonal Interactions and Activities

    ERIC Educational Resources Information Center

    Russell, Joshua A.

    2012-01-01

    In order to explore the factors that inform the occupational identity development of in-service music educators and to compare the identities of in-service teachers with those of preservice music educators as examined in previous research, the purposes of this study were to examine the reported occupational identity of in-service secondary music…

  13. Social Studies Classroom Activities for Secondary Schools. Schools in an Aging Society.

    ERIC Educational Resources Information Center

    Goranson, Donald G., Ed.

    Designed for secondary students, the 20 lessons in this volume promote education for, with, and about older adults and prepare students to participate in the changing world. Lessons 1-3 explore attitudes about aging through word association, confront the aging process, and examine values regarding time. Lessons 4-6 study aging in different times…

  14. Consumer-Oriented Laboratory Activities: A Manual for Secondary Science Students.

    ERIC Educational Resources Information Center

    Anderson, Jacqueline; McDuffie, Thomas E., Jr.

    This document provides a laboratory manual for use by secondary level students in performing consumer-oriented laboratory experiments. Each experiment includes an introductory question outlining the purpose of the investigation, a detailed discussion, detailed procedures, questions to be answered upon completing the experiment, and information for…

  15. Physical Activity and School Performance: A Survey among Students Not Qualified for Upper Secondary School

    ERIC Educational Resources Information Center

    Ericsson, Ingegerd; Cederberg, Margareta

    2015-01-01

    Background: Many students leave compulsory school without being qualified to apply for national upper secondary school programmes. Despite efforts, the number of unqualified students in Sweden has increased. Grades from compulsory school have direct implications for students' educational futures and the requirement to qualify for an upper…

  16. Enlivening Secondary History: 50 Classroom Activities for Teachers and Pupils. Second Edition

    ERIC Educational Resources Information Center

    Davies, Peter; Davies, Rhys

    2012-01-01

    "Enlivening Secondary History" is the ideal handbook for busy history teachers who want to do something different in their classrooms, but have little time to plan and organise their lessons. Featuring tried-and-tested practical ideas complete with relevant exemplars and step-by-step advice, this best-selling book is a compendium of creative…

  17. ALTERED DEVELOPMENT AND REPRODUCTION IN MOSQUITOFISH EXPOSED TO PULP AND PAPER MILL EFFLUENT IN THE FENHOLLOW RIVER, FLORIDA USA

    EPA Science Inventory

    Female mosquitofish exposed to pulp and paper mill effluent (PME) in the Fenholloway River, Florida, USA have masculinized secondary sex characteristics and altered aromatase enzyme activity. We and others have shown that the Fenholloway River PME contains androgenic and progesto...

  18. Impaired APP activity and altered Tau splicing in embryonic stem cell-derived astrocytes obtained from an APPsw transgenic minipig.

    PubMed

    Hall, Vanessa J; Lindblad, Maiken M; Jakobsen, Jannik E; Gunnarsson, Anders; Schmidt, Mette; Rasmussen, Mikkel A; Volke, Daniela; Zuchner, Thole; Hyttel, Poul

    2015-10-01

    Animal models of familial juvenile onset of Alzheimer's disease (AD) often fail to produce diverse pathological features of the disease by modification of single gene mutations that are responsible for the disease. They can hence be poor models for testing and development of novel drugs. Here, we analyze in vitro-produced stem cells and their derivatives from a large mammalian model of the disease created by overexpression of a single mutant human gene (APPsw). We produced hemizygous and homozygous radial glial-like cells following culture and differentiation of embryonic stem cells (ESCs) isolated from embryos obtained from mated hemizygous minipigs. These cells were confirmed to co-express varying neural markers, including NES, GFAP and BLBP, typical of type one radial glial cells (RGs) from the subgranular zone. These cells had altered expression of CCND1 and NOTCH1 and decreased expression of several ribosomal RNA genes. We found that these cells were able to differentiate into astrocytes upon directed differentiation. The astrocytes produced had decreased α- and β-secretase activity, increased γ-secretase activity and altered splicing of tau. This indicates novel aspects of early onset mechanisms related to cell renewal and function in familial AD astrocytes. These outcomes also highlight that radial glia could be a potentially useful population of cells for drug discovery, and that altered APP expression and altered tau phosphorylation can be detected in an in vitro model of the disease. Finally, it might be possible to use large mammal models to model familial AD by insertion of only a single mutation. PMID:26398935

  19. Expression of S-adenosylmethionine Hydrolase in Tissues Synthesizing Secondary Cell Walls Alters Specific Methylated Cell Wall Fractions and Improves Biomass Digestibility

    PubMed Central

    Eudes, Aymerick; Zhao, Nanxia; Sathitsuksanoh, Noppadon; Baidoo, Edward E. K.; Lao, Jeemeng; Wang, George; Yogiswara, Sasha; Lee, Taek Soon; Singh, Seema; Mortimer, Jenny C.; Keasling, Jay D.; Simmons, Blake A.; Loqué, Dominique

    2016-01-01

    Plant biomass is a large source of fermentable sugars for the synthesis of bioproducts using engineered microbes. These sugars are stored as cell wall polymers, mainly cellulose and hemicellulose, and are embedded with lignin, which makes their enzymatic hydrolysis challenging. One of the strategies to reduce cell wall recalcitrance is the modification of lignin content and composition. Lignin is a phenolic polymer of methylated aromatic alcohols and its synthesis in tissues developing secondary cell walls is a significant sink for the consumption of the methyl donor S-adenosylmethionine (AdoMet). In this study, we demonstrate in Arabidopsis stems that targeted expression of AdoMet hydrolase (AdoMetase, E.C. 3.3.1.2) in secondary cell wall synthesizing tissues reduces the AdoMet pool and impacts lignin content and composition. In particular, both NMR analysis and pyrolysis gas chromatography mass spectrometry of lignin in engineered biomass showed relative enrichment of non-methylated p-hydroxycinnamyl (H) units and a reduction of dimethylated syringyl (S) units. This indicates a lower degree of methylation compared to that in wild-type lignin. Quantification of cell wall-bound hydroxycinnamates revealed a reduction of ferulate in AdoMetase transgenic lines. Biomass from transgenic lines, in contrast to that in control plants, exhibits an enrichment of glucose content and a reduction in the degree of hemicellulose glucuronoxylan methylation. We also show that these modifications resulted in a reduction of cell wall recalcitrance, because sugar yield generated by enzymatic biomass saccharification was greater than that of wild-type plants. Considering that transgenic plants show no important diminution of biomass yields, and that heterologous expression of AdoMetase protein can be spatiotemporally optimized, this novel approach provides a valuable option for the improvement of lignocellulosic biomass feedstock. PMID:27486577

  20. Expression of S-adenosylmethionine Hydrolase in Tissues Synthesizing Secondary Cell Walls Alters Specific Methylated Cell Wall Fractions and Improves Biomass Digestibility.

    PubMed

    Eudes, Aymerick; Zhao, Nanxia; Sathitsuksanoh, Noppadon; Baidoo, Edward E K; Lao, Jeemeng; Wang, George; Yogiswara, Sasha; Lee, Taek Soon; Singh, Seema; Mortimer, Jenny C; Keasling, Jay D; Simmons, Blake A; Loqué, Dominique

    2016-01-01

    Plant biomass is a large source of fermentable sugars for the synthesis of bioproducts using engineered microbes. These sugars are stored as cell wall polymers, mainly cellulose and hemicellulose, and are embedded with lignin, which makes their enzymatic hydrolysis challenging. One of the strategies to reduce cell wall recalcitrance is the modification of lignin content and composition. Lignin is a phenolic polymer of methylated aromatic alcohols and its synthesis in tissues developing secondary cell walls is a significant sink for the consumption of the methyl donor S-adenosylmethionine (AdoMet). In this study, we demonstrate in Arabidopsis stems that targeted expression of AdoMet hydrolase (AdoMetase, E.C. 3.3.1.2) in secondary cell wall synthesizing tissues reduces the AdoMet pool and impacts lignin content and composition. In particular, both NMR analysis and pyrolysis gas chromatography mass spectrometry of lignin in engineered biomass showed relative enrichment of non-methylated p-hydroxycinnamyl (H) units and a reduction of dimethylated syringyl (S) units. This indicates a lower degree of methylation compared to that in wild-type lignin. Quantification of cell wall-bound hydroxycinnamates revealed a reduction of ferulate in AdoMetase transgenic lines. Biomass from transgenic lines, in contrast to that in control plants, exhibits an enrichment of glucose content and a reduction in the degree of hemicellulose glucuronoxylan methylation. We also show that these modifications resulted in a reduction of cell wall recalcitrance, because sugar yield generated by enzymatic biomass saccharification was greater than that of wild-type plants. Considering that transgenic plants show no important diminution of biomass yields, and that heterologous expression of AdoMetase protein can be spatiotemporally optimized, this novel approach provides a valuable option for the improvement of lignocellulosic biomass feedstock. PMID:27486577

  1. Altered neuronal activity in the pedunculopontine nucleus: An electrophysiological study in a rat model of Parkinson's disease.

    PubMed

    Geng, Xiwen; Xie, Jinlu; Wang, Xuenan; Wang, Xiusong; Zhang, Xiao; Hou, Yabing; Lei, Chengdong; Li, Min; Qu, Qingyang; He, Tingting; Han, Hongyu; Yao, Xiaomeng; Wang, Min

    2016-05-15

    The pedunculopontine nucleus (PPN) is a new deep brain stimulation target for treating Parkinson's disease (PD). But the alterations of the PPN electrophysiological activities in PD are still debated. To investigate these potential alterations, extracellular single unit and local field potential (LFP) activities in the PPN were recorded in unilateral hemispheric 6-hydroxydopamine (6-OHDA) lesioned rats and in control rats, respectively. The spike activity results revealed two types of neurons (Type I and Type II) with distinct electrophysiological characteristics in the PPN. Both types of neurons had increased firing rate and changed firing pattern in lesioned rats when compared to control rats. Specifically, Type II neurons showed an increased firing rate when the rat state was switched from rest to locomotion. The LFP results demonstrated that lesioned rats had lower LFP power at 0.7-12Hz and higher power at 12-30Hz than did control animals in either resting or locomotor state. These findings provide a better understanding of the effects of 6-OHDA lesion on neuronal activities in the PPN and also provide a proof of the link between this structure and locomotion, which contributes to better understanding the mechanisms of the PPN functioning in the pathophysiology of PD. PMID:26924016

  2. Maternal Diet-Induced Obesity Alters Mitochondrial Activity and Redox Status in Mouse Oocytes and Zygotes

    PubMed Central

    Igosheva, Natalia; Abramov, Andrey Y.; Poston, Lucilla; Eckert, Judith J.; Fleming, Tom P.; Duchen, Michael R.; McConnell, Josie

    2010-01-01

    The negative impact of obesity on reproductive success is well documented but the stages at which development of the conceptus is compromised and the mechanisms responsible for the developmental failure still remain unclear. Recent findings suggest that mitochondria may be a contributing factor. However to date no studies have directly addressed the consequences of maternal obesity on mitochondria in early embryogenesis. Using an established murine model of maternal diet induced obesity and a live cell dynamic fluorescence imaging techniques coupled with molecular biology we have investigated the underlying mechanisms of obesity-induced reduced fertility. Our study is the first to show that maternal obesity prior to conception is associated with altered mitochondria in mouse oocytes and zygotes. Specifically, maternal diet-induced obesity in mice led to an increase in mitochondrial potential, mitochondrial DNA content and biogenesis. Generation of reactive oxygen species (ROS) was raised while glutathione was depleted and the redox state became more oxidised, suggestive of oxidative stress. These altered mitochondrial properties were associated with significant developmental impairment as shown by the increased number of obese mothers who failed to support blastocyst formation compared to lean dams. We propose that compromised oocyte and early embryo mitochondrial metabolism, resulting from excessive nutrient exposure prior to and during conception, may underlie poor reproductive outcomes frequently reported in obese women. PMID:20404917

  3. Food reward without a timing component does not alter the timing of activity under positive energy balance.

    PubMed

    van der Vinne, V; Akkerman, J; Lanting, G D; Riede, S J; Hut, R A

    2015-09-24

    Circadian clocks drive daily rhythms in physiology and behavior which allow organisms to anticipate predictable daily changes in the environment. In most mammals, circadian rhythms result in nocturnal activity patterns although plasticity of the circadian system allows activity patterns to shift to different times of day. Such plasticity is seen when food access is restricted to a few hours during the resting (light) phase resulting in food anticipatory activity (FAA) in the hours preceding food availability. The mechanisms underlying FAA are unknown but data suggest the involvement of the reward system and homeostatic regulation of metabolism. We previously demonstrated the isolated effect of metabolism by inducing diurnality in response to energetic challenges. Here the importance of reward timing in inducing daytime activity is assessed. The daily activity distribution of mice earning palatable chocolate at their preferred time by working in a running wheel was compared with that of mice receiving a timed palatable meal at noon. Mice working for chocolate (WFC) without being energetically challenged increased their total daily activity but this did not result in a shift to diurnality. Providing a chocolate meal at noon each day increased daytime activity, identifying food timing as a factor capable of altering the daily distribution of activity and rest. These results show that timing of food reward and energetic challenges are both independently sufficient to induce diurnality in nocturnal mammals. FAA observed following timed food restriction is likely the result of an additive effect of distinct regulatory pathways activated by energetic challenges and food reward. PMID:26215921

  4. Altered Hub Functioning and Compensatory Activations in the Connectome: A Meta-Analysis of Functional Neuroimaging Studies in Schizophrenia

    PubMed Central

    Crossley, Nicolas A.; Mechelli, Andrea; Ginestet, Cedric; Rubinov, Mikail; Bullmore, Edward T.; McGuire, Philip

    2016-01-01

    Background: Functional neuroimaging studies of schizophrenia have identified abnormal activations in many brain regions. In an effort to interpret these findings from a network perspective, we carried out a meta-analysis of this literature, mapping anatomical locations of under- and over-activation to the topology of a normative human functional connectome. Methods: We included 314 task-based functional neuroimaging studies including more than 5000 patients with schizophrenia and over 5000 controls. Coordinates of significant under- or over-activations in patients relative to controls were mapped to nodes of a normative connectome defined by a prior meta-analysis of 1641 functional neuroimaging studies of task-related activation in healthy volunteers. Results: Under-activations and over-activations were reported in a wide diversity of brain regions. Both under- and over-activations were significantly more likely to be located in hub nodes that constitute the “rich club” or core of the normative connectome. In a subset of 121 studies that reported both under- and over-activations in the same patients, we found that, in network terms, these abnormalities were located in close topological proximity to each other. Under-activation in a peripheral node was more frequently associated specifically with over-activation of core nodes than with over-activation of another peripheral node. Conclusions: Although schizophrenia is associated with altered brain functional activation in a wide variety of regions, abnormal responses are concentrated in hubs of the normative connectome. Task-specific under-activation in schizophrenia is accompanied by over-activation of topologically central, less functionally specialized network nodes, which may represent a compensatory response. PMID:26472684

  5. Altered Brain Activation during Emotional Face Processing in Relation to Both Diagnosis and Polygenic Risk of Bipolar Disorder

    PubMed Central

    Tesli, Martin; Kauppi, Karolina; Bettella, Francesco; Brandt, Christine Lycke; Kaufmann, Tobias; Espeseth, Thomas; Mattingsdal, Morten; Agartz, Ingrid; Melle, Ingrid; Djurovic, Srdjan; Westlye, Lars T.; Andreassen, Ole A.

    2015-01-01

    Objectives Bipolar disorder (BD) is a highly heritable disorder with polygenic inheritance. Among the most consistent findings from functional magnetic imaging (fMRI) studies are limbic hyperactivation and dorsal hypoactivation. However, the relation between reported brain functional abnormalities and underlying genetic risk remains elusive. This is the first cross-sectional study applying a whole-brain explorative approach to investigate potential influence of BD case-control status and polygenic risk on brain activation. Methods A BD polygenic risk score (PGRS) was estimated from the Psychiatric Genomics Consortium BD case-control study, and assigned to each individual in our independent sample (N=85 BD cases and 121 healthy controls (HC)), all of whom participated in an fMRI emotional faces matching paradigm. Potential differences in BOLD response across diagnostic groups were explored at whole-brain level in addition to amygdala as a region of interest. Putative effects of BD PGRS on brain activation were also investigated. Results At whole-brain level, BD cases presented with significantly lower cuneus/precuneus activation than HC during negative face processing (Z-threshold=2.3 as cluster-level correction). The PGRS was associated positively with increased right inferior frontal gyrus (rIFG) activation during negative face processing. For amygdala activation, there were no correlations with diagnostic status or PGRS. Conclusions These findings are in line with previous reports of reduced precuneus and altered rIFG activation in BD. While these results demonstrate the ability of PGRS to reveal underlying genetic risk of altered brain activation in BD, the lack of convergence of effects at diagnostic and PGRS level suggests that this relation is a complex one. PMID:26222050

  6. Supplemental Feeding for Ecotourism Reverses Diel Activity and Alters Movement Patterns and Spatial Distribution of the Southern Stingray, Dasyatis americana

    PubMed Central

    Corcoran, Mark J.; Wetherbee, Bradley M.; Shivji, Mahmood S.; Potenski, Matthew D.; Chapman, Demian D.; Harvey, Guy M.

    2013-01-01

    Southern stingrays, Dasyatis americana, have been provided supplemental food in ecotourism operations at Stingray City Sandbar (SCS), Grand Cayman since 1986, with this site becoming one of the world’s most famous and heavily visited marine wildlife interaction venues. Given expansion of marine wildlife interactive tourism worldwide, there are questions about the effects of such activities on the focal species and their ecosystems. We used a combination of acoustic telemetry and tag-recapture efforts to test the hypothesis that human-sourced supplemental feeding has altered stingray activity patterns and habitat use at SCS relative to wild animals at control sites. Secondarily, we also qualitatively estimated the population size of stingrays supporting this major ecotourism venue. Tag-recapture data indicated that a population of at least 164 stingrays, over 80% female, utilized the small area at SCS for prolonged periods of time. Examination of comparative movements of mature female stingrays at SCS and control sites revealed strong differences between the two groups: The fed animals demonstrated a notable inversion of diel activity, being constantly active during the day with little movement at night compared to the nocturnally active wild stingrays; The fed stingrays utilized significantly (p<0.05) smaller 24 hour activity spaces compared to wild conspecifics, staying in close proximity to the ecotourism site; Fed stingrays showed a high degree of overlap in their core activity spaces compared to wild stingrays which were largely solitary in the spaces utilized (72% vs. 3% overlap respectively). Supplemental feeding has strikingly altered movement behavior and spatial distribution of the stingrays, and generated an atypically high density of animals at SCS which could have downstream fitness costs for individuals and potentially broader ecosystem effects. These findings should help environmental managers plan mitigating measures for existing operations, and

  7. Supramammillary serotonin reduction alters place learning and concomitant hippocampal, septal, and supramammillar theta activity in a Morris water maze.

    PubMed

    Hernández-Pérez, J Jesús; Gutiérrez-Guzmán, Blanca E; López-Vázquez, Miguel Á; Olvera-Cortés, María E

    2015-01-01

    Hippocampal theta activity is related to spatial information processing, and high-frequency theta activity, in particular, has been linked to efficient spatial memory performance. Theta activity is regulated by the synchronizing ascending system (SAS), which includes mesencephalic and diencephalic relays. The supramamillary nucleus (SUMn) is located between the reticularis pontis oralis and the medial septum (MS), in close relation with the posterior hypothalamic nucleus (PHn), all of which are part of this ascending system. It has been proposed that the SUMn plays a role in the modulation of hippocampal theta-frequency; this could occur through direct connections between the SUMn and the hippocampus or through the influence of the SUMn on the MS. Serotonergic raphe neurons prominently innervate the hippocampus and several components of the SAS, including the SUMn. Serotonin desynchronizes hippocampal theta activity, and it has been proposed that serotonin may regulate learning through the modulation of hippocampal synchrony. In agreement with this hypothesis, serotonin depletion in the SUMn/PHn results in deficient spatial learning and alterations in CA1 theta activity-related learning in a Morris water maze. Because it has been reported that SUMn inactivation with lidocaine impairs the consolidation of reference memory, we asked whether changes in hippocampal theta activity related to learning would occur through serotonin depletion in the SUMn, together with deficiencies in memory. We infused 5,7-DHT bilaterally into the SUMn in rats and evaluated place learning in the standard Morris water maze task. Hippocampal (CA1 and dentate gyrus), septal and SUMn EEG were recorded during training of the test. The EEG power in each region and the coherence between the different regions were evaluated. Serotonin depletion in the SUMn induced deficient spatial learning and altered the expression of hippocampal high-frequency theta activity. These results provide evidence in

  8. Supramammillary serotonin reduction alters place learning and concomitant hippocampal, septal, and supramammillar theta activity in a Morris water maze

    PubMed Central

    Hernández-Pérez, J. Jesús; Gutiérrez-Guzmán, Blanca E.; López-Vázquez, Miguel Á.; Olvera-Cortés, María E.

    2015-01-01

    Hippocampal theta activity is related to spatial information processing, and high-frequency theta activity, in particular, has been linked to efficient spatial memory performance. Theta activity is regulated by the synchronizing ascending system (SAS), which includes mesencephalic and diencephalic relays. The supramamillary nucleus (SUMn) is located between the reticularis pontis oralis and the medial septum (MS), in close relation with the posterior hypothalamic nucleus (PHn), all of which are part of this ascending system. It has been proposed that the SUMn plays a role in the modulation of hippocampal theta-frequency; this could occur through direct connections between the SUMn and the hippocampus or through the influence of the SUMn on the MS. Serotonergic raphe neurons prominently innervate the hippocampus and several components of the SAS, including the SUMn. Serotonin desynchronizes hippocampal theta activity, and it has been proposed that serotonin may regulate learning through the modulation of hippocampal synchrony. In agreement with this hypothesis, serotonin depletion in the SUMn/PHn results in deficient spatial learning and alterations in CA1 theta activity-related learning in a Morris water maze. Because it has been reported that SUMn inactivation with lidocaine impairs the consolidation of reference memory, we asked whether changes in hippocampal theta activity related to learning would occur through serotonin depletion in the SUMn, together with deficiencies in memory. We infused 5,7-DHT bilaterally into the SUMn in rats and evaluated place learning in the standard Morris water maze task. Hippocampal (CA1 and dentate gyrus), septal and SUMn EEG were recorded during training of the test. The EEG power in each region and the coherence between the different regions were evaluated. Serotonin depletion in the SUMn induced deficient spatial learning and altered the expression of hippocampal high-frequency theta activity. These results provide evidence in

  9. Supplemental feeding for ecotourism reverses diel activity and alters movement patterns and spatial distribution of the southern stingray, Dasyatis americana.

    PubMed

    Corcoran, Mark J; Wetherbee, Bradley M; Shivji, Mahmood S; Potenski, Matthew D; Chapman, Demian D; Harvey, Guy M

    2013-01-01

    Southern stingrays, Dasyatis americana, have been provided supplemental food in ecotourism operations at Stingray City Sandbar (SCS), Grand Cayman since 1986, with this site becoming one of the world's most famous and heavily visited marine wildlife interaction venues. Given expansion of marine wildlife interactive tourism worldwide, there are questions about the effects of such activities on the focal species and their ecosystems. We used a combination of acoustic telemetry and tag-recapture efforts to test the hypothesis that human-sourced supplemental feeding has altered stingray activity patterns and habitat use at SCS relative to wild animals at control sites. Secondarily, we also qualitatively estimated the population size of stingrays supporting this major ecotourism venue. Tag-recapture data indicated that a population of at least 164 stingrays, over 80% female, utilized the small area at SCS for prolonged periods of time. Examination of comparative movements of mature female stingrays at SCS and control sites revealed strong differences between the two groups: The fed animals demonstrated a notable inversion of diel activity, being constantly active during the day with little movement at night compared to the nocturnally active wild stingrays; The fed stingrays utilized significantly (p<0.05) smaller 24 hour activity spaces compared to wild conspecifics, staying in close proximity to the ecotourism site; Fed stingrays showed a high degree of overlap in their core activity spaces compared to wild stingrays which were largely solitary in the spaces utilized (72% vs. 3% overlap respectively). Supplemental feeding has strikingly altered movement behavior and spatial distribution of the stingrays, and generated an atypically high density of animals at SCS which could have downstream fitness costs for individuals and potentially broader ecosystem effects. These findings should help environmental managers plan mitigating measures for existing operations, and

  10. Current results on biological activities of lichen secondary metabolites: a review.

    PubMed

    Molnár, Katalin; Farkas, Edit

    2010-01-01

    Lichens are symbiotic organisms of fungi and algae or cyanobacteria. Lichen-forming fungi synthesize a great variety of secondary metabolites, many of which are unique. Developments in analytical techniques and experimental methods have resulted in the identification of about 1050 lichen substances (including those found in cultures). In addition to their role in lichen chemotaxonomy and systematics, lichen secondary compounds have several possible biological roles, including photoprotection against intense radiation, as well as allelochemical, antiviral, antitumor, antibacterial, antiherbivore, and antioxidant action. These compounds are also important factors in metal homeostasis and pollution tolerance of lichen thalli. Although our knowledge of the contribution of these extracellular products to the success of the lichen symbiosis has increased significantly in the last decades, their biotic and abiotic roles have not been entirely explored. PMID:20469633

  11. The rolB gene activates secondary metabolism in Arabidopsis calli via selective activation of genes encoding MYB and bHLH transcription factors.

    PubMed

    Bulgakov, Victor P; Veremeichik, Galina N; Grigorchuk, Valeria P; Rybin, Viacheslav G; Shkryl, Yuri N

    2016-05-01

    It is known that the rolB gene of Agrobacterium rhizogenes increases the production of secondary metabolites in transformed plant cells, but its mechanism of action remains unclear. In this report, we demonstrate that rolB expression in Arabidopsis thaliana calli led to the activation of most genes encoding secondary metabolism-specific MYB and bHLH transcription factors (TFs), such as MYB11, MYB12, MYB28, MYB76, MYB34, MYB51, MYB122, TT2 and TT8. Accordingly, a higher transcript abundance of main biosynthetic genes related to these factors was detected. The rolB-transformed calli produced 3-fold higher levels of indolic glucosinolates (GSs) compared with normal calli but did not produce secondary metabolites from other groups. Enhanced accumulation of indolic GSs was caused by activation of MYB34, MYB51 and MYB122, and the absence of aliphatic GSs in transformed calli was caused by the inability of rolB to induce MYB29. The inability of rolB-calli to produce flavonoids was caused by the lack of MYB111 expression, induced by the rolB-mediated conversion of MYB expression from cotyledon-specific to root-specific patterns. The high specificity of rolB on secondary metabolism-specific TFs was demonstrated for the first time. PMID:26913794

  12. Blockade of gap junction hemichannel protects secondary spinal cord injury from activated microglia-mediated glutamate exitoneurotoxicity.

    PubMed

    Umebayashi, Daisuke; Natsume, Atsushi; Takeuchi, Hideyuki; Hara, Masahito; Nishimura, Yusuke; Fukuyama, Ryuichi; Sumiyoshi, Naoyuki; Wakabayashi, Toshihiko

    2014-12-15

    We previously demonstrated that activated microglia release excessive glutamate through gap junction hemichannels and identified a novel gap junction hemichannel blocker, INI-0602, that was proven to penetrate the blood-brain barrier and be an effective treatment in mouse models of amyotrophic lateral sclerosis and Alzheimer disease. Spinal cord injury causes tissue damage in two successive waves. The initial injury is mechanical and directly causes primary tissue damage, which induces subsequent ischemia, inflammation, and neurotoxic factor release resulting in the secondary tissue damage. These lead to activation of glial cells. Activated glial cells such as microglia and astrocytes are common pathological observations in the damaged lesion. Activated microglia release glutamate, the major neurotoxic factor released into the extracellular space after neural injury, which causes neuronal death at high concentration. In the present study, we demonstrate that reduction of glutamate-mediated exitotoxicity via intraperitoneal administration of INI-0602 in the microenvironment of the injured spinal cord elicited neurobehavioral recovery and extensive suppression of glial scar formation by reducing secondary tissue damage. Further, this intervention stimulated anti-inflammatory cytokines, and subsequently elevated brain-derived neurotrophic factor. Thus, preventing microglial activation by a gap junction hemichannel blocker, INI-0602, may be a promising therapeutic strategy in spinal cord injury. PMID:24588281

  13. Secondary Plant Products Causing Photosensitization in Grazing Herbivores: Their Structure, Activity and Regulation

    PubMed Central

    Quinn, Jane C.; Kessell, Allan; Weston, Leslie A.

    2014-01-01

    Photosensitivity in animals is defined as a severe dermatitis that results from a heightened reactivity of skin cells and associated dermal tissues upon their exposure to sunlight, following ingestion or contact with UV reactive secondary plant products. Photosensitivity occurs in animal cells as a reaction that is mediated by a light absorbing molecule, specifically in this case a plant-produced metabolite that is heterocyclic or polyphenolic. In sensitive animals, this reaction is most severe in non-pigmented skin which has the least protection from UV or visible light exposure. Photosensitization in a biological system such as the epidermis is an oxidative or other chemical change in a molecule in response to light-induced excitation of endogenous or exogenously-delivered molecules within the tissue. Photo-oxidation can also occur in the plant itself, resulting in the generation of reactive oxygen species, free radical damage and eventual DNA degradation. Similar cellular changes occur in affected herbivores and are associated with an accumulation of photodynamic molecules in the affected dermal tissues or circulatory system of the herbivore. Recent advances in our ability to identify and detect secondary products at trace levels in the plant and surrounding environment, or in organisms that ingest plants, have provided additional evidence for the role of secondary metabolites in photosensitization of grazing herbivores. This review outlines the role of unique secondary products produced by higher plants in the animal photosensitization process, describes their chemistry and localization in the plant as well as impacts of the environment upon their production, discusses their direct and indirect effects on associated animal systems and presents several examples of well-characterized plant photosensitization in animal systems. PMID:24451131

  14. Secondary plant products causing photosensitization in grazing herbivores: their structure, activity and regulation.

    PubMed

    Quinn, Jane C; Kessell, Allan; Weston, Leslie A

    2014-01-01

    Photosensitivity in animals is defined as a severe dermatitis that results from a heightened reactivity of skin cells and associated dermal tissues upon their exposure to sunlight, following ingestion or contact with UV reactive secondary plant products. Photosensitivity occurs in animal cells as a reaction that is mediated by a light absorbing molecule, specifically in this case a plant-produced metabolite that is heterocyclic or polyphenolic. In sensitive animals, this reaction is most severe in non-pigmented skin which has the least protection from UV or visible light exposure. Photosensitization in a biological system such as the epidermis is an oxidative or other chemical change in a molecule in response to light-induced excitation of endogenous or exogenously-delivered molecules within the tissue. Photo-oxidation can also occur in the plant itself, resulting in the generation of reactive oxygen species, free radical damage and eventual DNA degradation. Similar cellular changes occur in affected herbivores and are associated with an accumulation of photodynamic molecules in the affected dermal tissues or circulatory system of the herbivore. Recent advances in our ability to identify and detect secondary products at trace levels in the plant and surrounding environment, or in organisms that ingest plants, have provided additional evidence for the role of secondary metabolites in photosensitization of grazing herbivores. This review outlines the role of unique secondary products produced by higher plants in the animal photosensitization process, describes their chemistry and localization in the plant as well as impacts of the environment upon their production, discusses their direct and indirect effects on associated animal systems and presents several examples of well-characterized plant photosensitization in animal systems. PMID:24451131

  15. Mineralogical, geochemical and isotopic characteristics of hydrothermal alteration processes in the active, submarine, felsic-hosted PACMANUS field, Manus Basin, Papua New Guinea

    NASA Astrophysics Data System (ADS)

    Lackschewitz, K. S.; Devey, C. W.; Stoffers, P.; Botz, R.; Eisenhauer, A.; Kummetz, M.; Schmidt, M.; Singer, A.

    2004-11-01

    During ODP Leg 193, 4 sites were drilled in the active PACMANUS hydrothermal field on the crest of the felsic Pual Ridge to examine the vertical and lateral variations in mineralization and alteration patterns. We present new data on clay mineral assemblages, clay and whole rock chemistry and clay mineral strontium and oxygen isotopic compositions of altered rocks from a site of diffuse low-temperature venting (Snowcap, Site 1188) and a site of high-temperature venting (Roman Ruins, Site 1189) in order to investigate the water-rock reactions and associated elemental exchanges. The volcanic succession at Snowcap has been hydrothermally altered, producing five alteration zones: (1) chlorite ± illite-cristobalite-plagioclase alteration apparently overprinted locally by pyrophyllite bleaching at temperatures of 260-310°C; (2) chlorite ± mixed-layer clay alteration at temperatures of 230°C; (3) chlorite and illite alteration; (4) illite and chlorite ± illite mixed-layer alteration at temperatures of 250-260°C; and (5) illite ± chlorite alteration at 290-300°C. Felsic rocks recovered from two holes (1189A and 1189B) at Roman Ruins, although very close together, show differing alteration features. Hole 1189A is characterized by a uniform chlorite-illite alteration formed at ˜250°C, overprinted by quartz veining at 350°C. In contrast, four alteration zones occur in Hole 1189B: (1) illite ± chlorite alteration formed at ˜300°C; (2) chlorite ± illite alteration at 235°C; (3) chlorite ± illite and mixed layer clay alteration; and (4) chlorite ± illite alteration at 220°C. Mass balance calculations indicate that the chloritization, illitization and bleaching (silica-pyrophyllite assemblages) alteration stages are accompanied by different chemical changes relative to a calculated pristine precursor lava. The element Cr appears to have a general enrichment in the altered samples from PACMANUS. The clay concentrate data show that Cr and Cu are predominantly

  16. Low back pain associates with altered activity of the cerebral cortex prior to arm movements that require postural adjustment

    PubMed Central

    Jacobs, Jesse V.; Henry, Sharon M.; Nagle, Keith J.

    2009-01-01

    Objective: To determine whether low back pain (LBP) associates with altered postural stabilization and concomitant changes in cerebrocortical motor physiology. Methods: Ten participants with LBP and 10 participants without LBP performed self-initiated, voluntary arm raises. Electromyographic onset latencies of the bilateral internal oblique and erector spinae muscles were analyzed relative to that of the deltoid muscle as measures of anticipatory postural adjustments (APAs). Amplitudes of alpha event-related desynchronization (ERD) and of Bereitschaftspotentials (BP) were calculated from scalp electroencephalography as measures of cerebrocortical motor physiology. Results: The APA was first evident in the trunk muscles contralateral to the arm raise for both groups. Significant alpha ERD was evident bilaterally at the central and parietal electrodes for participants with LBP but only at the electrodes contralateral and midline to the arm raise for those without LBP. The BP amplitudes negatively correlated with APA onset latencies for participants with (but not for those without) LBP. Conclusions: Cerebrocortical activity becomes altered prior to arm movements requiring APAs for individuals with chronic LBP. Significance: These results support a theoretical model that altered central motor neurophysiology associates with LBP, thereby implying that rehabilitation strategies should address these neuromotor impairments. PMID:20071225

  17. Short-term withdrawal from developmental exposure to cocaine activates the glucocorticoid receptor and alters spine dynamics.

    PubMed

    Caffino, Lucia; Giannotti, Giuseppe; Malpighi, Chiara; Racagni, Giorgio; Fumagalli, Fabio

    2015-10-01

    Although glucocorticoid receptors (GRs) contribute to the action of cocaine, their role following developmental exposure to the psychostimulant is still unknown. To address this issue, we exposed adolescent male rats to cocaine (20mg/kg/day) from post-natal day (PND) 28 to PND 42 and sacrificed them at PND 45 or 90. We studied the medial prefrontal cortex (mPFC), a brain region that is still developing during adolescence. In PND 45 rats we found enhanced GR transcription and translation as well as increased trafficking toward the nucleus of the receptor, with no alteration in plasma corticosterone levels. We also showed reduced expression of the GR co-chaperone FKBP51, that normally keeps the receptor in the cytoplasm, and increased expression of Src1, which cooperates in the activation of GR transcriptional activity, revealing that short withdrawal alters the finely tuned mechanisms regulating GR action. Since activation of GRs regulate dendritic spine morphology, we next investigated spine dynamics in cocaine-withdrawn rats. We found that PSD95, cofilin and F-actin, molecules regulating spine actin network, are reduced in the mPFC of PND 45 rats suggesting reduced spine density, confirmed by confocal imaging. Further, formation of filopodia, i.e. the inactive spines, is enhanced suggesting the formation of non-functional spines. Of note, no changes were found in molecules related to GR machinery or spine dynamics following long-term abstinence, i.e. in adult rats (PND 90). These findings demonstrate that short withdrawal promotes plastic changes in the developing brain via the dysregulation of the GR system and alterations in the spine network. PMID:26004981

  18. A new strategy to analyze possible association structures between dynamic nocturnal hormone activities and sleep alterations in humans.

    PubMed

    Kalus, Stefanie; Kneib, Thomas; Steiger, Axel; Holsboer, Florian; Yassouridis, Alexander

    2009-04-01

    The human sleep process shows dynamic alterations during the night. Methods are needed to examine whether and to what extent such alterations are affected by internal, possibly time-dependent, factors, such as endocrine activity. In an observational study, we examined simultaneously sleep EEG and nocturnal levels of renin, growth hormone (GH), and cortisol (between 2300 and 0700) in 47 healthy volunteers comprising 24 women (41.67 +/- 2.93 yr of age) and 23 men (37.26 +/- 2.85 yr of age). Hormone concentrations were measured every 20 min. Conventional sleep stage scoring at 30-s intervals was applied. Semiparametric multinomial logit models are used to study and quantify possible time-dependent hormone effects on sleep stage transition courses. Results show that increased cortisol levels decrease the probability of transition from rapid-eye-movement (REM) sleep to wakefulness (WAKE) and increase the probability of transition from REM to non-REM (NREM) sleep, irrespective of the time in the night. Via the model selection criterion Akaike's information criterion, it was found that all considered hormone effects on transition probabilities with the initial state WAKE change with time. Similarly, transition from slow-wave sleep (SWS) to light sleep (LS) is affected by a "hormone-time" interaction for cortisol and renin, but not GH. For example, there is a considerable increase in the probability of SWS-LS transition toward the end of the night, when cortisol concentrations are very high. In summary, alterations in human sleep possess dynamic forms and are partially influenced by the endocrine activity of certain hormones. Statistical methods, such as semiparametric multinomial and time-dependent logit regression, can offer ambitious ways to investigate and estimate the association intensities between the nonstationary sleep changes and the time-dependent endocrine activities. PMID:19144755

  19. Alterations of cytochrome P450-dependent monooxygenase activities in Eriocheir japonicus in response to water pollution.

    PubMed Central

    Ishizuka, M; Hoshi, H; Minamoto, N; Masuda, M; Kazusaka, A; Fujita, S

    1996-01-01

    Eriocheir japonicus, fresh-water crabs inhabiting rivers and estuaries in Japan, were investigated for cytochrome P450 (CYP)-dependent drug-metabolizing enzyme activities to see if these activities reflect the river pollution gradient. From the laboratory dose-response experiments, we found that the polycyclic aromatic hydrocarbon (PAH) 3-methylcholanthrene induced total CYP contents, ethoxycoumarin O-deethylase activity, and bunitrolol 4-hydroxylase activity in crab hepatopancreas. In the field studies, crabs collected from the river with the highest concentration of PAHs exhibited the highest levels of CYP, the highest activities of benzo[a]pyrene 3-hydroxylase, imipramine 2-hydroxylase, bunitrolol 4-hydroxylase, ethoxycoumarin O-deethylase, and the ability to metabolically activate benzo[a]pyrene, but erythromycin N-demethylase activity was not induced. The correlation between PAH levels and drug-metabolizing enzyme activities in female crabs were not as marked as in male crabs. The levels and activities of CYP did not appear to reflect the concentrations of organochlorines and polychlorinated biphenyl congeners (PCBs) studied in the fat of crab hepatopancreas. Images Figure 1. Figure 2. A Figure 2. B Figure 2. C Figure 3. Figure 4. A Figure 4. B Figure 5. A Figure 5. B Figure 5. C Figure 5. D Figure 5. E Figure 5. F Figure 6. PMID:8841764

  20. Differential Larval Toxicity and Oviposition Altering Activity of Some Indigenous Plant Extracts against Dengue and Chikungunya Vector Aedes albopictus

    PubMed Central

    Yadav, Ruchi; Tyagi, Varun; Tikar, Sachin N; Sharma, Ajay K; Mendki, Murlidhar J; Jain, Ashok K; Sukumaran, Devanathan

    2014-01-01

    Background: Mosquitoes are well known as vectors of several disease causing pathogens. The extensive use of synthetic insecticides in the mosquito control strategies resulted to the development of pesticide resistance and fostered environmental deterioration. Hence in recent years plants become alternative source of mosquito control agents. The present study assessed the larvicidal and oviposition altering activity of six different plants species-Alstonia scholaris, Callistemon viminalis, Hyptis suaveolens, Malvastrum coromandelianum, Prosopis juliflora, Vernonia cinerea against Aedes albopictus mosquito in laboratory. Methods: Leaf extracts of all the six plants species in five different solvents of various polarities were used in the range of 20–400ppm for larval bioassay and 50,100 and 200ppm for cage bioassay (for the study of oviposition behavior) against Ae. albopictus. The larval mortality data were recorded after 24 h and subjected to Probit analysis to determine the lethal concentrations (LC50), while OAI (Oviposition activity index) was calculated for oviposition altering activity of the plant extracts. Results: Vernonia cinerea extract in acetone and C. viminalis extract in isopropanol were highly effective against Aedes albopictus larvae with LC50 value 64.57, 71.34ppm respectively. Acetone extract of P. juliflora found to be strong oviposition-deterrent which inhibited >2 fold egg laying (OAI-0.466) at 100ppm. Conclusion: Vernonia cinerea and C. viminallis leaf extracts have the potential to be used as larvicide and P. juliflora as an oviposition-deterrent for the control of Ae. albopictus mosquito. PMID:26114131

  1. Drug-Metabolizing Activity, Protein and Gene Expression of UDP-Glucuronosyltransferases Are Significantly Altered in Hepatocellular Carcinoma Patients

    PubMed Central

    Lu, Linlin; Zhou, Juan; Shi, Jian; Peng, Xiao-juan; Qi, Xiao-xiao; Wang, Ying; Li, Fang-yuan; Zhou, Fu-Yuan; Liu, Liang; Liu, Zhong-Qiu

    2015-01-01

    UDP-glucuronosyltransferases (UGTs), the most important enzymes in body detoxification and homeostasis maintaining, govern the glucuronidation reaction of various endogenous and environmental carcinogens. The metabolic function of UGTs can be severely influenced by hepatocellular carcinoma (HCC), the fifth prevalent and third malignant cancer worldwide. Particularly in China, HBV-positive HCC account for approximately 80% of HCC patients. But rare papers addressed the alteration on the metabolism of UGTs specific substrates, translational and transcriptional activity of UGTs in HBV-positive HCC patients. In present study, we choose the main UGT isoforms, UGT1As, UGT1A1, UGT1A9, UGT1A4 and UGT2B7, to determine the alterations of metabolic activity, protein and gene expression of UGTs in HBV-positive HCC. The corresponding specific substrates such as genistein, SN-38, tamoxifen, propofol and zidovudine were utilized respectively in UGTs metabolic activity determination. Furthermore, the plausible mechanism responsible for UGTs alterations was addressed by analyzing the protein and gene expressions in tumor and the adjacent normal tissues in HBV-positive HCC. The results revealed that in the tumor human liver microsomes (HLMs), either Vmax (maximum reaction rate, Rmax for UGT1A1) or the clearance rates (Vmax/Km, Clint) of UGT1A, UGT1A1, UGT1A4, UGT1A9 and UGT2B7 were significant lower than those of in the adjacent normal HLMs. Subsequently, the relative protein and gene expressions of these isoforms were notably decreased in most of tumor tissues comparing with the adjacent normal tissues. More interestingly, in tumor tissues, the metabolic activity reduction ratio of each UGT isoform was closely related to its protein reduction ratio, indicating that decreasing protein level would contribute to the reduced metabolic function of UGTs in HBV-positive HCC. In summary, our study firstly determined the alteration of UGT function in HBV-positive HCC patients, which would

  2. Drug-Metabolizing Activity, Protein and Gene Expression of UDP-Glucuronosyltransferases Are Significantly Altered in Hepatocellular Carcinoma Patients.

    PubMed

    Lu, Linlin; Zhou, Juan; Shi, Jian; Peng, Xiao-juan; Qi, Xiao-xiao; Wang, Ying; Li, Fang-Yuan; Zhou, Fu-Yuan; Liu, Liang; Liu, Zhong-Qiu

    2015-01-01

    UDP-glucuronosyltransferases (UGTs), the most important enzymes in body detoxification and homeostasis maintaining, govern the glucuronidation reaction of various endogenous and environmental carcinogens. The metabolic function of UGTs can be severely influenced by hepatocellular carcinoma (HCC), the fifth prevalent and third malignant cancer worldwide. Particularly in China, HBV-positive HCC account for approximately 80% of HCC patients. But rare papers addressed the alteration on the metabolism of UGTs specific substrates, translational and transcriptional activity of UGTs in HBV-positive HCC patients. In present study, we choose the main UGT isoforms, UGT1As, UGT1A1, UGT1A9, UGT1A4 and UGT2B7, to determine the alterations of metabolic activity, protein and gene expression of UGTs in HBV-positive HCC. The corresponding specific substrates such as genistein, SN-38, tamoxifen, propofol and zidovudine were utilized respectively in UGTs metabolic activity determination. Furthermore, the plausible mechanism responsible for UGTs alterations was addressed by analyzing the protein and gene expressions in tumor and the adjacent normal tissues in HBV-positive HCC. The results revealed that in the tumor human liver microsomes (HLMs), either V(max) (maximum reaction rate, R(max) for UGT1A1) or the clearance rates (V(max)/K(m), Clint) of UGT1A, UGT1A1, UGT1A4, UGT1A9 and UGT2B7 were significant lower than those of in the adjacent normal HLMs. Subsequently, the relative protein and gene expressions of these isoforms were notably decreased in most of tumor tissues comparing with the adjacent normal tissues. More interestingly, in tumor tissues, the metabolic activity reduction ratio of each UGT isoform was closely related to its protein reduction ratio, indicating that decreasing protein level would contribute to the reduced metabolic function of UGTs in HBV-positive HCC. In summary, our study firstly determined the alteration of UGT function in HBV-positive HCC patients, which

  3. Mutations associated with retinopathies alter mitogen-activated protein kinase-induced phosphorylation of neural retina leucine-zipper

    PubMed Central

    Kumar, Sandeep; Patel, Dharmesh; Richong, Sushmita; Oberoi, Pranav; Ghosh, Madhumita; Swaroop, Anand

    2007-01-01

    Purpose Neural retina leucine-zipper (NRL), a member of the basic motif leucine zipper family of transcription factors, is preferentially expressed in rod photoreceptors of the mammalian retina. Mutations in NRL are associated with retinopathies; many of these are suggested to change phosphorylation status and alter NRL-mediated transactivation of rhodopsin promoter. The purpose of this study was to identify potential kinases responsible for the phosphorylation of NRL and determine if such kinase-dependent phosphorylation is altered in disease-associated NRL mutations. Methods Metabolic labeling with 33P-orthophosphate was used to study phosphorylation of NRL in transfected COS-1 cells. NRL or NRL mutants were expressed as glutathione S-transferase (GST)-fusion proteins and used as substrate to screen various kinases by in vitro phosphorylation assays. CV-1 cells were co-transfected with rhodopsin promoter-reporter construct and expression plasmids, with or without specific mitogen-activated protein kinase (MAPK) inhibitors, to examine their effect on NRL-mediated transactivation. Expression of activated MAPKs in postnatal mice retina was determined by immunoblot analysis. Results Metabolic labeling of NRL produces multiple phosphorylated protein bands in transfected COS-1 cells. Fewer but more intense radiolabeled bands are observed for NRL-S50T, -S50A, and -P51L mutants compared to wild-type NRL. We show that MAPK2 and p38 induce specific phosphorylation of NRL, but this pattern is altered in NRL mutants. Immunoblot analysis of extracts from developing mouse retina reveals enhanced expression of activated MAPK2 at postnatal day 0-3, concordant with the reported phosphorylation pattern of NRL in vivo. Inhibition of MAPK signaling pathways decreases NRL and CRX -mediated synergistic activation of rhodopsin promoter in transfected CV-1 cells. Conclusions Our results suggest that multiple MAPKs can phosphorylate NRL and this phosphorylation pattern is altered by

  4. Alterations in Membrane Caveolae and BKCa Channel Activity in Skin Fibroblasts in Smith-Lemli-Opitz Syndrome

    PubMed Central

    Ren, Gongyi; Jacob, Robert F.; Kaulin, Yuri; DiMuzio, Paul; Xie, Yi; Mason, R. Preston; Tint, G. Stephen; Steiner, Robert D.; Roulett, Jean-Baptiste; Merkens, Louise; Whitaker-Mendez, Diana; Frank, Phillipe G.; Lisanti, Michael; Cox, Robert H.; Tulenko, Thomas N.

    2011-01-01

    The Smith-Lemli-Opitz syndrome (SLOS) is an inherited disorder of cholesterol synthesis caused by mutations in DHCR7 which encodes the final enzyme in the cholesterol synthesis pathway. The immediate precursor to cholesterol synthesis, 7-dehydrocholesterol (7-DHC) accumulates in the plasma and cells of SLOS patients which has led to the idea that the accumulation of abnormal sterols and/or reduction in cholesterol underlies the phenotypic abnormalities of SLOS. We tested the hypothesis that 7-DHC accumulates in membrane caveolae where it disturbs caveolar bilayer structure-function. Membrane caveolae from skin fibroblasts obtained from SLOS patients were isolated and found to accumulate 7-DHC. In caveolar-like model membranes containing 7-DHC, subtle, but complex alterations in intermolecular packing, lipid order and membrane width were observed. In addition, the BKCa K+ channel, which co-migrates with caveolin-1 in a membrane fraction enriched with cholesterol, was impaired in SLOS cells as reflected by reduced single channel conductance and a 50 mV rightward shift in the channel activation voltage. In addition, a marked decrease in BKCa protein but not mRNA expression levels were seen suggesting post-translational alterations. Accompanying these changes was a reduction in caveolin-1 protein and mRNA levels, but membrane caveolar structure was not altered. These results are consistent with the hypothesis that 7-DHC accumulation in the caveolar membrane results in defective caveolar signaling. However, additional cellular alterations beyond mere changes associated with abnormal sterols in the membrane likely contribute to the pathogenesis of SLOS. PMID:21724437

  5. Altered Spontaneous Brain Activity in Patients with Acute Spinal Cord Injury Revealed by Resting-State Functional MRI

    PubMed Central

    Zhu, Ling; Wu, Guangyao; Zhou, Xin; Li, Jielan; Wen, Zhi; Lin, Fuchun

    2015-01-01

    Background Previous neuroimaging studies have provided evidence of structural and functional reorganization of brain in patients with chronic spinal cord injury (SCI). However, it remains unknown whether the spontaneous brain activity changes in acute SCI. In this study, we investigated intrinsic brain activity in acute SCI patients using a regional homogeneity (ReHo) analysis based on resting-state functional magnetic resonance imaging. Methods A total of 15 patients with acute SCI and 16 healthy controls participated in the study. The ReHo value was used to evaluate spontaneous brain activity, and voxel-wise comparisons of ReHo were performed to identify brain regions with altered spontaneous brain activity between groups. We also assessed the associations between ReHo and the clinical scores in brain regions showing changed spontaneous brain activity. Results Compared with the controls, the acute SCI patients showed decreased ReHo in the bilateral primary motor cortex/primary somatosensory cortex, bilateral supplementary motor area/dorsal lateral prefrontal cortex, right inferior frontal gyrus, bilateral dorsal anterior cingulate cortex and bilateral caudate; and increased ReHo in bilateral precuneus, the left inferior parietal lobe, the left brainstem/hippocampus, the left cingulate motor area, bilateral insula, bilateral thalamus and bilateral cerebellum. The average ReHo values of the left thalamus and right insula were negatively correlated with the international standards for the neurological classification of spinal cord injury motor scores. Conclusion Our findings indicate that acute distant neuronal damage has an immediate impact on spontaneous brain activity. In acute SCI patients, the ReHo was prominently altered in brain regions involved in motor execution and cognitive control, default mode network, and which are associated with sensorimotor compensatory reorganization. Abnormal ReHo values in the left thalamus and right insula could serve as

  6. Overexpression of cerebral and hepatic cytochrome P450s alters behavioral activity of rat offspring following prenatal exposure to lindane

    SciTech Connect

    Johri, Ashu; Yadav, Sanjay; Dhawan, Alok; Parmar, Devendra

    2007-12-15

    Oral administration of different doses (0.0625, 0.125 or 0.25 mg/kg corresponding to 1/1400th, 1/700th or 1/350th of LD{sub 50}) of lindane to the pregnant Wistar rats from gestation days 5 to 21 were found to produce a dose-dependent increase in the activity of cytochrome P450 (CYP)-dependent 7-ethoxyresorufin-O-deethylase (EROD), 7-pentoxyresorufin-O-dealkylase (PROD) and N-nitrosodimethylamine demethylase (NDMA-d) in brain and liver of offspring postnatally at 3 weeks. The increase in the activity of CYP monooxygenases was found to be associated with the increase in the mRNA and protein expression of xenobiotic metabolizing CYP1A, 2B and 2E1 isoenzymes in the brain and liver of offspring. Dose-dependent alterations in the parameters of spontaneous locomotor activity in the offspring postnatally at 3 weeks have suggested that increase in CYP activity may possibly lead to the formation of metabolites to the levels that may be sufficient to alter the behavioral activity of the offspring. Interestingly, the inductive effect on cerebral and hepatic CYPs was found to persist postnatally up to 6 weeks in the offspring at the relatively higher doses (0.125 and 0.25 mg/kg) of lindane and up to 9 weeks at the highest dose (0.25 mg/kg), though the magnitude of induction was less than that observed at 3 weeks. Alterations in the parameters of spontaneous locomotor activity in the offspring postnatally at 6 and 9 weeks, though significant only in the offspring at 3 and 6-week of age, have further indicated that due to the reduced activity of the CYPs during the ontogeny, lindane and its metabolites may not be effectively cleared from the brain. The data suggest that low dose prenatal exposure to the pesticide has the potential to produce overexpression of xenobiotic metabolizing CYPs in brain and liver of the offspring which may account for the behavioral changes observed in the offspring.

  7. Determining the Effects of Using Different Writing Activities on the Academic Achievements Secondary School 7th Grade Students and Their Attitudes Towards the Course

    ERIC Educational Resources Information Center

    Uzoglu, Mustafa

    2014-01-01

    The purpose of the study is to determine the effects of using writing activities with different learning purposes by the secondary school 7th grade students on their academic achievement and attitudes towards the course. The study was carried out in a secondary school located in the centre of Erzurum in 2012-2013 academic year; the study is a…

  8. Masked Priming Effects in Aphasia: Evidence of Altered Automatic Spreading Activation

    ERIC Educational Resources Information Center

    Silkes, JoAnn P.; Rogers, Margaret A.

    2012-01-01

    Purpose: Previous research has suggested that impairments of automatic spreading activation may underlie some aphasic language deficits. The current study further investigated the status of automatic spreading activation in individuals with aphasia as compared with typical adults. Method: Participants were 21 individuals with aphasia (12 fluent, 9…

  9. Binding among Select Episodic Elements Is Altered via Active Short-Term Retrieval

    ERIC Educational Resources Information Center

    Bridge, Donna J.; Voss, Joel L.

    2015-01-01

    Of the many elements that comprise an episode, are any disproportionately bound to the others? We tested whether active short-term retrieval selectively increases binding. Individual objects from multiobject displays were retrieved after brief delays. Memory was later tested for the other objects. Cueing with actively retrieved objects facilitated…

  10. Structure-Based Alteration of Substrate Specificity and Catalytic Activity of Sulfite Oxidase from Sulfite Oxidation to Nitrate Reduction

    SciTech Connect

    Qiu, James A.; Wilson, Heather L.; Rajagopalan, K.V.

    2012-04-18

    Eukaryotic sulfite oxidase is a dimeric protein that contains the molybdenum cofactor and catalyzes the metabolically essential conversion of sulfite to sulfate as the terminal step in the metabolism of cysteine and methionine. Nitrate reductase is an evolutionarily related molybdoprotein in lower organisms that is essential for growth on nitrate. In this study, we describe human and chicken sulfite oxidase variants in which the active site has been modified to alter substrate specificity and activity from sulfite oxidation to nitrate reduction. On the basis of sequence alignments and the known crystal structure of chicken sulfite oxidase, two residues are conserved in nitrate reductases that align with residues in the active site of sulfite oxidase. On the basis of the crystal structure of yeast nitrate reductase, both positions were mutated in human sulfite oxidase and chicken sulfite oxidase. The resulting double-mutant variants demonstrated a marked decrease in sulfite oxidase activity but gained nitrate reductase activity. An additional methionine residue in the active site was proposed to be important in nitrate catalysis, and therefore, the triple variant was also produced. The nitrate reducing ability of the human sulfite oxidase triple mutant was nearly 3-fold greater than that of the double mutant. To obtain detailed structural data for the active site of these variants, we introduced the analogous mutations into chicken sulfite oxidase to perform crystallographic analysis. The crystal structures of the Mo domains of the double and triple mutants were determined to 2.4 and 2.1 {angstrom} resolution, respectively.

  11. Using an active primary surface to correct for low-order manufacturing errors in secondary mirrors of large reflector antennas

    NASA Astrophysics Data System (ADS)

    Cortes-Medellin, German; Lovell, Amy J.; Enriquez, Rogerio; Smith, David R.

    2004-09-01

    In the fabrication of high-performance, low-cost secondary reflectors for radio telescopes, it is a significant challenge to avoid introduction of low-order surface errors such as astigmatism or coma. This arises primarily because low-order surface errors are easily induced by support structure placement or simple thermal variations in the manufacturing process. It is, of course, possible to bring these errors to within the required tolerance, but if an active primary reflector is present, it may be possible to relax the requirements on the secondary and perhaps lower its cost. In this paper, we take the Large Millimeter-wave Telescope (LMT/GTM) as an example system. We model the effects of correcting a deformed sub-reflector by using the existing segmented active primary. The sub-reflector deformation patterns employed are low-order (e.g., astigmatism or coma), but are allowed significant excursions from the nominal surface figure. For each case, we demonstrate the best theoretical performance, using the active primary to correct for the errors. Additionally, to determine whether such an approach would be practical, we also demonstrate the likely performance improvement that could be achieved using brief measurements on an astronomical source. In this approach, we introduce varying amounts of known low-order deformation patterns into the active primary and seek the combination that results in the maximum signal. Finally, we compare this result to the theoretical maximum and make recommendations on the practical utility of the approach.

  12. Reduced photoinhibition under low irradiance enhanced Kacip Fatimah (Labisia pumila Benth) secondary metabolites, phenyl alanine lyase and antioxidant activity.

    PubMed

    Ibrahim, Mohd Hafiz; Jaafar, Hawa Z E

    2012-01-01

    A randomized complete block design experiment was designed to characterize the relationship between production of total flavonoids and phenolics, anthocyanin, photosynthesis, maximum efficiency of photosystem II (Fv/Fm), electron transfer rate (Fm/Fo), phenyl alanine lyase activity (PAL) and antioxidant (DPPH) in Labisia pumila var. alata, under four levels of irradiance (225, 500, 625 and 900 μmol/m(2)/s) for 16 weeks. As irradiance levels increased from 225 to 900 μmol/m(2)/s, the production of plant secondary metabolites (total flavonoids, phenolics and antocyanin) was found to decrease steadily. Production of total flavonoids and phenolics reached their peaks under 225 followed by 500, 625 and 900 μmol/m(2)/s irradiances. Significant positive correlation of production of total phenolics, flavonoids and antocyanin content with Fv/Fm, Fm/Fo and photosynthesis indicated up-regulation of carbon-based secondary metabolites (CBSM) under reduced photoinhibition on the under low light levels condition. At the lowest irradiance levels, Labisia pumila extracts also exhibited a significantly higher antioxidant activity (DPPH) than under high irradiance. The improved antioxidative activity under low light levels might be due to high availability of total flavonoids, phenolics and anthocyanin content in the plant extract. It was also found that an increase in the production of CBSM was due to high PAL activity under low light, probably signifying more availability of phenylalanine (Phe) under this condition. PMID:22754297

  13. Neuropilin-1 expression characterizes T follicular helper (Tfh) cells activated during B cell differentiation in human secondary lymphoid organs.

    PubMed

    Renand, Amédée; Milpied, Pierre; Rossignol, Julien; Bruneau, Julie; Lemonnier, François; Dussiot, Michael; Coulon, Séverine; Hermine, Olivier

    2013-01-01

    T follicular helper (Tfh) cells play an essential role in the development of antigen-specific B cell immunity. Tfh cells regulate the differentiation and survival of activated B cells outside and inside germinal centers (GC) of secondary lymphoid organs. They act through cognate contacts with antigen-presenting B cells, but there is no current marker to specifically identify those Tfh cells which productively interact with B cells. Here we show that neuropilin 1 (Nrp1), a cell surface receptor, is selectively expressed by a subset of Tfh cells in human secondary lymphoid organs. Nrp1 expression on Tfh cells correlates with B cell differentiation in vivo and in vitro, is transient, and can be induced upon co-culture with autologous memory B cells in a cell contact-dependent manner. Comparative analysis of ex vivo Nrp1(+) and Nrp1(-) Tfh cells reveals gene expression modulation during activation. Finally, Nrp1 is expressed by malignant Tfh-like cells in a severe case of angioimmunoblastic T-cell lymphoma (AITL) associated with elevated terminal B cell differentiation. Thus, Nrp1 is a specific marker of Tfh cells cognate activation in humans, which may prove useful as a prognostic factor and a therapeutic target in neoplastic diseases associated with Tfh cells activity. PMID:24386482

  14. Reduced Photoinhibition under Low Irradiance Enhanced Kacip Fatimah (Labisia pumila Benth) Secondary Metabolites, Phenyl Alanine Lyase and Antioxidant Activity

    PubMed Central

    Ibrahim, Mohd Hafiz; Jaafar, Hawa Z.E.

    2012-01-01

    A randomized complete block design experiment was designed to characterize the relationship between production of total flavonoids and phenolics, anthocyanin, photosynthesis, maximum efficiency of photosystem II (Fv/Fm), electron transfer rate (Fm/Fo), phenyl alanine lyase activity (PAL) and antioxidant (DPPH) in Labisia pumila var. alata, under four levels of irradiance (225, 500, 625 and 900 μmol/m2/s) for 16 weeks. As irradiance levels increased from 225 to 900 μmol/m2/s, the production of plant secondary metabolites (total flavonoids, phenolics and antocyanin) was found to decrease steadily. Production of total flavonoids and phenolics reached their peaks under 225 followed by 500, 625 and 900 μmol/m2/s irradiances. Significant positive correlation of production of total phenolics, flavonoids and antocyanin content with Fv/Fm, Fm/Fo and photosynthesis indicated up-regulation of carbon-based secondary metabolites (CBSM) under reduced photoinhibition on the under low light levels condition. At the lowest irradiance levels, Labisia pumila extracts also exhibited a significantly higher antioxidant activity (DPPH) than under high irradiance. The improved antioxidative activity under low light levels might be due to high availability of total flavonoids, phenolics and anthocyanin content in the plant extract. It was also found that an increase in the production of CBSM was due to high PAL activity under low light, probably signifying more availability of phenylalanine (Phe) under this condition. PMID:22754297

  15. Negative stereotype activation alters interaction between neural correlates of arousal, inhibition and cognitive control.

    PubMed

    Forbes, Chad E; Cox, Christine L; Schmader, Toni; Ryan, Lee

    2012-10-01

    Priming negative stereotypes of African Americans can bias perceptions toward novel Black targets, but less is known about how these perceptions ultimately arise. Examining how neural regions involved in arousal, inhibition and control covary when negative stereotypes are activated can provide insight into whether individuals attempt to downregulate biases. Using fMRI, White egalitarian-motivated participants were shown Black and White faces at fast (32 ms) or slow (525 ms) presentation speeds. To create a racially negative stereotypic context, participants listened to violent and misogynistic rap (VMR) in the background. No music (NM) and death metal (DM) were used as control conditions in separate blocks. Fast exposure of Black faces elicited amygdala activation in the NM and VMR conditions (but not DM), that also negatively covaried with activation in prefrontal regions. Only in VMR, however, did amygdala activation for Black faces persist during slow exposure and positively covary with activation in dorsolateral prefrontal cortex while negatively covarying with activation in orbitofrontal cortex. Findings suggest that contexts that prime negative racial stereotypes seem to hinder the downregulation of amygdala activation that typically occurs when egalitarian perceivers are exposed to Black faces. PMID:21954239

  16. Negative stereotype activation alters interaction between neural correlates of arousal, inhibition and cognitive control

    PubMed Central

    Cox, Christine L.; Schmader, Toni; Ryan, Lee

    2012-01-01

    Priming negative stereotypes of African Americans can bias perceptions toward novel Black targets, but less is known about how these perceptions ultimately arise. Examining how neural regions involved in arousal, inhibition and control covary when negative stereotypes are activated can provide insight into whether individuals attempt to downregulate biases. Using fMRI, White egalitarian-motivated participants were shown Black and White faces at fast (32 ms) or slow (525 ms) presentation speeds. To create a racially negative stereotypic context, participants listened to violent and misogynistic rap (VMR) in the background. No music (NM) and death metal (DM) were used as control conditions in separate blocks. Fast exposure of Black faces elicited amygdala activation in the NM and VMR conditions (but not DM), that also negatively covaried with activation in prefrontal regions. Only in VMR, however, did amygdala activation for Black faces persist during slow exposure and positively covary with activation in dorsolateral prefrontal cortex while negatively covarying with activation in orbitofrontal cortex. Findings suggest that contexts that prime negative racial stereotypes seem to hinder the downregulation of amygdala activation that typically occurs when egalitarian perceivers are exposed to Black faces. PMID:21954239

  17. Low-dose photon irradiation alters cell differentiation via activation of hIK channels.

    PubMed

    Roth, Bastian; Gibhardt, Christine S; Becker, Patrick; Gebhardt, Manuela; Knoop, Jan; Fournier, Claudia; Moroni, Anna; Thiel, Gerhard

    2015-08-01

    To understand the impact of ionizing irradiation from diagnostics and radiotherapy on cells, we examined K(+) channel activity before and immediately after exposing cells to X-rays. Already, low dose in the cGy range caused in adenocarcinoma A549 cells within minutes a hyperpolarization following activation of the human intermediate-conductance Ca(2+)-activated K(+) channel (hIK). The response was specific for cells, which functionally expressed hIK channels and in which hIK activity was low before irradiation. HEK293 cells, which do not respond to X-ray irradiation, accordingly develop a sensitivity to this stress after heterologous expression of hIK channels. The data suggest that hIK activation involves a Ca(2+)-mediated signaling cascade because channel activation is suppressed by a strong cytosolic Ca(2+) buffer. The finding that an elevation of H2O2 causes an increase in the concentration of cytosolic Ca(2+) suggests that radicals, which emerge early in response to irradiation, trigger this Ca(2+) signaling cascade. Inhibition of hIK channels by specific blockers clotrimazole and TRAM-34 slowed cell proliferation and migration in "wound" scratch assays; ionizing irradiation, in turn, stimulated the latter process presumably via its activation of the hIK channels. These data stress an indirect radiosensitivity of hIK channels with an impact on cell differentiation. PMID:25277267

  18. Alterations in leukocyte transcriptional control pathway activity associated with major depressive disorder and antidepressant treatment.

    PubMed

    Mellon, S H; Wolkowitz, O M; Schonemann, M D; Epel, E S; Rosser, R; Burke, H B; Mahan, L; Reus, V I; Stamatiou, D; Liew, C-C; Cole, S W

    2016-01-01

    Major depressive disorder (MDD) is associated with a significantly elevated risk of developing serious medical illnesses such as cardiovascular disease, immune impairments, infection, dementia and premature death. Previous work has demonstrated immune dysregulation in subjects with MDD. Using genome-wide transcriptional profiling and promoter-based bioinformatic strategies, we assessed leukocyte transcription factor (TF) activity in leukocytes from 20 unmedicated MDD subjects versus 20 age-, sex- and ethnicity-matched healthy controls, before initiation of antidepressant therapy, and in 17 of the MDD subjects after 8 weeks of sertraline treatment. In leukocytes from unmedicated MDD subjects, bioinformatic analysis of transcription control pathway activity indicated an increased transcriptional activity of cAMP response element-binding/activating TF (CREB/ATF) and increased activity of TFs associated with cellular responses to oxidative stress (nuclear factor erythroid-derived 2-like 2, NFE2l2 or NRF2). Eight weeks of antidepressant therapy was associated with significant reductions in Hamilton Depression Rating Scale scores and reduced activity of NRF2, but not in CREB/ATF activity. Several other transcriptional regulation pathways, including the glucocorticoid receptor (GR), nuclear factor kappa-B cells (NF-κB), early growth response proteins 1-4 (EGR1-4) and interferon-responsive TFs, showed either no significant differences as a function of disease or treatment, or activities that were opposite to those previously hypothesized to be involved in the etiology of MDD or effective treatment. Our results suggest that CREB/ATF and NRF2 signaling may contribute to MDD by activating immune cell transcriptome dynamics that ultimately influence central nervous system (CNS) motivational and affective processes via circulating mediators. PMID:27219347

  19. Chemical activation of caudal medullary expiratory neurones alters the pattern of breathing in the cat.

    PubMed

    Bongianni, F; Corda, M; Fontana, G A; Pantaleo, T

    1994-02-01

    1. The purpose of this work was to ascertain whether the activation of caudal expiratory neurones located in the caudal part of the ventral respiratory group (VRG) may affect the pattern of breathing via medullary axon collaterals. 2. We used microinjections of DL-homocysteic acid (DLH) to activate this population of neurones in pentobarbitone-anaesthetized, vagotomized, paralysed and artificially ventilated cats. Both phrenic and abdominal nerve activities were monitored; extracellular recordings from medullary and upper cervical cord respiratory neurones were performed. 3. DLH (160 mM) microinjected (10-30 nl for a total of 1.6-4.8 nmol) into the caudal VRG, into sites where expiratory activity was encountered, provoked an intense and sustained activation of the expiratory motor output associated with a corresponding period of silence in phrenic nerve activity. During the progressive decline of the activation of abdominal motoneurones, rhythmic inspiratory activity resumed, displaying a decrease in frequency and a marked reduction or the complete suppression of postinspiratory activity as its most consistent features. 4. Medullary and upper cervical cord inspiratory neurones exhibited inhibitory responses consistent with those observed in phrenic nerve activity, while expiratory neurones in the caudal VRG on the side contralateral to the injection showed excitation patterns similar to those of abdominal motoneurones. On the other hand, in correspondence to expiratory motor output activation, expiratory neurones of the Bötzinger complex displayed tonic discharges whose intensity was markedly lower than the peak level of control breaths. 5. Bilateral lignocaine blockades of neural transmission at C2-C3 affecting the expiratory and, to a varying extent, the inspiratory bulbospinal pathways as well as spinal cord transections at C2-C3 or C1-C2, did not suppress the inhibitory effect on inspiratory neurones of either the ipsi- or contralateral VRG in response to DLH

  20. Reactive oxygen species in the tumor niche triggers altered activation of macrophages and immunosuppression: Role of fluoxetine.

    PubMed

    Ghosh, Sayan; Mukherjee, Sudeshna; Choudhury, Sreetama; Gupta, Payal; Adhikary, Arghya; Baral, Rathindranath; Chattopadhyay, Sreya

    2015-07-01

    Macrophages are projected as one of the key players responsible for the progression of cancer. Classically activated (M1) macrophages are pro-inflammatory and have a central role in host defense, while alternatively activated (M2) macrophages are associated with immunosuppression. Macrophages residing at the site of neoplastic growth are alternately activated and are referred to as tumor-associated macrophages (TAMs). These "cooperate" with tumor tissue, promoting increased proliferation and immune escape. Selective serotonin reuptake inhibitors like fluoxetine have recently been reported to possess anti-inflammatory activity. We used fluoxetine to target tumor-associated inflammation and consequent alternate polarization of macrophages. We established that murine peritoneal macrophages progressed towards an altered activation state when exposed to cell-free tumor fluid, as evidenced by increased IL-6, IL-4 and IL-10 levels. These polarized macrophages showed significant pro-oxidant bias and increased p65 nuclear localization. It was further observed that these altered macrophages could induce oxidative insult and apoptosis in cultured mouse CD3(+) T cells. To validate these findings, we replicated key experiments in vivo, and observed that there was increased serum IL-6, IL-4 and IL-10 in tumor-bearing animals, with increased % CD206(+) cells within the tumor niche. TAMs showed increased nuclear localization of p65 with decreased Nrf2 expression in the nucleus. These results were associated with increase in apoptosis of CD3(+) T cells co-cultured with TAM-spent media. We could establish that fluoxetine treatment could specifically re-educate the macrophages both in vitro and in vivo by skewing their phenotype such that immune suppression mediated by tumor-dictated macrophages was successfully mitigated. PMID:25819340

  1. Widespread alterations in the synaptic proteome of the adolescent cerebral cortex following prenatal immune activation in rats.

    PubMed

    Györffy, Balázs A; Gulyássy, Péter; Gellén, Barbara; Völgyi, Katalin; Madarasi, Dóra; Kis, Viktor; Ozohanics, Olivér; Papp, Ildikó; Kovács, Péter; Lubec, Gert; Dobolyi, Árpád; Kardos, József; Drahos, László; Juhász, Gábor; Kékesi, Katalin A

    2016-08-01

    An increasing number of studies have revealed associations between pre- and perinatal immune activation and the development of schizophrenia and autism spectrum disorders (ASDs). Accordingly, neuroimmune crosstalk has a considerably large impact on brain development during early ontogenesis. While a plethora of heterogeneous abnormalities have already been described in established maternal immune activation (MIA) rodent and primate animal models, which highly correlate to those found in human diseases, the underlying molecular background remains obscure. In the current study, we describe the long-term effects of MIA on the neocortical pre- and postsynaptic proteome of adolescent rat offspring in detail. Molecular differences were revealed in sub-synaptic fractions, which were first thoroughly characterized using independent methods. The widespread proteomic examination of cortical samples from offspring exposed to maternal lipopolysaccharide administration at embryonic day 13.5 was conducted via combinations of different gel-based proteomic techniques and tandem mass spectrometry. Our experimentally validated proteomic data revealed more pre- than postsynaptic protein level changes in the offspring. The results propose the relevance of altered synaptic vesicle recycling, cytoskeletal structure and energy metabolism in the presynaptic region in addition to alterations in vesicle trafficking, the cytoskeleton and signal transduction in the postsynaptic compartment in MIA offspring. Differing levels of the prominent signaling regulator molecule calcium/calmodulin-dependent protein kinase II in the postsynapse was validated and identified specifically in the prefrontal cortex. Finally, several potential common molecular regulators of these altered proteins, which are already known to be implicated in schizophrenia and ASD, were identified and assessed. In summary, unexpectedly widespread changes in the synaptic molecular machinery in MIA rats were demonstrated which

  2. Zebrafish locomotor capacity and brain acetylcholinesterase activity is altered by Aphanizomenon flos-aquae DC-1 aphantoxins.

    PubMed

    Zhang, De Lu; Hu, Chun Xiang; Li, Dun Hai; Liu, Yong Ding

    2013-08-15

    Aphanizomenon flos-aquae (A. flos-aquae) is a source of neurotoxins known as aphantoxins or paralytic shellfish poisons (PSPs) that present a major threat to the environment and to human health. Generally, altered neurological function is reflected in behavior. Although the molecular mechanism of action of PSPs is well known, its neurobehavioral effects on adult zebrafish and its relationship with altered neurological functions are poorly understood. Aphantoxins purified from a natural isolate of A. flos-aquae DC-1 were analyzed by HPLC. The major analogs found in the toxins were the gonyautoxins 1 and 5 (GTX1 and GTX5; 34.04% and 21.28%, respectively) and the neosaxitoxin (neoSTX, 12.77%). Zebrafish (Danio rerio) were intraperitoneally injected with 5.3 and 7.61 μg STXeq/kg (low and high dose, respectively) of A. flos-aquae DC-1 aphantoxins. The swimming activity was investigated by observation combined with video at 6 timepoints from 1 to 24 h post-exposure. Both aphantoxin doses were associated with delayed touch responses, reduced head-tail locomotory abilities, inflexible turning of head, and a tailward-shifted center of gravity. The normal S-pattern (or undulating) locomotor trajectory was replaced by a mechanical motor pattern of swinging the head after wagging the tail. Finally, these fish principally distributed at the top and/or bottom water of the aquarium, and showed a clear polarized distribution pattern at 12 h post-exposure. Further analysis of neurological function demonstrated that both aphantoxin doses inhibited brain acetylcholinesterase activity. All these changes were dose- and time-dependent. These results demonstrate that aphantoxins can alter locomotor capacity, touch responses and distribution patterns by damaging the cholinergic system of zebrafish, and suggest that zebrafish locomotor behavior and acetylcholinesterase can be used as indicators for investigating aphantoxins and blooms in nature. PMID:23792258

  3. Transient alterations in neuronal and behavioral activity following bensultap and fipronil treatment in rats.

    PubMed

    Szegedi, Viktor; Bárdos, György; Détári, László; Tóth, Attila; Banczerowski-Pelyhe, Ilona; Világi, Ildikó

    2005-10-15

    In the present multilevel study, neuromodulatory effect of two insecticides, bensultap and fipronil were investigated in rats. Although the new generation of insecticides shows greater affinity to invertebrate as compared to mammalian receptors, toxic effect of these compounds in vertebrates cannot be excluded. The aim of the study was to follow the course of neuronal changes in rats for 1 week after a high-dose insecticide exposure. Alterations in synaptic excitability, in sleep-wake pattern and in behavior were analyzed using conventional in vitro brain slice method, long-lasting EEG recordings, and open-field tests. The two chemicals examined in this study induced only weak and transient effects. Bensultap, acting on nicotinic acetylcholine receptors, caused a transient decrease in neuronal excitability. Sleep and behavioral changes demonstrated a similar time course. Fipronil, on the other hand, increased excitability and its effect lasted slightly longer. All effects were greatest on the first day following 'poisoning', and measured variables usually returned to normal within a week. These results suggest that the studied compounds do have some effects on the mammalian nervous system, but this effect is usually mild and temporary. PMID:16009481

  4. Altered Spontaneous Brain Activity in Cortical and Subcortical Regions in Parkinson's Disease

    PubMed Central

    Xiang, Jie; Jia, Xiuqin; Li, Huizhuo; Qin, Jiawei; Li, Kuncheng

    2016-01-01

    Purpose. The present study aimed to explore the changes of amplitude of low-frequency fluctuations (ALFF) at rest in patients with Parkinson's disease (PD). Methods. Twenty-four PD patients and 22 healthy age-matched controls participated in the study. ALFF was measured on the whole brain of all participants. A two-sample t-test was then performed to detect the group differences with age, gender, education level, head motion, and gray matter volume as covariates. Results. It was showed that PD patients had significantly decreased ALFF in the left thalamus/caudate and right insula/inferior prefrontal gyrus, whereas they had increased ALFF in the right medial prefrontal cortex (BA 8/6) and dorsolateral prefrontal cortex (BA 9/10). Conclusions. Our results indicated that significant alterations of ALFF in the subcortical regions and prefrontal cortex have been detected in PD patients, independent of age, gender, education, head motion, and structural atrophy. The current findings further provide insights into the biological mechanism of the disease. PMID:27413576

  5. Altered Spontaneous Brain Activity in Cortical and Subcortical Regions in Parkinson's Disease.

    PubMed

    Xiang, Jie; Jia, Xiuqin; Li, Huizhuo; Qin, Jiawei; Liang, Peipeng; Li, Kuncheng

    2016-01-01

    Purpose. The present study aimed to explore the changes of amplitude of low-frequency fluctuations (ALFF) at rest in patients with Parkinson's disease (PD). Methods. Twenty-four PD patients and 22 healthy age-matched controls participated in the study. ALFF was measured on the whole brain of all participants. A two-sample t-test was then performed to detect the group differences with age, gender, education level, head motion, and gray matter volume as covariates. Results. It was showed that PD patients had significantly decreased ALFF in the left thalamus/caudate and right insula/inferior prefrontal gyrus, whereas they had increased ALFF in the right medial prefrontal cortex (BA 8/6) and dorsolateral prefrontal cortex (BA 9/10). Conclusions. Our results indicated that significant alterations of ALFF in the subcortical regions and prefrontal cortex have been detected in PD patients, independent of age, gender, education, head motion, and structural atrophy. The current findings further provide insights into the biological mechanism of the disease. PMID:27413576

  6. Tamoxifen inhibits BK channels in chick cochlea without alterations in voltage-dependent activation.

    PubMed

    Tong, Mingjie; Duncan, R Keith

    2009-07-01

    Large-conductance, Ca(2+)-activated, and voltage-gated potassium channels (BK, BK(Ca), or Maxi-K) play an important role in electrical tuning in nonmammalian vertebrate hair cells. Systematic changes in tuning frequency along the tonotopic axis largely result from variations in BK channel kinetics, but the molecular changes underpinning these functional variations remain unknown. Auxiliary beta(1) have been implicated in low-frequency tuning at the cochlear apex because these subunits dramatically slow channel kinetics. Tamoxifen (Tx), a (xeno)estrogen compound known to activate BK channels through the beta-subunit, was used to test for the functional presence of beta(1). The hypotheses were that Tx would activate the majority of BK channels in hair cells from the cochlear apex due to the presence of beta(1) and that the level of activation would exhibit a tonotopic gradient following the expression profile of beta(1). Outside-out patches of BK channels were excised from tall hair cells along the apical half of the chicken basilar papilla. In low-density patches, single-channel conductance was reduced and the averaged open probability was unaffected by Tx. In high-density patches, the amplitude of ensemble-averaged BK current was inhibited, whereas half-activation potential and activation kinetics were unaffected by Tx. In both cases, no tonotopic Tx-dependent activation of channel activity was observed. Therefore, contrary to the hypotheses, electrophysiological assessment suggests that molecular mechanisms other than auxiliary beta-subunits are involved in generating a tonotopic distribution of BK channel kinetics and electric tuning in chick basilar papilla. PMID:19439526

  7. Alteration of natural (37)Ar activity concentration in the subsurface by gas transport and water infiltration.

    PubMed

    Guillon, Sophie; Sun, Yunwei; Purtschert, Roland; Raghoo, Lauren; Pili, Eric; Carrigan, Charles R

    2016-05-01

    High (37)Ar activity concentration in soil gas is proposed as a key evidence for the detection of underground nuclear explosion by the Comprehensive Nuclear Test-Ban Treaty. However, such a detection is challenged by the natural background of (37)Ar in the subsurface, mainly due to Ca activation by cosmic rays. A better understanding and improved capability to predict (37)Ar activity concentration in the subsurface and its spatial and temporal variability is thus required. A numerical model integrating (37)Ar production and transport in the subsurface is developed, including variable soil water content and water infiltration at the surface. A parameterized equation for (37)Ar production in the first 15 m below the surface is studied, taking into account the major production reactions and the moderation effect of soil water content. Using sensitivity analysis and uncertainty quantification, a realistic and comprehensive probability distribution of natural (37)Ar activity concentrations in soil gas is proposed, including the effects of water infiltration. Site location and soil composition are identified as the parameters allowing for a most effective reduction of the possible range of (37)Ar activity concentrations. The influence of soil water content on (37)Ar production is shown to be negligible to first order, while (37)Ar activity concentration in soil gas and its temporal variability appear to be strongly influenced by transient water infiltration events. These results will be used as a basis for practical CTBTO concepts of operation during an OSI. PMID:26939033

  8. Alterations in brain activation during cognitive empathy are related to social functioning in schizophrenia.

    PubMed

    Smith, Matthew J; Schroeder, Matthew P; Abram, Samantha V; Goldman, Morris B; Parrish, Todd B; Wang, Xue; Derntl, Birgit; Habel, Ute; Decety, Jean; Reilly, James L; Csernansky, John G; Breiter, Hans C

    2015-01-01

    Impaired cognitive empathy (ie, understanding the emotional experiences of others) is associated with poor social functioning in schizophrenia. However, it is unclear whether the neural activity underlying cognitive empathy relates to social functioning. This study examined the neural activation supporting cognitive empathy performance and whether empathy-related activation during correctly performed trials was associated with self-reported cognitive empathy and measures of social functioning. Thirty schizophrenia outpatients and 24 controls completed a cognitive empathy paradigm during functional magnetic resonance imaging. Neural activity corresponding to correct judgments about the expected emotional expression in a social interaction was compared in schizophrenia subjects relative to control subjects. Participants also completed a self-report measure of empathy and 2 social functioning measures (social competence and social attainment). Schizophrenia subjects demonstrated significantly lower accuracy in task performance and were characterized by hypoactivation in empathy-related frontal, temporal, and parietal regions as well as hyperactivation in occipital regions compared with control subjects during accurate cognitive empathy trials. A cluster with peak activation in the supplementary motor area (SMA) extending to the anterior midcingulate cortex (aMCC) correlated with social competence and social attainment in schizophrenia subjects but not controls. These results suggest that neural correlates of cognitive empathy may be promising targets for interventions aiming to improve social functioning and that brain activation in the SMA/aMCC region could be used as a biomarker for monitoring treatment response. PMID:24583906

  9. Altered anterior insula activation during anticipation and experience of painful stimuli in expert meditators

    PubMed Central

    Lutz, Antoine; McFarlin, Daniel R.; Perlman, David M.; Salomons, Tim V.; Davidson, Richard J.

    2013-01-01

    Experientially opening oneself to pain rather than avoiding it is said to reduce the mind’s tendency toward avoidance or anxiety which can further exacerbate the experience of pain. This is a central feature of mindfulness-based therapies. Little is known about the neural mechanisms of mindfulness on pain. During a meditation practice similar to mindfulness, functional magnetic resonance imaging was used in expert meditators (> 10,000 h of practice) to dissociate neural activation patterns associated with pain, its anticipation, and habituation. Compared to novices, expert meditators reported equal pain intensity, but less unpleasantness. This difference was associated with enhanced activity in the dorsal anterior insula (aI), and the anterior mid-cingulate (aMCC) the so-called ‘salience network’, for experts during pain. This enhanced activity during pain was associated with reduced baseline activity before pain in these regions and the amygdala for experts only. The reduced baseline activation in left aI correlated with lifetime meditation experience. This pattern of low baseline activity coupled with high response in aIns and aMCC was associated with enhanced neural habituation in amygdala and pain-related regions before painful stimulation and in the pain-related regions during painful stimulation. These findings suggest that cultivating experiential openness down-regulates anticipatory representation of aversive events, and increases the recruitment of attentional resources during pain, which is associated with faster neural habituation. PMID:23000783

  10. Alterations in Brain Activation During Cognitive Empathy Are Related to Social Functioning in Schizophrenia

    PubMed Central

    Smith, Matthew J.; Schroeder, Matthew P.; Abram, Samantha V.; Goldman, Morris B.; Parrish, Todd B.; Wang, Xue; Derntl, Birgit; Habel, Ute; Decety, Jean; Reilly, James L.; Csernansky, John G.; Breiter, Hans C.

    2015-01-01

    Impaired cognitive empathy (ie, understanding the emotional experiences of others) is associated with poor social functioning in schizophrenia. However, it is unclear whether the neural activity underlying cognitive empathy relates to social functioning. This study examined the neural activation supporting cognitive empathy performance and whether empathy-related activation during correctly performed trials was associated with self-reported cognitive empathy and measures of social functioning. Thirty schizophrenia outpatients and 24 controls completed a cognitive empathy paradigm during functional magnetic resonance imaging. Neural activity corresponding to correct judgments about the expected emotional expression in a social interaction was compared in schizophrenia subjects relative to control subjects. Participants also completed a self-report measure of empathy and 2 social functioning measures (social competence and social attainment). Schizophrenia subjects demonstrated significantly lower accuracy in task performance and were characterized by hypoactivation in empathy-related frontal, temporal, and parietal regions as well as hyperactivation in occipital regions compared with control subjects during accurate cognitive empathy trials. A cluster with peak activation in the supplementary motor area (SMA) extending to the anterior midcingulate cortex (aMCC) correlated with social competence and social attainment in schizophrenia subjects but not controls. These results suggest that neural correlates of cognitive empathy may be promising targets for interventions aiming to improve social functioning and that brain activation in the SMA/aMCC region could be used as a biomarker for monitoring treatment response. PMID:24583906

  11. An altered intestinal mucosal microbiome in HIV-1 infection is associated with mucosal and systemic immune activation and endotoxemia.

    PubMed

    Dillon, S M; Lee, E J; Kotter, C V; Austin, G L; Dong, Z; Hecht, D K; Gianella, S; Siewe, B; Smith, D M; Landay, A L; Robertson, C E; Frank, D N; Wilson, C C

    2014-07-01

    Human immunodeficiency virus-1 (HIV-1) infection disrupts the intestinal immune system, leading to microbial translocation and systemic immune activation. We investigated the impact of HIV-1 infection on the intestinal microbiome and its association with mucosal T-cell and dendritic cell (DC) frequency and activation, as well as with levels of systemic T-cell activation, inflammation, and microbial translocation. Bacterial 16S ribosomal DNA sequencing was performed on colon biopsies and fecal samples from subjects with chronic, untreated HIV-1 infection and uninfected control subjects. Colon biopsies of HIV-1-infected subjects had increased abundances of Proteobacteria and decreased abundances of Firmicutes compared with uninfected donors. Furthermore at the genus level, a significant increase in Prevotella and decrease in Bacteroides was observed in HIV-1-infected subjects, indicating a disruption in the Bacteroidetes bacterial community structure. This HIV-1-associated increase in Prevotella abundance was associated with increased numbers of activated colonic T cells and myeloid DCs. Principal coordinates analysis demonstrated an HIV-1-related change in the microbiome that was associated with increased mucosal cellular immune activation, microbial translocation, and blood T-cell activation. These observations suggest that an important relationship exists between altered mucosal bacterial communities and intestinal inflammation during chronic HIV-1 infection. PMID:24399150

  12. Altered E-NTPDase/E-ADA activities and CD39 expression in platelets of sickle cell anemia patients.

    PubMed

    Castilhos, Lívia G; Doleski, Pedro H; Adefegha, Stephen A; Becker, Lara V; Ruchel, Jader B; Leal, Daniela B R

    2016-04-01

    Sickle cell anemia (SCA) is a hemoglobinopathy characterized by hemolysis and vaso-occlusions caused by rigidly distorted red blood cells. Sickle cell crisis is associated with extracellular release of nucleotides and platelets, which are critical mediators of hemostasis participating actively in purinergic thromboregulatory enzymes system.This study aimed to investigate the activities of purinergic system ecto-enzymes present on the platelet surface as well as CD39 and CD73 expressions on platelets of SCA treated patients. Fifteen SCA treated patients and 30 health subjects (control group) were selected. Ecto-nucleoside triphosphate diphosphohydrolase (E-NTPDase), ecto-5'-nucleotidase (E-5'-NT) and ecto-adenosine deaminase (E-ADA) activities were measured in platelets isolated from these individuals. Results demonstrated an increase of 41 % in the E-NTPDase for ATP hydrolysis, 52% for ADP hydrolysis and 60 % in the E-ADA activity in SCA patients (P<0.05); however, a two folds decrease in the CD39 expression in platelets was observed in the same group (P<0.01). The increased E-NTPDase activity could be a compensatory mechanism associated with the low expression of CD39 in platelets. Besides, alteration of these enzymes activities suggests that the purinergic system could be involved in the thromboregulatory process in SCA patien